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Biotech SMART Report VOL 02, Oct - Dec 2009 PAGE 2 OF 69

VOL 02 OCT - DEC 2009

Biotech SMART Report

( Summarized Multipurpose Articles on Research and Technology )

Biotech SMART Report is a Quarterly publication from BIRAP, a programme of DBT, Govt. of India which is

dedicated to nurture, incubate and discover innovative research in the Biotechnology Industry.

The Report is an assemblage of updated news reports from company websites, e-newspapers, e-magazines and

market report updates in the area of Biotechnology.

BIOTECHNOLOGY INDUSTRY RESEARCH ASSISTANCE PROGRAM A program of

Department of Biotechnology, Ministry of Science and Technology,

Government of India In partnership with ABLE and BCIL

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CONTENTS

Page No

Section A : Medical Biotechnology (Healthcare)

A -01 Scientists take a step towards uncovering the Histone Code 06

A -02 Springer Adds Cardiovascular Engineering and Technology to Two Other BMES Journals in Publishing Program

07

A -03 Traits of People with Rare Accelerated Aging Syndrome Identified By Researchers 08

A -04 Boston University researchers develop faster, cheaper DNA sequencing method 09

A -05 Type of Cell Proves to Be Highly Significant in Genetic Studies 10

A -06 Missing Piece of DNA Replication Puzzle Identified 11

A -07 Researchers Discover New Ways to Treat Chronic Infections 12

A -08 End Of H1N1 'Second Wave' In Sight In The U.S., According To Quest Diagnostics 14

A -09 Neural Stem Cells In Mice Affected By Gene Associated With Longevity 15

A -10 Pulmonary Arterial Hypertension Reversed In Mouse Models 17

A -11 Researchers Discover RNA Repair System In Bacteria 18

A -12 Enhanced Stem Cells Promote Tissue Regeneration 18

A -13 Human Protein Helps Prevent Infection by H1N1 Influenza and Other Viruses 19

A -14 Hundreds of Leads Generated in Fight against H1N1 Pandemic 21

A -15 Cell Growth Protein Discovery May Lead To New Cancer Therapies 23

A -16 Cigarettes Equal One DNA Mutation 24

A -17 Disrupted Signaling Pathway Turns Tumor Suppressor into Cancer Promoter 25

A -18 What Is Yellow Fever? What Causes Yellow Fever? 26

A -19 Entire Genomes for Lung and Melanoma Cancers Sequenced By UK Researchers 30

A -20 MicroRNA Acts as Tumor Suppressor in Mouse Lung Cancer Model 31

A -21 Universal Flu Vaccine Passes First Hurdle 32

A -22 Anticancer Drug Benefits Diabetes Patients 33

A -23 Combined Lapatinib and Nab-Paclitaxel (Abraxane) Shows Good Activity in HER2+ Breast Cancer

34

A -24 Regular Coffee, Decaf, Tea Consumption Linked To Lower Diabetes Risk 34

A -25 Human trials of swine flu vaccine likely in two weeks 36

A -26 H1N1 Vaccine Administration Goes Well In Northwest Alabama 36

A -27 Cigarette Smoke May Impair Lungs Natural Defense Against Harmful Pathogen 37


A -28 Process That Determines Fate Of White Blood Cells Uncovered 38

A -29 Loss of Tumor-suppressor And DNA-maintenance Proteins Causes Tissue Demise 39

A -30 Scientists discover new cancer gene 40

A -31 Doctors Use Patient's Own Stem Cells To Grow Facial Bone In Groundbreaking Procedure 41

A -32 Swine Flu: Racing Against the Clock to Distribute H1N1 Flu Vaccine 43

A -33 Embryonic-like stem cells generated from cord blood cells 44

Section B : Nano Biotechnology:

B -01 Nanosensors Can Scan Blood for Cancer Biomarkers 45

B -02 Protecting Drugs from the Immune System 45

B -03 New 'Heart Patch' Tissue Created from Stem Cells 46

B -04 Bionic Eye Lets Man See after Years of Blindness 47

Section C : Pharmaceutical Biotechnology:

C -01 European Medicines Agency Grants Cell Therapeutics Orphan Drug Designation for Pixantrone in Diffuse Large B-Cell Lymphoma (DLBCL)

48

C -02 Need For a Global Strategy to Develop New Antibiotics 49

C -03 Ranbaxy recalls drugs for skin disease from US market 49

C -04 Cipla unveils drug to combat H1N1 virus 50

C -05 FDA nod to H1N1 vaccine for infants over 6 mths 50

C -06 Chemical Imaging System Helps Solve Major Hurdle in Pediatric Drug Development 51

C -07 Daiichi to leverage Ranbaxy abroad 52

C -08 US health bill to benefit local generic firms 53

C -09 Zydus first Indian co to file H1N1 clinical trials 54

C -10 Dr Reddy's files for marketing Lipitor generic 55

C -11 Indian scientists discover new genus of mite 55

C -12 ERYtech Pharma Starts Its Pivotal Clinical Trial For GRASPA(R) In Acute Lymphoblastic Leukaemia

56

C -13 Corporate revamping to cost jobs at Johnson & Johnson 56

C -14 Indus’ AIDS molecule gets approval for clinical trials 58

C -15 Quick and Easy Diagnosis For Mitochondrial Disorders 59

C -16 New Research Highlighted At Neuroscience 2009 60


C -17 Paracetamol dampens vaccine effect in kids: Study 61

C -18 Inovio Biomedical Announces Initiation Of HIV Clinical Trial For DNA Vaccine Delivered Using Electroporation

61

Section D : Agriculture Biotechnology:

D -01 Importance of Information & Communications Technology in agriculture emphasized 64

D -02 Rot-resistant Wheat Could Save Farmers Millions 65

D -03 CRRI develops new drought-resistant paddy seeds 65

D -04 Nanotubes can boost plant growth 66

Section E : Green Chemistry & Bio Fuels

E -01 Now, green plastics sans fossil fuel guilt 67

E -02 Genome Sequence Published For Important Biofuels Yeast 68


Section - A: Medical Biotechnology (Healthcare)

Headline: 1 - Scientists take a step towards uncovering the Histone Code

Published by: - Science-Daily

Date of Publication: - Dec. 21, 2009

Source: - www.sciencedaily.com

Researchers at Emory University School of Medicine have determined the structures of two enzymes that customize histones, the spool-like proteins around which DNA coils inside the cell. The structures provide insight into how DNA's packaging is just as important and intricate as the information in the DNA itself, and how these enzymes are part of a system of inspectors making sure the packaging is in order.

The results are published online this week in the journal Nature Structural and Molecular Biology.

A team of scientists led by Xiaodong Cheng, PhD, professor of biochemistry at Emory and a Georgia Research Alliance eminent scholar, used X-rays to probe the architecture of two enzymes, PHF8 and KIAA1718. The enzymes are known as histone demethylases because they remove methyl groups (chemical modifications of a protein) from histones.

Mutations in the gene encoding one of the enzymes, PHF8, cause a type of inherited mental retardation. Understanding how PHF8 works may help doctors better understand or even prevent mental retardation. Many biologists believe the modifications on histones are a code, analogous to the genetic code. Depending on the histones' structure, access to DNA in the nucleus can be restricted or relatively free. The idea is: the modifications tell enzymes that act on DNA valuable information about getting to the DNA itself.

"This work represents a step toward uncovering the molecular basis for how demethylases handle multiple signals on histones," says Paula Flicker, PhD, who oversees cell signaling grants at the National Institutes of Health's National Institute of General Medical Sciences. "Knowledge of how these complex signals help govern patterns of gene activity will bring us closer to understanding how cells determine their identity during development."

To understand histone demethylases' role in the cell, Cheng says, think of the cell as a library with thousands of books in it.

"To find a particular book in a library, you need some signs telling you how the stacks are organized," he says. "Similarly, the machinery that reads DNA needs some guidance to get to the right place."

Histones have a core that the DNA wraps around and flexible tails extending beyond the core. The cells' enzymes attach a variety of bells and whistles -- methyl groups are just one -- to the histone tails to remind the cell how to handle the associated DNA.

Methyl groups mean different things depending on where they are on the histone. In addition, the modifications vary from cell to cell. In the brain, for example, the modifications on a particular gene might signal "this gene should be read frequently," and in muscle, a different set of modifications will say "keep quiet."

"What these enzymes do is make sure all the signs are consistent with each other," Cheng says. "If a sign is out of place, they remove it."

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PHF8 and KIAA1718 are each made up of two attached modules. One module (called PHD) grabs a histone tail with a methyl group on it, while the other module (Jumonji) removes a methyl group from somewhere else on the tail. Scientists previously knew the structures of the methyl-binding and methyl-removing modules in isolation. What is new is seeing how the modules are connected and how one part regulates the other, Cheng says.

The research was supported by the National Institutes of Health and the Georgia Research Alliance.

Headline: 2 - Springer Adds Cardiovascular Engineering and Technology to Two Other BMES Journals in Publishing Program

Published by: - Medical News Today

Date of Publication: - 20 Dec 2009

Source: - www.medicalnewstoday.com

Springer and the Biomedical Engineering Society (BMES) have founded a new journal Cardiovascular Engineering and Technology (CVET). CVET is a forum for research on all aspects of cardiovascular physiology and medical treatment. The first issue of the new quarterly journal will appear in March 2010 and joins two other BMES publications at Springer, Annals of Biomedical Engineering and Cellular and Molecular Bioengineering.

Cardiovascular Engineering and Technology will present a wide spectrum of research, from basic to translational, covering cardiovascular physiology and medical treatment. It will offer academic and industrial investigators a platform for the dissemination of research that utilizes engineering principles and methods to advance knowledge and technological solutions related to the cardiovascular system. Coverage will range from subcellular to systems level topics, including implantable medical devices, tissue biomechanics, functional imaging, surgical devices and diagnostic instruments, among others. Ajit P. Yoganathan of the Georgia Institute of Technology in Atlanta, USA, is editor-in-chief.

Robert Tranquillo, Chair of the BMES Publications Committee, said, "The Biomedical Engineering Society is excited to build on its strong partnership with Springer in offering this journal. We expect the journal to flourish, given the broad interest in this topic among academic researchers and medical device companies. The capable leadership and renowned stature of its inaugural editor-in-chief, Dr. Yoganathan, and the excellent services provided by Springer promise success."

Michael D. Weston, Senior Editor of Biomedical Engineering at Springer, said, "Springer is committed to helping the Biomedical Engineering Society accomplish its mission of publishing the best possible journals in biomedical engineering and bioengineering. We are excited to launch Cardiovascular Engineering and Technology with BMES at a time when advances in cardiovascular research and therapy are rapidly developing. Springer is proud to partner with BMES on this new journal, while at the same time strengthening our commitment to the two other Society journals we publish, Annals of Biomedical Engineering and Cellular and Molecular Bioengineering."

http://www.medicalnewstoday.com/�


Headline: 3 - Traits of People with Rare Accelerated Aging Syndrome Identified By Researchers




UT Southwestern Medical Center researchers have provided the most extensive account to date of the unique observable characteristics seen in patients with an extremely rare premature aging syndrome. The findings, reported online and in the December issue of the Journal of Clinical Endocrinology and Metabolism, suggest that patients with atypical progeroid syndrome (APS) should not be lumped together with those diagnosed with two similar but more well-defined accelerated aging disorders called progeria and mandibuloacral dysplasia (MAD).

"Before this paper, APS was not recognized as a distinct disease," said Dr. Abhimanyu Garg, professor of internal medicine in the Center for Human Nutrition at UT Southwestern and the study's lead author. "Although APS is extremely rare, we believe it should be a distinct entity, particularly since it seems to be less severe than either of the related disorders, and the patients show unique clinical features and metabolic abnormalities."

There are currently 24 reported cases of APS worldwide, including the 11 evaluated in the recent UT Southwestern study.

UT Southwestern is considered a leading center in the world for the study of accelerated aging disorders MAD and APS. Patients come to UT Southwestern's Clinical and Translational Research Center from around the world to be evaluated and participate in various clinical trials.

"A few other centers have reported one or two patients, but our findings on 11 patients are the most extensive to date, by far," said Dr. Garg, chief of nutrition and metabolic diseases at UT Southwestern. "The challenge was that no one had spelled out the physical characteristics unique to the atypical syndrome."

Prior research has shown that APS, MAD and progeria are all caused by mutations in the LMNA gene. Mutations in this gene also are linked to muscular dystrophies, cardiomyopathies and a body-fat disorder called familial partial lipodystrophy.

Five males and six females participated in the recent UT Southwestern study, undergoing numerous diagnostic tests. Most of the participants were short for their ages, had beaked noses, thin lips and thin, shiny skin with abnormal pigmentation, frequent markers of accelerated aging disorders. Some had gray hair at a young age. In addition, eight of the 11 participants had lipodystrophy (abnormally low body fat), four had diabetes and five exhibited heart valve problems. The female participants all had poorly developed breasts.

Unlike most individuals diagnosed with either MAD or progeria, patients evaluated in the UT Southwestern report displayed only slight evidence of scalp hair loss; their jaws were more fully developed; and only a few showed minimal resorption of fingertips or clavicles. The onset of other clinical symptoms also seemed to be delayed, potentially explaining why those with APS often live longer.

Dr. Garg said the findings suggest that the variations between the clinical presentations of APS, MAD and progeria are largely due to unique mutations or blips in the LMNA gene linked to each disorder.


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"Based on our findings, we believe that using a one-size-fits-all approach to therapy will probably not work," he said.

The next step, Dr. Garg said, is to begin clinical trials to find novel therapies that may help slow the aging process.

Other UT Southwestern researchers involved in the research were Dr. Lalitha Subramanyam, former fellow in endocrinology; Dr. Anil Agarwal, associate professor of internal medicine; Dr. Vinaya Simha, clinical assistant professor of internal medicine; and Dr. Benjamin Levine, professor of internal medicine. Researchers from Tor Vergata University in Rome and St. James's University Hospital in Leeds, U.K., also contributed to the report.

The research was funded by the National Institutes of Health and Southwestern Medical Foundation.

Headline: 4 - Boston University researchers develop faster, cheaper DNA sequencing method

Published by: - GEN

Date of Publication: - Dec 20 2009,

Source: - www.genengnews.com

BOSTON EMBARGOED UNTIL 1 P.M. EST 12/20/09 -- Boston University biomedical engineers have devised a method for making future genome sequencing faster and cheaper by dramatically reducing the amount of DNA required, thus eliminating the expensive, time-consuming and error-prone step of DNA amplification.

In a study published in the Dec. 20 online edition of Nature Nanotechnology, a team led by Boston University Biomedical Engineering Associate Professor Amit Meller details pioneering work in detecting DNA molecules as they pass through silicon nanopores. The technique uses electrical fields to feed long strands of DNA through four-nanometer-wide pores, much like threading a needle. The method uses sensitive electrical current measurements to detect single DNA molecules as they pass through the nanopores.

"The current study shows that we can detect a much smaller amount of DNA sample than previously reported," said Meller. "When people start to implement genome sequencing or genome profiling using nanopores, they could use our nanopore capture approach to greatly reduce the number of copies used in those measurements."

Currently, genome sequencing utilizes DNA amplification to make billions of molecular copies in order to produce a sample large enough to be analyzed. In addition to the time and cost DNA amplification entails, some of the molecules like photocopies of photocopies come out less than perfect. Meller and his colleagues at BU, New York University and Bar-Ilan University in Israel have harnessed electrical fields surrounding the mouths of the nanopores to attract long, negatively charged strands of DNA and slide them through the nanopore where the DNA sequence can be detected. Since the DNA is drawn to the nanopores from a distance, far fewer copies of the molecule are needed.

Before creating this new method, the team had to develop an understanding of electro-physics at the nanoscale, where the rules that govern the larger world don't necessarily apply. They made a counterintuitive discovery: the longer the DNA strand, the more quickly it found the pore opening.

http://www.genengnews.com/�


"That's really surprising," Meller said. "You'd expect that if you have a longer 'spaghetti,' then finding the end would be much harder. At the same time this discovery means that the nanopore system is optimized for the detection of long DNA strands -- tens of thousands basepairs, or even more. This could dramatically speed future genomic sequencing by allowing analysis of a long DNA strand in one swipe, rather than having to assemble results from many short snippets.

"DNA amplification technologies limit DNA molecule length to under a thousand basepairs," Meller added. "Because our method avoids amplification, it not only reduces the cost, time and error rate of DNA replication techniques, but also enables the analysis of very long strands of DNA, much longer than current limitations."

With this knowledge in hand, Meller and his team set out to optimize the effect. They used salt gradients to alter the electrical field around the pores, which increased the rate at which DNA molecules were captured and shortened the lag time between molecules, thus reducing the quantity of DNA needed for accurate measurements. Rather than floating around until they happened upon a nanopore, DNA strands were funneled into the openings.

By boosting capture rates by a few orders of magnitude, and reducing the volume of the sample chamber the researchers reduced the number of DNA molecules required by a factor of 10,000 from about 1 billion sample molecules to 100,000.

Headline: 5 - Type of Cell Proves to Be Highly Significant in Genetic Studies




Choosing the right cell type is particularly important in genetic studies. This is apparent from research published on 16 October in PLoS Genetics. Dutch researcher Alice Gerrits has shown how variations in the genome can influence the activity of genes. This effect was found to be strongly dependent on the cell type in which these genes were active.

Although all the cells in our body contain essentially the same DNA (genome), they do not all exhibit the same functions. This is usually because different sets of genes are active in different types of cells. Gerrits investigated four types of blood cells in 25 mouse strains with slightly different genomes. In each of the four cell types, she looked for differences in gene activity between the 25 mouse strains and determined which pieces of the genome caused these differences. She discovered that some pieces of the genome had the same effect on the activity of genes in all four cell types. Yet interestingly, a far larger number of pieces exerted an effect on gene activity mostly in one, two or three of the four cell types.

Puzzling with genomes

The 25 different mouse strains were generated many years ago by crossing two clearly different laboratory mice with each other. The two mice differed, for example, in fur colour, average life expectancy and the number of blood-forming stem cells in their bone marrow. By repeatedly crossing the offspring of the two mice 25 different strains of mice were eventually obtained, all of which had a unique mosaic of the genomes of the two starting mice. Molecular markers were used to indicate which pieces of the genome originated from each of the two mice. By comparing variations in the genome of the 25 different mouse strains with variations in gene activity, Gerrits could see which pieces of the genome exerted an influence on the activity of which genes.



Far-reaching implications

It is known that some variations in the genome play a role in the development of diseases such as leukaemia. Gerrits' research revealed that variations in the genome do not always have the same effect on the activity of genes, but that this effect is strongly dependent on the type of cell in which these genes are active. This means that in future genetic studies as many different cell types as possible must be examined. This is the only way to properly investigate how variations in the genome can lead to changes in gene activity or eventually even to the development of diseases.

Gerrits carried out her research together with Yang Li and Bruno Tesson. The research was largely funded by the Vici grants of Gerald de Haan and Ritsert Jansen, received from NWO's Innovational Research Incentives Scheme.

Headline: 6 - Missing Piece of DNA Replication Puzzle Identified




DNA replication is a basic function of living organisms, allowing cells to divide and multiply, all while maintaining the genetic code and proper function of the original cell. The process, or mechanism, by which this is accomplished presents many challenges as the double helical (coil-shaped) DNA divides into two strands that are duplicated by different methods, yet both strands complete the replication at the same time.

New research by a team from UMDNJ-Robert Wood Johnson Medical School in conjunction with the University of Illinois and published in the Dec. 17 issue of Nature, has addressed this fundamental problem. The study identifies three essential ways the synthesis of the two strands is coordinated by enzymes, settling scientific deliberations on how the two DNA strands are copied in the same time span.

"DNA replication is a fundamental reaction required for the maintenance, survival, and propagation of living cells. It is also a very complex reaction that has been studied for decades without a clear understanding of how the two interwound strands are copied at the same time," says Smita Patel, PhD, professor of biochemistry at Robert Wood Johnson Medical School and lead author of the paper. "Our study explains how the replication is coordinated -- an important piece of the puzzle, because errors in DNA replication can cause disabilities and disease, such as cancer."

The helicase enzyme initiates DNA replication, by unwinding, or separating, the strands which are then reproduced by polymerase enzymes which are responsible for making an exact copy of the DNA. One strand, called the leading strand, is reproduced continuously, whereas the other, lagging strand is reproduced in fragments that are later joined together. How the two strands are replicated at the same time was not previously understood because the polymerase enzyme that replicates the lagging strand must recycle after the completion of each fragment.

According to Dr. Patel, the researchers used these state-of-the-art methods to measure the progression of DNA synthesis in the millisecond time scale. "We employed rapid kinetic methods to investigate this problem and coupled it with single molecule fluorescence measurements to show that the replication enzymes do not pause, as previously thought, but our studies suggest that the short fragments are synthesized at a slightly faster rate so lagging strand synthesis can keep up with the synthesis of the leading strand that is made continuously," said Dr. Patel.



These methods captured the replication enzymes in the act of making the DNA and identified the three ways the strands complete replication simultaneously. First, as Dr. Patel noted, the lagging strand polymerase keeps up with the leading strand polymerase by moving a little faster, which gives the lagging polymerase the extra time it needs to recycle and start the synthesis of a new DNA fragment. This finding supports an early model proposed by Bruce Alberts, a professor emeritus in the department of biochemistry and biophysics at the University of California, San Francisco, former president of the National Academy of Sciences and editor-in-chief of Science magazine.

The study also shows that the reproduction time is further reduced by making the RNA primer ahead of time as the lagging-strand synthesis progresses through the cycle. The RNA primer is a sequence of nucleotides (molecules that, when joined together, make up the structural units of RNA and DNA) copied from DNA. According to Dr. Patel, the polymerase needs RNA primer to initiate replication of a new fragment and that making it "on the fly" saves time in the replication process. Lastly, the research shows that the RNA primer is kept in physical proximity to the lagging strand polymerase by means of priming loop so that the polymerase enzyme can access it and begin replication of a new fragment quickly.

Thus, the faster movement of the lagging strand polymerase enzyme, the ability to make the RNA primer ahead of time and the ability for the polymerase enzyme to access the RNA primer quickly due to its close location allow the two strands of the DNA to be copied in the same time span.

The study was a collaboration of investigative teams led by Smita Patel, PhD, professor of biochemistry at Robert Wood Johnson Medical School and Taekjip Ha, PhD, HHMI investigator and professor of physics and a co-director of Center for the Physics of Living Cells at the University of Illinois at Urbana-Champaign. The study, officially titled "Coordinating DNA replication via priming loop and differential synthesis rate" was chosen for advanced online publication in November and appears in the December 17 print issue of Nature, pages 940-944. The first author of the paper is Manjula Pandey, PhD, a research teaching specialist and additional authors include graduate student Ilker Donmez and research teaching specialist Gayatri Patel of the department of biochemistry at Robert Wood Johnson Medical School and Salman Syed, research scientist in the department of physics at the University of Illinois at Urbana-Champaign.

The research was supported by grants from the National Institutes of Health and the National Science Foundation.

Headline: 7 - Researchers Discover New Ways to Treat Chronic Infections




Researchers at Binghamton University, State University of New York, have identified three key regulators required for the formation and development of biofilms. The discovery could lead to new ways of treating chronic infections.

Biofilms communities of bacteria in self-produced slime may be found almost anywhere that solids and liquids meet, whether in nature, in hospitals or in industrial settings. Biofilms are implicated in more than 80 percent of chronic inflammatory and infectious diseases caused by bacteria, including ear infections, gastrointestinal ulcers, urinary tract infections and pulmonary infections in cystic fibrosis patients, according to the Centers for Disease Control.





Biofilms are difficult to eradicate with conventional antimicrobial treatments since they can be nearly 1,500-fold more resistant to antibiotics than planktonic, free-floating cells. Biofilms also pose a persistent problem in many industrial processes, including drinking water distribution networks and manufacturing.

Karin Sauer, associate professor of biology at Binghamton University, and graduate student Olga Petrova published their findings of key regulatory events required for the formation and development of Pseudomonas aeruginosa biofilms in PLoS Pathogens, a peer-reviewed, open-access journal published online by the Public Library of Science.

"We have found a pathway of how the formation of biofilms is controlled," Sauer said. "If we can figure out how to make use of this newly discovered genetic program, we can interfere with the formation of biofilms and either prevent or treat biofilm infections more successfully."

Pseudomonas aeruginosa, an opportunistic pathogenic bacterium, is considered one of the primary causes of death in patients with cystic fibrosis, a common and life-threatening hereditary disease.

Petrova documented a previously unknown genetic program composed of several regulators by looking for changes in phosphorylation patterns in Pseudomonas aeruginosa. These regulators cannot only be used to stop the development of biofilms at various stages in their growth but also to revert established biofilms to an earlier developmental stage.

"The problem you have when you have a chronic infection is that your immune system is trying to clear the infection but is unable to," Sauer said. "And the longer the chronic infection goes on, the more damage there will be to tissue at the site of the infection. That's because the immune response often involves the release of toxic compounds that have no effect on biofilms but can damage the surrounding tissues."

Sauer's research is driven by several key questions, she said: "Can we outsmart the biofilms? Can we interfere with biofilm antibiotic resistance? Can we figure out how to prevent biofilms from forming and becoming resistant to antibiotics?"

Some recent findings seem to offer a resounding yes to these questions. In addition to regulators required for biofilm formation, Sauer and her team recently identified a regulator that is only expressed in biofilms and which seems to be responsible for regulating antibiotic resistance.

"We can modulate the resistance of biofilms now by over-expressing or inactivating this particular regulator," she said. "We hope to use these discoveries to treat infections by interfering with the way biofilms are growing and by reverting biofilms back to a state where they're more easily treatable."

Sauer's research is supported by the National Institutes of Health, which has awarded her more than $3 million, and the Army Research Office. Her two major NIH-funded projects, which began this fall, look at different aspects of biofilms. One focuses on antibiotic resistance and the mechanism behind it; the other centers on dispersion, the process by which a biofilm breaks down into individual bacterial cells.

"Dispersed cells or planktonic cells are way easier to treat," Sauer said. "We want to understand how bacteria decide when to leave the biofilm. We can use that as a way to treat chronic infections."



Headline: 8 - End Of H1N1 'Second Wave' In Sight In The U.S., According To Quest Diagnostics




Rates of 2009 H1N1 influenza virus testing in the U.S. have declined more than 75 percent since their peak in late October, suggesting that the "second wave" of virus infection that sickened tens of millions of Americans since it began four months ago may be coming to an end, according to a new report by Quest Diagnostics Incorporated (NYSE: DGX), the world's leading provider of diagnostic testing, information and services.

The Quest Diagnostics Health Trends(TM) Report "H1N1 Testing in America: End of the Second Wave?" also indicates that the virus is still the dominant influenza virus in the U.S. and that close to four in ten school-age children tested as recently as last week were infected with the pandemic virus.

"Our data are a welcome indication that H1N1 may not be the health threat during the holidays that it has been throughout the fall," said Jay M. Lieberman, M.D., medical director, infectious diseases, Quest Diagnostics. "Nonetheless, this is no time for people to be complacent about protecting themselves and their families from H1N1 infection. The 2009 H1N1 influenza virus continues to be far and away the most significant source of influenza in every region of the U.S., according to our data. Many millions of people remain susceptible to the virus, which continues to cause serious disease in some individuals.

"In addition, the prospect of a third wave of virus activity next year means it is far too soon to declare victory over H1N1," continued Dr. Lieberman.

Quest Diagnostics analyzed results of nearly 170,000 de-identified patient specimens it tested for the 2009 H1N1 influenza virus in the U.S. between May 11, 2009, when the company introduced its first test for detecting the pandemic virus, and December 9, 2009. Quest Diagnostics is the only company in the U.S. that both performs testing for H1N1 and also provides 2009 H1N1 laboratory testing kits, developed by its Focus Diagnostics business, that are FDA authorized for emergency use by qualified molecular laboratories. The tests employ real-time reverse transcription polymerase chain reaction to qualitatively detect the virus' RNA in a patient's nasal or nasopharyngeal specimens.

Influenza viruses often circulate in waves of activity. The report indicates that two major waves of H1N1 influenza virus activity have affected the U.S., based on the company's test data. The first wave started in early May, following the discovery of the virus in the U.S. in late April. A second wave began in late August and peaked the week ending October 28. Between the weeks ending October 28 and December 9, testing rates fell by 75 percent, and now are roughly equivalent with testing rates experienced when the second wave began.

Other key findings:

-- The number of specimens that tested positive for 2009 H1N1 influenza has declined in all age groups since late October. Children ages five to 14 continue to experience the highest percentage of H1N1 positive test results compared to negative results, with a positivity rate of close to 40 percent. "Our findings suggest that children continue to be most vulnerable to the H1N1 virus," said Dr. Lieberman.

-- Nearly every region experienced declines of 60 percent or more in positive test results during the two weeks ending December 9 compared to the two weeks ending November 25. The most striking






decline in positive test results occurred in the region comprised by Pennsylvania, Maryland, Delaware, Virginia and West Virginia, and the District of Columbia (87 percent decline).

-- The 2009 H1N1 influenza virus remains the predominant cause of influenza in the U.S., as more than 98 percent of positive influenza A specimens are positive for 2009 H1N1 influenza. "Our data provide no evidence that seasonal influenza viruses have begun to circulate," added Dr. Lieberman.

The Quest Diagnostics investigators believe the decline in testing demand is due to several factors, primarily lower rates of infection due to millions of Americans having already been infected with this influenza virus and the impact of H1N1 vaccines, both of which have reduced the number of people susceptible to infection, and changes in physician test-ordering practices.

About the FDA's Emergency Use Authorization

The Focus Diagnostics 2009 H1N1 influenza virus tests have not been FDA cleared or approved. These tests have been authorized by FDA under an Emergency Use Authorization (EUA). These H1N1 tests are only authorized for the duration of the declaration of emergency under section 564(b)(1) of the Act, 21 U.S.C. Section 360bbb-3(b)(1). The declaration of emergency will expire on April 26, 2010, unless it is terminated or revoked sooner or renewed.

About Quest Diagnostics

Quest Diagnostics is the world's leading provider of diagnostic testing, information and services that patients and doctors need to make better healthcare decisions. The company offers the broadest access to diagnostic testing services through its network of laboratories and patient service centers, and provides interpretive consultation through its extensive medical and scientific staff. Quest Diagnostics is a pioneer in developing innovative diagnostic tests and advanced healthcare information technology solutions that help improve patient care

Headline: 9 - Neural Stem Cells In Mice Affected By Gene Associated With Longevity


Date of Publication: - Nov. 5, 2009

Source: - http://www.sciencedaily.com

A gene associated with longevity in roundworms and humans has been shown to affect the function of stem cells that generate new neurons in the adult brain, according to researchers at the Stanford University School of Medicine. The study in mice suggests that the gene may play an important role in maintaining cognitive function during aging.

"It's intriguing to think that genes that regulate life span in invertebrates may have evolved to control stem cell pools in mammals," said Anne Brunet, PhD, assistant professor of genetics. She is the senior author of the research, which will be published Nov. 6 in Cell Stem Cell.

Unlike your skin or your intestine, your adult brain doesn't make a lot of new cells. But those it does are critical to learning, memory and spatial awareness. To meet these demands, your brain maintains two small caches of neural stem cells, which can both self-renew and give rise to neurons and other cells known as oligodendrocytes and astrocytes. Properly balancing these functions allows you to generate new nerve cells as needed while also maintaining a robust neural stem cell pool.



As mice and other organisms age, the pool of neural stem cells in the brain shrinks and fewer new neurons are generated. These natural changes correlate with the gradual loss of cognitive ability and sensory functions that occur as we approach the end of our lives. However, the life span of some laboratory animals can be artificially extended by mutating genes involved in metabolism, and some humans outlive their life expectancy (about 70 years for someone born in 1960) by decades. Brunet and her colleagues wanted to know why.

The researchers studied a family of transcription factors called FoxO known to be involved in proliferation, differentiation and programmed cell death. FoxO genes are required for the extreme longevity seen in some strains of laboratory roundworms, and a single mutation in the FoxO3 gene has recently been associated with long life in Japanese, German, American and Italian populations.

"We wanted to know if FoxO3 could be involved in regulating the pool of neural stem cells," said Brunet. To do so, the researchers examined laboratory mice in which the FoxO3 gene was knocked out. While mice can live without FoxO3, such mice usually die from cancer between 12 and 18 months after birth. The normal life span of a laboratory mouse is about 30 months.

Brunet and her colleagues used mice of three different ages, both with and without the gene: 1-day-old (newborns), 3-month-old (young adult) and 1-year-old (middle age). They found that, overall, adult and middle-aged mice without FoxO3 had fewer neural stem cells than did age-matched mice with this regulatory protein. There were no significant differences between the newborn mice with and without FoxO3, suggesting that FoxO3 loss only affects adults.

The researchers also discovered that the few stem cells found in the adult mice without FoxO3 more rapidly churned out neural cell precursors -- those cells destined to become new neurons -- than did the mice with normal FoxO3 levels. In fact, the brains of the mice that lacked FoxO3 were heavier than the control group, perhaps because they were burning through their pool of neural stem cells by making too many new nerve cells.

When the researchers looked at the neural stem cell in a laboratory dish, they found that those from young and middle-aged adult mice lacking FoxO3 -- but not those from newborn mice -- seemed to be compromised in their ability to self-renew and to generate the three types of nerve cells. Further investigation bolstered their findings when they discovered that the FoxO3 protein regulates the expression of genes involved in quiescence and differentiation in cells.

The researchers concluded that FoxO3 may be needed for the stem cells to re-enter a waiting state called quiescence that normally occurs after dividing. Cells that are unable to enter quiescence are less able to self-renew and may lose their ability to become any of the three nerve cell types.

Together, the research results suggest that FoxO3 is important to regulate the pool of neural stem cells in the adult brain.

Although the researchers studied mice of varying ages, from birth to about one year, Brunet stressed that their current study does not address changes that might occur in FoxO3 levels or activity over time -- a technically difficult endeavor they are now pursuing.

"We suspect that indeed there will be some changes," said Brunet. "But they will be relatively subtle. We know that the level of FoxO3 doesn't vary drastically, but it's possible the protein becomes less active over a mouse's life span. Or perhaps it simply becomes overwhelmed by the accumulated molecular changes of aging."

Brunet and her colleagues, along with collaborators at the University of Arkansas, are working on creating a mouse in which FoxO3 levels are artificially elevated. If their theory about the function of the protein in the brain is correct, it's possible that the neural stem cell pools of these mice will be protected from the ravages of time.


"We're very interested in understanding how everything unravels during the aging process," said Brunet.

Headline: 10 - Pulmonary Arterial Hypertension Reversed In Mouse Models


Date of Publication: - Oct. 26, 2009


Researchers at the University of California, San Diego, have identified a key protein that promotes the development of pulmonary arterial hypertension in humans and mice. This groundbreaking discovery has implications for future drug therapies that may extend the life of patients with pulmonary arterial hypertension and prevent the need for lung transplantation, currently the only cure for this debilitating disease.

In a paper to be published online in Nature Medicine on October 25, Patricia Thistlethwaite, MD, PhD, Professor of Surgery and cardiothoracic surgeon in UCSD's Department of Surgery, and colleagues describe the genetic pathway by which vascular smooth muscle cells associated with pulmonary arterial hypertension are switched on to proliferate by a receptor protein called Notch-3. With this finding, the researchers were able to block and reverse the pathway of disease in mice.

"The UCSD team found that pulmonary hypertension is characterized by overexpression of Notch-3 and that the severity of the disease correlates with the amount of this protein in the lung," said Thistelthwaite. "We showed that a mouse model lacking this protein does not develop pulmonary hypertension, and in addition, that the disease can be effectively treated with an enzyme called γ-secretase inhibitor, which blocks Notch-3 activation."

In Thistlethwaite's laboratory, mice with pulmonary arterial hypertension that were treated with the γ-secretase inhibitor showed reversal of the disease. Forms of this drug are currently in use in Phase 1 trials for the treatment of Alzheimer's disease.

Pulmonary arterial hypertension is a form of high blood pressure in the lung's arteries. The disease begins when tiny arteries in the lungs become narrow, blocked or destroyed causing resistance to blood to flow. As the pressure builds, the heart's lower right chamber becomes overworked and weakens, leading to ventricular failure. The condition afflicts more than 100,000 patients in the United States, causing 20,000 deaths per year.

"Pulmonary arterial hypertension is more common in the human population than is currently realized, and unfortunately, is often fatal," said co-author Stuart Jamieson, MB, FRCS, Distinguished Professor of Surgery and Chair of Cardiothoracic Surgery at UC San Diego Medical Center. "Current drugs to treat pulmonary arterial hypertension focus on dilating the arterial vessels but do not address the eventual thickening of the artery walls. Fortunately, by identifying this drug target it seems we are now on the right path to developing an intervention that prevents abnormal cell proliferation."



Headline: 11 - Researchers Discover RNA Repair System In Bacteria




In new papers appearing this month in Science and the Proceedings of the National Academy of Sciences, University of Illinois biochemistry professor Raven H. Huang and his colleagues describe the first RNA repair system to be discovered in bacteria. This is only the second RNA repair system discovered to date (with two proteins from T4 phage, a virus that attacks bacteria, as the first).

The novelty of the newly discovered bacterial RNA repair system is that, before the damaged RNA is sealed, a methyl group is added to the two-prime hydroxyl group at the cleavage site of the damaged RNA, making it impossible to cleave the site again. Thus, the repaired RNA is "better than new."

This discovery has implications for protecting cells against ribotoxins, a class of toxins that kills cells by cleaving essential RNAs involved in protein translation. Because the enzyme responsible for methylation in the newly-discovered RNA repair system is the Hen1 homolog in bacteria, the finding has also implications for the understanding of RNA interference and gene expression in plants, animals, and other eukaryotes. The eukaryotic Hen1 is one of three enzymes (along with Dicer and Argonaute) essential for the generation of small noncoding RNAs of 19-30 nucleotides in RNA interference.

While the Science paper describes the mechanism of the entire RNA repair process, the article in PNAS focuses on the chemistry of the methylation reaction, specifically the crystal structure of the methyltransferase domain of bacterial Hen1. Because the eukaryotic Hen1 carries out the same chemical reaction, the study should further understanding of RNA interference in eukaryotic organisms.

"Hen1 is one of three essential enzymes in generating small noncoding RNAs for RNA interference in eukaryotes," Huang said. "We found out that Hen1 homologs exist in bacteria, but bacteria have no RNA interference. Therefore, we were very curious to find out what bacterial Hen1 is used for."

"Our studies demonstrated that bacterial Hen1 carries out the same chemical reaction as its counterpart in eukaryotes, which was not surprising," he said. "What surprised us was that, instead of involvement in RNA interference, the bacterial Hen1 is part of a RNA repair and modification system. And Hen1 is responsible for producing the repaired RNA that is 'better than new.'"

Headline: 12 - Enhanced Stem Cells Promote Tissue Regeneration




MIT engineers have boosted stem cells' ability to regenerate vascular tissue (such as blood vessels) by equipping them with genes that produce extra growth factors (naturally occurring compounds that stimulate tissue growth). In a study in mice, the researchers found that the stem cells successfully generated blood vessels near the site of an injury, allowing damaged tissue to survive.




Stem cells hold great potential as a way to promote tissue regeneration. However, this approach has been limited because stem cells don't produce enough growth factors after transplantation. The researchers' new super-charged stem cells could be used to treat an infarction (death of tissue caused by blockage of the blood supply, by a clot or another obstruction), or to induce blood supply for engineered tissues.

After removing stem cells from mouse bone marrow, the researchers used specially developed nanoparticles to deliver the gene for the growth factor VEGF (vascular endothelial growth factor). The stem cells were then implanted into damaged tissue areas. These nanoparticles, which the MIT team has also tested to deliver cancer treatments, are believed to be safer than the viruses often used for gene delivery.

Though the results are promising, the technique needs more improvements before any human trials can begin, says Daniel Anderson, a senior author of the paper.

Headline: 13 - Human Protein Helps Prevent Infection by H1N1 Influenza and Other Viruses




Howard Hughes Medical Institute researchers have identified a naturally occurring human protein that helps prevent infection by H1N1 influenza and other viruses, including West Nile and dengue virus

A research team led by Howard Hughes Medical Institute investigator Stephen J. Elledge and his colleague, Abraham Brass, discovered that human cells respond to infection by the H1N1 influenza virus by ramping up production of proteins that have unexpectedly powerful antiviral effects. In cultured human cells, those proteins, whose functions were previously unknown, block the replication of H1N1 influenza virus, West Nile virus, and dengue virus.

The unexpected discovery could lead to the development of more effective antiviral drugs, including prophylactic drugs that could be used to slow influenza transmission.

The finding, reported December 17, 2009, in an early online article in the journal Cell, is the result of a collaborative effort by researchers at the Howard Hughes Medical Institute, Harvard Medical School, Massachusetts General Hospital, Yale Medical School, and the Wellcome Trust Sanger Institute in Cambridge, UK.

As with other viruses, the influenza virus has only a few genes of its own, and must commandeer proteins produced by its host cell to complete its life cycle. The current study began when Elledge and his colleagues set out to identify the host proteins that the H1N1 virus needs to enter cells and replicate inside them.

To sift quickly through thousands of proteins, Elledge and his colleagues set up large arrays of cultured human cells, and then used a robotic device to deliver small strands of interfering RNA (siRNA) to each well in the array. Each siRNA strand was designed to block the expression of an individual gene, and thus the production of the corresponding protein. For each such gene/protein "knockdown," the automated devices recorded the effect on H1N1 activity by measuring any change in the presence of viral protein on the surface on infected cells.



Using this high-speed screening method, the researchers soon identified more than 120 genes whose expression is required for H1N1 to infect cells. "But in the process of figuring that out, we found this other class of genes that actually have the opposite effect, so that if you get rid of them, influenza replicates much better," said Elledge, an HHMI investigator at Harvard Medical School.

The virus-fighting genes in question code for three members of the Interferon-Inducible Transmembrane (IFITM) protein family: IFITM1, IFITM2 and IFITM3. First described in 1984, IFITMs were known to be produced at low levels in most cells, and at higher levels in cells exposed to immune-stimulating interferon proteins. But their functions had never been understood.

Elledge and his colleagues began to suspect that they were natural antiviral proteins after the disruption of IFITM3 produced startling increases in H1N1 replication. "The virus replicated five to ten times better when IFITM3 wasn't there," said Elledge. "The viral protein level was higher and it would replicate faster. IFITM3 really stood out in this regard."

Elledge and his colleagues, who included HHMI investigator Erol Fikrig at Yale School of Medicine, found the same results for IFITM3 in other cell types, including human and mouse lung cells, and with different H1N1 strains. Then, instead of knocking down IFITM3 production in cells, they increased it -- and found that it completely blocked H1N1 replication.

"This work shows the power of comprehensive screens to identify cellular proteins that are involved in viral replication," said HHMI investigator Robert A. Lamb, a virologist at Northwestern University who was not involved in the study reported in Cell.

The gene for IFITM3 lies on chromosome 11, next to similar genes for IFITM1 and IFITM2. Although IFITM3 had the strongest and most consistent effects in tests, all three proteins, when overproduced, could block H1N1 and every other tested strain of the "Influenza A" virus type.

To the researchers' surprise, increased production of these proteins also blocked the replication of completely different viruses, including strains of West Nile virus and dengue virus.

The IFITMs were not effective against every virus tested; moreover, Elledge and his colleagues aren't sure precisely what these proteins evolved to do. "They have different levels of activity on their own, so they might be more specific for different types of viruses," Elledge said.

Either way, Elledge is convinced that the IFITMs represent a major part of the body's innate immune response to viruses. He and his colleagues found that most of the protective effects of interferons -- which normally trigger an immune response in the presence of a pathogen and are also used therapeutically to boost the immune system -- are lost when IFITM3 is absent from H1N1-infected cells.

How do IFITM3 and its cousins block viruses? The researchers aren't yet sure, but the first clue is that the proteins sit partly outside a cell's membrane. Based on tests conducted so far, Elledge suspects that the IFITMs cause molecules brought in through the cell membrane -- such as viruses -- to be routed to a disposal area where they are swiftly degraded and rendered harmless.

"That may be why the virus can't get away from these IFITMs -- because they affect a fundamental part of its life cycle," said Elledge.

Such traffic-rerouting might also have a negative impact on normal cell signaling and, Elledge notes, that might explain why IFITMs aren't produced in high amounts all the time. "Making too much of these proteins might not be good for people in the long run, but we don't really know yet," he added.

If it turns out to be safe to expose cells to higher than normal levels of IFITMs for days or weeks at a time, the proteins might become the basis of a broad-spectrum antiviral therapy. "It's possible that you


could deliver it directly to the surface of cells, and have protective effects during flu season, for example," Elledge said. IFITMs should have more specific effects than interferon, thus plausibly making them more benign, he added. Interferon-based drugs are used for treatment of cancer and other diseases, but boost many immune-related proteins and cause flu-like symptoms, among other side effects.

Elledge also sees the potential for boosting IFITM levels in animal populations, to control viruses such as influenza that can infect both animals and humans. Manipulating IFITM levels could help, too, in the production of vaccines. The H1N1 vaccine, for example, is based on a weakened form of the virus, and arrived too late to stop the recent epidemic because the virus couldn't be made to grow quickly enough. "If we could just get rid of this gene in virus-producing cells, the virus should grow much faster," Elledge said.

Finally, Elledge noted that in the recent H1N1 epidemic, some infections proved lethal in people who had otherwise seemed healthy. Genetic or other changes that affect IFITM levels could explain some of this increased viral vulnerability, he said: "I think it will be important to figure out how people vary in their abundance of these proteins."

"This work illustrates the important interplay between the cell innate immune response and virus replication," said Lamb. "If IFITM won the war there would not be any influenza virus replication. If influenza didn't induce an innate immune response, influenza would win the war and then the cell (organism) would die."

Headline: 14 - Hundreds of Leads Generated in Fight against H1N1 Pandemic




Scientists have generated hundreds of new leads in the fight against the H1N1 flu pandemic, according to two new studies published online December 17th in the journal Cell. Both research teams took comprehensive approaches to understanding the interaction of H1N1 strains with human cells, yielding results that point toward new targets for therapy and perhaps also new tools to speed vaccine production, the researchers say.

One study took a "multilayered" approach to understand the physical interactions between the virus and human host cell as well as changes in the host as it is manipulated by and responds to viral infection. Aviv Regev and Nir Hacohen of The Broad Institute of MIT and Harvard said their goal wasn't to drill down into any specific interaction; rather their findings provide the research community a global "roadmap" -a bird's eye view of the human-virus interaction -- that can now help guide future studies.

"Navigating with a map is very different than without it," Regev said. "Without a map, you might explore a small patch and stay very close to that. There might be a protein you know something about and you'll look around there. With a global map, you may find uncharted territory. It's like discovering America. You still have a lot to learn, but at least you know it's there."

"This approach generates questions we didn't have before," Hacohen added. "It allows us to stumble upon things we didn't know we needed to figure out."



Their findings reveal how the virus alters the expression of host proteins involved in the detection of viral RNA and in the inflammatory response. Their data also suggest roles for some unanticipated host and viral proteins in viral infection and the host response, including a network of proteins that bind RNA, components of a signaling pathway involved in cell proliferation, and subunits of the viral polymerase that were previously only thought to be responsible for replication of the viral genome.

The approach they took included assays to examine the direct physical interaction of viral and host proteins along with genome-wide expression profiling of infected human cells. Those studies led them to more than 1,700 candidate genes with potentially important roles to play in the infection with influenza or the host response to that infection. They then depleted each of those genes one by one in human lung cells to find those that affect viral replication.

In providing a big picture of the interaction, the researchers also show that the virus's 10 proteins "pack a lot of functions into each one," Hacohen said. "We were impressed by how many host proteins interact with each viral protein," Regev said. "The viral proteins contact the same [human] pathways again and again." That gives the virus many ways to manipulate important pathways, although the researchers don't understand the consequences of those interactions just yet.

In the second study led by Stephen Elledge of Harvard Medical School, researchers went in search of host cell modifiers of influenza A H1N1 viral infection. They used RNA interference to turn human genes off one by one to find out which of them change the way that the flu propagates in cells. That analysis landed them 120 key genes that they refer to as influenza A virus-dependency factors.

One family of related proteins in particular, known as IFITM, caught the team's eye as a particularly important early player that works to stop flu and they decided to explore it in more detail.

"Our protein is induced by interferon and it blocks virus at entry," Elledge said, explaining that interferon is produced as an alarm signal to other cells when a cell senses that it has been invaded by a virus. "If you get rid of IFITM, the virus is replicated five to 10 times more efficiently. It blocks 80 to 90 percent of the virus just by itself."

He said IFITM is a particularly small protein that sits on the surface of vesicles inside cells. Viruses are engulfed by those vesicles and are often destroyed by the cell before an infection can take hold.

Elledge suspects that differences in the amount of IFITM among people might explain differences in their susceptibility to getting sick with the flu. "Natural variation [in this gene] could easily translate into resistance or sensitivity," he said. "We know some people get the flu and are knocked out while others just sniffle a bit."

Drugs aimed at IFITM might fight the flu without an increase in interferon, he said. Interferons are used to combat some viruses such as hepatitis C, but they come with nasty side effects. "You might be able to turn up resistance without making people feel bad," Elledge said. It might even be possible to deliver the protein directly to cells via liposomes. Such a strategy might help in the fight against many infectious diseases, as Elledge showed that IFITM has a similar influence on other viruses, including those responsible for the prevalent mosquito-borne diseases, dengue and West Nile. Likewise, it should be possible to make transgenic animals such as swine or fowl that make more IFITM3 to prevent these animals from becoming reservoirs for flu, where it can recombine with human flu to generate more virulent strains for humans.

The many other proteins they found to be required for the replication of H1N1 could each also yield new ways to fight flu. For its part, IFITM proteins may additionally hold the key to faster production of the weakened virus, as is needed for the making of vaccine.

"If IFITM proteins are also rate-limiting for influenza A virus infection in other organisms such as chickens, whose embryos are employed to passage attenuated viruses for vaccine production, the


inhibition of IFITM protein expression could reduce the amount of time it takes to produce vaccine and thereby boost yields," Elledge's team wrote. "This has been a critical issue confounding vaccine production in the current [H1N1] influenza pandemic."

Headline: 15 - Cell Growth Protein Discovery May Lead To New Cancer Therapies




Researchers in Canada and the US have found a protein that appears to help cancer develop by playing a key role in cell growth and proliferation; they said the discovery helps us better understand cancer physiology and opens the door to new cancer therapies, including diagnostic tools and personalized treatments.

These are the findings of a study published online before print on 11 December in the Proceedings of the National Academy of Sciences (PNAS). The first author is Dr Armen Parsyan, a post-doctoral fellow in the Department of Biochemistry and Rosalind Morris Goodman Cancer Centre in the Faculty of Medicine at McGill University in Montreal in Quebec.

Cell growth and tumor growth rely on protein synthesis: a process where chains of amino acids are assembled according to the instruction manual in the genetic code. Before the amino acid chain can be assembled, the genetic code is first "translated" onto a specific polypeptide "template" using messenger RNA (mRNA).

For the study, Parsyan and colleagues investigated DHX29, a helicase protein that is necessary for translation initiation, and which has recently been described by co-author Dr Tatyana Pestova's laboratory at SUNY Downstate Medical Center in New York.

This study builds on Pestova's work, by documenting the role of DHX29 in protein synthesis and cancer development.

The researchers found that depleting DHX29 from living cells led to a significant decrease of cancer cell proliferation.

Lack of DHX29 appeared to impede cancer growth both in cultured cells and in xenografts (living tissue grafted onto laboratory animals): the tumors formed were much smaller than usual.

Parsyan told the press they were surprised to find yet another translation initiation factor playing a key role in cancer cell proliferation:

"This is another clear indication of the key role that translation initiation factors play in the etiology and pathogenesis of cancer. It's clear we're on the right direction and must continue on this avenue of research."

Lead author Dr Nahum Sonenberg, who last year won the Gairdner Prize for his discoveries in the areas of protein synthesis in human cells, said:

"Two decades ago we reported the first translation initiation factor that promotes tumorigenesis." "Since then several other translation initiation factors were documented to cause cancer, but it's still


http://www.medicalnewstoday.com/info/cancer-oncology/whatiscancer.php�


exciting to find novel initiation factors that add to our knowledge of cancer development," added Sonnenberg, who has also been named Researcher of the Year for Biomedical and Clinical Research by the Canadian Institutes of Health Research.

Headline: 16 - Cigarettes Equal One DNA Mutation




"15 cigarettes equal one DNA mutation" captures graphically the enormity of what was discovered when a UK-led team of scientists reported this week how they cracked the code of two killer cancers: small cell lung cancer and malingnant melanoma. Another compelling revelation was they said they could see "sunlight's signature" in the DNA mutations of the melanoma cells.

As part of a worldwide push by the International Cancer Genome Consortium to unravel the genomes of cancers of major social and clinical importance around the world, scientists at the Wellcome Trust Sanger Institute in Cambridge, revealed on Wednesday how they found nearly 23,000 mutations in lung cancer cells and over 30,000 in melanoma cells, compared to cells of normal tissue from the same individuals.

Peter Campbell, a haemotologist and cancer-genomics expert at the Sanger Institute, and one of the scientists who worked on both studies and co-authored the papers that appeared this week in Nature, described the vast number of mutations as remarkable, and reflecting on the team's estimate that a typical smoker acquires one lung cancer mutation for every 15 cigarettes he or she smokes, said:

"Every pack of cigarettes is like a game of Russian roulette."

"Most of those mutations will land where nothing happens in the genome and won't do major damage, but every once in a while they'll hit a cancer gene," added Campbell, as reported by Nature News.

The researchers also found that the mutations were not distributed evenly in the genome: many were outside the regions that code for genes, and they thought this was probably because cells work harder to repair DNA damage in gene-coding regions.

This is an important insight, and if proven, will help to shed light on some very important questions about the extent to which environment and lifestyle impact DNA: for instance, do carcinogens cause mutations directly (suggesting they are mostly preventable), or does cancer disrupt the DNA repair systems of cells?

The two studies suggest that it is the former, and that these two cancers are indeed largely preventable, because the researchers said they found that most of the DNA changes were traceable to cancer-causing effects of tobacco chemicals in the lung cancer genome and to ultraviolet light in the skin cancer genome.

Another important discovery the team sequencing the lung cancer genome made was that they found one mutation already discovered last year, in CHD7, a gene that controls other genes, appeared again and again, in three independent cells lines, suggesting that targeting recurrent mutations could be a new direction for drug development.

Not everyone is convinced that cancer-genome sequencing is about to transform the way cancer is diagnosed and treated: because it is still very expensive.


http://www.medicalnewstoday.com/info/lung-cancer/what-is-lung-cancer.php�




This was the view of Steve Elledge, a specialist in DNA damage and cancer genetics from Harvard Medical School in Boston, Massachusetts, who said such an approach won't be practical until scientists have hundreds of sequences readily available:

"It's still very expensive, and I think all these efforts should be coupled with an equal amount of effort on studying gene function," he told Nature News.

Headline: 17 - Disrupted Signaling Pathway Turns Tumor Suppressor into Cancer Promoter

Published by: - Biotech-Daily International


Source: - www.biotechdaily.com

Transforming growth factor beta-1 (TGF-beta-1) is an important regulatory protein in normal cells, but disrupted molecular signaling pathways caused by mutations can convert TGF-beta-1 into an active cancer-promoting agent. In normal cells, TGF-beta, acting through its signaling pathway, halts the cell cycle at the G1 stage to stop proliferation, induce differentiation, or promote apoptosis. When a cell is transformed into a cancer cell, parts of the TGF-beta signaling pathway are mutated, and TGF-beta no longer controls the cell. These cancer cells, as well as surrounding stromal cells (fibroblasts), proliferate. Both types of cells increase their production of TGF-beta. This TGF-beta acts on the surrounding stromal cells, immune cells, endothelial and smooth muscle cells to cause immunosuppression and angiogenesis, which makes the cancer more invasive. TGF-beta also converts effector T-cells, which normally attack cancer with an inflammatory reaction, into regulatory (suppressor) T-cells, which turn off the inflammatory reaction.

Investigators at the University of Texas Southwestern Medical Center (Dallas, USA) mapped the molecular relationships of TGF-beta-1 in normal and human breast cancer cells.

They reported in the December 1, 2009, online edition of The Journal of Clinical Investigation that TGF-beta-1 was critically linked to an enzyme, the ubiquitin ligase human murine double minute (HDM2), which is overexpressed in 40%–80% of late-stage metastatic cancers. Increased HDM2 protein expression caused destabilization of the p53 tumor suppressor protein in human cancer cell lines. Furthermore, histological analyses of human breast cancer samples demonstrated that approximately 65% of late-stage carcinomas were positive for activated HDM2, indicating a strong correlation between TGF-beta-1– mediated induction of HDM2 and late-stage tumor progression.

“These genetic changes would start prior to metastases, so if we detect them early, we might be able to tailor treatment in anticipation of a more aggressive cancer,” said contributing author Dr. David Boothman, professor of radiation oncology, and pharmacology at the University of Texas Southwestern Medical Center.

http://www.biotechdaily.com/�


Headline: 18 - What Is Yellow Fever? What Causes Yellow Fever?

Published by: Biotech-Daily International



Yellow fever is an acute systemic illness - a hemorrhagic fever - caused by the Flavivirus. Acute means it comes on (onset) rapidly, while systemic means it affects the whole body. In severe cases yellow fever causes a high fever, bleeding into the skin and the death of cells in the liver and kidney. Liver damage results in severe jaundice - yellowing of the skin; hence the name "yellow fever".

The mosquito Aedes aegypti, and some other species transmit the virus to humans. Aedes aegypti is found in tropical and subtropical parts of South America, parts of the Caribbean, and Africa (not Asia). Apart from mosquitoes, the only other known hosts of the virus are primates and humans.

Experts believe yellow fever originated in Africa and was introduced to South America via the slave trade in the 16th century. Several major yellow fever epidemics have taken place in Europe, the Americas and Africa since the 17th century. It was deemed one of the most dangerous infectious diseases in the 19th century.

According to the World Health Organization (WHO), there are approximately 200,000 cases of yellow fever worldwide each year, and 30,000 deaths. About 90% of all cases occur in Africa.

In the middle of the 20th century a safe and effective vaccine was created. However, since the 1980s the number of yellow fever cases has increased, making it a reemerging disease.

There are two classifications of yellow fever:

Jungle yellow fever - it is spread by jungle mosquitoes and mainly affects monkeys. Humans who go into the jungle can become infected by mosquitoes that became infected by biting infected monkeys, and can be the source of urban outbreaks of the disease.

Urban yellow fever - this is spread when an Aedes aegypti mosquito bites an infected human or monkey and then goes on to bite other people. Urban yellow fever is most likely to occur in settlements close to the jungle, where infected monkeys and mosquitoes live. Urban yellow fever is extremely rare in the Americas. Put simply, a human may go into the jungle, be bitten by an infected mosquito, come back to their settlement, and infect mosquitoes who bite them there; those mosquitoes will then infect other people.

According to Medilexicon's medical dictionary

Yellow fever is "a tropical mosquito-borne viral hepatitis, due to yellow fever virus, a member of the family Flaviviridae, with an urban form transmitted by Aedes aegypti, and a rural, jungle, or sylvatic form from tree-dwelling mammals by various mosquitoes of the Haemagogus species complex; characterized clinically by fever, slow pulse, albuminuria, jaundice, congestion of the face, and hemorrhages, especially hematemesis; used to occur in epidemics mainly in port cities, especially in late summer, with 20-40% case fatality rates; immunity to reinfection accompanies recovery."

:

Jungle yellow fever is "a form occurring in South America, transmitted by Aedes leucocelaenus and various treetop mosquitoes of the Haemagogus complex; transmitted normally to primates, occasionally by chance to humans to set off a human outbreak of classical yellow fever transmitted by Aedes aegypti."

What are the signs and symptoms of yellow fever?




http://www.medilexicon.com/medicaldictionary.php�


Yellow fever has an incubation period of between 3 and 6 days - i.e. it takes from 3 to 6 days for signs and symptoms to appear after a person is infected. The disease cannot spread from human-to-human; it is spread by infection-carrying mosquitoes to humans. Signs and symptoms are categorized into two stages: The acute stage (initial stage)

• Initial symptoms of yellow fever may include: • Aching muscles, particularly the back and knees • An elevated body temperature (fever) • Dizziness • Headache • Loss of appetite • Nausea • Shivers (chills) • Vomiting • These symptoms usually improve after a few days.

Toxic second stage

Although signs and symptoms may go away a few days after the toxic stage, approximately 15% of patients subsequently develop more severe symptoms, and enter the toxic stage. These more severe and sometimes life-threatening signs and symptoms may include:

• Recurring fever • Abdominal pain • Vomiting, sometimes with blood • Tiredness, sluggishness, lethargy • Jaundice (skin and whites of the eyes take on a yellow tinge) • Kidney failure • Liver failure • Hemorrhage • Delirium, seizures, and sometimes coma • Arrhythmias (irregular heartbeats) • Bleeding from the nose, mouth and eyes

Approximately between 20% and 50% of patients who develop toxic stage symptoms die within a couple of weeks. Experts say that out of all people who are infected with yellow fever, about 3% to 7.5% eventually die from it. Those who recover do not generally have any organ damage and are immune for life.

What are the causes of yellow fever?

Yellow fever is caused by a flavivirus; it is transmitted by the bite of mosquitoes, usually the Aedes aegypti mosquito, which had become infected by biting an infected human or animal (a monkey). An infected mosquito is a source of infection for the rest of its life.

Experts say that the flavivirus is endemic among monkeys that live on the tree tops of the jungle (the jungle canopy) in many parts of Africa and the Americas.

If the infected mosquito passes the flavivirus on to a person who is in the jungle, that person may become a source of infection when they return to their community (mosquitoes bite them and become infected and then go on to infect other people).





What are the risk factors for yellow fever?

A risk factor is something which increases the likelihood of developing a condition or disease. For example, obesity significantly raises the risk of developing diabetes type 2. Therefore, obesity is a risk factor for diabetes type 2.

Anybody who travels to an area which is known to have the yellow fever virus is at risk of becoming infected - these areas include parts of Africa (especially sub-Saharan Africa), tropical South America, as well as some parts of the Caribbean.

Do not rely just on reports indicating there have been no cases recently. This could be due to unreliable collection of data, or simply that the local population has been vaccinated. A yellow fever vaccine taken 10 to 14 days before traveling provides effective protection from the disease.

How is yellow fever diagnosed?

Diagnosis will be confirmed after the doctor has detected the signs and symptoms and carried out a blood test. Relying on signs and symptoms alone is not enough, because the following illnesses may also have similar signs and symptoms:

• Dengue fever • Leptospirosis • Malaria • Poisoning • Typhoid • Viral hepatitis • Some other viral hemorrhagic fevers

A blood test may reveal the virus itself; it will detect antibodies that are produced when the virus enters the body. A blood test may also reveal a drop in white blood cells (leucopenia). The blood tests are known as enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction (PCR). Test results may take several days.

What are the treatment options for yellow fever?

There is currently no effective antiviral medication for the treatment of yellow fever. The medical team's focus is mainly on supportive care in a hospital. This includes providing fluids, oxygen, making sure the patient's blood pressure is adequate, replacing lost blood, kidney dialysis if there is kidney failure, and treating any secondary infections.

Some patients may be given plasma transfusion to replace proteins that help with clotting.

The patient should be kept away from mosquitoes - if they bite the patient the mosquitoes will become infected and then pass the disease on to other people.

Prevention of yellow fever

Vaccine There is a very effective and safe vaccine which prevents yellow fever. If you are traveling to an area where yellow fever is known to exist, see your doctor and ask about having the vaccine at least 10 to 14 days before your departure. Some countries may insist on a valid immunization certificate before they let you in. A single vaccine dose provides at least 10 years' protection. Vaccine side effects may include:

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• Headaches • Low grade fevers • Muscle pain • Tiredness • Soreness at the injection site • Infants and elderly people may develop more serious reactions, such as encephalitis (very

rare)

The vaccine is deemed to be safe for patients aged over 9 months to 60 years.

• Children aged less than 9 months in the USA, 6 months in the UK (unless the risk of yellow fever is unavoidable)

The following groups of people should not have the vaccination:

• Pregnant women (unless the risk of yellow fever is unavoidable) • Breastfeeding mothers • People with weakened immune systems, (unless the risk of yellow fever is unavoidable) such

as those with HIV, or patients receiving chemotherapy and/or radiotherapy. • Patients who are allergic to eggs • If the patient is over 60 years of age he/she should discuss whether to have the vaccine with

a doctor

Mosquito protection: To reduce your exposure to mosquitoes:

• When possible, avoid outdoor activities during dawn, dusk and early evening - when mosquitoes are most prevalent.

• Cover your skin as much as possible; wear long-sleeved shirts and long pants (UK: trousers) if you plan to go into areas where there are mosquitoes.

• Stay indoors in places that have air-conditioning and good screening (window nets, etc). • Apply mosquito repellent which contains permethrin to clothing, shoes, camping equipment

and bed netting.

Do not use permethrin directly on your skin: Skin repellents containing DEET or picaridin provide protection from mosquitoes for longer periods, compared to other products. The higher the concentration the longer it will last. Do not use DEET on young children's hands or infants aged less than 2 months - in such cases cover their stroller (push-chair) or playpen with mosquito netting when outdoors.

Oil of lemon eucalyptus - the CDC (Centers for Disease Control and Prevention) says that oil of lemon eucalyptus offers the same protection as DEET when used in the same concentrations. However, do not use on children less than 3 years of age.




Headline: 19 - Entire Genomes for Lung and Melanoma Cancers Sequenced By UK Researchers

Published by: Medical News Today



Research teams led by UK scientists have sequenced the entire genome of two deadly cancers, malignant melanoma and lung cancer, revealing for the first time almost all of the tens of thousands of mutations in the DNA of cancer cells that occur during a person's lifetime.

The research was led by scientists from the Wellcome Trust Sanger Institute at Hinxton in Cambridge, and appears as two studies published online in advance in the 16 December issue of Nature. Cancer is driven by mutation, some of which is driven by lifestyle: these studies help to show how much.

For instance, take tobacco smoking: worldwide it is the main lifestyle-related cause of cancer because over 60 chemicals in tobacco smoke are known to bind to and mutate the DNA in our cells. About one million people worldwide die from lung cancer every year, and almost all cases are linked to smoking. The researchers found nearly 23,000 mutations in lung cancer cells, suggesting that for each packet of cigarettes, a typical smoker acquires one mutation in his or her DNA. In the lung cancer genome study the researchers used a small-cell lung cancer cell line from one person, and in the melanoma genome study they used a malignant melanoma and a lymphoblastoid cell line from another person.

The melanoma genome showed even more mutations: over 30,000 in all, giving a record of how and when the patient acquired them. Although malignant melanoma only accounts for 3 per cent of skin cancers, it causes 75 per cent of skin cancer deaths.

Professor Mike Stratton, from the Cancer Genome Project at the Wellcome Trust Sanger Institute, and co-author of both studies, told the press that:

"These are the two main cancers in the developed world for which we know the primary exposure."

"For lung cancer, it is cigarette smoke and for malignant melanoma it is exposure to sunlight," he added, explaining that:

"With these genome sequences, we have been able to explore deep into the past of each tumour, uncovering with remarkable clarity the imprints of these environmental mutagens on DNA, which occurred years before the tumour became apparent."

In a rather poignant observation, Stratton described how he and his team could also see:

"The desperate attempts of our genome to defend itself against the damage wreaked by the chemicals in cigarette smoke or the damage from ultraviolet radiation."

"Our cells fight back furiously to repair the damage, but frequently lose that fight," he added.

For the two studies, Stratton and colleagues used powerful new DNA sequencing technologies to decode completely the genome of both tumour tissue and normal tissue. They then compared the genome sequences of each of the cancers to that of the corresponding healthy tissue and picked out the cancer-specific changes. A press statement from the Wellcome Trust said these studies are:

"The first to produce comprehensive genome-wide descriptions of all classes of mutation, producing rich accounts of the genetic changes in the development of the two cancers."




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Dr Andy Futreal of the Wellcome Trust Sanger Institute, and another co-author of both studies, said:

"In the melanoma sample, we can see sunlight's signature writ large in the genome."

But he said because they had sequenced what were essentially complete catalogues of the mutations in both cancers, they could also see other "more mysterious processes acting on the DNA", including what they suspect to be the mutations that actually drive the cells to become cancerous. We already know that only some mutations found in cancer actually promote cancer growth, the others are often described as "passengers".

Tracking down the mutations that drive cancer will be their major challenge for the next few years, said Futreal. Dr Peter Campbell, who also co-authored both studies and is also from the Wellcome Trust Sanger Institute, said we have spent the last 10 years reaping the benefits of sequencing the entire human genome, and there is still a lot of work to do on cancer genomes, but:

"The knowledge we extract over the next few years will have major implications for treatment."

"By identifying all the cancer genes we will be able to develop new drugs that target the specific mutated genes and work out which patients will benefit from these novel treatments," said Campbell. The idea is that it will one day it will not only be possible but also cost-effective to map the entire genome of a each cancer patient and thus select and direct treatments specifically for the individual patient.

The research behind these two studies is part of the International Cancer Genome Consortium, whose ultimate goal is to sequence the genomes of over 100 different types of cancer, using the model of the Human Genome project to coordinate cancer genome sequencing across the globe.

Eventually this will lead to a catalogue of mutations across the wide and diverse range of cancer types, and give researchers, practitioners, all of us, better ways of understanding, preventing, detecting and treating cancer.

Headline: 20 - MicroRNA Acts as Tumor Suppressor in Mouse Lung Cancer Model




MicroRNA (mRNA) have been found to act as a tumor suppressors and may form the basis for a new generation of anticancer drugs. MicroRNAs (miRNAs) are small, noncoding RNA molecules that occur naturally in human cells.

Misregulation of these critical cellular components is a frequent event in the development of genetically manifested human diseases such as cancer.

Investigators at Yale University (New Haven, CT, USA) and their colleagues at Mirna Therapeutics (Austin, TX, USA) have been working with the let-7 family of mRNAs. In the current study, they examined the link between let-7 and non-small-cell lung cancer (NSCLC) in a mouse model.

Results published in the December 7, 2009, online edition of the journal Oncogene revealed that let-7 acted as a tumor suppressor, since loss of let-7 function enhanced lung tumor formation. Treatment of mice with existing tumors with let-7 reduced the number and size of the tumors by almost two-thirds.



"This is the first time anybody has shown a positive effect of microRNAs in shrinking lung cancer," said senior author Dr. Frank Slack, professor of molecular, cellular, and developmental biology at Yale University. "We hope it will be valuable in the treatment of many other forms of cancer."

The investigators are now conducting studies to determine whether let-7 therapy in combination with chemotherapy and radiation can induce full remission.

Headline: 21 - Universal Flu Vaccine Passes First Hurdle




What potentially may become the first universal flu vaccine successfully passed its initial Phase I/II clinical trial and was demonstrated to be safe for use in humans.

The Multimeric-001 Universal Flu Vaccine, developed by BiondVax Pharmaceuticals (Rehovot, Israel), was tested in a randomized, single-blind, placebo-controlled, escalating double-dose safety study on a total of 60 participants, males and females aged 18-49. Each subject received two intramuscular injections containing the Multimeric-001 vaccine, either with or without adjuvant, and at two different dose levels.

Results of the study showed that the vaccine was safe to use at all doses tested, both with and without adjuvant. All participants who received the vaccine developed a high level of antibodies against the Multimeric-001 Universal Flu Vaccine. These antibodies also specifically identified a number of different strains of influenza, including the swine flu strain (A/H1N1). Furthermore, those receiving the vaccine showed a meaningful increase in white blood cells inducing the secretion of interferon gamma and Interleukin-2. Thus, the vaccine activated both the humoral (antibody) and the innate (cellular) arms of the human immune system.

The Multimeric-001 Universal Vaccine is a single formulation consisting of nine conserved linear epitopes in triplicate. The epitopes selected were taken from hemagglutinin (HA), nucleoprotein (NP), and matrix (M) proteins, therefore ensuring high antigen content. These epitopes are common to practically all existing and future flu virus strains, including both seasonal and pandemic flu strains such as the avian and swine flu, regardless of their antigenic drift and shifts.

This trial was the first of two Phase I/II clinical trials of the Multimeric-001 Universal Flu Vaccine being conducted by BiondVax. The second trial has already commenced with 60 participants aged 55-75, and is expected to be completed in the first quarter of 2010.

Dr. Ron Babecoff, BiondVax CEO, said, "We are very proud of the success of the Phase I/II clinical trial for the Multimeric-001 Universal Flu Vaccine, and of this initial proof of the immunogenicity and safety of our vaccine. The results obtained in this trial are an important indication of a significant milestone towards the realization of the Company's vision of ensuring protection against all flu strains through the use of a single vaccine. Such a vaccine is expected to do away with the need for annual vaccinations as required by current existing vaccines."



Headline: 22 - Anticancer Drug Benefits Diabetes Patients




Results of a phase II clinical study suggest that the cancer drug rituximab may be of use in treating patients newly diagnosed with type I (insulin-dependent) diabetes.

Rituximab is a monoclonal antibody specific for the cell surface CD20 protein and is used to treat non-Hodgkin's lymphoma (NHL) characterized by overgrowth of B-cells. More than 90% of B-cell cancers express the CD20 protein on the cell surface, a requirement for the proper function of rituximab. By binding the CD20 protein on the B-cell, the antibody targets it for removal from the circulation. Its developers believe that rituximab triggers both cell-mediated and complement-mediated means to kill the B-cells.

In the current study investigators at the University of Texas Southwestern Medical Center (Dallas, USA) evaluated results of a randomized, double-blind study in which 87 patients between 8 and 40 years of age who had newly diagnosed type I diabetes were assigned to receive infusions of rituximab or placebo on days 1, 8, 15, and 22 of the study. The primary outcome, assessed one year after the first infusion, was the geometric mean area under the curve (AUC) for the serum C-peptide level during the first two hours of a mixed-meal tolerance test. Secondary outcomes included safety and changes in the glycated hemoglobin level and insulin dose.

Results published in the November 26, 2009, issue of the journal New England Journal of Medicine (NEJM) revealed that after one year, the mean AUC for the level of C-peptide was significantly higher in the rituximab group than in the placebo group. The rituximab group also had significantly lower levels of glycated hemoglobin and required less insulin. More patients in the rituximab group than in the placebo group had adverse events after the first infusion. The reactions appeared to be minimal with subsequent infusions. There was no increase in infections or neutropenia with rituximab.

The finding that B-lymphocytes contribute to the pathogenesis of type I diabetes may open a new pathway for exploration in the treatment of patients with this condition.

“Our findings in no way suggest that rituximab should be used as a treatment or that it will eliminate the need for daily insulin injections,” said senior author Dr. Philip Raskin, professor of internal medicine at the University of Texas Southwestern Medical Center. “This is not a cure for type I diabetes. The results do, however, provide evidence that B- cells play a significant role in type I diabetes and that selective suppression of these B-cells may deter the destruction of the body’s beta cells.”



Headline: 23 - Combined Lapatinib and Nab-Paclitaxel (Abraxane) Shows Good Activity in HER2+ Breast Cancer




SAN ANTONIO - Investigators are reporting favorable results in a pilot neoadjuvant trial that tested a combination of lapatinib and nab-paclitaxel (AbraxaneR) for the treatment of HER2+ breast cancer.

The findings were announced at the 32nd Annual CTRC-AACR San Antonio Breast Cancer Symposium (SABCS) by Virginia Kaklamani, MD, with Northwestern University in Chicago, Illinois. Lapatinib, a dual kinase inhibitor against EGFR and HER2, has activity in metastatic HER2+ breast cancer, Dr. Kaklamani noted. Nab-paclitaxel is a unique albumin formulation of a non-crystalline, amorphous form of paclitaxel in an insoluble nanoparticle state.

While nab-paclitaxel has been shown to be one of the most active agents in metastatic breast cancer, it has not been examined as part of combination therapy in the neoadjuvant setting, she added.

According to the study protocol, women with newly diagnosed HER2+ stage I to III breast cancer received four cycles of lapatinib 1000 mg po/d and nab-paclitaxel 260 mg/m2 IV every three weeks. Postoperative therapy was at the discretion of the investigator. A total of 28 patients have completed therapy, and the accrual goal of 30 patients has been met. The study's primary endpoint was the clinical response rate (CRR) as determined by clinical examination and imaging studies.

Response data in 29 patients showed a CRR of 82%, with 4 (13.8%) patients demonstrating a complete response and 20 (69%) showing a partial response. Five (17.2%) patients had stable disease.

Five (18.5%) patients achieved pathologic complete response (pCR).

The most common toxicities were rash, neuropathy, fatigue, and myalgias. Most toxicities were grade ½ although one patient developed grade 3 rash and five patients developed grade 3 diarrhea. There were no cases of cardiac toxicity. Toxicities such as diarrhea and rash were medically managed, and patients did not receive prophylactic medications for rash or diarrhea. The nab-paclitaxel dose was reduced in eight of 104 treatment cycles and the lapatinib dose was reduced in eleven cycles.

"The combination of lapatinib and nab-paclitaxel is very active as first-line treatment in HER+ breast cancer," Dr. Kaklamani said.

Headline: 24 - Regular Coffee, Decaf, Tea Consumption Linked To Lower Diabetes Risk




High intakes of coffee, decaffeinated coffee, and tea are linked to a reduced risk of diabetes, according to a pooled review of studies covering nearly half a million participants: the international









team of researchers recommends that randomized trials should now be done to investigate this finding more robustly.

The systematic review and meta-analysis was the work of first author Dr Rachel Huxley, of The George Institute for International Health, University of Sydney, Australia and colleagues from the UK, The Netherlands, France and the US, and was published online in the Archives on Internal Medicine on December 14. Estimates suggest that by 2025 there will be about 380 people with type 2 diabetes around the world.

The extent to which diet and lifestyle contributes to this remains somewhat uncertain, despite considerable research attention, except perhaps for studies that consistently point to obesity and physical inactivity, wrote the authors. They also said that a number of studies have reported higher levels of coffee consumption are linked to lower risk of developing type 2 diabetes mellitus, and similar links have been reported for decaffeinated coffee and tea.

And while an earlier meta-analysis suggested there might be a link between coffee drinking and reduced risk of diabetes, since then the number of studies has more than doubled, so they decided to do a new one.

For their investigation, Huxley and colleagues searched for prospective studies published between 1966 and July 2009 that reported an estimate of the link between coffee, decaffeinated coffee, or tea with incident diabetes and found 18 studies covering a total of 457,922 participants.

Among these, six studies covering over 225,000 participants included information about decaffeinated coffee, whereas seven studies with over 286,000 participants reported on tea consumption.

When they pooled and analyzed the data, they found that: Drinking coffee was inversely related to risk of diabetes, i.e. more coffee was linked to lower risk.

After adjusting for potential confounders, every extra cup of coffee consumed in a day was linked to a 7 per cent reduction in the excess risk of diabetes.

Drinking 3 to 4 cups per day was linked to a 25 per cent lower risk than drinking none or up to two cups per day. In those studies that assessed decaffeinated coffee consumption, drinking more than 3 to 4 cups a day was linked to about one third lower risk of diabetes compared to none.

Drinking more than 3 to 4 cups of tea per day was linked to a one fifth lower risk of diabetes compared to non-tea drinking.

The authors concluded that:

"High intakes of coffee, decaffeinated coffee, and tea are associated with reduced risk of diabetes. The putative protective effects of these beverages warrant further investigation in randomized trials."

They also said their results should be interpreted with caution since "owing to the presence of small-study bias, our results may represent an overestimate of the true magnitude of the association".

The authors suggested the effect of tea and coffee consumption on diabetes risk could be due to direct biological effects, since their apparent protective effect appears to be independent of potential confounding variables. The apparent link between decaffeinated coffee and diabetes risk caffeine alone is unlikely to be the reason. It could partly be due to other compounds present in tea and coffee, such as magnesium, antioxidants known as lignans or chlorogenic acids, they suggested.

"If such beneficial effects were observed in interventional trials to be real, the implications for the millions of individuals who have diabetes mellitus, or who are at future risk of developing it, would be substantial," they wrote.

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If we could find out what these active compounds are, we might find possible new ways of preventing type 2 diabetes, they added.

"It could also be envisaged that we will advise our patients most at risk for diabetes mellitus to increase their consumption of tea and coffee in addition to increasing their levels of physical activity and weight loss," wrote the authors.

Headline: 25 - Human trials of swine flu vaccine likely in two weeks

Published by: - The Hindu


Source: - http://beta.thehindu.com

Pre-market human trials of swine flu vaccine to check its efficacy on Indians may start in the next fortnight as the Indian Council of Medical research is in final stages of “positive” negotiations with an international pharmaceutical company in this regard.

“We will finalise the deal with the international vaccine manufacturing company by December 15 with which we will place the order. So far, negotiations have been positive,” a Health Ministry official said.

“Government is negotiating with three international vaccine manufacturers. By next fortnight, the phase IV trials are expected to begin. This will be done to check the safety and the immunogenicity of the foreign-made vaccine on Indian population,” Dr V. M. Katoch, DG, ICMR said.

Sources in the Health Ministry also said international vaccine manufacturer Glaxo Smith Kline has quoted the lowest price and is under consideration. More than 21,000 people have been affected by swine flu virus in India. Nearly 700 deaths have been reported from different cities here.

Dr. Katoch said, “Since no Indian company is ready yet for the phase IV trial, we are considering the foreign brands as they are already tried, tested and in use in other countries.

“Zydus Cadila of Ahmedabad, the Indian swine flu vaccine manufacturing company, has recently got a nod from the Drug Controller General of India to carry out human studies of its vaccine. They can carry it out any time in December.”

Headline: 26 - H1N1 Vaccine Administration Goes Well In Northwest Alabama

Published by: - Medical News

Date of Publication: - Dec 10, 2009

Source: - http://www.medicalnewstoday.com/

Staff members of Public Health Area 1 in Northwest Alabama have administered 11,700 doses of H1N1 influenza vaccine at county health departments and school-based clinics.

Vaccine is being made available before the Christmas break in school-based clinics for children under age 10 at schools throughout the area. Nasal mist vaccine, which uses a weakened virus, is being administered at area schools. Parental permission is required. County health department clinics continue to make H1N1 vaccine available to risk groups at their local health departments. Dr. Karen

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Landers, a pediatrician and area health officer, said, "The H1N1 vaccine is safe and effective. Vaccination is the best way to reduce the risk of infection with this virus."

Since H1N1 was first identified in Alabama in April 2009, there have been two known influenza related deaths in the area, one in Colbert County and one in Walker County. There have been 36 documented influenza-related deaths in Alabama since July 2009.

Headline: 27 - Cigarette Smoke May Impair Lungs Natural Defense Against Harmful Pathogen



Source: - www.sciencedaily.com/

Exposure to cigarette smoke may impair the ability of immune cells to clear bacterial infections from the lungs, specifically nontypeable Haemophilus influenzae (NTHI), a pathogen often associated with respiratory infections and the progression of respiratory diseases.

The researchers from Spain and the United Kingdom report their findings in the October 2009 issue of the journal Infection and Immunity.

NTHI, commonly found in the human respiratory tract, may remain asymptomatic in healthy individuals or it can cause invasive diseases such as meningitis, sinusitis, pneumonia, and bronchitis. It is also the pathogen most frequently isolated in the respiratory tract of patients with chronic obstructive pulmonary disease (COPD) and chronic bronchitis. Alveolar macrophages are part of the lungs' innate defense system and they play an essential role in the clearance of bacterial infections. Prior associations between cigarette smoke and respiratory infections caused by NTHI have been established and now researchers are hypothesizing that cigarette smoke may disrupt the capability of alveolar macrophages to clear NTHI from the lungs.

In the study researchers first examined the interaction between NTHI and alveolar macrophages and found that the macrophages adhere to and ingest NTHI, a process known as phagocytosis. Researchers also observed the effect of cigarette smoke in macrophage cell lines and human alveolar macrophages obtained from smokers and patients with COPD and found that cigarette smoke extract impaired the alveolar macrophage process. Additionally, cells exposed to cigarette smoke extract were treated with glucocorticoid, an anti-inflammatory drug commonly used to treat respiratory conditions, and results showed that the drug did not compensate for the impairment to the alveolar macrophage process caused by the cigarette smoke.

"This study revealed novel effects of cigarette smoking on alveolar macrophage physiological functions which could contribute to lung bacterial colonization by opportunistic pathogens, such as NTHI," say the researchers.



Headline: 28 - Process That Determines Fate Of White Blood Cells Uncovered




Like an unusually forceful career counselor, the Id3 protein decides the fate of a given white blood cell precursor, according to researchers at Fox Chase Cancer Center. Their findings, published today in the journal Immunity, describe how Id3 directs blood cell progenitors to become gamma-delta T cells.

Gamma-delta T cells are unique in that they possess attributes of both the adaptive arm of the immune system, which is invigorated by vaccination, and the innate arm, which represents the body's first line of defense against infections.

"Unlike the other major type of T cells (alpha-beta), gamma-delta T cells seem to focus most of their efforts on protecting the body surfaces in contact with the outside world, like skin, gut, and lung and in fact are required to repel invaders at those sites," says co-author David Wiest, Ph.D., Fox Chase professor and co-leader of the center's Immune Cell Development and Host Defense Program. "Their origins have been something of a mystery and, as it turns out, their creation requires distinct molecular machinery than the other major type of T cells."

In recent years, studying the origins of blood cells has provided researchers with useful insights on how all the cells in the body form from a small group of embryonic stem cells. All blood cells originate from a type of stem cell – called hematopoietic ("blood-forming") stem cells – located in bone marrow. A small portion of these cells move on to the thymus – a small organ near the lungs – where their ultimate fate as one of many types of white blood cells is decided through a series of molecular pathways.

Among these cells are T cells, of which there are two recognized types, based on the structure of their most defining feature, the T Cell Receptor (TCR), which enables the cell to detect bits of foreign molecules called antigens. The majority of T cells are alpha-beta T cells, meaning their TCR are comprised of alpha and beta subunits. Only five percent of T cells are gamma-delta T cells, yet researchers believe that they have a remarkable effect on human health.

Using a mouse model of human blood cell development, Wiest and his colleagues demonstrated that gamma-delta T cells require the Id3 gene for formation. Moreover, they showed that elevating the levels of Id3 alone was sufficient to push progenitor cells in the thymus into becoming delta-gamma T cells. This is not true of the development of other major T lineage, alpha-beta, for which the function of Id3 is dispensable.

One of the weapons utilized by gamma-delta cells is a substance called interferon-gamma, which has known anti-viral and anti-tumor properties. Interferon-gamma is also known to contribute inflammation at the site of infection, such as a wound, but also may be a source of autoimmune disease.

"By better understanding the process that drives gamma-delta T cell production, we may one day become capable of producing them outside of the body for use as a therapy in people when warranted," Wiest says.

"While we are only beginning to understand the functions of gamma-delta T cells, one setting where they might be useful therapeutically, is cancer," Wiest says, "since gamma-delta T cells seem to be well equipped to combat cutaneous malignancies."



Funding for this research comes from grants from the National Institutes for Health, an appropriation from the Commonwealth of Pennsylvania, and the Fox Chase Keystone Program in Blood Cell Development and Cancer.

Headline: 29 - Loss of Tumor-suppressor And DNA-maintenance Proteins Causes Tissue Demise




A study published in the October issue of Nature Genetics demonstrates that loss of the tumor-suppressor protein p53, coupled with elimination of the DNA-maintenance protein ATR, severely disrupts tissue maintenance in mice. As a result, tissues deteriorate rapidly, which is generally fatal in these animals. In addition, the study provides supportive evidence for the use of inhibitors of ATR in cancer therapy.

Essentially, says senior author Eric Brown, PhD, Assistant Professor of Cancer Biology at the University Of Pennsylvania School Of Medicine, the findings highlight the fact that day-to-day maintenance required to keep proliferative tissues like skin and intestines functional is about more than just regeneration, a stem cell-based process that forms the basis of tissue renewal. It's also about housekeeping, the clearing away of damaged cells.

Whereas loss of ATR causes DNA damage, the job of p53 is to monitor cells for such damage and either stimulate the early demise of such cells or prevent their replication, the housekeeping part of the equation. The findings indicate that as messy as things can become in the absence of a DNA maintenance protein like ATR, failing to remove resulting damaged cells by also deleting p53, is worse. "Because the persistence of damaged cells in the absence of p53 prevents appropriate tissue renewal, these and other studies have underscored the importance not only of maintaining competent stem cells, but also of eliminating what gets in the way of regeneration," explains Brown.

"An analogy to our findings is what happens to trees during the changing seasons," says Brown. "In springtime, leaves are new and undamaged. But as the summer wears on, the effects of various influences - insects, drought, and disease - cause them to lose the pristine qualities they once had. However, the subsequent fall of these leaves presents a unique opportunity for regeneration later on, a chance to rejuvenate from anew without pre-existing obstacles. Similarly, by suppressing the accumulation of damaged cells in tissues, p53 permits more efficient tissue renewal when ATR is deleted."

Cells without ATR that remain uncleared may be block tissue regeneration either by effectively refusing to relinquish space to undamaged cells, or by secreting signals that halt regeneration until they have been removed.

These results came as something of a surprise, says Brown. Previous studies pairing DNA-repair mutations with p53 mutations always led to a partial rescue of the DNA repair mutation "We think this happens because p53 loss helps cells with just a little DNA damage to continue to contribute to the tissue" says Brown. So at a minimum, the team expected nothing to happen.

"But we got the opposite result: Absence of p53 did not rescue the tissue degeneration caused by ATR loss, it made it much worse. This result suggested that allowing mutant cells without ATR to



persist is more harmful to tissues than eliminating them in the first place." Brown speculates that could be because the ATR mutation produces much more damage than most other DNA-repair defects.

According to Brown, their findings and those of other laboratories also reinforce the potential of a new therapeutic for cancer. That's because, among their other discoveries, the team noticed that cells missing both ATR and p53 have more DNA damage than those missing either gene alone. As a large fraction of human cancers have p53 mutations, he says, "p53-deficient tumors might be especially susceptible to ATR inhibition." Indeed, clinical trials already are underway involving an ATR partner protein called Chk1. "Our study provides supportive evidence for the potential use of ATR/Chk1 inhibitors in cancer therapy," says Brown

The report was supported by the National Institute on Aging and the Abramson Family Cancer Research Institute.

Laboratory members Yaroslava Ruzankina, PhD and MD/PhD student David Schoppy are lead authors of this study. Amma Asare, Carolyn Clark, and Robert Vonderheide, all from Penn, are co-authors.

Headline: 30- Scientists discover new cancer gene

Published by: - The Times of India


Source: - http://timesofindia.indiatimes.com/

WASHINGTON: A research group at the Sahlgrenska Academy has discovered a new cancer gene.

The gene causes an insidious form of glandular cancer usually in the head and neck and in women also in the breast. The discovery could lead to quicker and better diagnosis and more effective treatment, according to the study which is published in the prestigious scientific journal Proceedings of the National Academy of Sciences (PNAS).

The cancer caused by this new cancer gene is called adenoid cystic carcinoma and is a slow-growing but deadly form of cancer. The research group can now show that the gene is found in 100 percent of these tumours, which means that a genetic test can easily be used to make a correct diagnosis.

"Now that we know what the cancer is down to, we can also develop new and more effective treatments for this often highly malignant and insidious form of cancer," says professor GÃ¶ran Stenman, who heads the research group at the Lundberg Laboratory for Cancer Research at the Sahlgrenska Academy.

"One possibility might be to develop a drug that quite simply turns off this gene," the expert added.

The newly discovered cancer gene is what is known as a fusion gene, created when two healthy genes join together as a result of a chromosome change.

"Previously it was thought that fusion genes pretty much only caused leukaemia, but our group can now show that this type of cancer gene is also common in glandular cancer," says Stenman.

One of the two genes that form the fusion gene is known as MYB. Among other things, this gene controls cell growth and makes sure that the body gets rid of cells that are no longer needed. It has long been known to be a highly potent cancer gene in animals, but for a long time there was no evidence of the gene being involved in the development of tumours in humans.

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"We suggested back in 1986 that the MYB gene might be involved in this form of cancer, but it's only recently that we've had access to the tools needed to prove it," says Stenman.

The research group has also looked at the mechanism behind the transformation of the normal MYB gene into a cancer gene. Genes can be compared to blueprints for proteins. Carefully controlled regulating systems then determine when and how much of each protein is formed. One such regulating system, discovered recently, is microRNA, which can turn genes on and off. When this cancer gene forms, this important control system is put out of action, leading to activation of the gene and massive overproduction of an abnormal MYB protein with carcinogenic properties.

Headline: 31 - Doctors Use Patient's Own Stem Cells To Grow Facial Bone In Groundbreaking Procedure




In a first-of-its kind procedure, physicians have used stem cells taken from the fat tissue of a 14-year-old boy and combined them with growth protein and donor tissue to grow viable cheek bones in the teen.

The new procedure dramatically improves the options surgeons have for repairing bone deficiencies caused by traumatic injuries such as those from car accidents or soldiers wounded in battle or by disease and genetic conditions, according to Jesse Taylor, M.D., a surgeon and researcher in the Division of Craniofacial and Pediatric Plastic Surgery at Cincinnati Children's Hospital Medical Center. An estimated 7 million people in the United States have defects in bone continuity so severe that repair is difficult.

"We think this will benefit millions of people who, through traumatic injury or disease, have significant bone defects," Dr. Taylor explained. "The current methods we have like borrowing bone from another part of the body, or implanting cadaver bone or something artificial are reasonable alternatives, but far less than perfect."

Because the body rejects or absorbs implanted donor material, many reconstructive surgeries can have high failure rates. In procedures where bone is borrowed from one part of the body to replace another, the corrective surgery itself can be disfiguring to the person doctors are trying to help.

The new procedure avoids these problems because it uses the patient's own cells, Dr. Taylor explained. His team developed the procedure based in part on scientific research conducted in pigs at Cincinnati Children's. The operation is the first to blend and refine several techniques used or under study in surgical practice for repairing bone deficiencies.

The teenage recipient of the surgery, performed on May 28, has a rare genetic condition known as Treacher Collins syndrome, which includes underdeveloped or missing cheek bones. In this case the teenage patient, Brad Guilkey of Cincinnati, did not have developed zygomatic bones on either side of his face. The zygomatic bones form the prominence of the cheek and part of the outer rim of the eye socket.

The missing bones affected the active teenager's appearance, but more importantly put his eyes at increased risk of injury, Dr. Taylor said. The bones are supposed to surround most of the lower and side areas of the eye sockets, with a portion protruding toward the ear at the cranial base.



"This bone is critical structurally and acts as a shock absorber for the face, protecting the eyes and other critical structures in the event of facial impact," explained Dr. Taylor. "This young man is extremely active, he loves to play basketball and baseball, and growing new bone in this area of his craniofacial structure is critically important for him."

Dr. Taylor said the procedure has been successful and, more than four months after the surgery, computer tomography (CT) scans show the teenager's cheek bones have filled in normally with viable bone. The new bone structure enhances his appearance and improves protection for his eyes. Additional touchup surgery to the teenager's eye lids is under consideration to address a slight downward slant, also characteristic of Treacher Collins syndrome.

During the day-long operation, surgeons used a section of donor bone to craft what essentially were mineral-based scaffolding implants (known as allografts), which also served as a growth guide for the new bone. Surgeons drilled holes in the allografts, which then were filled with mesenchymal stem cells taken from the patient's abdominal fat. Also injected into the allografts was a growth protein called bone morphogenic protein-2 (BMP-2) that instructs the stem cells to become bone cells called osteoblasts. One of nature's roles for mesenchymal stem cells is to become cell types for a variety of different tissues in the body - including connective tissue and bone - giving the body a ready reserve of replacement cells as older cells die. In the surgery, and in the earlier lab experiments involving pigs, the doctors used BMP-2 to jumpstart nature's normal process of transforming these malleable stem cells.

"We only need to use a fairly small amount of bone morphogenic protein to serve as a cue to tell the mesenchymal stem cells that they're going to become bone," explained Donna Jones, Ph.D., a researcher at Cincinnati Children's and part of the scientific team that conducted experiments leading to the procedure. "The actual molecular mechanisms BMP-2 uses to do this are not well understood, but once we use BMP-2 to start the process, the body's own biological processes take over and it produces its own BMP-2 to continue the transformation."

Particularly critical to that process is wrapping the donor allograft bone in a thin membrane of tissue that coats bone surfaces called periosteum. The periosteum used in this surgery was taken from the patient's thigh. Periosteum is important to the body's normal production of BMP-2, and just as vital to providing a blood supply to nourish new bone formation.

Drs. Taylor, Jones and their fellow researchers are conducting ongoing studies into growing mandible bones in pigs. In a research paper being prepared for peer-review journal publication, they explain the use of the procedure to grow viable, dense bone in the animals and the duplication of results numerous times. The researchers worked with pigs because the porcine immune system is very similar to that of humans, making the animals a good model for simulating engineered bone growth in people.

Peer-review presentations of results from aspects of the study results have occurred at national re-constructive surgery conferences including the American Association of Plastic Surgeons and the Plastic Surgery Research Council and received with great enthusiasm, said Christopher Runyan, M.D., Ph.D., a member of the research team at Cincinnati Children's.

The team also plans additional research projects to test the procedure's ability to engineer bones of different lengths and sizes. Drs. Taylor and Jones said the technology may have the potential to grow almost any bone in the human body. As for Brad, now 15, and his mother, Christine, they're just happy Brad can play sports and participate in other activities without having to worry about a lack of facial bone making him more susceptible to serious eye injury.


"Until we had the CT scans before surgery, we had no idea that Brad was missing the bones that protect his eyes, and that's very dangerous," said Christine. "I was nervous about the procedure, but we're glad we did it and amazed with the results. The people at Cincinnati Children's do a great job of explaining things to you and we have a lot of trust in the doctors and staff."

About Cincinnati Children's

Cincinnati Children's Hospital Medical Center is one of 10 children's hospitals in the United States to make the Honor Roll in U.S. News and World Reports 2009-10 America's Best Children's Hospitals issue. It is #1 ranked for digestive disorders and is also highly ranked for its expertise in respiratory diseases, cancer, neonatal care, heart care, neurosurgery, diabetes, orthopedics, kidney disorders and urology. One of the three largest children's hospitals in the U.S., Cincinnati Children's is affiliated with the University of Cincinnati College of Medicine and is one of the top two recipients of pediatric research grants from the National Institutes of Health.

President Barack Obama in June 2009 cited Cincinnati Children's as an "island of excellence" in health care. For its achievements in transforming health care, Cincinnati Children's is one of six U.S. hospitals since 2002 to be awarded the American Hospital Association-McKesson Quest for Quality Prize for leadership and innovation in quality, safety and commitment to patient care. The hospital is a national and international referral center for complex cases.

Headline: 32 - Swine Flu: Racing Against the Clock to Distribute H1N1 Flu Vaccine




Drug companies are sprinting ahead in a race against the clock to deliver millions of doses of vaccine for the H1N1 influenza virus before cooler weather ushers in the 2009-2010 flu season. A two-part cover story in the current issue of Chemical & Engineering News, ACS' weekly newsmagazine, focuses on that topic and efforts to develop antiviral drugs for flu infections.

C&EN senior correspondent Ann Thayer cites World Health Organization (WHO) estimates that one-third of the world's population - 2.2 billion people - will be exposed to the H1N1 virus. Although antiviral drugs can help limit the spread of H1N1, a vaccine offers the best means to prevent infection, the article notes.

Although the H1N1 virus just emerged in April, vaccine developers have made an effective vaccine. However, WHO says that only a fraction of the potential supply will be ready for distribution before flu season starts - in October in the Northern Hemisphere. The article describes how at least nine countries have pledged to donate vaccines to help fight the pandemic in developing countries and two vaccine manufacturers have earmarked a portion of their production for developing countries. That generosity will help protect populations that otherwise would not have access to vaccines, the article notes.



Headline: 33 - Embryonic-like stem cells generated from cord blood cells



Source: - http://www.thehindu.com/

Cord blood cells appear to be far more versatile to treat many diseases than previously considered. Two teams have successfully re-programmed cord blood cells to exhibit properties similar to embryonic stem cells. Re-programmed cells that have the characteristics of the embryonic-like stem cells are called induced pluripotent stem (iPS) cells.

Their results have been published in the online version of the journal Cell Stem Cell. The success is significant as nearly 4,00,000 cord blood units are stored in many banks, both private and public, and they could produce an unlimited number of iPS cells.

Scientists first re-programmed adult skin cells into iPS cells in 2006. But the process has certain challenges. Skin cells, compared with cord blood cells, are old, and hence have greater chances of accumulating genetic errors through mutations. Re-programming efficiencies are also lower.

Further, there are issues with harvesting adult cells. But cord blood cells have none of these shortcomings. Since they are very young, the chances of mutations getting accumulated are far less. Higher re-programming efficiencies can be achieved as demonstrated by both the teams. One of the papers found that cord blood cells had nearly 50 per cent chances of acquiring human embryonic-like stem cell characteristics.

Most importantly, cord blood units become a readily available source for producing iPS cells, as they are already collected and stored. Harvesting cord blood is easy and safe. It has less chances of contamination and does not cause harm to the mother or infant.

According to Alexandra Haase of the Hannover Medical School, Germany, the first author of one of the papers, cord blood cells outperformed adult blood stem cells on several counts.

"We believe that cord blood cells could represent, rather than just another cell type that can be re-programmed, a real alternative for a safer source of iPS cells," J.C. Izpisua Belmonte of the Center of Regenerative Medicine in Barcelona, Spain, the senior author of the second paper, was quoted as saying in Cell Press.

Dr. Belmonte and his team found that cord blood units cryopreserved for more than five years were able to produce iPS cells. "These data showed that the standard cryopreservation protocol does not affect the re-programming ability of these cells," says the paper by Dr. Belmonte et al.

The other team was able to demonstrate that the iPS cells produced from cord blood cells had the potential to differentiate into multiple mature cell types. The potential to treat many diseases is immense when cord blood is re-programmed to iPS cells. Cord blood units stored in private and public banks have a great potential to treat many diseases. However, unlike those stored in private banks, the units stored in public banks provide an almost unlimited number of cells for producing iPS cells that can be used for treating unrelated persons.

"Cord blood could readily become available for paediatric patients and, in particular, for newborns with genetic diseases or congenital malformations," the paper by Dr. Haase et al notes.

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Section B: Nano Biotechnology

Headline: 1 - Nanosensors Can Scan Blood for Cancer Biomarkers

Published by: - Tudor Vieru, Science Editor

Date of Publication: - December 14, 2009

Source: - http://news.softpedia.com

A team of experts at the Yale University has recently announced that it has developed a new series of nanosensors, a class of devices that is able to analyze whole blood samples, and detect the presence of cancer biomarkers in them. The latter are chemical agents that tumors and cancer cells produce, and their existence in the body can only mean one thing. The amazing achievement could soon enable physicians to cut the cancer-detection process short, leaving more time for the actual treatments.

“Nanosensors have been around for the past decade, but they only worked in controlled, laboratory settings. This is the first time we've been able to use them with whole blood, which is a complicated solution containing proteins and ions and other things that affect detection,” the Yale Harold Hodgkinson Professor of Engineering & Applied Science, Mark Reed, explains. He has also been one of the co-leaders of the investigation, alongside Associate Professor of Biomedical and Chemical Engineering Tarek Fahmy, also from the university.

Biomarkers that are usually produced in prostate and breast cancer were the main targets of the new investigation. The team constructed the nanosensors out of nanowires, a feat that enabled them to detect and measure the concentrations of both types of markers. This was only made possible by a revolutionary, new device the Yale group designed. The filter captures antigens specific to prostate and breast cancer on a small chip, while washing away all of the excess blood. This allows for a highly accurate detection process, the experts say.

“Doctors could have these small, portable devices in their offices and get nearly instant readings. They could also carry them into the field and test patients on site,” Fahmy believes. “The advantage of this technology is that it takes the same effort to make a million devices as it does to make just one. We've brought the power of modern microelectronics to cancer detection,” Reed adds. Details of the innovative system appear online, in the December 13 advanced issue of the respected scientific journal Nature Nanotechnology. Scientists from the Cornell University and the Harvard University have also been involved in the work.

Headline: 2 - Protecting Drugs from the Immune System




A wide array of drugs used in modern therapies are target-specific, meaning that they only have an effect if they are delivered to a certain location inside the body. But doing this is a very tricky business. Though it allowed itself to get infected once, the immune system is not willing to do the same over and over again, and so it ruthlessly attacks everything inserted into the blood stream, including the drugs meant to help it. A startup company now plans to make drugs more resistant to

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immune actions, which could drastically increase their chances of success, Technology Review reports.

The Stanford University-based company does not plan to create an entire new breed of drugs, but rather to chemically alter existing ones, so as to make them less susceptible to the action of red and white blood cells. The big plan is to laden the drugs with various molecules that would help them bind to the inside of cells, hitching a ride outside the reach of the immune system. Additional molecules will also be added on the surface of existing drugs to boost their abilities of binding to specific sick cells around the body. Each disease creates its own biomarkers, and drugs to follow these markers to their origins are well on their way.

This line of research could lead to drugs with longer half lives, which are the amount of time they endure within our bodies before they are eliminated. The team has already demonstrated the technology with a protease inhibitor, a drug regularly used to fight HIV in infected patients. “We're hoping this will be quite generally useful. One of the things I like about this approach is the combinatorial nature of the synthesis of the molecules,” says SU biologist Gerald Crabtree. His lab hosted the initial work that led to the formation of the company, Amplyx Pharmaceuticals.

“We wondered if we could generalize [our research] to a way of increasing stability for many drugs with problematic pharmacology, which can make them unusable or inconvenient to take. Some drugs have to be taken five times per day, which in turn leads to patient compliance issues,” the expert adds. “Red blood cells have a lot of the binding proteins, so the drug binds tightly to them and slowly leaches out of blood cells,” concludes University of Michigan biologist and Amplyx collaborator Jason Gestwicki.

Headline: 3 - New 'Heart Patch' Tissue Created from Stem Cells




Working in environments that mimic a human post-heart-attack heart, experts at the University of California in San Diego (UCSD) have recently managed to make adult stem cells differentiate into a force that can heal damaged heart cells. The new accomplishment is likely to raise the bar on how regenerative therapies for cardiovascular diseases are approached and performed in the future, the team says. The work could also influence a number of other treatments for other conditions too, they add.

The new results, which were reached a short while ago, were presented this week in San Diego, during the 2009 annual meeting of the American Society for Cell Biology (ASCB). In charge of the new experiments were scientists from the UCSD Jacobs School of Engineering Department of Bioengineering, led by expert Adam Engler. Their relentless work may represent a new ray of hope for the over 900,000 people in the United States that die from heart diseases each year. What this method essentially does is improve on an existing one of injecting stem cells directly into the scarred heart muscle, shortly after a heart attack.

In similar approaches, which have been dubbed cellular cardiomyoplasty, the stem cells are simply placed at the affected location. They are not stimulated into becoming useful for the heart via external sources. Rather, they receive their impulses from cells in their immediate surroundings, which have natural mechanisms of signaling that a change needs to be made at a particular location in the heart muscle. But the method sees the stem cells transform into small calcified lesions. They actually transform into bone-like cells, on account of the fact that the scarred and stiff muscle does not send the correct signals in its surroundings.

http://www.technologyreview.com/biomedicine/24150/?a=f�



The method that the UCSD team is proposing relies on using a supportive material for the stem cells, one that would allow the cells to change stiffness over a longer period of time. “Our evidence suggests that tissue-specific stiffness arises from key developmental changes, which implies that cells should be cultured in the appropriate physical conditions that mimic embryonic tissue progression, from soft, pre-cardiac tissue at early embryonic age to a mature, less compliant tissue at the conclusion of development,” explains the first author of the presentation, UCSD bioengineering PhD. candidate Jennifer Young.

“Results from this study may not only have a profound impact on cardiovascular engineering, but may influence the way in which many regenerative therapies are conducted. In this instance we have studied the developing tissue as a model, and from it generated a set of design criteria to mimic in our new material,” concludes Engler, a UCSD Jacobs School of Engineering bioengineering professor.

Headline: 4 - Bionic Eye Lets Man See after Years of Blindness


Date of Publication: - November 27, 2009


Fifty-one-year-old Peter Lane is one of the first people in the world to benefit from the obvious advantages of the new bionic eye technology. The therapy relies on implanted electronics in the retina, which allow for the conversion of images collected from an external camera into electrical impulses, to be sent directly down the path of the nervous system and into the brain. The technology is, of course, still in its infancy, but the earliest results are very promising, and so investigations into it will continue at an accelerated pace, The Daily Mail reveals.

According to Lane, the implanted device has for the first time in more than 30 years of blindness allowed him to make out the contours of furniture and doorways. This may seem minor at first, but after years of bumping into things this must look like a blessing. The implants have also allowed the man to read large letters for the first time in decades. He tells that he views them through a series of dots, which is how most of the information is conveyed to his visual cortex. However, even these basic capacities are better than nothing. The Manchester, UK resident is part of a narrow study, which aims at testing the new implants before they are made widely available.

“I'm just reading small words at the moment, but it's a start. The doctors have said they'll get me a screen so I can read at home and I'm hoping I'll be able to read letters I get in the post by myself eventually. I get around inside my flat okay without the glasses because I know where everything is, but outside they give me more confidence and a bit more independence. The images I see move and that takes a bit of getting used to, but I can see cars – they look like cotton wool. It's exciting to be part of the trial,” Lane says of his new “acquisitions”. He went blind in his early 20s because he was suffering from a degenerative eye condition known as retinitis pigmentosa.

Only 32 people around the world are part of these trials, the British news outlet informs. Though major advancements have been made since this course of treatment was first proposed, experts still need to ensure that there are no lasting side-effects, and also that the brain can adapt to seeing again, after years of not exercising the visual cortex. The system is fairly simple. A camera is mounted on special glasses, which then sends a video signal to an array of sensors in the eye, which are connected to the visual nerve. These arrays bypass and replace the function of the retina, transforming video input into electrical signals, which it then sends to the brain for processing.

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http://www.dailymail.co.uk/health/article-1231172/Blind-man-fitted-bionic-eye-sees-time-30-years.html�


Section C: Pharmaceutical Biotechnology

Headline: 1 - European Medicines Agency Grants Cell Therapeutics Orphan Drug Designation for Pixantrone in Diffuse Large B-Cell Lymphoma (DLBCL)

Published by: - GEN


Source: - www.genengnews.com

SEATTLE, Dec. 21 /PRNewswire-FirstCall/ --Cell Therapeutics, Inc. ("CTI") (Nasdaq and MTA: CTIC) announced today that the European Medicines Agency (EMEA) has granted pixantrone orphan drug designation for the treatment of DLBCL which accounts for about 80% of aggressive non-Hodgkin's lymphoma. CTI expects to file the Marketing Authorization Application (MAA) in Europe for approval of pixantrone in mid-2010 and would be granted 10 year market exclusivity if it is approved. In the U.S., the Food & Drug Administration's (FDA) Oncologic Drugs Advisory Committee (ODAC) plans to review the New Drug Application (NDA) for pixantrone for the treatment of relapsed/refractory aggressive non-Hodgkin's lymphoma (NHL) on February 10, 2010. Pixantrone is a fast track designated product in the U.S. and is in review for approval by the FDA, with a Prescription Drug User Fee Act (PDUFA) date of April 23, 2010.

Orphan drug designation is available in Europe for medical treatments and drugs intended to treat life-threatening or chronically debilitating conditions. Orphan drug designation can confer numerous benefits to companies developing such treatments, including regulatory assistance, reduced regulatory fees associated with applying for marketing approval, and assistance with clinical trial design.

"Orphan drug designation for pixantrone in Europe demonstrates that there is clear unmet medical need for patients with DLBCL," stated Craig W. Philips, President of CTI. "We will continue to work with the EMEA to move our application forward in Europe expeditiously as we prepare for potential commercial launch of pixantrone in the United States."

About Pixantrone

Pixantrone (BBR 2778), is a novel topoisomerase II inhibitor with an aza-anthracenedione molecular structure that differentiates it from the anthracyclines and other related chemotherapy agents. Anthracyclines are the cornerstone therapeutic for the treatment of lymphoma, leukemia, and breast cancer. Although they are sufficiently effective to be used as first-line (initial) treatment, they cause cumulative heart damage that may result in congestive heart failure many years later. As a result, there is a lifetime limit of anthracycline doses and most patients who previously have been treated with an anthracycline are not able to receive further anthracycline treatment if their disease returns.

About Cell Therapeutics, Inc.

Headquartered in Seattle, CTI is a biopharmaceutical company committed to developing an integrated portfolio of oncology products aimed at making cancer more treatable. For additional information, please visit www.CellTherapeutics.com.

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http://www.celltherapeutics.com/�


Headline: 2 - Need For a Global Strategy to Develop New Antibiotics

Published by: - Medical News


Source: - http://www.medicalnewstoday.com

In this week´s The Lancet, an editorial supports the recent calls for a universal effort in developing new antibiotics. It reports that prospects for replacing current antimicrobial drugs are reduced. According to the report "Bad Bugs, No Drugs: No ESKAPE!" published in January, 2009, by the Infectious Diseases Society of America (IDSA), since 2006 only one single new antibacterial (doripenem) has been approved in the USA. Equally discouraging, a recent EU report revealed that just fifteen antibacterial drugs offering a potential benefit over existing drugs are in development. In addition, only five have reached phase 3 clinical trials.

The editorial states: "Pharmaceutical companies may not perceive development of antimicrobial drugs to be attractive - owing perhaps to a clinical need restricted to short courses of therapy, and the likelihood that the drugs' useful lives will be truncated by resistance."

The editorial backs up the recent challenge by IDSA to the USA and EU to develop ten new licensed antibiotics within the next ten years, dubbed the 10 / '20 Initiative. This call followed a summit held on Nov 2-3 in Washington, DC. At this event, US President Barack Obama and Swedish Prime Minister Fredrik Reinfeldt, representing the EU, established a transatlantic task force to promote research and development of new antimicrobial drugs. The editorial says in closing: "A global strategy is badly needed to enact the 10 / '20 Initiative and create a stable research infrastructure for antimicrobial development. How much money will be available, who will provide it, and how will academic and company researchers work together to surmount obstacles in drug development? Leadership from WHO could help to lift this issue up the public health agenda."

Headline: 3 - Ranbaxy recalls drugs for skin disease from US market


Date of Publication: - Nov.20, 2009


Ranbaxy Laboratories has recalled from the US market a batch of 4,348 cartons of Sotret Isotretinoin capsules used in treating skin infections.

According to the information available on US health regulator Food and Drug Administration’s (FDA) website, Ranbaxy through its US-based subsidiary Ranbaxy Laboratories Inc, has issued a ‘nation-wide class III recall’ for a batch of Sotret Isotretinoin capsules of 40 mg strength. The company has issued the recall after ceratin reports suggested that the product may “exceed impurity specifications” during its shelf life period.

However, a class III recall signifies that the use of the product is not likely to be harmful. This is the second time in last four months that Ranbaxy has initiated a recall. Earlier in July, it had called back a lot of Sotret from the US market.

When contacted the spokesperson of Gurgaon-based firm said this is a Class III recall and is being conducted with the full knowledge of the USFDA.




“Ranbaxy Laboratories Inc, Princeton, New Jersy, is conducting a voluntary recall of Sotret Isotretinoin Capsules, USP 40mg, which is limited to a single batch, currently available in the US market,” the company said. Asked about the impact of recall on company’s revenues, the company declined to comment over the issue.

Headline: 4 - Cipla unveils drug to combat H1N1 virus



Source: - http://www.financialexpress.com/

Mumbai-based Cipla has launched Oseltamivir, a generic version of Roche’s Tamiflu, used in the treatment of the H1N1 virus, under the brand name, Antiflu, in India. Cipla’s Oseltamivir brand will cost Rs 475 for 10 capsules, and its 75 ml syrup will be similarly priced. Cipla’s drug is also pre-qualified by the World Health Organisation (WHO). The H1N1 virus outbreak from the early part of the year was declared a pandemic in June and continues to spread globally.

On Monday, the health ministry said more than 500 people have died from the flu in India since the first fatality was reported in August, with Maharashtra seeing the largest toll of 207 deaths. More than 14,000 people have tested positive for the flu across India during the period. More than 5,700 people have died worldwide since the virus was first discovered in April.

“Influenza, a perceivably benign condition, kills about 2.5 to 5 lakh people every year worldwide, according to the WHO. These are generally the elderly or those with chronic conditions of the lung, heart or kidney. The fatality pattern this year with the 2009 H1N1 virus has been unusual, with the virus attacking healthy adults and children and pregnant women,” said JA Gogtay, medical director, Cipla. The company's shares closed at Rs 304.75 on the BSE on Wednesday, up 1.43%.

According to YK Hamied, chairman, Cipla, the company has offered to supply Antiflu to the United States. “There is a shortage in the US. We have made an offer. It’s up to them,” he said. Cipla can produce two million doses of Oseltamivir a month if needed, he added.

Headline: 5 - FDA nod to H1N1 vaccine for infants over 6 mths



Source: - www.

New Delhi: The US Food and Drug Administration (FDA) has approved CSLs H1N1 influenza vaccine for use in children aged six months and above. The companys vaccine was previously approved only for use in people over 18 years.

timesofindia.indiatimes.com/

Australia-based CSLs vaccine is perhaps only the second vaccine approved for use in infants aged six months and above, as the ones by Novartis and MedImmune have not yet been approved for use in infants. The only other vaccine approved by FDA for use in this age category is manufactured by Sanofi. Both Novartis and MedImmune vaccines for H1N1 have been approved for use in children above 4 years, according to data submitted to the FDA.

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Since CSLs seasonal and H1N1 monovalent vaccines contain a small amount of egg protein, it should not be administered to anyone allergic to eggs or egg products.

Because children are among those most vulnerable to the 2009 H1N1 virus, having a broader range of childrens vaccines available is an important step in responding to the H1N1 outbreak, said Margaret A Hamburg, commissioner of food and drugs.

The expanded approval also covers the companys seasonal flu vaccine. The approval was based on a study of the companys seasonal flu vaccine in children showing the vaccines safety and efficacy in inducing antibodies to protect against influenza. These findings fetched an approval under FDAs accelerated approval regulation, which helps safe and effective medical products for serious or life-threatening diseases to become available sooner to the public.

Typically, common adverse effects experienced by children after administration of seasonal and H1N1 vaccines include pain, redness and swelling at the injection site and, in some cases, irritability , loss of appetite and drowsiness , says a FDA statement.

As with any medical product, unexpected or rare/serious adverse effects may occur. The vaccines will be available in single-dose, preservative-free, pre-filled syringes and in multi-dose vials that contain thimerosal , a mercury derivative, as a preservative.

Headline: 6 - Chemical Imaging System Helps Solve Major Hurdle in Pediatric Drug Development

Published by: - Biotech-Daily International



New near-infrared chemical imaging (NIR-CI) technology is able to provide fast and flexible spatial and chemical information, with wide sampling dynamic range and depth of field.

Researchers from the Institute of Pharmaceutics and Biopharmaceutics at the University of Düsseldorf (Germany) have taken delivery of a near infrared chemical imaging (NIR-CI) system from Malvern Instruments (Malvern, UK). The ideal solution for analyzing curved tablets, whole granules, and pellets, and anything in between, the new instrument is set to transform many of the Institute’s groundbreaking projects in novel solid drug dosage forms. The system is already being used by Prof. Dr. J. Breitkreutz and his research team for testing oral drug-loaded films, also called wafers, in a project designed to tackle the difficulties of administering drugs to young children.

Prof. Dr. Jörg Breitkreutz said, “Pediatric drug delivery is a major challenge. There is currently a lack of suitable and safe solid drug formulations for children and new EU [European Union] legislation will enforce pediatric clinical trials and drug development. Current advances in this area include interesting new drug delivery concepts such as multiparticulate dosage forms, minitablets, fast-dissolving formulations, small-sized oral films, and wafers designed to stick to the roof of the patient’s mouth. However, novel dosage forms often need special methods to assess their properties for both development and quality control, as standard testing procedures are not available in the pharmacopoeias. This increases the need for flexible analytical methodology and instrumentation. Malvern’s near infrared chemical imaging system accommodates the sample variability encompassed by modern pharmaceutical development and was therefore our ideal solution for visualization of drug distribution within the dosage forms.”



On May 29, 2009, the European Journal of Pharmaceutics and Biopharmaceutics published an article that described a study that aims to compensate for the lack of adequate methods for the characterization of the novel wafers by applying advanced analytic techniques. The Malvern chemical imaging system plays a critical role within the morphologic investigation as it can depict visually unrecognized differences in the distribution of the active pharmaceutical ingredient within wafers.

Malvern Instruments provides a range of complementary materials characterization tools that deliver inter-related measurements reflecting the complexities of particulates and disperse systems, nanomaterials, and macromolecules. Analytic instruments from Malvern are used in the characterization of a wide variety of materials, from industrial bulk powders to nanomaterials and delicate macromolecules. A wide range of innovative technologies is combined with intelligent, user-friendly software. These systems deliver industrially relevant data to make the connection between micro (such as particle size) and macro (bulk) material properties (rheology) and chemical composition (chemical imaging).

Headline: 7 - Daiichi to leverage Ranbaxy abroad

Published by: - The Economics Times


Source: - http://economictimes.indiatimes.com

Japan’s Daiichi Sankyo, which controls Ranbaxy Laboratories, will use the Indian company as a launch pad to sell its patented drugs in Europe, China and the US and will work together in developing new products, a senior company official said.

“Ranbaxy will launch our products that go off patent in developed markets such as Europe and the US and even for our drugs that are patented. We will collaborate on new drug discovery,” Tsutomu Une, senior executive officer for global corporate strategy at Daiichi Sankyo and chairman of Ranbaxy told ET NOW on the sidelines of the India Economic Summit.

Daiichi bought 64% stake in Ranbaxy for Rs 20,000 crore last year to take advantage of low-cost manufacturing base and marketing strength in 100 countries and subsidiaries in 50. But the Japanese company was in for some surprises in the form of currency losses and adverse regulatory developments ever since it acquired Ranbaxy. Daiichi, which has been working to turn the situation around, is slowly capitalising on Ranbaxy’s global infrastructure built over the last decade.

Ranbaxy has been a pioneer among Indian drugmakers in challenging patents in the US and promised to make huge profits once some of those drugs went off patent. But the strategy backfired. In the process, two of its plants were banned by the US Food and Drug Administration . It also acquired companies in Europe, including countries such as Romania to benefit from the European Union’s growth.

But under Daiichi, there are efforts to undo the damages and it is planning to sell drugs in the US market from its new Mohali facility. “We have filed the new drug application and these will trigger an FDA inspection of the facility. We expect to start selling drugs in the US from the plant sometime next year,” Atul Sobti, Ranbaxy’s CEO and MD said.

In September last year, USFDA banned the company from importing more than 30 generic drugs into the US because of violations of certain manufacturing process at Dewas and alleged data falsification at Poanta Sahib. At present, Ranbaxy uses its plant in the US to sell the drugs that were earlier filed from the two plants under scrutiny.

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Ranbaxy will be the chosen one to further its China plan. In China, the Japanese company plans to launch an anti-flu drug though Ranbaxy’s subsidiary.

The companies have set up a new division in Mexico to sell Daiichi’s products and in Romania they have started selling an osteoporosis drug whose marketing rights is with the Japanese company

Headline: 8 - US health bill to benefit local generic firms




The US healthcare bill, which has been passed by the US House of Representatives and is awaiting nod from the Senate, holds a lot of promise for generic drug manufacturers from India. With emphasis on increasing the coverage and reducing healthcare costs, the bill is going to provide a big fillip to the usage of low-cost generic drugs.

The bill seeks to bring an additional 40 million US citizens under medical insurance coverage. This will open up a big market for generic drug makers. Besides, even for the existing population under insurance coverage, there is likely to be a shift in the usage from patented to generic drugs.

Indian pharma companies — most of them being exporters of generic drugs and intermediates to the US, the world’s largest drug market — are going to gain by passing of this bill. While the impact is long term in the form of increase in procurement of generic drugs by the US, it is nevertheless a positive sign. One other major aspect of the bill, which is likely to be important for Indian pharma companies, is the provision in the bill on bio-similars.

The bill has provided for a data exclusivity protection period of 12 years for biologics innovator companies. This is much longer than the period of five years, provided by the US government in case of chemical drugs. This provision, while throwing some light on the pathway to launch bio-similars in the US, will slow down the long-term growth of bio-similars in the US.

However, the good news is that this would not impact the immediate pipeline of Indian biotech players. Most biologic drugs were developed between 2000 and 2004 in the US. Indian companies, which are developing bio-similars for these biologics, will just be ready with their products by 2016 — the time when the 12-year protection period ends for the biologics in the US. However, Indian companies will have to go slow on future product development in bio-similars.

The bill also has provisions that impose restrictions on the Para IV settlements done between the innovator and generic companies. While the settlements have not been banned altogether, the restrictions may bring some deterrence to go for settlement.

The bill, however, is facing a lot of resistance and protests in its current form. It will be too naive to think that large insurance companies and big pharma firms in the US would take these sweeping changes lying down. This may lead to several compromises before it sees the light of the day as a piece of legislation.

Even in a truncated and compromised form, it is likely to benefit generic players. And Indian companies (aggressive that they are on the generic front) are likely to be natural beneficiaries.



Headline: 9 - Zydus first Indian co to file H1N1 clinical trials




AHMEDABAD: The race among Indian pharma companies engaged in swine flu vaccine development may soon throw up a winner just when the pandemic enters a critical stage with the onset of winter.

Drug Controller General (India) Dr Surindra Singh told ET that the Rs 3,000-crore pharma major Zydus Group has become the first domestic company to file for clinical trial protocol for H1N1 vaccine with the DCGI. With this filing, the Ahmedabad-based major leads other Indian pharma majors including Bharat Biotech, Panacea Biotech and Serum Institute of India, the three entities mandated by the Indian government to develop the vacccine.

Interestingly, another pharma major Cadila Pharmaceuticals which too is developing a swine flu vaccine with US collaboration using an advanced technology belongs to Gujarat, whose chief minister Narendra Modi is still recovering from Swine Flu.

According to DCGI Dr Singh: "Zydus is the first and the only Indian company to file for swine flu vaccine's trial." Among the multinationals, GlaxoSmithKline (GSK), Novartis, Baxter International and Sanofi-Aventis had applied for test license to the DCGI for carrying out clinical trials in India for their version of swine flu vaccines. "Although, it's a long process, amongst the MNCs, GSK is comparatively ahead," says Mr Singh.

When contacted, Zydus did not confirm the development, but top level sources close to the company said Zydus would be the first Indian company to hit the market with the vaccine. The Gujarat pharma company is learnt to have entered into a collaboration with European biotech company BioCryst Pharmaceuticals for the development of the H1N1 vaccine.

It may be mentioned here that earlier this year, swine flu has been declared as a global pandemic by the World Health Organisation (WHO) which feared around 2 billion population might get affected. In India, the influenza virus has so far claimed 484 lives and affected 14,406 people.

Globally, the H1N1 vaccine market is forecast to grow beyond $7 billion in next two years from $676 million as of now.

The Indian government, earlier this year, mandated three Indian vaccine makers - Serum Institute of India Ltd, Bharat Biotech and Panacea Biotec -- to develop swine flu vaccine on a war footing. However, their research is yet to reach any significant stage.

In reply to an earlier ET query, the executive director of Serum Institute of India Dr Suresh Jadhav said: "We are developing two types of vaccine - one is injectable (inactivated) and other is intranasal route (live attenuated). Both these vaccines have nearly completed the optimization process of manufacture and are in pre-clinical studies. Immunogenicity trials are nearly over and both the vaccines will come into toxological studies by 2nd week of November 2009. The vaccine would be be made available to the Indian government by March 2010."

Interestingly, Gujarat is the only state that has two pharma giants in advanced stages of the vaccine development. Earlier this year, Cadila Pharmaceuticals Ltd, another Ahmedabad-based pharma major, joined hands with with US-based Novavax Inc. to develop and manufacture seasonal as well as swine flu vaccines using the latest technology - Virus Like Particle technology.



Headline: 10 - Dr Reddy's files for marketing Lipitor generic




MUMBAI: Dr Reddy's Laboratories has filed for marketing a generic version of Pfizer's cholesterol-lowering drug Lipitor in the US, the company said on Saturday.

"We have filed an ANDA (abbreviated new drug filing) for atrovastatin and notified Pfizer accordingly," Dr Reddy's told news agency in response to an email query.

Earlier on Saturday, the Business Standard newspaper reported that Dr Reddy's had developed a generic version for Lipitor, and along with its US subsidiary, had informed Pfizer about applying to the US Food and Drug Administration for marketing the drug.

Lipitor is the world's largest selling drug, with global sales of $8.3 billion in the last nine months. So far, Ranbaxy is the only other Indian drugmaker to develop a generic for the drug, whose US patent expires in 2010.

Under a settlement with Pfizer, Ranbaxy has agreed to launch its generic by November 2011.

Headline: 11 - Indian scientists discover new genus of mite




US scientists say a new mite discovered by their counterparts at the Indian Council of Agriculture Research (ICAR) and christened Mangalaus represents "a new genus".

The taxonomists of the ICAR Network Project on Insect Biosystematics, who discovered the new mite, named it after Director General Mangal Rai.

Renowned mites and ticks expert (acarologist) James Amrine of the West Virginia University said: "This mite has an eye-like ocelli and represents a new genus."

Ronald Ochoa of the US Department of Agriculture said there was no report of such structure in this mite family. "The round area, yes almost it does look like an eye, but as you know, there is no report of such structure in this mite family," he said.

The mite, which is too small to be seen by the naked eye, was found in the farm of the Indian Agricultural Research Institute, New Delhi. The mite with an average length of 200 microns (one micron is 1,000th of a millimetre) feeds on a leaf called Erineum on the fragrant plant Manjarack or Indian cherry. The scientists named it after Rai because of his "abiding interest" in insect bio-systematics.


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Headline: 12 - ERYtech Pharma Starts Its Pivotal Clinical Trial For GRASPA(R) In Acute Lymphoblastic Leukaemia




ERYtech Pharma announces the start of its pivotal clinical trial for GRASPA®, its lead product in Acute Lymphoblastic Leukaemia. This phase III trial has begun in France and will be enlarged to a European scale. Up to 80 patients with relapsed Acute Lymphoblastic Leukaemia, aged from 1 to 55 years old will be enrolled. The endpoint combines safety and efficacy with regard to the asparagine depletion level.

Professor Yves Bertrand, Head of Paediatric Onco-hematology in Lyon and main investigator says, "I would be really content to see confirmation of the very encouraging phase II trial with GRASPA®. We designed this trial to fit with the medical needs."

GRASPA® is a new enzyme formulation of L-asparaginase with a safer and broader range of clinical uses, compared to existing forms, due to the entrapment and protection of the enzyme inside the homologous red blood cell. GRASPA®'s (encapsulating L-asparaginase in red blood cells) interest lies in overcoming all existing limitations associated with conventional L-asparaginase through longer efficacy, better compliance, reduced dosage and an increased safety profile; making it satisfactory for every ALL patients, even high risk ones (hypersensitive, elderly patients), or patients with neutralising antibodies.

L-asparaginase is a critical and irreplaceable component of combination chemotherapy for ALL and has been used in the clinic for over 30 years. The enzyme depletes the plasmatic amino acid asparagine, which leukaemia cells require to continue their rapid, malignant growth. While normal cells are able to make a sufficient amount of asparagine internally, leukaemia cells cannot. Infusion of L-asparaginase destroys the external source of asparagine, which starves leukaemia cells of this amino acid and leads to cellular death.

Doctor Yann Godfrin, Co-Founder and CEO of ERYtech Pharma claims: ''I am very proud to say that this study is the result of a strong collaboration between the physicians, the experts of the EMEA and our clinical development team. This trial is a great opportunity for the physicians of several European countries to use GRASPA®. It is so exciting while the 5-year old birthday of the company to start a pivotal study with the target of gaining market authorization''.

Headline: 13 - Corporate revamping to cost jobs at Johnson & Johnson



Source: - www. conomictimes.indiatimes.com

In what had already been a year of drastic job cuts in the drug industry, the health care giant Johnson & Johnson said on Tuesday that it would eliminate 6 to 7 per cent of its worldwide work force – about 7,000 to 8,200 jobs – as part of a corporate revamping.



The company, which makes drugs, medical devices and personal care products like Listerine, currently has about 117,000 employees worldwide. Many of the cuts are expected to occur overseas.

Factors specific to the drug industry, including a wave of consolidation and the uncertainties of legislation pending in Congress, have combined with the sluggish global economy to put pressure on drugmakers.

Slower than many other businesses to contract in recent years, the health care industry is now hurrying to catch up by trying to adopt leaner research and development, manufacturing and marketing operations – often, by relying on a reduced corps of employees to take on greater responsibilities.

Even before the announcement from Johnson & Johnson, 2009 was shaping up as a record year for job cuts in the pharmaceutical industry, according to a report from Challenger, Gray & Christmas, an employment firm that tracks job cut announcements by drugmakers.

Through October, drugmakers had said they planned to cut nearly 58,700 jobs, more than 60 per cent higher than in the comparable period last year.

Health care companies still have growth opportunities if they can come up with new treatments for conditions like diabetes and Alzheimer’s disease, but the industry needs new approaches to capitalize on them, William C. Weldon, the chief executive of Johnson & Johnson, said in a call with analysts on Tuesday.

The company’s overhaul plan, Weldon said, is meant to reduce layers of management and streamline decision making, to let the company devote more resources to investing in innovative medical products and bringing them to market.

The company said that it planned to take a special pretax restructuring charge in the current quarter of $1.1 billion to $1.3 billion, but that it also expected the job cuts and other reduced expenditures to result in long-term savings. The company said it expected pretax cost savings next year of $800 million to $900 million. And in 2011, when the reorganization is completed, it expects pretax cost savings of $1.4 billion to $1.7 billion.

An analyst’s report from Credit Suisse on Tuesday said the absolute savings would amount to 3 to 4 per cent of the company’s total spending for 2009.

"The plans and associated savings we are announcing today," Weldon said during the call, "will increase our operational efficiency and allow us to continue growing our strong core businesses and ensure the success of new products that are launching or pending approval in the near term."

Job cuts at the company would be global, he said, and were likely to be heavier outside of the United States. A spokesman said the company would not comment on how the job cuts would play out across the company’s drug, device and consumer divisions.

Within the industry, many of the major pharmaceutical companies are facing patent expirations on their billion-dollar blockbuster drugs that will expose them to competition from cheaper generics. Meanwhile, a slow and expensive drug development process, in which it often takes more than a decade and costs more than $1 billion to bring a new medicine to market, has slowed down product pipelines. Besides economic and business pressures, health care companies are also under increased scrutiny by federal regulators and lawmakers.


The increased emphasis by regulators on safety, analysts said, has resulted in a longer, costlier, more complicated approval process for prescription drugs – a business from which Johnson & Johnson derived $24.6 billion of its $63.7 billion total revenue last year, from drugs like Remicade, a treatment for plaque psoriasis and rheumatoid arthritis.

And the makers of medical devices are not exempt from increased government attention. Johnson & Johnson generated about 36 per cent of its overall revenue last year from devices that include knee and hip replacements, sutures, and contact lenses.

The Food and Drug Administration recently said it had asked an independent group of scientific experts to review the agency’s vetting of medical devices. And, to help pay for the cost of a congressional overhaul of the health care system, some lawmakers have called for the makers of medical devices to pay billions in extra taxes over the next decade.

"Companies with massive global infrastructure are asking themselves if they can get the job done in more efficient ways," said Rick Wise, an analyst who covers Johnson & Johnson for Leerink Swann, a health care investment bank.

For major drugmakers that announced mergers this year, efficiency is a code for word for cuts to eliminate overlapping jobs. The $68 billion merger of the drug giants Pfizer and Wyeth, completed last month, is expected to result in a work force reduction of 15 per cent, or about 19,500 jobs.

The $41.1 billion merger of Merck and Schering-Plough, which was expected to be completed late Tuesday afternoon, is projected to result eventually in the elimination of 16,000 jobs.

Eli Lilly, which bought the biotech company ImClone Systems last year for $6.5 billion, recently said it planned to reduce its work force to 35,000 – a loss of about 5,500 jobs – by 2011. But Johnson & Johnson may be in a better position to weather challenges than many of its competitors, analysts said. It has promising new products – this year, the FDA approved four of the company’s new drugs, including Simponi for rheumatoid arthritis and Stelara for psoriasis.

And the company recently bought 18 per cent stakes in Elan and Crucell, two innovative smaller companies with which Johnson & Johnson plans to develop, respectively, Alzheimer’s drugs and vaccines. Moreover, as a diversified company that markets surgical devices and consumer products as well as drugs, Johnson & Johnson is less exposed to pressures unique to the pharmaceutical industry, analysts said.

Headline: 14 - Indus’ AIDS molecule gets approval for clinical trials


Date of Publication: - Oct 27, 2009


MUMBAI: Pune-based research company Indus Biotech has received approval from the US Food and Drug Administration (USFDA) for clinical trials of its molecule, IND02, which can be used to treat AIDS and will begin the phase 1 trials in the US shortly, its managing director Sunil Bhaskaran says.



The 12-year old company, which focuses on developing new chemical entities (NCEs) from plant extracts, has also submitted a dossier to the Drug Controller General of India (DCGI) and is awaiting the green signal to proceed with phase 3 clinical trials, he added.

The company on Friday said that its molecule could convert an HIV patient into a ‘HIV Controller,’ a person who despite being affected with HIV, manages to control the progression of the disease and protect the immune cells.

“We have also discovered that the same molecule can be used to cure H1N1 and have filed an application with the USFDA and the DCGI for that as well. Once the approval for the H1N1 indication is cleared we will start trials for that,” Mr Bhaskaran said. Indus Biotech is the first Indian company to receive IND approval.

Rajan Srinivasan, executive director at Indus said, “The idea of developing drugs based on plant extracts is so that the toxicology is low. These are plants that are part of the food raw chain yet do not fall under the ayurvedic or alternative medicine category. Till date we have been focusing on the US since the guidelines for botanical drugs are defined and there is no such clarity in India. However, the discovery of the molecule’s effect on H1N1 made us approach the DCGI who had constituted a committee to look into the documents we have submitted.”

The company has already tested its molecule and found it to be effective against against various strains of the. These studies were done in collaboration with the National Taiwan University and Hospital. Indus Biotech, which has recently raised funds from Kotak Private Equity, is considering raising additional money through share sale to fund its clinical trials in the US. " Clinical trails in India won’t cost too much but we will consider raising funds for the US trials," Mr Bhaskaran said.

India currently has six million people suffering from AIDS while globally the figure is 40 million. However, with HIV drugs falling under the orphan drugs category (a drug for a disorder affecting fewer than 2 lakh people in the US) most pharma companies are not interested in investing funds in developing molecules in this space, making increasing the opportunity for a successful drug.

Headline: 15 - Quick and Easy Diagnosis For Mitochondrial Disorders




Soon you could be genetically screened for mitochondrial disorders quickly and comprehensively. Research published in BioMed Central's open access journal, Genome Medicine, outlines an innovative clinical diagnostic test for the early identification of a wide range of mitochondrial disorders. Mutations to one of the mitochondrial genes, or to a number of nuclear genes with roles in mitochondrial function, can cause diseases which have very similar symptoms, making them difficult to diagnose and treat.

Researchers from the Seattle Children's Research Institute teamed up with researchers from the Genome Sciences and Pediatrics Departments of the University of Washington to create a molecular diagnostic tool that uses targeted genetic sequencing to screen patient's DNA for variations in 362 genes which have been associated with mitochondrial disease or mitochondrial function. They tested this tool by using it to screen three DNA samples. Two of these samples were taken from patients



with mitochondrial disorders, who had been previously diagnosed by traditional sequencing methods, while the third came from a healthy individual selected from the Coriell Repositories HapMap catalogue of human DNA samples. The researchers then assessed the potential impact of all the novel mutations they detected. They found that the new method was able to accurately identify the mutation underlying each patient's condition. The large number of candidate genes examined is likely to increase sensitivity for identifying previously unknown genes responsible for mitochondrial disorders. "Early and effective diagnosis [of mitochondrial disorders] is crucial for permitting appropriate management and accurate counselling", say lead authors, Jay Shendure and Sihoun Hahn. "Mitochondrial diseases affect as many as 1 in 5000 children; however diagnosis is notoriously difficult due to the huge number of genes potentially responsible for these disorders. For these reasons, some patients may remain undiagnosed and even die of untreated disease" according to Dr Hahn. In addition to providing accurate diagnosis, the large number of genes used in this method allows a large number of potentially harmful mutations to be detected which might otherwise be missed. He adds, "Our study indicates that the use of next generation sequencing technology holds great promise as a tool for screening mitochondrial disorders."

Headline: 16 - New Research Highlighted At Neuroscience 2009




Research presented at Neuroscience 2009, the annual meeting of the Society for Neuroscience (SfN) and the world's largest source of emerging news about brain science and health, provides a better understanding of the brain, nervous system, and related disorders.

Specific research just released shows:

The benefits of exercise on both the brain and body, and, more specifically, underscores the positive influence of regular physical activity on Parkinson's disease, depression, premenstrual syndrome, and memory.

New tools are enabling researchers to identify neural similarities and differences between species. The findings may help to explain faculties, like language, and diseases, like Parkinson's, that are unique to humans.

New insights into male behavior support the idea that many gender differences lie in the brain and are influenced by both genes and environment.

Scientists are developing novel ways to bypass the blood-brain barrier, a network of blood vessels that prevents more than 95 percent of all chemicals from entering the brain from the bloodstream. Researchers describe new methods for transporting drugs across the BBB as well as ways to enhance the brain's own immune response, which is separated from the body's immune system by the BBB



Headline: 17 - Paracetamol dampens vaccine effect in kids: Study



Source: - http://timesofindia.indiatimes.com

LONDON: Giving paracetamol to babies to prevent fever after routine vaccinations may reduce the effect of the shots themselves, Czech scientists said on Friday.

While the paracetamol, known as acetaminophen in the United States, generally does limit post-vaccination fever, it also reduces the childâ€™s response to some of the vaccine antigens, according to a study in the Lancet journal.

Mothers in developed countries whose babies have a series of routine vaccinations at around the age three months are often told by medical staff to give paracetamol to try to cut the risk of fever or febrile convulsions.

But Roman Prymula of the Czech University of Defence said his study showed that giving so-called anti-pyretic medicines like paracetamol after vaccinations should â€œno longer be routinely recommended without careful weighing of the expected benefits and risks.

The vaccinations which are generally offered to children as protection against pneumococcal disease, Haemophilus influenzae type b (Hib), diphtheria, tetanus, whooping cough, hepatitis B, polio and rotavirus.

The effect of some of the vaccines in particular Hib, diphtheria, tetanus and pneumococcal â€” is reduced if kids are given paracetamol, the expert said.

Headline: 18 - Inovio Biomedical Announces Initiation Of HIV Clinical Trial For DNA Vaccine Delivered Using Electroporation




Inovio Biomedical Corporation (NYSE Amex: INO), a leader in DNA vaccine design, development and delivery, and the HIV Vaccine Trials Network (HVTN) announced today the initiation of a phase I clinical study of Inovio's PENNVAX™-B preventive DNA vaccine delivered using its proprietary electroporation technology. The multi-center study will be conducted at several HVTN clinical sites under a protocol designated HVTN-080.

The study will enroll healthy volunteers to assess the safety of and immune responses to this DNA-based vaccine delivered via in vivo electroporation. Inovio previously reported data from non-human primates demonstrating up to a 100-fold enhancement in immune responses resulting from the vaccine when delivered via in vivo electroporation compared to syringe injection without electroporation. PENNVAX™-B is currently in a clinical study, being conducted under the HVTN-070 protocol by the same group of collaborators, to test safety and immunogenicity of the vaccine delivered via intramuscular syringe injection without electroporation. The HVTN-080 follow-on study is sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), an NIH agency.




Dr. J. Joseph Kim, Inovio's president and CEO, said, "We are pleased to collaborate with the NIH and HVTN to test the SynCon™ PENNVAX-B HIV vaccine delivered via electroporation. With our recently announced positive interim immunogenicity data from our clinical trial for our human papillomavirus/cervical cancer DNA vaccine using a similar technology approach, we are optimistic that electroporation delivery of PENNVAX™-B vaccine will demonstrate similar levels of safety and immunogenicity in this trial."

HIV is characterized by its ability to rapidly mutate and evade the immune system or target-specific biopharmaceuticals. Inovio developed its SynCon™ approach to target multiple variants of the antigenic protein(s) associated with a virus that the body will recognize as foreign and attack. The methodology was designed to create DNA plasmid vaccines representing a broad consensus of antigenic variants that emerge through ongoing mutation.

Inovio's PENNVAX™-B DNA vaccine targets clade B human immunodeficiency virus, the most common type of HIV in North America and Europe. It is designed to produce and induce an immune response against the env, gag and pol proteins of HIV. Using its SynCon™ approach, Inovio created this DNA vaccine using three plasmids designed to each produce a "consensus" version of one of the three selected antigens, with the potential to provide a broader degree of protection. The SynCon™ env plasmid is based on env antigen sequences derived from clade B HIV. The SynCon™ gag and pol plasmids are based on gag and pol antigen sequences derived from sequences which encompass most global HIV viruses.

Inovio recently announced safety and immunogenicity data from a Phase I therapeutic HPV/cervical cancer vaccine trial showing enhanced immune responses at low DNA doses followed by electroporation. These HPV and HIV studies represent Inovio's first two internal product development programs to reach the clinical trial stage with its combination SynCon™ vaccines and in vivo electroporation delivery devices.

Inovio continues its separate work on a previously awarded $23.5 million HVDDT contract from the NIAID to develop a universal, preventive HIV vaccine, PENNVAX™-GP, with broader global coverage.

About HIV, HVTN, NIAID and NIH

The HIV/AIDS epidemic has already claimed more than 25 million lives and another 40 million people are currently estimated to be living with HIV/AIDS worldwide. (UNAIDS) A safe and effective HIV preventive vaccine is urgently needed and is the best long-term hope to bring the HIV/AIDS epidemic under control. (CDC)

The HIV Vaccine Trials Network (HVTN) is an international collaboration of scientists and educators searching for an effective and safe HIV vaccine. The HVTN's mission is to facilitate the process of testing preventive vaccines against HIV/AIDS. HVTN conducts all phases of clinical trials, from evaluating experimental vaccines for safety and the ability to stimulate immune responses, to testing vaccine efficacy. The HVTN is supported by a cooperative agreement with NIAID. More info: http://www.hvtn.org

NIAID conducts and supports research-at NIH, throughout the United States, and worldwide-to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at http://www.niaid.nih.gov.

The National Institutes of Health (NIH)-The Nation's Medical Research Agency-includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical

http://www.hvtn.org/�

http://www.niaid.nih.gov/�


research, and it investigates the causes, treatments and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.

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Section D: Agriculture Biotechnology

Headline: 1 - Importance of Information & Communications Technology in agriculture emphasized




ICRISAT calls for use of Information and Communications Technology (ICT) for empowering farmers

Information and Communications Technology (ICT) has immense potential in empowering farming communities, and it should be put to greater use by the agricultural research and extension institutions.

The need for increased use of ICT in agriculture research was emphasized by the Deputy Director General (Research) of the International Crops Research Institute for the Semi-Arid Tropics (ICRISAT) Dr. Dave Hoisington, at the inaugural of the five-day International Consultation on Agricultural Research for Development and Innovation, addressing emerging challenges and exploiting opportunities through Information and Communication Technologies, on 7 December.

The five-day workshop on ICT in Patancheru looks at challenges of using ICT in agricultural research and transfer of technologies to poor farmers. The workshop is jointly organized by ICRISAT, Global Forum on Agricultural Research (GFAR), Food and Agriculture Organization (FAO) and Asia-Pacific Association of Agricultural Research Institutions (APAARI).

Dr. Hoisington pointed out that politicians were able to effectively use new technologies including ICT and the agricultural scientists must take a cue from them. “Unfortunately, till now ICT is not given the due importance it deserves, and this has to be corrected to achieve more positive results,” he added.

In his special message, ICRISAT’s Director General, Dr. William D. Dar, highlighted the importance of information in agriculture, and encouraged the workshop to come up with fresh and innovative ideas that could be mainstreamed in the new paradigm of international agricultural research.

Dr. Ajit Maru, of GFAR, Rome, defined the theme of the consultations and opined that ICT should be accorded prominence by treating it as frontier technology on par with biotechnology and nano-technology. “Once this is done, it should be able to attract more investments to take on new and challenging tasks of improving the livelihoods of resource-poor smallholders and producers,” he said.

Dr. Stephen Rudgard, Chief, WAICENT Outreach and Capacity Building Branch of the FAO of the United Nations, Rome, stressed the importance of ICT and its usefulness in transferring technologies to the poor farming communities.

Dr. Attaluri Srinivasacharyulu of APAARI, Bangkok, said that ICT should be further extended to benefit the growing number of farming families, especially in the Asia-Pacific region.

Dr. V. Balaji, Global Leader, Knowledge Management and Sharing, ICRISAT, thanked everyone for participating in the workshop and said that about 60 participants drawn from 27 countries and 8 international organizations are attending the workshop.



Headline: 2 - Rot-resistant Wheat Could Save Farmers Millions



Source: - http://www.sciencedaily.com/

CSIRO researchers have identified wheat and barley lines resistant to Crown Rot -- a disease that costs Australian wheat and barley farmers $79 million in lost yield every year. Crown Rot, which is a chronic problem throughout the Australian wheat belt, is caused by the fungus Fusarium. Dr Chunji Liu and his CSIRO Plant Industry team in Brisbane are using sophisticated screening methods to scan over 2400 wheat lines and 1000 barley lines from around the world to find the ones resistant the fungal disease.

"The wheat and barley lines showing resistance to Crown Rot are now being used in pre-breeding programs to incorporate the resistance into adapted varieties for delivery to the wheat breeding companies," Dr Liu says.

Crown Rot infects many grasses and weeds found in wheat growing regions and minimum till cropping encourages Fusarium which survives in cereal stubbles. Minimum till cropping minimises soil disturbance and retains plant stubble from previous crops in order to promote soil health and limit erosion.

Developing Crown Rot resistant wheat and barley varieties is an essential strategy in fighting the disease.

"As well as developing Crown Rot resistant varieties, we are also studying how Fusarium invades the plant, how plants resist Fusarium infection and what genes may be involved in defending the plant against Fusarium or reducing its effect on yield," Dr Liu says. Another of the most serious wheat diseases in Australia, Head Blight, is also caused by Fusarium.

This work is being carried out with funding from CSIRO and the Grains Research and Development Corporation and in collaboration with numerous national and international groups.

Headline: 3 - CRRI develops new drought-resistant paddy seeds


Date of Publication: - Oct 27, 2009

Source: - http://beta.thehindu.com/sci-tech

The Central Rice Research Institute (CRRI) has developed an unique drought-resistant variety of paddy seed that can survive and produce crop even without water for over three weeks.

“The new seed is named ‘Sahabhagi’ The paddy seed got clearance of Central Variety Release Committee (CVRC) two days ago”, CRRI director T K Adhya told PTI.

Highlighting its drought-resistance characteristics, Mr. Adhya said the roots of Sahabhagi variety paddy can penetrate deeper into the soil enabling it to draw ground water.

“The new paddy seed can survive without water for over three weeks”, he said.


http://beta.thehindu.com/sci-tech/agriculture/article39294.ece�


Though scientists had earlier developed a drought resistant paddy seed - “Kalinga”, this new type could produce 3.5 tonne of paddy per hectare.

‘Kalinga’ could generate maximum 2.5 tonne of paddy per hectare under suitable condition, he said.

The Sahabhagi seeds were being tested for the last three years before being released for commercial use, the CRRI director said.

Stating that Orissa was prone to natural calamities, Mr. Adhya claimed that the CRRI had already taken a lead role in developing rice varieties to tackle such adversity.

CRRI had developed 70 high yielding and hybrid seeds, including submergence tolerant and drought resistant varieties. As eastern India shared 70 to 80 per cent of country’s rice production, E A Siddiq, visiting professor and ex-deputy director general (crop science), ICAR, New Delhi said paddy cultivation in the region play a key role in food security.

“Farming systems developed by CRRI scientists can give an annual income of more than Rs one lakh per hectare”, he said adding a farmer’s family could get employment for 270 to 300 days by adopting CRRI system. CRRI also celebrated “Dhan Diwas” yesterday to mark the beginning of harvesting by farmers.

The farmers adopting CRRI technologies were felicitated at a function held at Cuttack.

Headline: 4 - Nanotubes can boost plant growth



Source: - http://www.thehindu.com/

If the results of a new research are anything to go by, carbon nanotubes are able fertilizers that can boost germination in plants.

According to a report in New Scientist, the research was carried out by plant biologist Mariya Khodakovskaya and nanotechnologist Alexandru Biris, both at the University of Arkansas at Little Rock, US.

They planted tomato seeds in a growth medium that contained carbon nanotubes. They found that the seeds germinated sooner and seedlings grew faster than those in a non-treated medium.

Nanostructures have been reported to boost germination before, but no explanation for the phenomenon has been offered until now. The pair noticed that the nanotubes appear to penetrate the thick seed coat, which would allow water to enter the dry seeds more rapidly. This could explain how they boost germination, according to Khodakovskaya.

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http://www.thehindu.com/�


Section E: Green Chemistry & Bio Fuels

Headline: 1 - Now, green plastics sans fossil fuel guilt



Source: - http://timesofindia.indiatimes.com

WASHINGTON: Scientists have successfully bio-engineered polymers, completely bypassing fossil fuel based chemicals. This breakthrough opens the way for the commercial production of "green" plastics. Polymers are molecules found in the form of plastics and rubbers. The team, from KAIST University, South Korea and LG Chem, led by Sang Yup Lee, professor, focused on polylactic acid (PLA), a bio-based polymer, the key to producing plastics through renewable resources.

"The polyesters and other polymers we use every day are mostly derived from fossil oils made through the refinery or chemical process," said Lee.

"The idea of producing polymers from renewable biomass has attracted much attention due to the increasing concerns of environmental problems and the limited nature of fossil resources. PLA is considered a good alternative to petroleum-based plastics, as it is both biodegradable and has a low toxicity to humans," Sang added. Until now PLA has been produced in a two-step fermentation and polymerisation, which is both complex and expensive. Now, through the use of a metabolically engineered strain of E coli, the team has produced polylactic acid and its co-polymers through direct fermentation. This makes the renewable production of PLA and lactate-containing copolymers cheaper and more commercially viable, said a KAIST University release.

"By developing a strategy which combines metabolic engineering and enzyme engineering, weâ€™ve developed an efficient bio-based one-step production process for PLA and its copolymers," said Lee. "This means that a developed E coli strain is now capable of efficiently producing unnatural polymers, through a one-step fermentation process."

In an unrelated report, researchers have said that a plastic chemical found in plastics appears to contribute to attention-deficit/hyperactivity disorder (ADHD) in kids. Korean scientists have found a positive association between plastic chemical phthalates and behavioural and cognitive problems in children. They found higher the concentration of phthalate metabolites in the urine, worse were the ADHD symptoms and/or test scores.

"These data represent the first documented association between phthalate exposure and ADHD symptoms in school-aged children," said senior author Yun-Chul Hong.

Some studies on phthalates have linked exposure to these chemicals to hormone disruptions, birth defects, asthma, and reproductive problems, while others have found no significant association between exposure and adverse effects.



Headline: 2 - Genome Sequence Published For Important Biofuels Yeast




A strain of yeast that thrives on turning sugar cane into ethanol for biofuel has had its genome completely sequenced by researchers at Duke University Medical Center.

"Understanding this microbe may enable more efficient biofuel production, and also will produce even more robust industrial organisms that are versatile and capable of producing advanced biofuels from non-food crops like switchgrass," said Lucas Argueso, Ph.D., lead author and research scholar in the Duke Department of Molecular Genetics and Microbiology.

Argueso worked with researchers from Brazil and the University of North Carolina on the study, which was published in Genome Research.

When oil prices crept to new highs in the 1970s, Brazil invested in alternative biofuels created from the country's abundant sugar cane crops. Commercially available baker's yeast was used to break down the sugar cane into ethanol, but genetic tests showed that this yeast quickly disappeared in the harsh environment of industrial fermentation vats. However, a yeast that grows naturally on the sugar cane was still viable in the vats and lasted through many more generations.

This is the yeast strain that Argueso and colleagues studied and mapped, known as PE-2.

"We took an organism that is hugely important from an industrial standpoint but completely unknown in terms of its genetic and molecular properties," Argueso said. "We learned much more about how a complex genome is organized and may contribute to a robust and well-adapted organism."

"Now we have sequenced the genome, so we have a road map that will allow us to build upon its natural abilities," he said. "This opens the door to crossing yeast strains to make even more efficient yeasts for enhanced biofuel production."

Knowing more about what makes yeast hearty will help as biofuel production evolves. In addition to the sugar cane fuels of Brazil, scientists and farmers are also looking into new carbohydrate sources that could easily be farmed in the United States and other areas, since sugar cane farming is limited to warm climates. Switchgrass and giant grass, also known as elephant grass, are possibilities, along with miscanthus grass.

Argueso said the PE-2 genome will aid research into finding the best and strongest yeasts for converting the cellulose in grasses into biofuel, Argueso said.

"I believe this strain has a natural talent for carbohydrate biofuels that have not yet been introduced in the United States," he said. "When the technology is engineered to effectively break down cellulose, I believe this strain of yeast will be an ideal delivery vehicle for that technology."

The study also yielded some interesting genetic information about Saccharomyces cerevisiae, the most studied and utilized yeast species.

"The paper suggests that industrial yeast strains may have a high rate of evolution, helping them adapt to the stressful conditions of batch fermentation," said Tom Petes, Ph.D., senior author and professor of molecular genetics and microbiology at Duke University.



PE-2 yeast is what is known as diploid, having two copies each of 16 different chromosomes. In the case of this yeast, the genetic structure lends itself to robust life, Petes says, because the two copies of each chromosome are slightly different. The greatest differences between paired chromosomes occur at the ends of these worm-like structures, making reconfiguration easier and speeding adaptation to evolve.

The study was funded by two grants from the National Institutes of Health, a BRASKEM/FAPESP grant, and support from ETH Bioenergia, a Brazilian company that produces ethanol and sugar from sugar cane.

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