RESEARCH - Sciencescience.sciencemag.org/content/sci/351/6280/twis.full.pdf1413-B 25 MARCH 2016 •...

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SCIENCE sciencemag.org 25 MARCH 2016 • VOL 351 ISSUE 6280 1411 CREDITS: (TOP TO BOTTOM) JARDINE ET AL.; HIDEYUKI HOTTA/CHIBA UNIVERSITY MAGNETOHYDRODYNAMICS Simulating turbulent solar magnetic fields An accurate simulation of solar magnetic fields must reproduce both the large-scale dynamo and small-scale turbulence. Simply increasing the computational resolution does not always help, because it can prevent the 11-year solar cycle from emerging. Hotta et al. show how both large- and small-scale phenomena can be reproduced in some of the highest-resolution simulations yet available. This will improve our understanding of both the solar magnetic field and other turbulent magnetohydrody- namic systems. — KTS Science, this issue p. 1427 RESEARCH Edited by Stella Hurtley IN SCIENCE JOURNALS C-H BOND ACTIVATION Methane borylation in a cyclohexane sea Although methane combusts readily at high temperatures, it is generally the hardest hydrocarbon to transform under gentler conditions, owing to its particularly strong C-H bonds. Cook et al. now show that soluble rhodium, iridium, and ruthenium catalysts can slice through these C-H bonds to add boron substituents to methane at 150°C. Smith et al. report the iridium-catalyzed reaction using phosphine ligands to enhance activity. Both studies were performed in cyclohexane solvent, revealing a remarkable selective prefer- ence for the methane reaction over functionalization of the cyclic hydrocarbon. — JSY Science, this issue pp. 1421 and 1424 SOLAR CELLS Perovskite solar cells recycle photons Inorganic-organic perovskite solar cells are very efficient in part because the charge carriers exhibit very long path lengths. Pazos-Outón et al. show that photon recycling, as seen previ- ously in highly efficient gallium arsenide solar cells, contributes to this effect (see the Perspective by Yabionovitch). In most solar cells, the recombination of photogenerated charge carriers (electrons and holes) wastes all of the energy. In these lead tri-iodide cells, recombination emits a photon that can be reabsorbed and create more charge carriers. — PDS Science, this issue p. 1430; see also p. 1401 STRUCTURAL BIOLOGY A human spliceosomal subcomplex The spliceosome is an RNA and protein molecular machine that cuts out introns from messenger RNAs. Agafonov et al. used cryo– electron microscopy to determine the structure of the largest intermediate subcomplex on the assembly pathway for the human spliceosome (see the Perspective by Cate). The structure shows substantial differences from the equivalent yeast complex. It also reveals how the subcomplex must dock onto the rest of the spliceo- some and hints at the structural changes the complex must go through to form the mature spli- ceosome. — GR Science, this issue p. 1416; see also p. 1390 ECONOMICS Another social science looks at itself Experimental economists have joined the reproducibility discus- sion by replicating selected published experiments from two top-tier journals in economics. Camerer et al. found that two- thirds of the 18 studies examined yielded replicable estimates of effect size and direction. This proportion is somewhat lower than unaffiliated experts were willing to bet in an associated prediction market, but roughly in line with expectations from sam- ple sizes and P values. — GJC Science, this issue p. 1433 MEMORY FORMATION Coding what is known and what is new Do neural activity patterns during sleep reflect the replay of a novel experience or an invariant preex- isting dynamic? Grosmark and Buzsáki observed that both famil- iar and novel aspects of learned information are replayed during synchronous bursts of activity in the hippocampus. Familiarity was encoded by fast-firing less- modifiable neurons that showed rate and sequence correlations that persisted into postlearning sleep. The novel features of an MAG Sim sol A n a ma b p in sim will both other t namic sys An example of one of the solar magnetic field simulations HIV: Toward broadly neutralizing antibodies for all Jardine et al., p. 1458 Published by AAAS

Transcript of RESEARCH - Sciencescience.sciencemag.org/content/sci/351/6280/twis.full.pdf1413-B 25 MARCH 2016 •...

Page 1: RESEARCH - Sciencescience.sciencemag.org/content/sci/351/6280/twis.full.pdf1413-B 25 MARCH 2016 • VOL 351 ISSUE 6280 sciencemag.org SCIENCE RESEARCH SYNTHETIC BIOLOGY Designing and

SCIENCE sciencemag.org 25 MARCH 2016 • VOL 351 ISSUE 6280 1411

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MAGNETOHYDRODYNAMICS

Simulating turbulent solar magnetic fields

An accurate simulation of solar

magnetic fields must reproduce

both the large-scale dynamo and

small-scale turbulence. Simply

increasing the computational

resolution does not always

help, because it can prevent

the 11-year solar cycle from

emerging. Hotta et al. show

how both large- and small-scale

phenomena can be reproduced

in some of the highest-resolution

simulations yet available. This

will improve our understanding of

both the solar magnetic field and

other turbulent magnetohydrody-

namic systems. — KTS

Science, this issue p. 1427

RESEARCHEdited by Stella Hurtley

I N SC IENCE J O U R NA L S

C-H BOND ACTIVATION

Methane borylation in a cyclohexane sea Although methane combusts

readily at high temperatures,

it is generally the hardest

hydrocarbon to transform

under gentler conditions, owing

to its particularly strong C-H

bonds. Cook et al. now show

that soluble rhodium, iridium,

and ruthenium catalysts can

slice through these C-H bonds

to add boron substituents to

methane at 150°C. Smith et al.

report the iridium-catalyzed

reaction using phosphine

ligands to enhance activity.

Both studies were performed in

cyclohexane solvent, revealing

a remarkable selective prefer-

ence for the methane reaction

over functionalization of the

cyclic hydrocarbon. — JSY

Science, this issue pp. 1421 and 1424

SOLAR CELLS

Perovskite solar cells recycle photonsInorganic-organic perovskite

solar cells are very efficient in

part because the charge carriers

exhibit very long path lengths.

Pazos-Outón et al. show that

photon recycling, as seen previ-

ously in highly efficient gallium

arsenide solar cells, contributes

to this effect (see the Perspective

by Yabionovitch). In most solar

cells, the recombination of

photogenerated charge carriers

(electrons and holes) wastes all of

the energy. In these lead tri-iodide

cells, recombination emits a

photon that can be reabsorbed

and create more charge carriers.

— PDS

Science, this issue p. 1430;

see also p. 1401

STRUCTURAL BIOLOGY

A human spliceosomal subcomplex The spliceosome is an RNA and

protein molecular machine that

cuts out introns from messenger

RNAs. Agafonov et al. used cryo–

electron microscopy to determine

the structure of the largest

intermediate subcomplex on the

assembly pathway for the human

spliceosome (see the Perspective

by Cate). The structure shows

substantial differences from the

equivalent yeast complex. It also

reveals how the subcomplex must

dock onto the rest of the spliceo-

some and hints at the structural

changes the complex must go

through to form the mature spli-

ceosome. — GR

Science, this issue p. 1416;

see also p. 1390

ECONOMICS

Another social science looks at itselfExperimental economists have

joined the reproducibility discus-

sion by replicating selected

published experiments from two

top-tier journals in economics.

Camerer et al. found that two-

thirds of the 18 studies examined

yielded replicable estimates of

effect size and direction. This

proportion is somewhat lower

than unaffiliated experts were

willing to bet in an associated

prediction market, but roughly in

line with expectations from sam-

ple sizes and P values. — GJC

Science, this issue p. 1433

MEMORY FORMATION

Coding what is known and what is newDo neural activity patterns during

sleep reflect the replay of a novel

experience or an invariant preex-

isting dynamic? Grosmark and

Buzsáki observed that both famil-

iar and novel aspects of learned

information are replayed during

synchronous bursts of activity

in the hippocampus. Familiarity

was encoded by fast-firing less-

modifiable neurons that showed

rate and sequence correlations

that persisted into postlearning

sleep. The novel features of an

MAG

SimsolAn a

ma

b

p

in

sim

will

both

other t

namic sys

An example of one of the solar magnetic field simulations

HIV: Toward broadly neutralizing antibodies for all Jardine et al., p. 1458

Published by AAAS

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sciencemag.org SCIENCE1412 25 MARCH 2016 • VOL 351 ISSUE 6280

experience were represented by a different set of slowly firing and highly plastic cells. — PRS

Science, this issue p. 1440

CLOUD FORMATION

Organic contributions to cloud theoryCurrent theories about the formation of cloud droplets from aerosol particles containing organic components assume that the organic molecules are distributed throughout the droplet. Ruehl et al. show that this assumption is not always correct (see the Perspective by Noziere). During droplet nucleation, droplet diameters were 50% larger than predicted by the standard model. This suggests that the organic particles reside in a surface layer rather than in the bulk of the droplet. Models that neglect organic surface activity will thus underestimate how well organic-rich particles seed clouds. — HJS

Science, this issue p. 1447;

see also p. 1396

TUMOR IMMUNOLOGY

The cellular ancestry of tumor antigens One contributing factor in antitumor immunity is the reper-toire of neoantigens created by genetic mutations within tumor cells. Like the corresponding mutations, these neoantigens show intratumoral heteroge-neity. Some are present in all tumor cells (clonal), and others are present in only a fraction

of cells (subclonal). In a study of lung cancer and melanoma, McGranahan et al. found that a high burden of clonal tumor neoantigens correlated with improved patient survival, an increased presence of tumor-infiltrating lymphocytes, and a durable response to immuno-therapy. — PAK

Science, this issue p. 1463

CANCER

The spread of bad neighborhoods Our genomes have complex three-dimensional (3D) arrange-ments that partition and regulate gene expression. Cancer cells frequently have their genomes grossly rearranged, disturbing this intricate 3D organization. Hnisz et al. show that the disrup-tion of these 3D neighborhoods can bring oncogenes under the control of regulatory elements normally kept separate from them (see the Perspective by Wala and Beroukim). These novel juxtapositions can result in the inappropriate activation of onco-genes. — GR

Science, this issue p. 1454;

see also p. 1398

FOREST ECOSYSTEMS

Forest recovery in China is not so clear cut Frequently in developing nations, forests shrink as trees are cut and agriculture expands. This trend does not tend to reverse until significant economic devel-opment and urbanization occur. Viña et al. used remote sensing and analytical models to show that heavily deforested regions in China experienced regrowth between 2000 and 2010 in spite of China’s status as a developing

nation. The key to this success was China’s strong conser-

vation policies. Despite this, densely forested regions still shrank, and forest growth may have come

at the expense of forests shrinking elsewhere. — SN

Sci. Adv.2 10.1126.sciadv.00965

(2016).

STRUCTURAL BIOLOGY

A domain swap makes motor ringsCells are packed with protein complexes. Cells must appropri-ately assemble these complexes while ensuring that component proteins do not aggregate pre-maturely. Baker et al. show that the FliG protein, part of the bac-terial flagellar motor complex, can polymerize to forms rings by “domain swapping.” Domains within a single FliG can interact with each other or “swap” with neighboring FliG proteins to form the same interaction—a molecular form of linking arms. The flexibility of the peptides that tether these domains ensures that FliG remains a monomer in the cytoplasm. FliG binding to a scaffolding ring promotes motor assembly by increasing the local concen-tration of FliG and promoting domain swapping. — GR

Nat. Struct. Mol. Biol. 197, 23 (2016).

GENETICS

When Mom or Dad’s inheritance countsRetinoblastoma (Rb), a largely inherited form of pediatric eye cancer, arises when patients carry two utant copies of the RB1 tumor suppressor gene. However, not all individuals car-rying two mutant copies of RB1

go on to develop cancer. Eloy et

al. investigated why, focusing on one specific mutation of RB1,and found differences depend-ing on whether the mutant gene was maternally or paternally inherited. Maternal inheritance led to higher Rb protein expres-sion, and because the particular mutation allowed for some residual protein function, this probably protected some indi-viduals from developing cancer. Thus, in some cases, parent-of-origin effects can explain why genetic carriers may not always go on to develop disease. — LMZ

PLOS Genet. 12, e1005888 (2016).

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RESEARCH | IN SCIENCE JOURNALS

Tumors contain cells expressing

a variety of novel antigens

Edited by Kristen Mueller

and Jesse SmithIN OTHER JOURNALS

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Published by AAAS

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sciencemag.org SCIENCE1413-B 25 MARCH 2016 • VOL 351 ISSUE 6280

RESEARCH

SYNTHETIC BIOLOGY

Designing and building a minimal genome A goal in biology is to understand

the molecular and biological

function of every gene in a cell.

One way to approach this is to

build a minimal genome that

includes only the genes essential

for life. In 2010, a 1079-kb

genome based on the genome

of Mycoplasma mycoides

(JCV-syn1.0) was chemically

synthesized and supported cell

growth when transplanted into

cytoplasm. Hutchison III et al.

used a design, build, and test

cycle to reduce this genome to

531 kb (473 genes). The result-

ing JCV-syn3.0 retains genes

involved in key processes such

as transcription and translation,

but also contains 149 genes of

unknown function. — VV

Science, this issue p. 1414

TRANSPORTER FUNCTION

A proton pump in action

P-type adenosine triphos-

phatases (ATPases) use the

energy from ATP hydrolysis to

pump cations across biological

membranes. The electrochemi-

cal gradients that are generated

control many essential cellular

processes. Veshaguri et al. incor-

porated a plant proton pump

into vesicles and monitored

the dynamics of single pumps.

Pumping was stochastically

interrupted by long-lived inactive

or leaky states. The work reveals

how these proton pumps are

regulated by a protein domain

and by pH gradients. — VV

Science, this issue p. 1469

PHYSIOLOGICAL ECOLOGY

Variability for a day or a season Species that experience larger

seasonal climatic fluctuations

are likely to be more physiologi-

cally flexible and thus likely to

occur across a wider elevational

range. Daily changes in tempera-

ture are also common but have

rarely been considered. Chan et

al. used a global data set of ver-

tebrates to look at how these two

different sets of variation affect a

species’ elevational distribution

(see the Perspective by Perez et

al.). Unexpectedly, larger daily

fluctuations were associated

with smaller elevational distri-

butions. Thus, specialists are

favored where daily fluctuations

are dominant, whereas general-

ists are favored where seasonal

fluctuations are the main climate

influence. — SNV

Science, this issue p. 1437;

see also p. 1392

PROTEIN EVOLUTION

Variation and transcription factor binding Little is known about the phe-

notypic and functional effects

of genetic variants that result

in amino acid changes within

functional proteins. Barrera et

al. investigated whether amino

acid variants changed the DNA

binding specificity or affinity of

transcription factors. Predictive

analyses identified changes in

the proteins, and protein-binding

microarrays verified changes

that affected transcription

factor function, including those

associated with disease. Thus,

within-human protein sequence

variation can affect transcrip-

tional regulatory networks,

which, depending on the genetic

variant, may confer robust-

ness and buffer against amino

acid changes and could explain

phenotypic variation among

individuals. — LMZ

Science, this issue p. 1450

DFT METHODS

A comparison of DFT methods Density functional theory (DFT)

is now routinely used for simu-

lating material properties. Many

software packages are available,

which makes it challenging

to know which are the best to

use for a specific calculation.

Lejaeghere et al. compared the

calculated values for the equa-

tion of states for 71 elemental

crystals from 15 different widely

used DFT codes employing

40 different potentials (see

the Perspective by Skylaris).

Although there were variations

in the calculated values, most

recent codes and methods

converged toward a single value,

with errors comparable to those

of experiment. — MSL

Science, this issue p. 1415;

see also p. 1394

HIV-1 VACCINES

Baby steps toward bNAbs

Some HIV-infected individu-

als develop heavily mutated,

broadly neutralizing antibod-

ies (bNAbs) that target HIV.

Scientists aim to design

vaccines that would elicit such

antibodies. Jardine et al. report

an important step toward this

goal: They engineered an immu-

nogen that could engage B cells

from HIV-uninfected individu-

als that express the germline

versions of the immunoglobulin

genes harbored by a particular

class of bNAbs. The frequencies

of these B cells, their affinities

for the immunogen, and struc-

tural analysis suggest that the

immunogen is a promising can-

didate. Further shaping of the B

cell response with subsequent

immunogens may eventually

elicit bNAbs in people. — KLM

Science, this issue p. 1458

NEURODEVELOPMENT

Tracking neuronal transcriptional programs Early in brain development,

cortical neurons are born near

the ventricles, then migrate to

their functional destinations.

Telley et al. used a fluorescent

labeling technique to see what

transcripts characterize these

earliest stages of neural develop-

ment. Waves of transcriptional

programs are initiated, then

passed by as the neuron

progresses from proliferative

to migratory and finally to con-

nectivity phases. — PJH

Science, this issue p. 1443

CARDIOVASCULAR BIOLOGY

A GRK2 peptide prevents heart failureDuring cardiac hypertrophy,

sustained high blood pressure

causes the heart walls to thicken

to deal with the increased load.

If left unchecked, cardiac hyper-

trophy leads to heart failure. A

particular part of the kinase and

scaffolding protein GRK2 inhibits

a G protein that promotes car-

diac hypertrophy. Schumacher

et al. generated mice that

overexpressed a peptide of this

inhibitory region of GRK2 in the

heart. Under conditions that

cause heart failure, these mice

developed less cardiac hypertro-

phy and retained greater cardiac

function. — WW

Sci. Signal. 9, ra30 (2016).

AUTOIMMUNITY

A glucose balancing act

In autoimmune diseases, T

cells engage their hyperdrive,

both proliferating and secret-

ing inflammatory cytokines at

greater rates than normal. Little

is known about the metabolic

changes that fuel this process.

Yang et al. report that a defect in

reactive oxygen species (ROS)

could boost proinflammatory

T cells in rheumatoid arthritis.

A defect in glycolytic flux led to

increased ROS consumption,

which bypassed a cell cycle

checkpoint and contributed to

hyperproliferation and proin-

flammatory cell differentiation.

What’s more, restoring intracel-

lular ROS reduced proliferation

and suppressed inflammation.

— ACC

Sci. Transl. Med. 8, 331ra38 (2016).

Edited by Stella HurtleyALSO IN SCIENCE JOURNALS

Published by AAAS