SCIENCE sciencemag.org 31 JULY 2015 • VOL 349 ISSUE 6247 491

proteins that play crucial roles in

numerous cellular activities. ACD

is exceptionally potent, even

though its substrate is the most

abundant protein of a eukaryotic

cell: actin. — SMH

Science, this issue p. 535

CALCIUM CHANNELS

One gene for three calcium currentsMammals produce alterna-

tive forms of the Orai1 protein,

which forms the pore of various

calcium channels. This involves

using two different transla-

tion initiation start sites in the

encoding transcripts. Desai et

al. showed that these long and

short forms produce calcium

channels with distinct properties.

Both forms can participate in two

kinds of channels that respond

to the depletion of calcium from

internal stores. However, only

the long form contributes to

a channel that is activated by

arachidonic acid and leukotriene

C4, lipids that promote inflamma-

tion. Thus, alternative translation

initiation of the Orai1 message

produces at least three types of

calcium channels with distinct

signaling and regulatory proper-

ties. — NRG

Sci. Signal. 8, ra74 (2015).

METABOLISM

S-nitrosylation links obesity and cell stress Obesity and other diseases are

somehow linked to malfunc-

tion of the protein-protecting

functions of the endoplasmic

reticulum (ER). Yang et al.

Edited by Sacha Vignieri

and Jesse SmithIN OTHER JOURNALS

SIGNAL TRANSDUCTION

Signaling probed by single-molecule trackingDevelopmental signaling through

the so-called Hedgehog pathway

is transduced through the

receptor-like protein

Smoothened. Hedgehog signaling

requires highly specific localiza-

tion of Smoothened in target cells

at the primary cilium, a structure

that functions somewhat like an

antenna to receive and transmit

signals. Milenkovic et al. tracked

movement of single molecules

of Smoothened in the cilia

of cultured mouse embryo

fibroblasts. Movement of

Smoothened was restricted by

binding events at the base of the

cilium. Activation of Hedgehog

signaling decreased the affinity

of such binding. Such regulated

binding of Smoothened to its

yet-to-be-defined partner(s)

within the cilium is likely an

important step in the Hedgehog

signaling mechanism. – LBR

Proc. Natl. Acad. Sci. U.S.A. 10.1073/

pnas.1510094112 (2015).

NEUROSCIENCE

At the center of our own spatial social network Neurons in the hippocampus

propose a mechanism by

which obesity and associated

chronic inflammation may be

linked to the accumulation of

unfolded proteins in the ER.

Such stress would normally

trigger the process known as

the unfolded protein response

(UPR). However, obese mice

had increased S-nitrosylation

of inositol-requiring protein-1

(IRE1α), a ribonuclease that

regulates the UPR. The modified

IRE1α had decreased RNAse

activity. The authors expressed

an IRE1α mutant protein that

could not be nitrosylated in

the liver of obese mice. This

approach improved the UPR

and helped restore glucose

homeostasis. — LBR

Science, this issue p. 500

HIV

How antibodies matureAntibodies are stalwart protec-

tors against infection, but even

they need a little help from

their friends. Through a process

called affinity maturation, T fol-

licular helper (TFH

) cells guide B

cells to produce antibodies with

improved specificity to a partic-

ular pathogen. Now Yamamoto

et al. report that in nonhuman

primates, the frequency and

quality of TFH

cells were associ-

ated with the development of

broadly neutralizing antibodies

that might be protective against

simian HIV. These findings

suggest that HIV vaccines that

incorporate TFH

cell stimulation

could boost broadly neutralizing

antibody production. — ACC

Sci. Transl. Med. 7, 298ra120 (2015).

Obese mice exhibit more cellular stress

Innate lymphoid

cells help control

damaging Clostridium

difficile infection

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INFECTIOUS DISEASE

Innate lymphoid cells to the rescue

Most people enter the hospital with the hope of getting

better, but recent increases in hospital-acquired infec-

tions have made hospitals deadly in their own right.

For instance, deaths caused by the enteric bacterium

Clostridium difficile increased by 400% in the last

decade. C. difficile is an opportunistic pathogen that takes

advantage of disruptions in the microbiota caused by antibi-

otic treatment. Abt et al. provide new insight into how the host

defends itself against this unwelcome intruder. Studying

C. difficile–infected mice, the authors found that the mice

required innate lymphoid cells (ILCs) to survive the infection.

ILCs did not substantially contribute to reducing pathogen

burden but instead appeared to limit pathology and systemic

dissemination. – KLM

Cell Host Microbe 18, 27 (2015).

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RESEARCH | IN OTHER JOURNALS

create a maplike representation

of the environment, forming

what is called spatial memory.

Tavares et al. suggest that

humans also create a 3D map

of social space with themselves

at the center. They measured

the representation of a map

of social interactions based

on a role-playing game where

participants could interact with

fictional characters along power

(dominance, hierarchy, etc.) and

affiliation (intimacy, trustwor-

thiness, etc.) gradients, while

placed in an fMRI scanner. Left

hippocampal activity correlated

with the angle of a vector cre-

ated by these two measures,

but not by either of them alone,

while the strength of correlation

also depended on the social

skills and personality traits like

neuroticism and conscientious-

ness of the individual. – LNS

Neuron 87, 231 10.1016/j.

neuron.2015.06.011 (2015).

OBESITY MANAGEMENT

New drug—and new hope—for a losing gameMany people would gladly trade

a dip in the fountain of youth for

a safe drug that makes them

thinner. Despite years of effort,

the pharmaceutical industry has

yet to deliver such a drug. New

hope is offered by Pi-Sunyer et

al., who report the results of a

56-week, double-blind clinical

trial examining the metabolic

effects of a drug called liraglu-

tide, which mimics a hormone

produced in the gastrointestinal

tract (glucacon-like peptide 1)

that increases satiety. People

taking liraglutide, in conjunc-

tion with dieting and exercise,

lost a mean of 8.4 kilograms as

compared with 2.8 kilograms

in those taking a placebo.

Drawbacks include the delivery

method (injection) and hints

that cessation of the drug results

in regain of weight. – PAK

New Engl. J. Med. 373, 11 (2015).

NUCLEAR CHEMISTRY

Subsurface corrosion of uraniumUranium dioxide, the most

common form of nuclear fuel,

becomes mobile as it oxidizes.

Although oxidative corrosion is

inherently a surface-mediated

process, interstitial oxygen

atoms can induce oxidation

many atomic layers deeper. By

detailing the surface structure

and composition of UO2 after

exposure to oxygen in air and

water, Stubbs et al. show that

oxidation does not follow a clas-

sical diffusion pattern. Instead,

interstitial oxygens preferentially

occupy every third atomic layer

below the terminal (111) surface.

This pattern is a product of the

delocalized electronic structure

of nonsurface U atoms, which

also allows for the coexistence of

three U oxidation states. — NW

Phys. Rev. Lett. 114, 246103 (2015).

APPLIED OPTICS

Dealing with big dataData generation often occurs at

such a high rate that it cannot be

analyzed on the fly but must be

stored and archived for access

later on. While banks of mag-

netic hard drives are the storage

medium of choice at present, the

total capacity, recording times,

and required energy burden are

not expected to keep pace with

the data generation rate. Li et al.

look to optical recording as a pos-

sible solution. Combining

superresolution nanoscopy

to record tiny binary bits in

a photosensitive medium

with multifocusing array

techniques to access

multiple layers within the

medium, it should be pos-

sible to achieve storage

capacities of about 30

terabits per disk and data

recording rates exceeding

gigabits per second. — ISO

Optica 2, 567 (2015).

GEOPHYSICS

Allowing faults out of lock-up

The crust around a locked, earthquake-prone fault responds to the two sides pulling in oppo-

site directions by bowing and bulging over time. Meltzner et al. and Wesson et al. challenge

a common assumption that this deformation progresses mostly in a uniform, linear way.

Deformation shows up in seafloor bathymetry, which changes abruptly for both Sumatra and

Isla Santa Maria, Chile, over a seismic cycle. Periods during which the fault is weakly locked

explains the non-uniform behavior. Quantifying the effect clarifies subduction zone mechanics,

which may require updating estimates of earthquake hazard. — BG

Quat. Sci. Rev. 10.1016/j.quascirev.2015.06.003 (2015);

Nat. Geosci. 10.1038/ngeo2468 (2015).

Injectable weight loss: In the long run, is it

too good to be true?

Relict microatoll

on southeastern island

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Dealing with big dataIan S. Osborne

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