Preventive therapy p.147
Stem-cell trials must be made easier, so that treatments can be based on real data.doi: 10.1038/494147b
Volume 494 Issue 7436
리서치 하이라이트
표지 기사： 소행성 4 베스타의 충돌 크레이터에 대한 3차원 시뮬레이션 모델
GPCR에 대한 분자 생물학적 구조 분석
마리온 융기에서의 맨틀 감소를 증명하는 얇은 지각
자가 식작용 유발 펩타이드 및 이를 이용한 치료법 개발 가능성
마이크로메커니컬 공진기를 가진 하이브리드 회로 공동 양자 일렉트로다이나믹스
아민 및 알코올의 거울 이성질체 합성에 대한 단순한 유기 분자 촉매
초기 사지 동물에서의 척추 형태 분석
생물다양성이 숙주의 병원균 감염에 미치는 영향
운동 개시와 함께 활성화되는 기저핵 신경 회로
간에 존재하는 Lgr5 발현 줄기 세포와 이를 이용한 간 재생
흑색종의 베라무페닙에 약물 저항성을 억제하는 약물 투여 간격 조절
컨텐츠
Editorials
A deal on the horizon p.147
Leaders have finally thrashed out the European Union budget for the next seven years. But how much money will go to research is yet to be confirmed.doi: 10.1038/494147a
Damage control p.148
Planning for extreme events must incorporate not just infrastructure but societal preparedness.doi: 10.1038/494148a
News
When Google got flu wrong p.155
US outbreak foxes a leading web-based method for tracking seasonal flu.doi: 10.1038/494155a
Data barriers limit genetic diagnosis p.156
Tools for data-sharing promise to improve chances of connecting mutations with symptoms of rare diseases.doi: 10.1038/494156a
Science agencies prepare for cuts p.158
Scientists already feeling the bite of US budget sequester.doi: 10.1038/494158a
Europe scales back research plans p.159
Leaders propose 13% cut to commission's proposals.doi: 10.1038/494159a
Malaria drug made in yeast causes market ferment p.160
Synthetic biology delivers combination therapies into an uncertain market.doi: 10.1038/494160a
Company offers portable peer review p.161
Author-pays service cuts down on redundant reviews.doi: 10.1038/494161a
News Features
Natural hazards: New York vs the sea p.162
In the wake of Hurricane Sandy, scientists and officials are trying to protect the largest US city from future floods.doi: 10.1038/494162a
Stem cells in Texas: Cowboy culture p.166
By offering unproven therapies, a Texas biotechnology firm has sparked a bitter debate about how stem cells should be regulated.doi: 10.1038/494166a
News & Views
Neuroscience: To go or not to go p.178
A study shows that, rather than sequentially starting and stopping a movement, two parallel pathways involving neurons in the brain's basal ganglia seem to work in tandem to accomplish the complex task of motion. See Letter p.238doi: 10.1038/nature11856
Asymmetric synthesis: Relay catalysis at a boron centre p.179
A boron complex catalyses the addition of allyl groups — hydrocarbon motifs — to 'activated imines' in a relay-like process, generating synthetically useful compounds as single mirror-image isomers. See Letter p.216doi: 10.1038/494179a
Cell biology: Beneficial lessons from viruses p.181
To thwart the antimicrobial responses of their hosts, pathogens have evolved diverse mechanisms, including autophagy. Knowledge of such mechanisms has now led to a pro-autophagy peptide that may be of therapeutic value. See Article p.201doi: 10.1038/nature11947
Earth science: All rise for the case of the missing magma p.182
A detailed geological analysis of a ridge in the Indian Ocean suggests that compositional variations in Earth's mantle have a surprisingly crucial role in the uplift of a bathymetric bulge along the ridge. See Article p.195doi: 10.1038/nature11950
Review
Molecular signatures of G-protein-coupled receptors p.185
A systematic investigation of high-resolution G-protein-coupled receptor (GPCR) structures uncovers a conserved inter-helical network of non-covalent contacts that defines the GPCR fold, and provides insights into the molecular determinants of different GPCR conformations.doi: 10.1038/nature11896
Articles
Thin crust as evidence for depleted mantle supporting the Marion Rise p.195
The global ridge system is dominated by oceanic rises reflecting large variations in axial depth associated with mantle hotspots. The little-studied Marion Rise is as large as the Icelandic Rise, considering both length and depth, but has an axial rift (rather than a high) nearly its entire length. Uniquely along the Southwest Indian Ridge systematic sampling allows direct examination of crustal architecture over its full length. Here we show that, unlike the Icelandic Rise, peridotites are extensively exposed high on the rise, revealing that the crust is generally thin, and often missing, over a rifted rise. Therefore the Marion Rise must be largely an isostatic response to ancient melting events that created low-density depleted mantle beneath the Southwest Indian Ridge rather than thickened crust or a large thermal anomaly. The origin of this depleted mantle is probably the mantle emplaced into the African asthenosphere during the Karoo and Madagascar flood basalt events.
doi: 10.1038/nature11842
Identification of a candidate therapeutic autophagy-inducing peptide p.201
The lysosomal degradation pathway of autophagy has a crucial role in defence against infection, neurodegenerative disorders, cancer and ageing. Accordingly, agents that induce autophagy may have broad therapeutic applications. One approach to developing such agents is to exploit autophagy manipulation strategies used by microbial virulence factors. Here we show that a peptide, Tat–beclin 1—derived from a region of the autophagy protein, beclin 1, which binds human immunodeficiency virus (HIV)-1 Nef—is a potent inducer of autophagy, and interacts with a newly identified negative regulator of autophagy, GAPR-1 (also called GLIPR2). Tat–beclin 1 decreases the accumulation of polyglutamine expansion protein aggregates and the replication of several pathogens (including HIV-1) in vitro, and reduces mortality in mice infected with chikungunya or West Nile virus. Thus, through the characterization of a domain of beclin 1 that interacts with HIV-1 Nef, we have developed an autophagy-inducing peptide that has potential efficacy in the treatment of human diseases.
doi: 10.1038/nature11866
Letters
The structure of the asteroid 4 Vesta as revealed by models of planet-scale collisions p.207
Three-dimensional simulations of the global evolution of asteroid 4 Vesta under two overlapping planet-scale collisions closely reproduce its observed shape; but expected large areas of olivine-rich rocks and pure diogenites are not observed on the surface, possibly implying that the outer ~100 km is composed mainly of a basaltic crust (eucrites) with ultramafic intrusions (diogenites).doi: 10.1038/nature11892
Hybrid circuit cavity quantum electrodynamics with a micromechanical resonator p.211
The properties of a quantum bit coupled to both a microwave cavity and a phonon mode in a micromechanical resonator suggest that such systems may allow for storage of quantum information in long-lived phonon states and read-out via microwave photons, with applications in quantum information control.doi: 10.1038/nature11821
Simple organic molecules as catalysts for enantioselective synthesis of amines and alcohols p.216
A set of small organic molecules catalyse reactions of unsaturated organoboron reagents with imines and carbonyls to produce amines and alcohols in high enantiomeric purity efficiently, speedily and at low cost through sustainable protocols.doi: 10.1038/nature11844
Insolation-induced mid-Brunhes transition in Southern Ocean ventilation and deep-ocean temperature p.222
Model simulations show that in response to insolation changes only, southern westerlies and feedbacks between sea ice, temperature, evaporation and salinity caused vigorous Southern Ocean ventilation and cooler deep ocean during the interglacials before the mid-Brunhes transition, suggesting that this transition may in fact have resulted from a series of individual interglacial responses to various combinations of insolation conditions.doi: 10.1038/nature11790
Vertebral architecture in the earliest stem tetrapods p.226
X-ray synchrotron microtomography has revealed the three-dimensional vertebral architecture of Ichthyostega, and other crucial and celebrated early tetrapods; a surprising feature is the relationship between the vertebral elements, with the pleurocentra unexpectedly attached to the succeeding intercentrum, suggesting a ‘reverse’ rhachitomous design.doi: 10.1038/nature11825
Biodiversity decreases disease through predictable changes in host community competence p.230
A combination of extensive field surveys and realistic experiments involving an amphibian disease system reveals that biodiversity reduces pathogen transmission due to a predictable link between species richness and the ability of communities to support infection.doi: 10.1038/nature11883
Finding the sources of missing heritability in a yeast cross p.234
In a cross between two yeast strains, detected loci are found to explain nearly the entire additive contribution to heritable variation for a number of quantitative traits.doi: 10.1038/nature11867
Concurrent activation of striatal direct and indirect pathways during action initiation p.238
In mice performing an operant task, increases in neural activity in direct- and indirect-pathway spiny projection neurons (SPNs) are associated with action initiation but not with inactivity, and concurrent activation of SPNs from both pathways in one hemisphere precedes the initiation of contraversive movements.doi: 10.1038/nature11846
A direct and melanopsin-dependent fetal light response regulates mouse eye development p.243
During retinal vascular development there is simultaneous regression of the hyaloid vasculature and formation of the retinal vasculature; here it is demonstrated that regression of developing vasculature is light dependent and acts via the photoreceptor melanopsin.doi: 10.1038/nature11823
In vitro expansion of single Lgr5+ liver stem cells induced by Wnt-driven regeneration
p.247
A mouse model of liver damage has identified a population of Lrg5+ liver stem cells that can generate hepatoctyes and bile ducts in vivo.
doi: 10.1038/nature11826
Modelling vemurafenib resistance in melanoma reveals a strategy to forestall drug resistance p.251
BRAF inhibitors such as vemurafenib have shown promising effects in patients with BRAF-mutant melanomas, but the tumours generally develop resistance; vemurafenib-resistant melanomas are now shown to be drug dependent, and an intermittent dosing schedule can help prevent drug resistance.doi: 10.1038/nature11814
Biguanides suppress hepatic glucagon signalling by decreasing production of cyclic AMP p.256
Biguanides such as metformin, which is the most widely prescribed drug for type-2 diabetes, are shown to antagonize the actions of glucagon by decreasing the levels of cyclic AMP.doi: 10.1038/nature11808
A T-bet gradient controls the fate and function of CCR6− RORγt+ innate lymphoid cells
p.261
The graded expression of the transcription factor T-bet in CCR6−RORγt+ innate lymphoid cells is found to be involved in the control of interferon-γ expression, a cytokine that is required to protect the epithelial barrier against Salmonella infections.
doi: 10.1038/nature11813
A complete mass-spectrometric map of the yeast proteome applied to quantitative trait analysis p.266
High-throughput peptide synthesis and mass spectrometry are used to generate a near-complete reference map of the Saccharomyces cerevisiae proteome; two versions of the map (supporting discovery- and hypothesis-driven proteomics) are then applied to a protein-based quantitative trait locus analysis.doi: 10.1038/nature11835
