第五期20160304-论文烩

本期论文烩，是Nature　Volume 531 Number 7592 pp7-134，这次决定把这期Nature全部整理完。因为Nature主要是和生物有关，感兴趣的不多。但是坚持看看还是有好处的。毕竟知道这么多人在研究的领域还是值得我们了解。

有意思的研究，

2.高脂肪饮食和小肠癌症的关系，

3．细菌如何引发和合成桥壳结构,

7.纳米布沙漠甲虫等仿生学得到的对于液滴的操纵，非常有趣。生物如何巧妙的利用表面结构的突起形成的几何来引导液滴生长并且定向传输。而且效率提高了六倍( We further observe an unprecedented sixfold-higher exponent of growth rate, faster onset, higher steady-state turnover rate, and a greater volume of water collected compared to other surfaces.)

一点小发现，冷冻透射电镜很火啊，居然两篇连着都是。

1.Genomic analyses identify molecular subtypes of pancreatic cancer

http://www.nature.com/nature/journal/v531/n7592/full/nature16965.html

Subject terms:

Cancer genomics
Pancreatic cancer

摘要

Integrated genomic analysis of 456 pancreatic ductal adenocarcinomas identified 32 recurrently mutated genes that aggregate into 10 pathways: KRAS, TGF-β, WNT, NOTCH, ROBO/SLITsignalling, G1/S transition, SWI-SNF, chromatin modification, DNA repair and RNA processing. Expression analysis defined 4 subtypes: (1) squamous; (2) pancreatic progenitor; (3) immunogenic; and (4) aberrantly differentiated endocrine exocrine (ADEX) that correlate with histopathological characteristics. Squamous tumours are enriched for TP53 and KDM6Amutations, upregulation of the TP63∆N transcriptional network, hypermethylation of pancreatic endodermal cell-fate determining genes and have a poor prognosis. Pancreatic progenitor tumours preferentially express genes involved in early pancreatic development (FOXA2/3, PDX1and MNX1). ADEX tumours displayed upregulation of genes that regulate networks involved inKRAS activation, exocrine (NR5A2 and RBPJL), and endocrine differentiation (NEUROD1 andNKX2-2). Immunogenic tumours contained upregulated immune networks including pathways involved in acquired immune suppression. These data infer differences in the molecular evolution of pancreatic cancer subtypes and identify opportunities for therapeutic development.

2.High-fat diet enhances stemness and tumorigenicity of intestinal progenitors

http://www.nature.com/nature/journal/v531/n7592/full/nature17173.html

Subject terms:

Intestinal stem cells
Oncogenesis
Colon cancer

摘要

Little is known about how pro-obesity diets regulate tissue stem and progenitor cell function. Here we show that high-fat diet (HFD)-induced obesity augments the numbers and function of Lgr5+
intestinal stem cells of the mammalian intestine. Mechanistically, a HFD induces a robust peroxisome proliferator-activated receptor delta (PPAR-δ) signature in intestinal stem cells and progenitor cells (non-intestinal stem cells), and pharmacological activation of PPAR-δ recapitulates the effects of a HFD on these cells. Like a HFD, ex vivo treatment of intestinal organoid cultures with fatty acid constituents of the HFD enhances the self-renewal potential of these organoid bodies in a PPAR-δ-dependent manner. Notably, HFD- and agonist-activated PPAR-δ signalling endow organoid-initiating capacity to progenitors, and enforced PPAR-δ signalling permits these progenitors to form in vivo tumours after loss of the tumour suppressorApc. These findings highlight how diet-modulated PPAR-δ activation alters not only the function of intestinal stem and progenitor cells, but also their capacity to initiate tumours.

3.Priming and polymerization of a bacterial contractile tail structure

http://www.nature.com/nature/journal/v531/n7592/full/nature17182.html

Subject terms:

Bacterial secretion
Bacterial structural biology
Pathogens

摘要

Contractile tails are composed of an inner tube wrapped by an outer sheath assembled in an extended, metastable conformation that stores mechanical energy necessary for its contraction. Contraction is used to propel the rigid inner tube towards target cells for DNA or toxin delivery. Although recent studies have revealed the structure of the contractile sheath of the type VI secretion system, the mechanisms by which its polymerization is controlled and coordinated with the assembly of the inner tube remain unknown. Here we show that the starfish-like TssA dodecameric complex interacts with tube and sheath components. Fluorescence microscopy experiments in enteroaggregative Escherichia coli reveal that TssA binds first to the type VI secretion system membrane core complex and then initiates tail polymerization. TssA remains at the tip of the growing structure and incorporates new tube and sheath blocks. On the basis of these results, we propose that TssA primes and coordinates tail tube and sheath biogenesis.

**a**, **b**, Schematic representation of the different stages of the assembly and mechanism of action of the T6SS (from left to right) highlighting the role of TssA. The TssA dodecamer (red) is recruited to the T6SS membrane complex. A negative-stain electron microscopy image of the TssJLM–TssA complex is shown in[Extended Data Fig. 2d](http://www.nature.com/nature/journal/v531/n7592/fig_tab/nature17182_SF2.html). TssA then recruits the baseplate and initiates polymerization of the tail by the incorporation of Hcp (black rectangles) and TssBC (blue rectangles) building blocks (**a**) or the incorporation of Hcp–TssBC building blocks (**b**). During the polymerization, TssA remains at the distal end of the structure. TssA is released after sheath contraction. Docking experiments of TssA at the distal extremity of the extended and contracted sheath are shown in [Extended Data Fig. 8a–c](http://www.nature.com/nature/journal/v531/n7592/fig_tab/nature17182_SF8.html). A dynamic representation of this working model is shown in [Supplementary Video 1](http://www.nature.com/nature/journal/v531/n7592/fig_tab/nature17182_SV1.html).

4.Structural basis of outer membrane protein insertion by the BAM complex

http://www.nature.com/nature/journal/v531/n7592/full/nature17199.html

Subject terms:

X-ray crystallography
Bacterial structural biology
Membrane structure and assembly

摘要

All Gram-negative bacteria, mitochondria and chloroplasts have outer membrane proteins (OMPs) that perform many fundamental biological processes. The OMPs in Gram-negative bacteria are inserted and folded into the outer membrane by the β-barrel assembly machinery (BAM). The mechanism involved is poorly understood, owing to the absence of a structure of the entire BAM complex. Here we report two crystal structures of the Escherichia coli BAM complex in two distinct states: an inward-open state and a lateral-open state. Our structures reveal that the five polypeptide transport-associated domains of BamA form a ring architecture with four associated lipoproteins, BamB–BamE, in the periplasm. Our structural, functional studies and molecular dynamics simulations indicate that these subunits rotate with respect to the integral membrane β-barrel of BamA to induce movement of the β-strands of the barrel and promote insertion of the nascent OMP.

5.A large light-mass component of cosmic rays at 1017–1017.5 electronvolts from radio observations

http://www.nature.com/nature/journal/v531/n7592/full/nature16976.html

Subject terms:

High-energy astrophysics
Particle astrophysics

摘要

Screenshot - 2016年03月04日 - 22时19分28秒.png

6.Controlling spin relaxation with a cavity

http://www.nature.com/nature/journal/v531/n7592/full/nature16944.html

Subject terms:

Quantum mechanics
Quantum information
Quantum optics

摘要

Screenshot - 2016年03月04日 - 22时23分19秒.png

7.Condensation on slippery asymmetric bumps

http://www.nature.com/nature/journal/v531/n7592/full/nature16956.html

Subject terms:

Materials science
Engineering

摘要

Screenshot - 2016年03月04日 - 22时28分48秒.png

The convex millimetric bump topography of water-harvesting desert beetles inspired the rational design of bumps that optimize fast, localized droplet growth by focusing vapour diffusion flux (green dotted arrows) at the apex. We further designed the bump to include an asymmetric slope analogous to that of cactus spines for capillary-guided directional transport of harvested droplets, and a pitcher-plant-inspired molecularly smooth lubricant immobilized on nanotexture. The green dash-dotted line represents the depletion layer. The green, black and red solid arrows represent the directions of convection, gravity *g* and drop transport, respectively. Approximate species dimensions are: desert beetle, 1.5 cm long; cactus, 20 cm in diameter; pitcher plant, 15 cm tall. Images are adapted with permission from Wikimedia Commons (desert beetle photograph by Hans Hillewaert, cactus photograph by Stan Shebs), and ref. [26](http://www.nature.com/nature/journal/v531/n7592/full/nature16956.html#ref26) (pitcher plant photograph, copyright (2004) National Academy of Sciences, USA).

In summary, we have achieved unprecedented droplet growth and transport by designing surfaces covered with slippery asymmetric bumps based on quantitative models that integrate three mechanisms—(1) optimization of focused diffusion flux by the radius of curvature and shape of the apex, (2) asymmetric topography that guides the droplet off the bump by optimizing the free-energy profile, and (3) positive feedback between capillary transport and continued growth by coalescence along the slope.

The rapid turnover kinetics, with fast onset and sustained continuous shedding rate, combined with the ability to defy a temperature gradient, are crucial not only for water-harvesting applications, particularly in hot, arid regions where condensed water droplets will evaporate if they do not shed after a limited time, but also for many phase-change heat-transfer applications requiring reliable steady-state performance. It may also be possible to create switchable water-transporting surfaces with flexible topographical features that can be tuned by external stimuli, and to discover fundamental principles of droplet growth and transport in practical and more complex situations such as with strong airflow.

8.Stable amorphous georgeite as a precursor to a high-activity catalyst

http://www.nature.com/nature/journal/v531/n7592/full/nature16935.html

Subject terms:

Catalyst synthesis
Nanoparticles

摘要

Screenshot - 2016年03月04日 - 23时03分09秒.png

9.Electrostatic catalysis of a Diels–Alder reaction

http://www.nature.com/nature/journal/v531/n7592/full/nature16989.html

Subject terms:

Electrocatalysis
Scanning probe microscopy

摘要

It is often thought that the ability to control reaction rates with an applied electrical potential gradient is unique to redox systems. However, recent theoretical studies suggest that oriented electric fields could affect the outcomes of a range of chemical reactions, regardless of whether a redox system is involved1, 2, 3, 4
. This possibility arises because many formally covalent species can be stabilized via minor charge-separated resonance contributors. When an applied electric field is aligned in such a way as to electrostatically stabilize one of these minor forms, the degree of resonance increases, resulting in the overall stabilization of the molecule or transition state. This means that it should be possible to manipulate the kinetics and thermodynamics of non-redox processes using an external electric field, as long as the orientation of the approaching reactants with respect to the field stimulus can be controlled. Here, we provide experimental evidence that the formation of carbon–carbon bonds is accelerated by an electric field. We have designed a surface model system to probe the Diels–Alder reaction, and coupled it with a scanning tunnelling microscopy break-junction approach5, 6, 7
. This technique, performed at the single-molecule level, is perfectly suited to deliver an electric-field stimulus across approaching reactants. We find a fivefold increase in the frequency of formation of single-molecule junctions, resulting from the reaction that occurs when the electric field is present and aligned so as to favour electron flow from the dienophile to the diene. Our results are qualitatively consistent with those predicted by quantum-chemical calculations in a theoretical model of this system, and herald a new approach to chemical catalysis.

10.Upper-plate controls on co-seismic slip in the 2011 magnitude 9.0 Tohoku-oki earthquake

http://www.nature.com/nature/journal/v531/n7592/full/nature16945.html

Subject terms:

Geology
Geophysics
Seismology

摘要

The March 2011 Tohoku-oki earthquake was only the second giant (moment magnitude Mw
 ≥ 9.0) earthquake to occur in the last 50 years and is the most recent to be recorded using modern geophysical techniques. Available data place high-resolution constraints on the kinematics of earthquake rupture1
, which have challenged prior knowledge about how much a fault can slip in a single earthquake and the seismic potential of a partially coupled megathrust interface2
. But it is not clear what physical or structural characteristics controlled either the rupture extent or the amplitude of slip in this earthquake. Here we use residual topography and gravity anomalies to constrain the geological structure of the overthrusting (upper) plate offshore northeast Japan. These data reveal an abrupt southwest–northeast-striking boundary in upper-plate structure, across which gravity modelling indicates a south-to-north increase in the density of rocks overlying the megathrust of 150–200 kilograms per cubic metre. We suggest that this boundary represents the offshore continuation of the Median Tectonic Line, which onshore juxtaposes geological terranes composed of granite batholiths (in the north) and accretionary complexes (in the south)3
. The megathrust north of the Median Tectonic Line is interseismically locked2
, has a history of large earthquakes (18 with Mw
 > 7 since 1896) and produced peak slip exceeding 40 metres in the Tohoku-oki earthquake1
. In contrast, the megathrust south of this boundary has higher rates of interseismic creep2
, has not generated an earthquake with MJ
 > 7 (local magnitude estimated by the Japan Meteorological Agency) since 1923, and experienced relatively minor (if any) co-seismic slip in 20111
. We propose that the structure and frictional properties of the overthrusting plate control megathrust coupling and seismogenic behaviour in northeast Japan.

11.Evidence from cyclostomes for complex regionalization of the ancestral vertebrate brain

http://www.nature.com/nature/journal/v531/n7592/full/nature16518.html

Subject terms:

Evolutionary developmental biology
Neuroscience

摘要

The vertebrate brain is highly complex, but its evolutionary origin remains elusive. Because of the absence of certain developmental domains generally marked by the expression of regulatory genes, the embryonic brain of the lamprey, a jawless vertebrate, had been regarded as representing a less complex, ancestral state of the vertebrate brain. Specifically, the absence of a Hedgehog- and Nkx2.1-positive domain in the lamprey subpallium was thought to be similar to mouse mutants in which the suppression of Nkx2-1 leads to a loss of the medial ganglionic eminence1, 2
. Here we show that the brain of the inshore hagfish (Eptatretus burgeri), another cyclostome group, develops domains equivalent to the medial ganglionic eminence and rhombic lip, resembling the gnathostome brain. Moreover, further investigation of lamprey larvae revealed that these domains are also present, ruling out the possibility of convergent evolution between hagfish and gnathostomes. Thus, brain regionalization as seen in crown gnathostomes is not an evolutionary innovation of this group, but dates back to the latest vertebrate ancestor before the divergence of cyclostomes and gnathostomes more than 500 million years ago.

12.Late acquisition of mitochondria by a host with chimaeric prokaryotic ancestry

http://www.nature.com/nature/journal/v531/n7592/full/nature16941.html

Subject terms:

Evolution
Evolutionary theory
Organelles

摘要

Screenshot - 2016年03月04日 - 23时16分12秒.png

13.Deriving human ENS lineages for cell therapy and drug discovery in Hirschsprung disease

http://www.nature.com/nature/journal/v531/n7592/full/nature16951.html

Subject terms:

Embryonic stem cells
Developmental disorders
Regeneration
Stem-cell differentiation

摘要

The enteric nervous system (ENS) is the largest component of the autonomic nervous system, with neuron numbers surpassing those present in the spinal cord1
. The ENS has been called the ‘second brain’1
given its autonomy, remarkable neurotransmitter diversity and complex cytoarchitecture. Defects in ENS development are responsible for many human disorders including Hirschsprung disease (HSCR). HSCR is caused by the developmental failure of ENS progenitors to migrate into the gastrointestinal tract, particularly the distal colon2
. Human ENS development remains poorly understood owing to the lack of an easily accessible model system. Here we demonstrate the efficient derivation and isolation of ENS progenitors from human pluripotent stem (PS) cells, and their further differentiation into functional enteric neurons. ENS precursors derived in vitroare capable of targeted migration in the developing chick embryo and extensive colonization of the adult mouse colon. The in vivo engraftment and migration of human PS-cell-derived ENS precursors rescue disease-related mortality in HSCR mice (Ednrbs-l/s-l
), although the mechanism of action remains unclear. Finally, EDNRB-null mutant ENS precursors enable modelling of HSCR-related migration defects, and the identification of pepstatin A as a candidate therapeutic target. Our study establishes the first, to our knowledge, human PS-cell-based platform for the study of human ENS development, and presents cell- and drug-based strategies for the treatment of HSCR.

14.Mutant Kras copy number defines metabolic reprogramming and therapeutic susceptibilities

http://www.nature.com/nature/journal/v531/n7592/full/nature16967.html

Subject terms:

Non-small-cell lung cancer
Cancer metabolism
Cancer models

摘要

Screenshot - 2016年03月04日 - 23时22分58秒.png

15.Cryo-electron microscopy structure of a coronavirus spike glycoprotein trimer

http://www.nature.com/nature/journal/v531/n7592/full/nature16988.html

Subject terms:

Viral membrane fusion
Cryoelectron microscopy

摘要

Screenshot - 2016年03月04日 - 23时25分45秒.png

16.Pre-fusion structure of a human coronavirus spike protein

http://www.nature.com/nature/journal/v531/n7592/full/nature17200.html

Subject terms:

SARS virus
Cryoelectron microscopy

摘要

Screenshot - 2016年03月04日 - 23时30分43秒.png

17.Crystal structure of eukaryotic translation initiation factor 2B

http://www.nature.com/nature/journal/v531/n7592/full/nature16991.html

Subject terms:

Translation
X-ray crystallography
GTP-binding protein regulators
Proteins

摘要

Screenshot - 2016年03月04日 - 23时33分43秒.png