| | Non-coding RNA: Antibiotic tricks a switch
A screen for compounds that block a bacterial biosynthetic pathway has uncovered an antibiotic lead that shuts off pathogen growth by targeting a molecular switch in a regulatory RNA structure.
| Neurobiology: Individuality sniffed out in flies
The discovery that certain neurons' odour responses differ between individual fruit flies, but are consistent across the hemispheres of each fly's brain, indicates that sensory processing depends on an individual's experience.
| HIV: Antiviral action countered by Nef
The HIV protein Nef is a viral 'Swiss army knife' with many functions. New work now shows how Nef increases infectivity — by inhibiting two of the host cell's antiviral proteins, SERINC3 and SERINC5.
| Structure and mechanism of the mammalian fructose transporter GLUT5
This study has determined the X-ray crystal structures of GLUT5 from Rattus norvegicus in an open, outward-facing conformation and GLUT5 from Bos taurus in an open, inward-facing conformation; comparison of these structures with previously published structures of the related Escherichia coli d-xylose:H+ symporter XylE suggests that transport in GLUT5 is controlled by both a global 'rocker-switch'-type motion and a local 'gated-pore'-type transport mechanism.
| Structural basis for gene regulation by a B12-dependent photoreceptor
Crystal structures are presented of Thermus thermophilus CarH, a photoreceptor that uses a vitamin B12 derivative, in all three relevant states: in the dark, both free and bound to operator DNA, and after light exposure.
| HIV-1 Nef promotes infection by excluding SERINC5 from virion incorporation
The transmembrane protein SERINC5 is identified as a potent inhibitor of HIV-1 particle infectivity that is counteracted by Nef; Nef redirects SERINC5 from the plasma membrane to a Rab7-positive endosomal compartment, thus excluding it from HIV-1 particles, emphasizing the potential of SERINC5 as a potent anti-retroviral factor.
| SERINC3 and SERINC5 restrict HIV-1 infectivity and are counteracted by Nef
The transmembrane proteins SERINC3 and SERINC5 are identified as new restriction factors for HIV-1 replication; this restriction is counteracted by Nef and glycoGag, which prevent SERINC3 and SERINC5 from becoming incorporated into HIV-1 virions and from profoundly blocking HIV-1 infectivity, suggesting a potential new therapeutic strategy for immunodeficiency viruses.
| Selective small-molecule inhibition of an RNA structural element
A novel drug, ribocil, is shown to mimic the binding of a natural ligand to a bacterial riboflavin riboswitch (a non-coding stretch of messenger RNA whose structure is affected by a ligand—usually one related to the function of the protein encoded by the messenger RNA) to cause inhibition of bacterial growth; the ability to target an RNA structural element with a synthetic small molecule may expand our view of the target space susceptible to therapeutic intervention.
| Mediator kinase inhibition further activates super-enhancer-associated genes in AML
A small-molecule inhibitor of the Mediator-associated kinases CDK8 and CDK19 inhibits growth of acute myeloid leukaemia (AML) cells and induces upregulation of super-enhancer-associated genes with tumour suppressor and lineage-controlling functions; Mediator kinase inhibition therefore represents a promising therapeutic approach for AML.
| Inhibition of Gli1 mobilizes endogenous neural stem cells for remyelination
A subset of adult neural stem cells, responsive to sonic hedgehog, are more effective at remyelination when the transcription factor Gli1 is inhibited.
| The genomic landscape of response to EGFR blockade in colorectal cancer
The effect of somatic genetic changes in colorectal cancer on sensitivity to anti-EGFR antibody therapy is analysed.
| Crystal structure of human glycine receptor-α3 bound to antagonist strychnine
The X-ray crystal structure of the human glycine receptor in the presence of strychnine, an antagonist, reveals how antagonist binding leads to closure of the channel pore.
| Identification of carbohydrate anomers using ion mobility–mass spectrometry
The branched structure and stereoisomerism of carbohydrates make them difficult to analyse; here, ion mobility–mass spectrometry is used to distinguish unambiguously between synthetic trisaccharides that differ in connectivity or configuration.
| A novel locus of resistance to severe malaria in a region of ancient balancing selection
A multi-centre genome-wide association study of severe malaria in African children uncovers a new resistance locus close to a cluster of genes encoding glycophorins, which are receptors used by the malaria-causing parasite to invade red blood cells.
| Plasticity-driven individualization of olfactory coding in mushroom body output neurons
Neuronal representations of sensory stimuli tend to become sparse and decorrelated, with different odours giving rise to fewer neuronal spikes in rare neurons, as signal processing moves up to higher brain layers; here comprehensive recording from the Drosophila olfactory processing centre finds instead some highly correlated tuning curves that vary flexibly from animal to animal.
| Two independent and primitive envelopes of the bilobate nucleus of comet 67P
The 'onion-like' stratification of the two lobes of the comet 67P/Churyumov–Gerasimenko reveals that its unusual shape is the result of a gentle collision merging two kilometre-sized objects in the early stages of the Solar System.
| Erratum: Structural imprints in vivo decode RNA regulatory mechanisms
| Corrigendum: Improving survival by exploiting tumour dependence on stabilized mutant p53 for treatment
| | | Brief Communications Arising | | | | | | |  See why BlotCycler is the next big thing in life science research... Western blot processing with precise results, automatically! Run 12 blots simultaneously with no wasted time — simply set it up and run blots.
100% satisfaction guaranteed! Detailed application note here — and a $500 discount! | | | | | | | | | | | | | CRISPR-Cas immunity in prokaryotes
The CRISPR-Cas systems of bacteria and archaea provide adaptive immunity against invading mobile genetic elements such as phages and plasmids; this Review describes the discovery of these systems and the mechanisms of immunity, including recent progress in establishing the molecular basis of host immunization.
Luciano A. Marraffini | | The origins of high hardening and low ductility in magnesium
Practical applications of magnesium as a lightweight structural metal are limited by its high work hardening, low ductility and fracture at very low strains; now molecular dynamics simulations reveal the origins of these problems and offer a route to design magnesium alloys with improved mechanical properties.
Zhaoxuan Wu, W. A. Curtin | A global reference for human genetic variation OPEN
Results for the final phase of the 1000 Genomes Project are presented including whole-genome sequencing, targeted exome sequencing, and genotyping on high-density SNP arrays for 2,504 individuals across 26 populations, providing a global reference data set to support biomedical genetics.
The 1000 Genomes Project Consortium | An integrated map of structural variation in 2,504 human genomes OPEN
The Structural Variation Analysis Group of The 1000 Genomes Project reports an integrated structural variation map based on discovery and genotyping of eight major structural variation classes in 2,504 unrelated individuals from across 26 populations; structural variation is compared within and between populations and its functional impact is quantified.
A list of authors and their affiliations appears at the end of the paper, Peter H. Sudmant, Tobias Rausch et al. | The UK10K project identifies rare variants in health and disease OPEN
Low read depth sequencing of whole genomes and high read depth exomes of nearly 10,000 extensively phenotyped individuals are combined to help characterize novel sequence variants, generate a highly accurate imputation reference panel and identify novel alleles associated with lipid-related traits; in addition to describing population structure and providing functional annotation of rare and low-frequency variants the authors use the data to estimate the benefits of sequencing for association studies.
The UK10K Consortium | | A subthermionic tunnel field-effect transistor with an atomically thin channel
A new type of device, the band-to-band tunnel transistor, which has atomically thin molybdenum disulfide as the active channel, operates in a fundamentally different way from a conventional silicon (MOSFET) transistor; it has turn-on characteristics and low-power operation that are better than those of state-of-the-art MOSFETs or any tunnelling transistor reported so far.
Deblina Sarkar, Xuejun Xie, Wei Liu et al. | Binding of dinitrogen to an iron–sulfur–carbon site
A synthetic complex with a sulfur-rich coordination sphere is described that, upon reduction, breaks an Fe–S bond and binds N2, providing a model for the iron–molybdenum cofactor used by nitrogenase enzymes to produce ammonia.
Ilija Čorić, Brandon Q. Mercado, Eckhard Bill et al. | Observed latitudinal variations in erosion as a function of glacier dynamics
Erosion and velocity data from 15 outlet glaciers covering temperate to polar glacier thermal regimes from Patagonia to the Antarctic Peninsula reveal that over the past century the basin-averaged erosion rates vary by three orders of magnitude as a function of climate across this latitudinal transect.
Michéle Koppes, Bernard Hallet, Eric Rignot et al. | Declining global warming effects on the phenology of spring leaf unfolding
Spring leaf unfolding has been occurring earlier in the year because of rising temperatures; however, long-term evidence in the field from 7 European tree species studied in 1,245 sites shows that this early unfolding effect is being reduced in recent years, possibly because the reducing chilling and/or insolation render trees less responsive to warming.
Yongshuo H. Fu, Hongfang Zhao, Shilong Piao et al. | New genomic and fossil data illuminate the origin of enamel
Enamel is a tissue unique to vertebrates, and nowadays associated with teeth; here, histological material from a fossil bony fish and genomic data from an extant, armour-plated fish are analysed to show that enamel originated on the body surface and only later colonized the teeth.
Qingming Qu, Tatjana Haitina, Min Zhu et al. | Whole‐genome sequencing identifies EN1 as a determinant of bone density and fracture
Human population genomic studies, including whole‐genome sequencing, were undertaken to identify determinants of bone mineral density (BMD), a major predictor of osteoporotic fractures. Non‐coding variants with large effects on BMD and fractures were identified near the EN1 locus and mouse studies confirmed this gene has an important role in skeletal biology.
Hou‐Feng Zheng, Vincenzo Forgetta, Yi‐Hsiang Hsu et al. | Nanoparticle biointerfacing by platelet membrane cloaking
The authors report a new biomimetic nanodelivery platform in which polymeric nanoparticles enclosed in the plasma membrane of human platelets are used for disease-relevant targeting, and the therapeutic potential of the concept is demonstrated in animal models of coronary restenosis and systemic bacterial infection.
Che-Ming J. Hu, Ronnie H. Fang, Kuei-Chun Wang et al. | The soft palate is an important site of adaptation for transmissible influenza viruses
Efficient airborne transmission of influenza viruses between humans is associated with use of α2,6-linked sialic acids, not α2,3-linked sialic acids; however, using a loss-of-function approach in which a 2009 pandemic H1N1 influenza virus was engineered to bind α2,3 sialic acids, this study shows in ferrets that the soft palate is an important site for the switch of receptor usage to take place, and reveals that this tissue rapidly selects for transmissible influenza virus with human receptor preference.
Seema S. Lakdawala, Akila Jayaraman, Rebecca A. Halpin et al. | Deep imaging of bone marrow shows non-dividing stem cells are mainly perisinusoidal
α-catulin is identified as a marker to locate functional haematopoiteic stem cells in deep imaging experiments of bone marrow, showing that α-catulin–GFP+c-kit+ cells commonly reside in perisinusoidal niches throughout the bone marrow.
Melih Acar, Kiranmai S. Kocherlakota, Malea M. Murphy et al. | Single-cell analysis reveals a stem-cell program in human metastatic breast cancer cells
Single-cell analysis of gene expression in metastatic cells from distinct human breast tumour models shows that early metastatic cells possess basal, stem and mesenchymal cell properties, whereas advanced metastatic cells have more proliferative properties and are more mature, enabling them to be targeted with an anti-proliferative compound.
Devon A. Lawson, Nirav R. Bhakta, Kai Kessenbrock et al. | Multiple mechanisms for CRISPR–Cas inhibition by anti-CRISPR proteins
Bacterial cells evolved an immune system known as CRISPR–Cas to protect themselves from viral infection, triggering viruses to evolve anti-CRISPR proteins; here, three anti-CRISPR proteins are characterized, with each one interfering with the host CRISPR system at a different point.
Joseph Bondy-Denomy, Bianca Garcia, Scott Strum et al. | In situ structural analysis of the human nuclear pore complex
The most comprehensive architectural model to date of the nuclear pore complex reveals previously unknown local interactions, and a role for nucleoporin 358 in Y-complex oligomerization.
Alexander von Appen, Jan Kosinski, Lenore Sparks et al. | | | | |
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