| | Microbiology: How bacteria get spacers from invaders
Bacteria use CRISPR–Cas systems to develop immunity to viruses. Details of how these systems select viral DNA fragments and integrate them into bacterial DNA to create a memory of invaders have now been reported. | HIV: Tied down by its own receptor
An engineered protein that binds to the envelope of HIV viruses protects monkeys against infection with a simian–human virus that causes AIDS. This gene-therapy approach might provide an alternative to elusive HIV vaccines. | Neuroscience: A cellular basis for the munchies
How does marijuana cause the irresistible hunger pangs known as the munchies? Paradoxically, the answer seems to involve an unusual mode of activation of a brain circuit best known for suppressing appetite. | Crystal structure of the V(D)J recombinase RAG1–RAG2
The crystal structure of the RAG1–RAG2 heterotetramer forms a Y-shaped structure, with each arm containing a RAG1–RAG2 heterodimer; the overall structure is reminiscent of hairpin-forming transposases, attesting to its evolutionary history as a specialized form of a transposition activity. | Integrase-mediated spacer acquisition during CRISPR–Cas adaptive immunity
The bacterial CRISPR/Cas system acquires short phage sequences known as spacers that integrate between CRISPR repeats and constitute a record of phage infection; this study shows that the Cas1–Cas2 complex is the minimal machinery required for spacer acquisition and the complex integrates oligonucleotide DNA substrates into acceptor DNA in a manner similar to retroviral integrases and DNA transposases with Cas 1 as the catalytic subunit and Cas2 acting to increase integration activity. | Cas9 specifies functional viral targets during CRISPR–Cas adaptation
Bacterial CRISPR–Cas loci acquire short phage sequences called spacers that integrate between DNA repeats and how these viral sequences are chosen was unknown; in these studies of the type II CRISPR–Cas system of Streptococcus pyogenes, the Cas9 nuclease known to inactivate invading viral DNA was found to be required for the selection of functional spacers during CRISPR immunity. | Hypothalamic POMC neurons promote cannabinoid-induced feeding
Cannabinoid-induced feeding signals are shown to enhance pro-opiomelanocortin (POMC) neuronal activity in mice, causing an enhancement of β-endorphin release, which is crucial in causing this cannabinoid-induced response; these results uncover an overlooked role of hypothalamic POMC neurons in the promotion of feeding by cannabinoids. | An epigenome-wide association study of total serum immunoglobulin E concentration
A survey of epigenetic associations between serum immunoglobulin E concentrations indicating allergy and methylation at CpG islands in families and a population sample has revealed associations at 36 loci that harbour genes encoding proteins including eosinophil products and phospholipid inflammatory mediators. | Exit from dormancy provokes DNA-damage-induced attrition in haematopoietic stem cells
Here, DNA damage is shown to occur as a direct consequence of inducing haematopoietic stem cells to exit quiescence in response to conditions of stress; in mice with mutations modelling those seen in Fanconi anaemia, this leads to a complete collapse of the haematopoietic system. | Vertically transmitted faecal IgA levels determine extra-chromosomal phenotypic variation
Microbially driven dichotomous faecal immunoglobulin-A levels in wild-type mice within the same facility mimic the effects of chromosomal mutations, indicating that phenotypic comparisons between mice must take into account the non-chromosomal hereditary variation between different breeders. | Super-enhancers delineate disease-associated regulatory nodes in T cells
A study of the super-enhancer landscape in three mouse T-helper lymphocyte subsets identifies nodes that have key roles in cell identity, with the locus encoding Bach2, a key negative regulator of effector differentiation, emerging as the most prominent T-cell super-enhancer. | An extremely high-altitude plume seen at Mars’ morning terminator
Examination of amateur observations of Mars shows atmospheric plumes 200 to 250 kilometres high that are observed in the morning but not in the evening over a period of more than a week; our current understanding of Martian atmospheric dynamics and plume formation cannot account for the creation of such enormous plumes. | Isotopic evidence for biological nitrogen fixation by molybdenum-nitrogenase from 3.2 Gyr
Nitrogen isotope ratios from rocks between 3.2 and 2.75 billion years old are most readily explained by biological nitrogen fixation, most probably using the metal molybdenum as a cofactor, showing that nitrogen fixation is at least 3.2 billion years old and suggesting that molybdenum was available to organisms long before the Great Oxidation Event. | AAV-expressed eCD4-Ig provides durable protection from multiple SHIV challenges
The new entry inhibitor eCD4-Ig, consisting of the immunoadhesin form of CD4 (CD4-Ig) fused to a small CCR5-mimetic sulfopeptide, avidly binds two highly conserved sites of the HIV-1 Env protein; the inhibitor has high potency and breadth and can neutralize 100% of a diverse panel of neutralization-resistant HIV-1 viruses, and when delivered to macaques using an adeno-associated virus vector, it can provide effective long-term protection from multiple challenges with simian/human immunodeficiency virus. | | Integrative analysis of 111 reference human epigenomes OPEN
This study describes the integrative analysis of 111 reference human epigenomes, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression; the results annotate candidate regulatory elements in diverse tissues and cell types, their candidate regulators, and the set of human traits for which they show genetic variant enrichment, providing a resource for interpreting the molecular basis of human disease.
Roadmap Epigenomics Consortium, Anshul Kundaje, Wouter Meuleman et al. | Chromatin architecture reorganization during stem cell differentiation OPEN
An analysis of genome-wide chromatin interactions during human embryonic stem cell differentiation reveals changes in chromatic organization and simultaneously identifies allele-resolved chromatin structure and differences in gene expression during differentiation.
Jesse R. Dixon, Inkyung Jung, Siddarth Selvaraj et al. | Genetic and epigenetic fine mapping of causal autoimmune disease variants
Genome-wide association studies combined with data from epigenomic maps for immune cells have been used to fine-map causal variants for 21 autoimmune diseases; disease risk tends to be linked to single nucleotide polymorphisms in cell-type-specific enhancers, often in regions adjacent to transcription factor binding motifs.
Kyle Kai-How Farh, Alexander Marson, Jiang Zhu et al. | Transcription factor binding dynamics during human ES cell differentiation OPEN
Lineage-specific transcription factors and signalling pathways cooperate with pluripotency regulators to control the transcriptional networks that drive cell specification and exit from an embryonic stem cell state; here, we report genome-wide binding data for 38 transcription factors combined with analysis of epigenomic and gene expression data during the differentiation of human embryonic stem cells into the three germ layers.
Alexander M. Tsankov, Hongcang Gu, Veronika Akopian et al. | Evolution of Darwin’s finches and their beaks revealed by genome sequencing
Comprehensive genome sequencing of 120 individuals representing all of the Darwin’s finch species and two close relatives reveals important discrepancies with morphology-based taxonomy, widespread hybridization, and a gene, ALX1, underlying variation in beak shape.
Sangeet Lamichhaney, Jonas Berglund, Markus Sällman Almén et al. | Architecture of the RNA polymerase II–Mediator core initiation complex
Mediator is the key transcription co-activator complex that enables basal and regulated transcription initiation by RNA polymerase (Pol) II; here a 15-subunit yeast core Mediator bound to a core Pol II initiation complex is reconstituted and its structure determined by cryo-electron microscopy at subnanometre resolution.
C. Plaschka, L. Larivière, L. Wenzeck et al. | | Integrative analysis of haplotype-resolved epigenomes across human tissues OPEN
As part of the Epigenome Roadmap project, this study uses a chromosome-spanning haplotype reconstruction strategy to construct haplotype-resolved epigenomic maps for a diverse set of human tissues; the maps reveal extensive allelic biases in chromatin state and transcription, which vary across individuals due to genetic backgrounds.
Danny Leung, Inkyung Jung, Nisha Rajagopal et al. | Dissecting neural differentiation regulatory networks through epigenetic footprinting
The integrative analysis of epigenetic footprints along consecutive stages of neural progenitors derived from human ES cells reveals regulatory mechanisms that orchestrate stage-specific differentiation.
Michael J. Ziller, Reuven Edri, Yakey Yaffe et al. | Cell-of-origin chromatin organization shapes the mutational landscape of cancer OPEN
An analysis of cell-type-specific epigenomic features reveals a relationship between epigenomic and mutational profiles; chromatin characteristics can explain a large proportion of mutational variance in cancer genomes and the mutational distribution can identify the probable cell type from which a given cancer originated from.
Paz Polak, Rosa Karlić, Amnon Koren et al. | Conserved epigenomic signals in mice and humans reveal immune basis of Alzheimer’s disease OPEN
Analysis of transcriptional and epigenomic changes in the hippocampus of a mouse model of Alzheimer’s disease shows that immune function genes and regulatory regions are upregulated, whereas genes and regulatory regions involved in synaptic plasticity, learning and memory are downregulated; genetic variants associated with Alzheimer’s disease are only enriched in orthologues of upregulated immune regions, suggesting that dysregulation of immune processes may underlie Alzheimer’s disease predisposition.
Elizabeta Gjoneska, Andreas R. Pfenning, Hansruedi Mathys et al. | Explosive lithium production in the classical nova V339 Del (Nova Delphini 2013)
The origin of lithium is key to understanding the enrichment history of the Universe; now the classical nova V339 Del (Nova Delphini 2013) reveals that nova explosions could have been contributing to the recent rapid increase of the amount of lithium in the Universe.
Akito Tajitsu, Kozo Sadakane, Hiroyuki Naito et al. | Direct observation of bond formation in solution with femtosecond X-ray scattering
Time-resolved X-ray solution scattering is used to visualize and probe the dynamics of the individual steps in the formation of a gold trimer complex, including covalent bond formation, with a time resolution of ∼500 femtoseconds.
Kyung Hwan Kim, Jong Goo Kim, Shunsuke Nozawa et al. | Intensification and spatial homogenization of coastal upwelling under climate change
An ensemble of climate models shows that by the end of the twenty-first century the coastal upwelling season near the eastern boundaries of the Atlantic and Pacific oceans will start earlier, end later and become more intense at high latitudes, thus becoming more homogeneous; these changes may affect the geographical distribution of marine biodiversity.
Daiwei Wang, Tarik C. Gouhier, Bruce A. Menge et al. | Seismic evidence of effects of water on melt transport in the Lau back-arc mantle
Tomographically derived seismic velocities are used to infer the distribution of partial melt below the Lau Basin, revealing an unexpected relationship between the amount of in situ melt and the water content of the magma, indicating that subducted water enhances melt extraction.
S. Shawn Wei, Douglas A. Wiens, Yang Zha et al. | Functional organization of excitatory synaptic strength in primary visual cortex
In complex networks of the cerebral cortex, the majority of connections are weak and only a minority strong, but it is not known why; here the authors show that excitatory neurons in primary visual cortex follow a rule by which strong connections are sparse and occur between neurons with correlated responses to visual stimuli, whereas only weak connections link neurons with uncorrelated responses.
Lee Cossell, Maria Florencia Iacaruso, Dylan R. Muir et al. | Modulation of the proteoglycan receptor PTPσ promotes recovery after spinal cord injury
Regeneration and plasticity after spinal cord injury are limited by inhibitory proteoglycans; here, modulation of a receptor for proteoglycans in rats is shown to lead to functional recovery after injury.
Bradley T. Lang, Jared M. Cregg, Marc A. DePaul et al. | Towards a therapy for Angelman syndrome by targeting a long non-coding RNA
Angelman syndrome is a neurodevelopmental disorder caused by disrupted function of the maternal copy of the imprinted UBE3A gene; here, targeting a long non-coding RNA that is responsible for silencing the paternal copy of UBE3A with antisense oligonucleotides is shown to partially restore UBE3A expression in the central nervous system and correct some cognitive deficits in a mouse model of the disease.
Linyan Meng, Amanda J. Ward, Seung Chun et al. | Intracellular α-ketoglutarate maintains the pluripotency of embryonic stem cells
If deprived of exogenous glutamine, naive mouse embryonic stem cells are shown to be capable of generating the amino acid from other sources to enable their proliferation; the stem cells use glutamine and glucose catabolism to maintain a high level of intracellular α-ketoglutarate and promote demethylation of chromatin and ensure sufficient expression of pluripotency-associated genes.
Bryce W. Carey, Lydia W. S. Finley, Justin R. Cross et al. | Deubiquitinase DUBA is a post-translational brake on interleukin-17 production in T cells
The deubiquitinase enzyme DUBA is shown to act as a negative regulator of interleukin-17A (IL-17A) in TH17 cells; DUBA interacts with and stabilizes the ubiquitin ligase UBR5, which in turn targets RORγt for degradation in the proteaseome, thus limiting IL-17A production.
Sascha Rutz, Nobuhiko Kayagaki, Qui T. Phung et al. | Dynamics of genomic clones in breast cancer patient xenografts at single-cell resolution
Deep-genome and single-cell sequencing analyses of patient-derived breast cancer xenografts reveal extensive, dynamic and reproducible changes in intra-tumoral mutational clonal composition on engraftment and serial propagation.
Peter Eirew, Adi Steif, Jaswinder Khattra et al. | Catalysts from synthetic genetic polymers
Four different XNAs — polymers with backbone chemistries not found in nature, namely, arabino nucleic acids, 2′-fluoroarabino nucleic acids, hexitol nucleic acids and cyclohexene nucleic acids — are found to be able to support the evolution of synthetic enzymes (XNAzymes) that catalyse several chemical reactions.
Alexander I. Taylor, Vitor B. Pinheiro, Matthew J. Smola et al. | Structure of the key species in the enzymatic oxidation of methane to methanol
Time-resolved resonance Raman vibrational spectroscopy was used to study the mechanism of soluble methane monooxygenase and obtain structural information on the key reaction cycle intermediate, compound Q, which contains a unique dinuclear FeIV cluster that breaks the strong C-H bond of methane and inserts an oxygen atom (from O2) to form methanol.
Rahul Banerjee, Yegor Proshlyakov, John D. Lipscomb et al. | Structure of human cytoplasmic dynein-2 primed for its power stroke
The X-ray crystal structure of the human cytoplasmic dynein-2 motor bound to the ATP-hydrolysis transition state analogue ADP.vanadate is described.
Helgo Schmidt, Ruta Zalyte, Linas Urnavicius et al. | | | | |
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