ALBERT

Beschreibung: A diverse set of innate immune mechanisms protects cells from viral infections. The APOBEC3 family of DNA cytosine deaminases is an integral part of these defenses. For instance, APOBEC3D, APOBEC3F, APOBEC3G, and APOBEC3H would have the potential to destroy HIV-1 complementary DNA replication intermediates if not for neutralization by a proteasomal degradation mechanism directed by the viral protein Vif. At the core of this complex, Vif heterodimerizes with the transcription cofactor CBF-β, which results in fewer transcription complexes between CBF-β and its normal RUNX partners. Recent studies have shown that the Vif/CBF-β interaction is specific to the primate lentiviruses HIV-1 and SIV (simian immunodeficiency virus), although related nonprimate lentiviruses still require a Vif-dependent mechanism for protection from host species’ APOBEC3 enzymes. We provide a molecular explanation for this evolutionary conundrum by showing that CBF-β is required for expression of the aforementioned HIV-1–restrictive APOBEC3 gene repertoire. Knockdown and knockout studies demonstrate that CBF-β is required for APOBEC3 mRNA expression in the nonpermissive T cell line H9 and in primary CD4 + T lymphocytes. Complementation experiments using CBF-β separation-of-function alleles show that the interaction with RUNX transcription factors is required for APOBEC3 transcriptional regulation. Accordingly, the infectivity of Vif-deficient HIV-1 increases in cells lacking CBF-β, demonstrating the importance of CBF-β/RUNX–mediated transcription in establishing the APOBEC3 antiviral state. These findings demonstrate a major layer of APOBEC3 gene regulation in lymphocytes and suggest that primate lentiviruses evolved to hijack CBF-β in order to simultaneously suppress this potent antiviral defense system at both transcriptional and posttranslational levels.

Beschreibung: Life histories of the imperilled freshwater gastropod genus Leptoxis are poorly known, and this information is required to achieve a basic understanding of the evolution of this diverse group and to develop management strategies for species conservation and recovery. We describe egg-laying behaviours and associated traits for all 13 extant Leptoxis species. We also explore patterns of shell growth and assess the extent to which intraspecific shell variation is a result of phenotypic plasticity or genetic differences. Each Leptoxis species exhibits one of three distinct oviposition strategies: deposition of single eggs, deposition of eggs in a single line or deposition in circular clutches. Temperature cues for initiating egg laying varied from 12 to 26 °C depending on the species. There were significant differences in clutch size among species and between populations of L. ampla and L. taeniata . Furthermore, 1- and 2-year-old female L. foremani laid significantly fewer eggs per clutch than females 4 years or older. Finally, discrete shell morphologies that are characteristic of any given species are genetically controlled and not an ecophenotypic response. Clutch egg laying likely represents increased parental investment compared with other behaviours and clutches may provide individual eggs protection from predation or passive dislodgement. Data from this study, including necessary conditions for successful culturing and period of oviposition for each species, can inform captive propagation efforts for imperilled Leptoxis species and aid in predicting how they will respond to future habitat alteration and climate change.

Beschreibung: SOX10 is required for melanocyte development and maintenance, and has been linked to melanoma initiation and progression. However, the molecular mechanisms by which SOX10 guides the appropriate gene expression programs necessary to promote the melanocyte lineage are not fully understood. Here we employ genetic and epigenomic analysis approaches to uncover novel genomic targets and previously unappreciated molecular roles of SOX10 in melanocytes. Through global analysis of SOX10-binding sites and epigenetic characteristics of chromatin states, we uncover an extensive catalog of SOX10 targets genome-wide. Our findings reveal that SOX10 predominantly engages ‘open’ chromatin regions and binds to distal regulatory elements, including novel and previously known melanocyte enhancers. Integrated chromatin occupancy and transcriptome analysis suggest a role for SOX10 in both transcriptional activation and repression to regulate functionally distinct classes of genes. We demonstrate that distinct epigenetic signatures and cis -regulatory sequence motifs predicted to bind putative co-regulatory transcription factors define SOX10-activated and SOX10-repressed target genes. Collectively, these findings uncover a central role of SOX10 as a global regulator of gene expression in the melanocyte lineage by targeting diverse regulatory pathways.

Beschreibung: PomBase ( http://www.pombase.org ) is the model organism database for the fission yeast Schizosaccharomyces pombe . PomBase provides a central hub for the fission yeast community, supporting both exploratory and hypothesis-driven research. It provides users easy access to data ranging from the sequence level, to molecular and phenotypic annotations, through to the display of genome-wide high-throughput studies. Recent improvements to the site extend annotation specificity, improve usability and allow for monthly data updates. Both in-house curators and community researchers provide manually curated data to PomBase. The genome browser provides access to published high-throughput data sets and the genomes of three additional Schizosaccharomyces species ( Schizosaccharomyces cryophilus , Schizosaccharomyces japonicus and Schizosaccharomyces octosporus ).

Beschreibung: A large population of neurons can, in principle, produce an astronomical number of distinct firing patterns. In cortex, however, these patterns lie in a space of lower dimension, as if individual neurons were "obedient members of a huge orchestra". Here we use recordings from the visual cortex of mouse (Mus musculus) and monkey (Macaca mulatta) to investigate the relationship between individual neurons and the population, and to establish the underlying circuit mechanisms. We show that neighbouring neurons can differ in their coupling to the overall firing of the population, ranging from strongly coupled 'choristers' to weakly coupled 'soloists'. Population coupling is largely independent of sensory preferences, and it is a fixed cellular attribute, invariant to stimulus conditions. Neurons with high population coupling are more strongly affected by non-sensory behavioural variables such as motor intention. Population coupling reflects a causal relationship, predicting the response of a neuron to optogenetically driven increases in local activity. Moreover, population coupling indicates synaptic connectivity; the population coupling of a neuron, measured in vivo, predicted subsequent in vitro estimates of the number of synapses received from its neighbours. Finally, population coupling provides a compact summary of population activity; knowledge of the population couplings of n neurons predicts a substantial portion of their n(2) pairwise correlations. Population coupling therefore represents a novel, simple measure that characterizes the relationship of each neuron to a larger population, explaining seemingly complex network firing patterns in terms of basic circuit variables.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4449271/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4449271/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Okun, Michael -- Steinmetz, Nicholas A -- Cossell, Lee -- Iacaruso, M Florencia -- Ko, Ho -- Bartho, Peter -- Moore, Tirin -- Hofer, Sonja B -- Mrsic-Flogel, Thomas D -- Carandini, Matteo -- Harris, Kenneth D -- 095668/Wellcome Trust/United Kingdom -- 095669/Wellcome Trust/United Kingdom -- 095853/Wellcome Trust/United Kingdom -- EY014924/EY/NEI NIH HHS/ -- R01 EY014924/EY/NEI NIH HHS/ -- T32 MH020016/MH/NIMH NIH HHS/ -- Howard Hughes Medical Institute/ -- Medical Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- England -- Nature. 2015 May 28;521(7553):511-5. doi: 10.1038/nature14273. Epub 2015 Apr 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] UCL Institute of Neurology, University College London, London WC1N 3BG, UK [2] Department of Neuroscience, Physiology and Pharmacology, University College London, London WC1E 6DE, UK [3] UCL Institute of Ophthalmology, University College London, London EC1V 9EL, UK. ; 1] UCL Institute of Neurology, University College London, London WC1N 3BG, UK [2] Department of Neuroscience, Physiology and Pharmacology, University College London, London WC1E 6DE, UK [3] UCL Institute of Ophthalmology, University College London, London EC1V 9EL, UK [4] Howard Hughes Medical Institute and Department of Neurobiology, Stanford University, Stanford, California 94305-5125, USA. ; 1] Department of Neuroscience, Physiology and Pharmacology, University College London, London WC1E 6DE, UK [2] Biozentrum, University of Basel, Klingelbergstrasse 50/70, CH-4056 Basel, Switzerland. ; Department of Neuroscience, Physiology and Pharmacology, University College London, London WC1E 6DE, UK. ; Center for Molecular and Behavioral Neuroscience, Rutgers University, 197 University Avenue, Newark, New Jersey 07102, USA. ; Howard Hughes Medical Institute and Department of Neurobiology, Stanford University, Stanford, California 94305-5125, USA. ; UCL Institute of Ophthalmology, University College London, London EC1V 9EL, UK. ; 1] UCL Institute of Neurology, University College London, London WC1N 3BG, UK [2] Department of Neuroscience, Physiology and Pharmacology, University College London, London WC1E 6DE, UK [3] Center for Molecular and Behavioral Neuroscience, Rutgers University, 197 University Avenue, Newark, New Jersey 07102, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25849776" target="_blank"〉PubMed〈/a〉

Beschreibung: Aberrant expression of RNA-binding proteins has profound implications for cellular physiology and the pathogenesis of human diseases such as cancer. We previously identified the Fragile X-Related 1 gene (FXR1) as one amplified candidate driver gene at 3q26-29 in lung squamous cell carcinoma (SCC). FXR1 is an autosomal paralog of Fragile...

Beschreibung: A complete analysis of strain tolerance in a stretchable transparent conductor (TC) should include tracking of both electrical conductivity and transparency during strain; however, transparency is generally neglected in contemporary analyses. In this paper, we describe an apparatus that tracks both parameters while TCs of arbitrary composition are deformed under stretching-mode strain. We demonstrate the tool by recording the electrical resistance and light transmission spectra for indium tin oxide-coated plastic substrates under both linearly increasing strain and complex cyclic strain processes. The optics are sensitive across the visible spectrum and into the near-infrared region (∼400-900 nm), and without specifically optimizing for sampling speed, we achieve a time resolution of ∼200 ms. In our automated analysis routine, we include a calculation of a common TC figure of merit (FOM), and because solar cell electrodes represent a key TC application, we also weigh both our transparency and FOM results against the solar power spectrum to determine “solar transparency” and “solar FOM.” Finally, we demonstrate how the apparatus may be adapted to measure the basic performance metrics for complete solar cells under uniaxial strain.

Beschreibung: Multidrug resistance, strong side effects, and compliance problems in TB chemotherapy mandate new ways to kill Mycobacterium tuberculosis (Mtb). Here we show that deletion of the gene encoding homoserine transacetylase (metA) inactivates methionine and S-adenosylmethionine (SAM) biosynthesis in Mtb and renders this pathogen exquisitely sensitive to killing in immunocompetent or...