bluuebunny/crossref_metadata_2025_split huggingface dataset:
Large scale and significant expression from pseudogenes in Sodalis glossinidius - a facultative bacterial endosymbiont
Authors: Goodhead Ian , Blow Frances , Brownridge Philip , Hughes Margaret , Kenny John , Krishna Ritesh , McLean Lynn , Pongchaikul Pisut , Beynon Rob , Darby Alistair C. 
Published: July 2017

AbstractThe majority of bacterial genomes have high coding efficiencies, but there are some genomes of intracellular bacteria that have low gene density. The genome of the endosymbiont Sodalis glossinidius contains almost 50% pseudogenes containing mutations that putatively silence them at the genomic level. We have applied multiple ‘omic strategies, combining: Illumina and Pacific Biosciences Single-Molecule Real Time DNA-sequencing and annotation; stranded RNA-sequencing; and proteome analysis to better understand the transcriptional and translational landscape of Sodalis pseudogenes, and potential mechanisms for their control. Between 53% and 74% of the Sodalis transcriptome remains active in cell-free culture. Mean sense transcription from Coding Domain Sequences (CDS) is four-times greater than that from pseudogenes. Comparative genomic analysis of six Illumina-sequenced Sodalis isolates from different host Glossina species shows pseudogenes make up ~40% of the 2,729 genes in the core genome, suggesting that they are stable and/or Sodalis is a recent introduction across the Glossina genus as a facultative symbiont. These data further shed light on the importance of transcriptional and translational control in deciphering host-microbe interactions. The combination of genomics, transcriptomics and proteomics give a multidimensional perspective for studying prokaryotic genomes with a view to elucidating evolutionary adaptation to novel environmental niches.ImportanceBacterial genes are generally 1Kb in length, organized efficiently (i.e. with few gaps between genes or operons), and few open reading frames (ORFs) lack any predicted function. Intracellular bacteria have been removed from extracellular selection pressures acting on pathways of declining importance to fitness and thus, these bacteria tend to delete redundant genes in favour of smaller functional repertoires. In the genomes of endosymbionts with a recent evolutionary relationship with their host, however, this process of genome reduction is not complete; Genes and pathways may be at an intermediate stage, undergoing mutation linked to reduced selection and small population numbers being vertically transmitted from mother to offspring in their hosts, resulting in an increase in abundance of pseudogenes and reduced coding capacities. A greater knowledge of the genomic architecture of persistent pseudogenes, with respect to their DNA structure, mRNA transcription and even putative translation to protein products, will lead to a better understanding of the evolutionary trajectory of endosymbiont genomes, many of which have important roles in arthropod ecology.
Structural covariance networks are coupled to expression of genes enriched in supragranular layers of the human cortex
Authors: Romero-Garcia Rafael , Whitaker Kirstie J , Váša František , Seidlitz Jakob , Shinn Maxwell , Fonagy Peter , Dolan Raymond J , Jones Peter B , Goodyer Ian M ,   the NSPN Consortium, Bullmore Edward T , Vértes Petra E 
Published: July 2017

ABSTRACTComplex network topology is characteristic of many biological systems, including anatomical and functional brain networks (connectomes). Here, we first constructed a structural covariance network (SCN) from MRI measures of cortical thickness on 296 healthy volunteers, aged 14-24 years. Next, we designed a new algorithm for matching sample locations from the Allen Brain Atlas to the nodes of the SCN. Subsequently we use this to define, transcriptomic brain networks (TBN) by estimating gene co-expression between pairs of cortical regions. Finally, we explore the hypothesis that TBN and the SCN are coupled.TBN and SCN were correlated across connection weights and showed qualitatively similar complex topological properties. There were differences between networks in degree and distance distributions. However, cortical areas connected to each other within modules of the SCN network had significantly higher levels of whole genome co-expression than expected by chance.Nodes connected in the SCN had significantly higher levels of expression and co-expression of a Human Supragranular Enriched (HSE) gene set that are known to be important for large-scale cortico-cortical connectivity. This coupling of brain transcriptome and connectome topologies was largely but not completely related to the common constraint of physical distance on both networks.
A real-time compression library for microscopy images
Authors: Balázs Bálint , Deschamps Joran , Albert Marvin , Ries Jonas , Hufnagel Lars 
Published: July 2017

AbstractFluorescence imaging techniques such as single molecule localization microscopy, high-content screening and light-sheet microscopy are producing ever-larger datasets, which poses increasing challenges in data handling and data sharing. Here, we introduce a real-time compression library that allows for very fast (beyond 1 GB/s) compression and de-compression of microscopy datasets during acquisition. In addition to an efficient lossless mode, our algorithm also includes a lossy option, which limits pixel deviations to the intrinsic noise level of the image and yields compression ratio of up to 100-fold. We present a detailed performance analysis of the different compression modes for various biological samples and imaging modalities.
Coat color allele and mtDNA haplotype distributions in Russian cat populations: a citizen-science research
Authors: Zaytseva Olga O. , Tsepilov Yakov A. , Yudayeva Ekaterina S. , Kasianov Artem , Kulakovskiy Ivan V. , Logacheva Maria , Belayeva Daria , Gracheva Anna A. , Homenko Ksenia , Knyazeva Anastasia , Kolesnikova Ekaterina , Nikolayeva Daria , Bevova Mariana R. , Borodin Pavel M. , Aulchenko Yurii S. 
Published: July 2017

AbstractThis work has started as a project for the summer school in molecular and theoretical biology. Efficient teaching and learning modern methods of molecular biology and population genetics in a two-week study course for high school students needs an attractive subject. We chose phylogeography of the domestic cat as the subject of our project because 1) everybody likes cats; 2) cats are polymorphic for several coat color mutations, which can be easily detected by street survey or in the photographs; 3) samples for DNA extraction are easy to collect without posing ethical and biosafety problems; 4) rich background information of geographical distribution of coat color alleles and variation in mtDNA is available; 5) phylogeography of cat population in Russia is poorly studied and therefore new data collected in this large territory may shed a light on the global cat distribution and on the origin of the fancy breeds.During the project students studied coat color and mitotype distribution across Russian random bred cats. The basics of field (observations of natural cat populations, hair collection), formal (inheritance of coat colors), mathematical population (allele frequency distributions and their comparisons, building phylogenetic trees, multidimensional scaling), and molecular (DNA extraction and amplification, quality control of DNA sequencing data) genetics were covered.We scored coat color phenotypes in 1182 cats and sequenced mtDNA control region from hair samples of 38 cats from 18 geographical sites. Analysis of coat color alleles frequencies and mitotype distribution confirmed relative homogeneity of gene pools of Russian cat populations, indicating their recent origin. We found several unique mitotypes and demonstrated that OL1 mitotype, previously found only in Siberian fancy breed, was present in random bred cats from several Russian cities. This contributes to the discussion on the origin of the Siberian breed of cats, and supports the view that Siberians is a recent breed created in the 1980s by breeding of selected representatives of the random bred population.
Differential epigenetic landscapes and transcription factors explain X-linked gene behaviours during X-chromosome reactivation in the mouse inner cell mass
Authors: Borensztein Maud , Okamoto Ikuhiro , Syx Laurène , Guilbaud Guillaume , Picard Christel , Ancelin Katia , Galupa Rafael , Diabangouaya Patricia , Servant Nicolas , Barillot Emmanuel , Surani Azim , Saitou Mitinori , Chen Chong-Jian , Anastassiadis Konstantinos , Heard Edith 
Published: July 2017

AbstractX-chromosome inactivation (XCI) is established in two waves during mouse development. First, silencing of the paternal X chromosome (Xp) is triggered, with transcriptional repression of most genes and enrichment of epigenetic marks such as H3K27me3 being achieved in all cells by the early blastocyst stage. XCI is then reversed in the inner cell mass (ICM), followed by a second wave of maternal or paternal XCI, in the embryo-proper. Although the role of Xist RNA in triggering XCI is now clear, the mechanisms underlying Xp reactivation in the inner cell mass have remained enigmatic. Here we usein vivosingle cell approaches (allele-specific RNAseq, nascent RNA FISH and immunofluorescence) and find that different genes show very different timing of reactivation. We observe that the genes reactivate at different stages and that initial enrichment in H3K27me3 anti-correlates with the speed of reactivation. To define whether this repressive histone mark is lost actively or passively, we investigate embryos mutant for the X-encoded H3K27me3 demethylase, UTX. Xp genes that normally reactivate slowly are retarded in their reactivation inUtxmutants, while those that reactive rapidly are unaffected. Therefore, efficient reprogramming of some X-linked genes in the inner cell mass is very rapid, indicating minimal epigenetic memory and potentially driven by transcription factors, whereas others may require active erasure of chromatin marks such as H3K27me3.
Modeling cell-substrate de-adhesion dynamics under fluid shear
Authors: Maan Renu , Rani Garima , Menon Gautam I. , Pullarkat Pramod A. 
Published: July 2017

AbstractChanges in cell-substrate adhesion are believed to signal the onset of cancer metastasis, but such changes must be quantified against background levels of intrinsic heterogeneity between cells. Variations in cell-substrate adhesion strengths can be probed through biophysical measurements of cell detachment from substrates upon the application of an external force. Here, we investigate, theoretically and experimentally, the detachment of cells adhered to substrates when these cells are subjected to fluid shear. We present a theoretical framework within which we calculate the fraction of detached cells as a function of shear stress for fast ramps as well as for the decay in the fraction of detached cells at fixed shear stress as a function of time. Using HEK and 3T3 fibroblast cells as experimental model systems, we extract characteristic force scales for cell adhesion as well as characteristic detachment times. We estimate force-scales of ~ 500pNassociated to a single focal contact, and characteristic time-scales of 190 ≤τ≤ 350s representing cell-spread-area dependent mean first passage times to the detached state at intermediate values of the shear stress. Variations in adhesion across cell types are especially prominent when cell detachment is probed by applying a time-varying shear stress. These methods can be applied to characterizing changes in cell adhesion in a variety of contexts, including metastasis.
Loss of CHIP Expression Perturbs Glucose Homeostasis and Leads to Type II Diabetes through Defects in Microtubule Polymerization and Glucose Transporter Localization
Authors: McDonough Holly , Lenhart Kaitlin C. , Ronnebaum Sarah M. , Zhang Chunlian , An Jie , Portbury Andrea , Newgard Christopher B. , Willis Monte S. , Patterson Cam , Schisler Jonathan C. 
Published: July 2017

ABSTRACTRecent evidence has implicated CHIP (carboxyl terminus of Hsc/Hsp70-interacting protein), a co-chaperone and ubiquitin ligase, in the functional support of several metabolism-related proteins, including AMPK and SirT6. In addition to previously reported aging and stress intolerance phenotypes, we find that CHIP-/-mice also demonstrate a Type II diabetes-like phenotype, including poor glucose tolerance, decreased sensitivity to insulin, and decreased insulin-stimulated glucose uptake in isolated skeletal muscle, characteristic of insulin resistance. In CHIP-deficient cells, glucose stimulation fails to induce translocation of Glut4 to the plasma membrane. This impairment in Glut4 translocation in CHIP-deficient cells is accompanied by decreased tubulin polymerization associated with decreased phosphorylation of stathmin, a microtubule-associated protein required for polymerization-dependent protein trafficking within the cell. Together, these data describe a novel role for CHIP in regulating microtubule polymerization that assists in glucose transporter translocation, promoting whole-body glucose homeostasis and sensitivity to insulin.
Predicting eye movements from deep neural network activity decoded from fMRI responses to natural scenes
Authors: O’Connell Thomas P. , Chun Marvin M. 
Published: July 2017

ABSTRACTComputational models of selective spatial attention can reliably predict eye movements to complex images. However, researchers lack a simple way to measure covert representations of spatial attention in the brain and their link to overt eye movement behavior, especially in response to natural scenes. Here, we predict eye movement patterns from spatial priority maps reconstructed from brain activity measured with functional magnetic resonance imaging (fMRI). First, we define a computational spatial attention model using a deep convolutional neural network (CNN) pre-trained for scene categorization. Next, we decode CNN unit activity from fMRI activity and reconstruct spatial priority maps by applying our computational spatial attention model to decoded CNN activity. Finally, we predict eye movements in a subsequent behavioral experiment within and between individuals using reconstructed spatial priority maps. These results demonstrate that features represented in CNN unit activity can guide spatial attention and eye movements, providing a crucial link between CNN models, brain activity, and behavior.
Dramatic expansion of microbial groups that shape the global sulfur cycle
Authors: Anantharaman Karthik , Jungbluth Sean P. , Kantor Rose S. , Lavy Adi , Warren Lesley A. , Rappé Michael S. , Thomas Brian C. , Banfield Jillian F. 
Published: July 2017

AbstractThe biogeochemical cycle of sulfur on Earth is driven by microbial sulfate reduction, yet organisms from relatively few lineages have been implicated in this process. Recent studies using functional marker genes have detected abundant, novel dissimilatory sulfite reductases that confer the capacity for microbial sulfate reduction and could do not be affiliated with known organisms. Thus, the identity of a significant fraction of sulfate reducing microbes has remained elusive. Here we report the discovery of the capacity for sulfate reduction in the genomes of organisms from twelve bacterial and archaeal phyla, thereby doubling the number of microbial phyla associated with this process. Eight of the twelve newly identified groups are candidate phyla that lack isolated representatives, a finding only possible given genomes from metagenomes. Two candidate phyla,CandidatusRokubacteria andCandidatusHydrothermarchaeota contain the earliest evolved genes. The capacity for sulfate reduction has been laterally transferred in multiple events within some phyla, and a key gene potentially capable of switching sulfur oxidation to sulfate reduction in associated cells has been acquired by putatively symbiotic bacteria. We conclude that functional predictions based on phylogeny will significantly underestimate the extent of sulfate reduction across Earth’s ecosystems. Understanding the prevalence of this capacity is integral to interpreting the carbon cycle because sulfate reduction is often coupled to turnover of buried organic carbon. Our findings expand the diversity of microbial groups associated with sulfur transformations in the environment and motivate revision of biogeochemical process models based on microbial community composition.
Time-gated detection of protein-protein interactions with transcriptional readout
Authors: Kim Min Woo , Wang Wenjing , Sanchez Mateo I. , Coukos Robert , Zastrow Mark Von , Ting Alice Y. 
Published: July 2017

AbstractTranscriptional assays such as yeast two hybrid, split ubiquitin, and Tango that convert transient protein-protein interactions (PPIs) in cells into stable expression of transgenes are powerful tools for PPI discovery, high-throughput screens, and analysis of large cell populations. However, these assays frequently suffer from high background and they lose all information about PPI dynamics. To address these limitations, we developed a light-gated transcriptional assay for PPI detection called PPI-FLARE (PPI-Fast Light- and Activity-Regulated Expression). PPI-FLARE requiresbotha PPI to deliver TEV protease proximal to its cleavage peptide,andexternally-applied blue light to uncage the cleavage peptide, in order to release a membrane-tethered transcription factor (TF) for translocation to the nucleus. We used PPI-FLARE to detect the ligand-induced association of 12 different PPIs in living mammalian cells, with a temporal resolution of 5 minutes and a ±ligand signal ratio up to 37. By systematically shifting the light irradiation window, we could reconstruct PPI time-courses, distinguishing between GPCRs that engage in transient versus sustained interactions with the cytosolic effector arrestin. When combined with FACS, PPI-FLARE enabled >100-fold enrichment of cells experiencing a specific GPCR-arrestin PPI during a short 10-minute light window over cells missing that PPI during the same time window. Due to its high specificity, sensitivity, and generality, PPI-FLARE should be a broadly useful tool for PPI analysis and discovery.
Frank-Starling Mechanism and Short-Term Adjustment of Cardiac Flow
Authors: Chaui-Berlinck José Guilherme , Monteiro Luiz Henrique Alves 
Published: July 2017

AbstractThe Frank-Starling Law of the heart is a filling-force mechanism, a positive relationship between the distension of a ventricular chamber and its force of ejection. The functioning of the cardiovascular system is usually described by means of two intersecting curves: the cardiac and vascular functions, the former related to the contractility of the heart and the latter related to the after-load imposed to the ventricle. The crossing of these functions is the so-called operation point, and the filling-force mechanism is supposed to play a stabilizing role for the short-term variations in the working of the system. In the present study, we analyze whether the filling-force mechanism is responsible for such a stability within two different settings: one-ventricle, as in fishes, and two-ventricle hearts, as in birds and mammals. Each setting was analyzed under two scenarios: presence of the filling-force mechanism and its absence. To approach the query, we linearized the region around an arbitrary operation point and put forward a dynamical system of differential equations to describe the relationship among volumes of ventricular chambers and volumes of vascular beds in face of blood flows governed by pressure differences between adjacent compartments. Our results show that the filling-force mechanism is not necessary to give stability to an operation point. The results indicate that the role of the filling-force mechanism is related to decrease the controlling effort over the circulatory system, to smooth out perturbations and to guarantee faster transitions among operation points.Summary StatementWe address the role of the Frank-Starling mechanism and show that it has no role in the stability of the circulatory system. Rather, it accounts for decreasing the controlling effort and speeding up changes in cardiac output.
ISG15 induces IL-10 production in human monocytes and is a biomarker of disease severity during active tuberculosis
Authors: dos Santos Paula Fernandes , Van Weyenbergh Johan , Delgobo Murilo , de Oliveira Patricio Daniel , Ferguson Brian J. , Guabiraba Rodrigo , Dierckx Tim , Menezes Soraya Maria , Báfica André , Mansur Daniel Santos 
Published: July 2017

AbstractInterferon stimulated gene 15 (ISG15) deficiency in humans leads to severe interferonopathies and mycobacterial disease, the latter being previously attributed to its extracellular cytokine-like activity. Here, we demonstrate a novel role for secreted ISG15 as an IL-10 inducer, unique to primary human monocytes. Employingex vivosystems analysis of human transcriptome datasets, we observed a significant correlation of ISG15-induced monocyte IL-10 and lymphocyte IFNγ expression. This effect was associated with p38 MAPK and PI3K signalling in healthy volunteers. The specificity and MAPK/PI3K-dependence of ISG15-induced monocyte IL-10 production was confirmedin vitrousing CRISPR/Cas9 knockout and pharmacological inhibitors. Moreover, thisISG15/IL10axis was amplified in leprosy but disrupted in human active tuberculosis (TB) patients. Importantly, ISG15 strongly correlated with inflammation and disease severity during active TB. In conclusion, this study identifies a novel anti-inflammatory ISG15/IL-10 myeloid axis that is disrupted in active TB, revealing a potential biomarker for disease severity in this major human disease.
Automated analysis of internally programmed grooming behavior inDrosophilausing ak-nearest neighbors classifier
Authors: Qiao Bing , Li Chiyuan , Allen Victoria W. , Shirasu-Hiza Mimi M. , Syed Sheyum 
Published: July 2017

AbstractDespite being pervasive, the control of programmed grooming is poorly understood. We have addressed this gap in knowledge by developing a high-throughput platform that allows long-term detection of grooming in the fruit flyDrosophila melanogaster. Automatic classification of daily behavior shows flies spend 30% of their active time grooming. We show that a large proportion of this behavior is driven by two major internal programs. One of these programs is the circadian clock that modulates rhythms in daily grooming. The second program depends oncycleandclockand regulates the amount of time flies spend grooming. This emerging dual control model of programmed grooming in which one regulator controls the timing and another controls the duration, resembles the well-established two-process regulatory model of fly sleep. Together, our quantitative approach inDrosophilahas revealed that grooming is an important internally driven behavior under the control of two regulatory programs.