bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome Wide Association Scan identifies new variants associated with a cognitive predictor of dyslexia
Authors: Gialluisi Alessandro , Andlauer Till F M , Mirza-Schreiber Nazanin , Moll Kristina , Hoffmann Per , Ludwig Kerstin U , Czamara Darina , Francks Clyde , St Pourcain Beate , Brandler William , Honbolygó Ferenc , Tóth Dénes , Csépe Valéria , Huguet Guillaume , Morris Andrew P , Hulslander Jacqueline , Willcutt Erik G , DeFries John C , Olson Richard K , Smith Shelley D , Pennington Bruce F , Vaessen Anniek , Maurer Urs , Lyytinen Heikki , Peyrard-Janvid Myriam , Leppänen Paavo H T , Brandeis Daniel , Bonte Milene , Stein John F , Talcott Joel B , Fauchereau Fabien , Bourgeron Thomas , Monaco Anthony P , Ramus Franck , Landerl Karin , Kere Juha , Scerri Thomas S , Paracchini Silvia , Fisher Simon E , Schumacher Johannes , Nöthen Markus M , Müller-Myhsok Bertram , Schulte-Körne Gerd 
Published: May 2018

AbstractDevelopmental dyslexia (DD) is one of the most prevalent learning disorders among children and is characterized by deficits in different cognitive skills, including reading, spelling, short term memory and others. To help unravel the genetic basis of these skills, we conducted a Genome Wide Association Study (GWAS), including nine cohorts of reading-impaired and typically developing children of European ancestry, recruited across different countries (N=2,562-3,468).We observed a genome-wide significant effect (p<1×10−8) on rapid automatized naming of letters (RANlet) for variants on 18q12.2 withinMIR924HG (micro-RNA 924 host gene;p= 4.73×10−9), and a suggestive association on 8q12.3 withinNKAIN3(encoding a cation transporter;p= 2.25 ×10−8). RAN represents one of the best universal predictors of reading fluency across orthographies and linkage to RAN has been previously reported withinCELF4(18q12.2), a gene highly expressed in the fetal brain which is co-expressed withNKAIN3and predicted to be a target ofMIR924. These findings suggest new candidate DD susceptibility genes and provide insights into the genetics and neurobiology of dyslexia.
Supporting global biodiversity assessment through high-resolution macroecological modelling: Methodological underpinnings of the BILBI framework
Authors: Hoskins Andrew J , Harwood Thomas D , Ware Chris , Williams Kristen J , Perry Justin J , Ota Noboru , Croft Jim R , Yeates David K , Jetz Walter , Golebiewski Maciej , Purvis Andy , Robertson Tim , Ferrier Simon 
Published: May 2018

ABSTRACTAimGlobal indicators of change in the state of terrestrial biodiversity are often derived by intersecting observed or projected changes in the distribution of habitat transformation, or of protected areas, with underlying patterns in the distribution of biodiversity. However the two main sources of data used to account for biodiversity patterns in such assessments – i.e. ecoregional boundaries, and vertebrate species ranges – are typically delineated at a much coarser resolution than the spatial grain of key ecological processes shaping both land-use and biological distributions at landscape scale. Species distribution modelling provides one widely used means of refining the resolution of mapped species distributions, but is limited to a subset of species which is biased both taxonomically and geographically, with some regions of the world lacking adequate data to generate reliable models even for better-known biological groups.InnovationMacroecological modelling of collective properties of biodiversity (e.g. alpha and beta diversity) as a correlative function of environmental predictors offers an alternative, yet highly complementary, approach to refining the spatial resolution with which patterns in the distribution of biodiversity can be mapped across our planet. Here we introduce a new capability – BILBI (the Biogeographic Infrastructure for Large-scaled Biodiversity Indicators) – which has implemented this approach by integrating advances in macroecological modelling, biodiversity informatics, remote sensing and high-performance computing to assess spatial-temporal change in biodiversity at ~1km grid resolution across the entire terrestrial surface of the planet. The initial implementation of this infrastructure focuses on modelling beta-diversity patterns using a novel extension of generalised dissimilarity modelling (GDM) designed to extract maximum value from sparsely and unevenly distributed occurrence records for over 400,000 species of plants, invertebrates and vertebrates.Main conclusionsModels generated by BILBI greatly refine the mapping of beta-diversity patterns relative to more traditional biodiversity surrogates such as ecoregions. This capability is already proving of considerable value in informing global biodiversity assessment through: 1) generation of indicators of past-to-present change in biodiversity based on observed changes in habitat condition and protected-area coverage; and 2) projection of potential future change in biodiversity as a consequence of alternative scenarios of global change in drivers and policy options.
Short-term effectiveness of HIV care coordination among persons with recent HIV diagnosis or history of poor HIV outcomes
Authors: Nash Denis , Robertson McKaylee M. , Penrose Kate , Chamberlin Stephanie , Robbins Rebekkah S. , Braunstein Sarah L. , Myers Julie E. , Abraham Bisrat , Kulkarni Sarah , Waldron Levi , Levin Bruce , Irvine Mary K. 
Published: May 2018

AbstractThe New York City HIV Care Coordination Program (CCP) combines multiple evidence-based strategies to support persons living with HIV (PLWH) at risk for, or with a recent history of, poor HIV outcomes. We assessed the comparative effectiveness of the CCP by merging programmatic data on CCP clients with population-based surveillance data on all New York City PLWH. A non-CCP comparison group of similar PLWH who met CCP eligibility criteria was identified using surveillance data. The CCP and non-CCP groups were matched on propensity for CCP enrollment within four baseline treatment status groups (newly diagnosed or previously diagnosed and either consistently unsuppressed, inconsistently suppressed or consistently suppressed). We compared CCP to non-CCP proportions with viral load suppression at 12-month follow-up. Among the 13,624 persons included, 15·3% were newly diagnosed; among the 84·7% previously diagnosed, 14·2% were consistently suppressed, 28·9% were inconsistently suppressed, and 41 ·6% were consistently unsuppressed in the year prior to baseline. At 12-month follow-up, 59·9% of CCP and 53·9% of non-CCP participants had viral load suppression (Relative Risk=1.11, 95%CI:1.08-1.14). Among those newly diagnosed and those consistently unsuppressed at baseline, the relative risk of viral load suppression in the CCP versus non-CCP participants was 1.15 (95%CI:1.09-1.23) and 1.32 (95%CI:1.23-1.42), respectively. CCP exposure shows benefits over no CCP exposure for persons newly diagnosed or consistently unsuppressed, but not for persons suppressed in the year prior to baseline. We recommend more targeted case finding for CCP enrollment and increased attention to viral load suppression maintenance.
Structural basis for transfer RNA mimicry by a bacterial Y RNA
Authors: Wang Wei , Chen Xinguo , Wolin Sandra L. , Xiong Yong 
Published: May 2018

SUMMARYNoncoding Y RNAs are present in both animal cells and many bacteria. In all species examined, Y RNAs tether the Ro60 protein to an effector protein to perform various cellular functions. For example, in the bacteriumDeinococcus radiodurans, Y RNA tethers Ro60 to the exoribonuclease polynucleotide phosphorylase, specializing this nuclease for structured RNA degradation. Recently, a new Y RNA subfamily was identified in bacteria. Bioinformatic analyses of these YrlA (Y RNA-like A) RNAs predict that the effector-binding domain resembles tRNA. We present the structure of this domain, the overall folding of which is strikingly similar to canonical tRNAs. The tertiary interactions that are responsible for stabilizing tRNA are present in YrlA, making it a close tRNA mimic. However, YrlA lacks a free CCA end and contains a kink in the stem corresponding to the anticodon stem. Since nucleotides in the D and T stems are conserved among YrlAs, they may be an interaction site for an unknown factor. Our experiments identify YrlA RNAs as a new class of tRNA mimics.
Broom: Application for non-redundant storage of High Throughput Sequencing data
Authors: Albayrak Levent , Khanipov Kamil , Golovko George , Fofanov Yuriy 
Published: May 2018

AbstractMotivationThe data generation capabilities of High Throughput Sequencing (HTS) instruments have exponentially increased over the last few years, while the cost of sequencing has dramatically decreased allowing this technology to become widely used in biomedical studies. For small labs and individual researchers, however, storage and transfer of large amounts of HTS data present a significant challenge. The recent trends in increased sequencing quality and genome coverage can be used to reconsider HTS data storage strategies.ResultsWe present Broom, a stand-alone application designed to select and store only high-quality sequencing reads at extremely high compression rates. Written in C++, the application accepts single and paired-end reads in FASTQ and FASTA formats and decompresses data in FASTA format.AvailabilityC++ code available at https://scsb.utmb.edu/labgroups/fofanov/broom.aspContactlealbayr@utmb.edu
Germline genetic variants associated with leukocyte-genes predict tumor recurrence in breast cancer patients
Authors: Milanese Jean-Sébastien , Tibiche Chabane , Zou Jinfeng , Meng Zhi Gang , Nantel Andre , Drouin Simon , Marcotte Richard , Wang Edwin 
Published: May 2018

AbstractGermline genetic variants such as BRCA1/2 play an important role in tumorigenesis and clinical outcomes of cancer patients. However, only a small fraction (i.e., 5-10%) of inherited variants has been associated with clinical outcomes (e.g., BRCA1/2, APC, TP53, PTEN and so on). The challenge remains in using these inherited germline variants to predict clinical outcomes of cancer patient population. In an attempt to solve this issue, we applied our recently developed algorithm, eTumorMetastasis, which constructs predictive models, on exome sequencing data to ER+ breast (n=755) cancer patients. Gene signatures derived from the genes containing functionally germline genetic variants significantly distinguished recurred and non-recurred patients in two ER+ breast cancer independent cohorts (n=200 and 295, P=1.4×10−3). Furthermore, we found that recurred patients possessed a higher rate of germline genetic variants. In addition, the inherited germline variants from these gene signatures were predominately enriched in T cell function, antigen presentation and cytokine interactions, likely impairing the adaptive and innate immune response thus favoring a pro-tumorigenic environment. Hence, germline genomic information could be used for developing non-invasive genomic tests for predicting patients’ outcomes (or drug response) in breast cancer, other cancer types and even other complex diseases.
Pollen metabarcoding as a tool for tracking long-distance insect migrations
Authors: Suchan Tomasz , Talavera Gerard , Sáez Llorenç , Ronikier Michał , Vila Roger 
Published: May 2018

AbstractInsects account for the main fraction of Earth’s biodiversity and are key players for ecosystems, notably as pollinators. While insect migration is suspected to represent a natural phenomenon of major importance, remarkably little is known about it, except for a few flagship species. The reason for this situation is mainly due to technical limitations in the study of insect movement. Here we propose using metabarcoding of pollen carried by insects as a method for tracking their migrations. We developed a flexible and simple protocol allowing high multiplexing and not requiring DNA extraction, one of the most time consuming part of metabarcoding protocols, and apply this method to the study of the longdistance migration of the butterflyVanessa cardui,an emerging model for insect migration. We collected 47 butterfly samples along the Mediterranean coast of Spain in spring and performed metabarcoding of pollen collected from their bodies to test for potential arrivals from the African continent. In total, we detected 157 plant species from 23 orders, most of which (82.8%) were insect-pollinated. African or African-Arabian endemic taxa contributed 21.0% of our dataset, strongly supporting the hypothesis that migratory butterflies colonize southern Europe from Africa in spring. Moreover, our data suggest that a northwards trans-Saharan migration in spring is plausible for early arrivals (February) into Europe, as shown by the presence of Saharan floristic elements. Our results demonstrate the possibility of regular insect-mediated transcontinental pollination, with potential implications for ecosystem functioning, agriculture and plant phylogeography. Despite current limitations, mostly regarding the availability of plant reference sequences and distribution data, the method proved to be useful and demonstrates great potential as plant genetic libraries and distribution datasets improve.
Simu-dependent clearance of dying cells regulates macrophage function and inflammation resolution
Authors: Roddie Hannah Grace , Armitage Emma Louise , Johnston Simon Andrew , Evans Iwan Robert 
Published: May 2018

AbstractMacrophages encounter and clear apoptotic cells during normal development and homeostasis, including at numerous sites of pathology. Clearance of apoptotic cells has been intensively studied, but the effects of macrophage-apoptotic cell interactions on macrophage behaviour are poorly understood. UsingDrosophilaembryos, we have exploited the ease of manipulating cell death and apoptotic cell clearance in this model to identify that the loss of the apoptotic cell clearance receptor Simu leads to perturbation of macrophage migration and inflammatory responses via pathological levels of apoptotic cells. Removal of apoptosis ameliorates these phenotypes, while acute induction of apoptosis phenocopies these defects and reveals that phagocytosis of apoptotic cells is not necessary for their anti-inflammatory action. Furthermore, Simu is necessary for clearance of necrotic debris and rentention of macrophages at wounds. Thus, Simu is a general detector of damaged self and represents a novel molecular player in controlling resolution of inflammation.
An image-based assay to quantify changes in proliferation and viability upon drug treatment in 3D microenvironments
Authors: Murali Vasanth S. , Chang Bo-Jui , Fiolka Reto , Danuser Gaudenz , Cobanoglu Murat Can , Welf Erik S. 
Published: May 2018

AbstractBackgroundEvery biological experiment requires a choice of throughput balanced against physiological relevance. Most primary drugs screens neglect critical parameters such as microenvironmental conditions, cell-cell heterogeneity, and specific readouts of cell fate for the sake of throughput.MethodsHere we describe a methodology to quantify proliferation and viability of single cells in 3D culture conditions by leveraging automated microscopy and image analysis to facilitate reliable and high-throughput measurements. We detail experimental conditions that can be adjusted to increase either throughput or robustness of the assay, and we provide a stand alone image analysis program for users who wish to implement this 3D drug screening assay in high throughput.ResultsWe demonstrate this approach by evaluating a combination of RAF and MEK inhibitors on melanoma cells, showing that cells cultured in 3D collagen-based matrices are more sensitive than cells grown in 2D culture, and that cell proliferation is much more sensitive than cell viability. We also find that cells grown in 3D cultured spheroids exhibit equivalent sensitivity to single cells grown in 3D collagen, suggesting that for the case of melanoma, a 3D single cell model may be equally effective for drug identification as 3D spheroids models. The single cell resolution of this approach enables stratification of heterogeneous populations of cells into differentially responsive subtypes upon drug treatment, which we demonstrate by determining the effect of RAK/MEK inhibition on melanoma cells co-cultured with fibroblasts. Furthermore, we show that spheroids grown from single cells exhibit dramatic heterogeneity to drug response, suggesting that heritable drug resistance can arise stochastically in single cells but be retained by subsequent generations.ConclusionIn summary, image-based analysis renders cell fate detection robust, sensitive, and high-throughput, enabling cell fate evaluation of single cells in more complex microenvironmental conditions.
Myosin-II activity generates a dynamic steady state with continuous actin turnover in a minimal actin cortex
Authors: Sonal  , Ganzinger Kristina A. , Vogel Sven K. , Mücksch Jonas , Blumhardt Philipp , Schwille Petra 
Published: May 2018

ABSTRACTDynamic reorganization of the actomyosin cytoskeleton allows a fine-tuning of cell shape that is vital to many cellular functions. It is well established that myosin-II motors generate the forces required for remodeling the cell surface by imparting contractility to actin networks. An additional, less understood, role of myosin-II in cytoskeletal dynamics is believed to be in the regulation of actin turnover; it has been proposed that myosin activity increases actin turnover in various cellular contexts, presumably by contributing to disassembly. In vitro reconstitution of actomyosin networks has confirmed the role of myosin in actin network disassembly, but factors such as diffusional constraints and the use of stabilized filaments have thus far limited the observation of myosin-assisted actin turnover in these networks. Here, we present the reconstitution of a minimal dynamic actin cortex where actin polymerization is catalyzed on the membrane in the presence of myosin-II activity. We demonstrate that myosin activity leads to disassembly and redistribution in this simplified cortex. Consequently, a new dynamic steady state emerges in which actin filaments undergo constant turnover. Our findings suggest a multi-faceted role of myosin-II in fast remodeling of the eukaryotic actin cortex.
Overcome Competitive Exclusion in Ecosystems
Authors: Wang Xin , Liu Yang-Yu 
Published: May 2018

AbstractExplaining biodiversity in nature is a fundamental problem in ecology. One great challenge is embodied in the so-called competitive exclusion principle1-4: the number of species in steady coexistence cannot exceed the number of resources4-7. In the past five decades, various mechanisms have been proposed to overcome the limit on diversity set by the competitive exclusion principle8-25. Yet, none of the existing mechanisms can generically overcome competitive exclusion at steady state4,26. Here we show that by forming chasing triplets in the predation process among the consumers and resources, the number of coexisting species of consumers can exceed that of resources at steady state, naturally breaking the competitive exclusion principle. Our model can be broadly applicable to explain the biodiversity of many consumer-resource ecosystems and deepen our understanding of biodiversity in nature.
Genomic and phenotypic divergence unveil microgeographic adaptation in the Amazonian hyperdominant tree Eperua falcata Aubl. (Fabaceae)
Authors: Brousseau Louise , Fine Paul V. A. , Dreyer Erwin , Vendramin Giovanni G. , Scotti Ivan 
Published: May 2018

AbstractPlant populations can undergo very localized adaptation, allowing widely distributed populations to adapt to divergent habitats in spite of recurrent gene flow. Neotropical trees - whose large and undisturbed populations often span a variety of environmental conditions and local habitats - are particularly good models to study this process. Here, we carried out a genome scan for selection through whole-genome sequencing of pools of populations, sampled according to a replicated sampling design, to evaluate microgeographic adaptation in the hyperdominant Amazonian tree Eperua falcata Aubl. (Fabaceae). A high-coverage genomic resource of ∼250 Mb was assembled de novo and annotated, leading to 32,789 predicted genes. 97,062 bi-allelic SNPs were detected over 25,803 contigs, and a custom Bayesian model was implemented to uncover candidate genomic targets of divergent selection. A set of 290 divergence outlier SNPs was detected at the regional scale (between study sites), while 185 SNPs located in the vicinity of 106 protein-coding genes were detected as replicated outliers between microhabitats within regions. Outlier genomic regions are involved in a variety of physiological processes, including plant responses to stress (e.g., oxidative stress, hypoxia and metal toxicity) and biotic interactions. Together with evidence suggesting microgeographic divergence in functional traits, the discovery of genomic targets of microgeographic adaptation in the Neotropics is consistent with the hypothesis that local adaptation is a key driver of ecological diversification, operating across multiple spatial scales, from large- (i.e. regional) to microgeographic- (i.e. landscape) scales.
Resolving the origins of membrane phospholipid biosynthesis genes using outgroupfree rooting
Authors: Coleman Gareth A. , Pancost Richard D. , Williams Tom A. 
Published: May 2018

AbstractOne of the key differences between Bacteria and Archaea are their canonical membrane phospholipids, which are synthesized by distinct biosynthetic pathways with non-homologous enzymes. This “lipid divide” has important implications for the early evolution of cells and the type of membrane phospholipids present in the last universal common ancestor (LUCA). One of the main challenges in studies of membrane evolution is that the key biosynthetic genes are ancient and their evolutionary histories are poorly resolved. This poses major challenges for traditional rooting methods because the only available outgroups are distantly related. Here, we address this issue by using the best available substitution models for single gene trees, by expanding our analyses to the diversity of uncultivated prokaryotes recently revealed by environmental genomics, and by using two complementary approaches to rooting that do not depend on outgroups. Consistent with some previous analyses, our rooted gene trees support extensive inter-domain horizontal transfer of membrane phospholipid biosynthetic genes, primarily from Archaea to Bacteria. They also suggest that the capacity to make archaeal-type membrane phospholipids was already present in LUCA.
Cis-activation in the Notch signaling pathway
Authors: Nandagopal Nagarajan , Santat Leah A. , Elowitz Michael B. 
Published: May 2018

AbstractThe Notch signaling pathway consists of transmembrane ligands and receptors that can interact both within the same cell (cis) and across cell boundaries (trans). Previous work has shown thatcis-interactions act to inhibit productive signaling. Here, by analyzing Notch activation in single cells while controlling cell density and ligand expression level, we show thatcis-ligands can in fact activate Notch receptors. Thiscis-activation process resemblestrans-activation in its ligand level dependence, susceptibility tocis-inhibition, and sensitivity to Fringe modification. Cis-activation occurred for multiple ligand-receptor pairs, in diverse cell types, and affected survival and differentiation in neural stem cells. Finally, mathematical modeling shows howcis-activation could potentially expand the capabilities of Notch signaling, for example enabling “negative” signaling. These results establishcis-activation as a prevalent mode of signaling in the Notch pathway, and should contribute to a more complete understanding of how Notch signaling functions in developmental, physiological, and biomedical contexts.