bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intermittent hypoxia promotes functional neuroprotection from retinal ischemia in untreated first-generation offspring
Authors: Harman Jarrod C. , Guidry Jessie J. , Gidday Jeffrey M. 
Published: February 2020

ABSTRACTEnvironmental stimuli can promote short- or long-lasting changes in phenotype through epigenetics. Under certain circumstances, induced phenotypes can be passed through the germline to subsequent generations, providing a novel mechanistic basis for disease heritability. In the present study, we tested the hypothesis that repetitively exposing parents to a nonharmful epigenetic stimulus can promote disease resilience in offspring. Male and female mice were mated following brief exposures to mild systemic hypoxia every other day for 16 weeks. Electroretinographic determinations of postischemic function in response to transient unilateral retinal ischemia in their 5-month-old F1 progeny revealed significant resilience to injury relative to animals derived from normoxic control parents. Mass spectrometry identified hundreds of differentially expressed proteins between protected and injured retinae; bioinformatic analyses of the pathways and networks these proteins comprise provided specific mechanistic insights into the molecular manifestation of this injury-resilient phenotype. Thus, epigenetics can modify heritability to promote disease resilience.
Model of ciprofloxacin subdiffusion inPseudomonas aeruginosabiofilm formed in artificial sputum medium
Authors: Kosztołowicz Tadeusz , Metzler Ralf , Wa̧sik Sławomir , Arabski Michał 
Published: February 2020

AbstractWe study theoretically and empirically ciprofioxacin antibiotic diffusion through a gel-like artificial sputum medium (ASM) mimicking physiological conditions typical for a cystic fibrosis layer, in which regions occupied byPseudomonas aeruginosabacteria are present. Our theoretical model is based on the subdiffusion-absorption equation with a fractional time derivative that describes molecules diffusion in a medium structured as Thompson’s plumpudding model; the pudding ‘background’ represents ASM and the plums represent the bacterial biofilm. We show that the process can be divided into three successive stages: (1) only antibiotic subdiffusion with constant biofilm parameters, (2) subdiffusion and absorption of antibiotic molecules with variable biofilm parameters, (3) subdiffusion and absorption in the medium but biofilm parameters are constant. Stage 2 is interpreted as the appearance of an intensive defence bulid-up of bacteria against the action of an antibiotic, in the stage 3 it is likely that the bacteria have been inactivated. Times at which stages change are determined from the experimentally obtained temporal evolution of the amount of substance that has diffused through the ASM with bacteria. Our analysis shows good agreement between experimental and our theoretical results.
Natural selection influenced the genetic architecture of brain structure, behavioral and neuropsychiatric traits
Authors: Wendt Frank R , Pathak Gita A , Overstreet Cassie , Tylee Daniel S , Gelernter Joel , Atkinson Elizabeth G , Polimanti Renato 
Published: February 2020

AbstractNatural selection has shaped the phenotypic characteristics of human populations. Genome-wide association studies (GWAS) have elucidated contributions of thousands of common variants with small effects on an individual’s predisposition to complex traits (polygenicity), as well as wide-spread sharing of risk alleles across traits in the human phenome (pleiotropy). It remains unclear how the pervasive effects of natural selection influence polygenicity in brain-related traits. We investigate these effects by annotating the genome with measures of background (BGS) and positive selection, indications of Neanderthal introgression, measures of functional significance including loss-of-function (LoF) intolerant and genic regions, and genotype networks in 75 brain-related traits. Evidence of natural selection was determined using binary annotations of top 2%, 1%, and 0.5% of selection scores genome-wide. We detected enrichment (q<0.05) of SNP-heritability at loci with elevated BGS (7 phenotypes) and in genic (34 phenotypes) and LoF-intolerant regions (67 phenotypes). BGS (top 2%) significantly predicted effect size variance for trait-associated loci (σ2parameter) in 75 brain-related traits (β=4.39×10−5,p=1.43×10−5, modelr2=0.548). By including the number of DSM-5 diagnostic combinations per psychiatric disorder, we substantially improved model fit (σ2~ BTop2%× Genic × diagnostic combinations; modelr2=0.661). We show that GWAS with larger variance in risk locus effect sizes are collectively predicted by the effects of loci under strong BGS and in regulatory regions of the genome. We further show that diagnostic complexity exacerbates this relationship and perhaps dampens the ability to detect psychiatric risk loci.
The cue-reactivity paradigm: An ensemble of networks driving attention and cognition when viewing drug and natural reward-related stimuli
Authors: Hill-Bowen Lauren D. , Riedel Michael C. , Poudel Ranjita , Salo Taylor , Flannery Jessica S. , Camilleri Julia A. , Eickhoff Simon B. , Laird Angela R. , Sutherland Matthew T. 
Published: February 2020

ABSTRACTBackgroundThe cue-reactivity paradigm is a widely adopted neuroimaging probe engendering brain activity linked with attentional, affective, and reward processes following presentation of appetitive stimuli. Given the multiple mental operations invoked, we sought to decompose cue-related brain activity into constituent components employing emergent meta-analytic techniques when considering drug and natural reward-related cues.MethodsWe conducted multiple coordinate-based meta-analyses delineatingcommonanddistinctbrain activity convergence across cue-reactivity studies (N=196 articles) involving drug (n=133) or natural reward-related (n=63) visual stimuli. Subsequently, we characterized the connectivity profiles of identified brain regions by using them as seeds in task-independent and task-dependent functional connectivity analyses. Using hierarchical clustering on these connectivity profiles, we grouped cue-related brain regions into subnetworks. Functional decoding was then employed to characterize mental operations linked with each subnetwork.ResultsAcross all studies,pooledactivity convergence was observed in the striatum, amygdala, thalamus, cingulate, insula, and multiple frontal, parietal, and occipital regions.Drug-distinctconvergence (drug>natural) was observed notably in the posterior cingulate cortex (PCC), dorsolateral prefrontal cortex (dlPFC), and temporal and parietal regions, whereasdistinct naturalreward convergence (natural>drug) was observed in thalamic, insular, orbitofrontal, and occipital regions. Hierarchical clustering using each regions’ connectivity profiles identified six subnetworks, involving: 1) occipital and thalamic (lateral geniculate nucleus) regions functionally linked with early visual processing, 2) occipital-temporal regions associated with higher level visual association, 3) parietal-frontal regions linked with cognitive control mechanisms, 4) posterior and ventral insula as well as anterior cingulate cortex (ACC) functionally linked with salient event detection, 5) nucleus accumbens, PCC, precuneus, ACC, and thalamus (mediodorsal) associated with subjective valuation, and 6) bilateral amygdalae, orbitofrontal, and dorsal insula regions linked with affective processes.ConclusionsThese outcomes suggest multifaceted brain activity during the cue-reactivity paradigm can be decomposed into more elemental processes and indicate that while drugs of abuse usurp the brain’s natural reward processing system, some regions appear distinctly related to drug cue-reactivity (e.g., PCC, dlPFC).
Tissue mimetic hyaluronan bioink containing collagen fibers with controlled orientation modulating cell morphology and alignment
Authors: Schwab Andrea , Helary Christophe , Richards Geoff , Alini Mauro , Eglin David , D’Este Matteo 
Published: February 2020

AbstractBiofabrication is providing scientists and clinicians the ability to produce engineered tissues with desired shapes, and gradients of composition and biological cues. Typical resolutions achieved with extrusion-based bioprinting are at the macroscopic level. However, for capturing the fibrillar nature of the extracellular matrix (ECM), it is necessary to arrange ECM components at smaller scales, down to the micron and the molecular level.In this study, we introduce a bioink containing hyaluronan (HA) as tyramine derivative (THA) and collagen type 1 (Col 1). Similarly to other connective tissues, in this bioink Col is present in fibrillar form and HA as viscoelastic space filler. THA was enzymatically crosslinked under mild conditions allowing simultaneous Col fibrillogenesis, thus achieving a homogeneous distribution of Col fibrils within the viscoelastic HA-based matrix. THA-Col composite displayed synergistic properties in terms of storage modulus and shear-thinning, translating into good printability.Shear-induced alignment of the Col fibrils along the printing direction was achieved and quantified via immunofluorescence and second harmonic generation. Cell-free and cell-laden constructs were printed and characterized, analyzing the influence of the controlled microscopic anisotropy on human bone marrow derived mesenchymal stromal cells (hMSC) migration.THA-Col showed cell instructive properties modulating hMSC adhesion, morphology and sprouting from spheroids stimulated by the presence and the orientation of Col fibers. Actin filament staining showed that hMSCs embedded into aligned constructs displayed increased cytoskeleton alignment along the fibril direction. Based on gene expression of cartilage/bone markers and ECM production, hMSCs embedded into the bioink displayed chondrogenic differentiation comparable to standard pellet culture by means of proteoglycan production (Safranin O staining and proteoglycan quantification).The possibility of printing matrix components with control over microscopic alignment brings biofabrication one step closer to capturing the complexity of native tissues.
Drosha Regulates Oogenesis and microRNAs Germline Autonomously and Non-autonomously inC. elegans
Authors: Minogue Amanda L. , Trimmer Kenneth A. , Seemann Jacob H. , Kalia Awdhesh , Arur Swathi 
Published: February 2020

ABSTRACTSmall non-coding RNAs regulate multiple aspects of development including germ cell development. The microRNA pathway genes Dicer, Drosha and Pasha have been shown to regulate oocyte meiotic maturation inC. elegans. However, Dicer controls oocyte meiotic maturation through endo-siRNAs, rather than microRNAs. A repertoire of Drosha-dependent oocyte-expressed microRNAs were identified which regulate various aspects of oogenesis but not oocyte meiotic maturation. These data lead to the following models: (a) microRNAs function redundantly to regulate oocyte meiotic maturation, (b) Drosha and microRNAs function germline non-autonomously to regulate meiotic maturation. We investigated these models and observed that Drosha regulates oocyte meiotic maturation in a germline non-autonomous manner. Additionally, we uncovered a role for Drosha in regulating pachytene progression and oocyte development in a germline autonomous manner through miR-35 family and miR-51 respectively. Interestingly we also find that though Drosha-dependent oocyte-expressed microRNAs, miR-61 and miR-72, are sufficient to regulate pachytene progression and oocyte development respectively, they are generated in a germline non-autonomous manner. Collectively these data reveal a Drosha-dependent microRNA circuit, which coordinates oocyte development germline autonomously as well as through soma-germline communication.
Long-term in vivo Monitoring of Gliotic Sheathing of Ultrathin Entropic Coated Brain Microprobes with Fiber-based Optical Coherence Tomography
Authors: Dryg Ian , Xie Yijing , Bergmann Michael , Urban Gerald , Shain William , Hofmann Ulrich G. 
Published: February 2020

AbstractMicrofabricated neuroprosthetic devices have made possible important observations on neuron activity; however, long-term high-fidelity recording performance of these devices has yet to be realized. Tissue-device interactions appear to be a primary source of lost recording performance. The current state of the art for visualizing the tissue response surrounding brain implants in animals is Immunohistochemistry + Confocal Microscopy, which is mainly performed after sacrificing the animal. Monitoring the tissue response as it develops could reveal important features of the response which may inform improvements in electrode design. Optical Coherence Tomography (OCT), an imaging technique commonly used in ophthalmology, has already been adapted for imaging of brain tissue. Here, we use OCT to achieve real-time,in vivomonitoring of the tissue response surrounding chronically implanted neural devices. The employed tissue-response-provoking implants are coated with a plasma-deposited nanofilms, which have been demonstrated as a biocompatible and anti-inflammatory interface for indwelling devices. We evaluate the method by comparing the OCT results to traditional histology qualitatively and quantitatively. The differences in OCT signal across the implantation period between the plasma group and the control reveal that the Parylene-type coating of otherwise rigid brain probes (glass and silicon) does not improve the glial encapsulation in the brain parenchyma.
Languages, evolution and statistics: human sound systems were shaped by changes in bite configuration.Response to Tarasov & Uyeda (2020)
Authors: Blasi Damián E. , Moran Steven , Moisik Scott R. , Widmer Paul , Dediu Dan , Bickel Balthasar 
Published: February 2020

AbstractIn Blasi et al. (2019) we have shown, through a series of statistical analyses and models, that human sound systems have been affected by a transition in bite configuration starting from the Neolithic. Tarasov and Uyeda (2020) (henceforth T&U) raise a number of observations in relation to our article. We appreciate T&U’s engagement with our work and their sharing of the code and data of the analyses reported. In brief, their technical comment involves five analyses:Binomial Causal Models (BCM)Linear Regression of across-area variation in labiodentals and subsistencePredictive Posterior Simulations (PPS)Poisson Linear Regression (PLR): model comparisonPhylogenetic AnalysesIn what follows, we show that the discrepancies they report between our findings and theirs are due mostly to ill-specified models, weak (or missing) statistical evidence, and a misinterpretation of our results. After these issues are addressed, we conclude that T&U’s claims do not hold.
Recovery plans need better science to support decisions that allow species to decline in abundance but be recovered
Authors: Li Ya-Wei , Malcom Jacob W. , Che-Castaldo Judy P. , Neel Maile C. 
Published: February 2020

AbstractThe U.S. Endangered Species Act (ESA) is widely considered the strongest biodiversity conservation law in the world. Part of its strength comes from the mandate to use the best available science to make decisions under the law, including whether to list a species, setting the criteria for when a species can be considered recovered, and determining when those criteria have been met and a species can be delisted. Both biological status and threat factors are considered at each stage of the listing and delisting process. In most cases, conservation science would suggest that species at risk enough to be listed under the Act should be more abundant and secure at delisting than they were at listing. Surprisingly, we identified 130 ESA-listed species that the U.S. Fish and Wildlife Service could consider recovered with fewer populations or individuals than existed at the time of listing. We ask whether their ESA recovery plans present scientific data, rationale, or evidence to support a decline in abundance as part of recovery. We find that almost no plan clearly explains why a decline is allowed. Fewer than half of the plans provide scientific support for a decline in the form of literature references or modeling results. We recommend that the U.S. Fish and Wildlife Service and the National Marine Fisheries Service create a decision support system to inform when species can decline in abundance and still recover, including guidance on (a) the need to explicitly address the declines and (b) the science used to support the decisions.
Propagation of Hippocampal Ripples to the Neocortex by Way of a Subiculum-Retrosplenial Pathway
Authors: Nitzan Noam , McKenzie Sam , Beed Prateep , English Daniel Fine , Oldani Silvia , Tukker John Jan , Buzsáki György , Schmitz Dietmar 
Published: February 2020

SUMMARYBouts of high frequency activity known as sharp wave ripples (SPW-Rs) facilitate communication between the hippocampus and neocortex. However, the paths and mechanisms by which SPW-Rs broadcast their content are not well understood. Due to its anatomical positioning, the granular retrosplenial cortex (gRSC) may be a bridge for this hippocampo-cortical dialogue. Using silicon probe recordings in awake, head-fixed mice, we show the existence of SPW-R analogues in gRSC and demonstrate their coupling to hippocampal SPW-Rs. gRSC neurons reliably distinguished different subclasses of hippocampal SPW-Rs according to ensemble activity patterns in CA1. We demonstrate that this coupling is brain state-dependent, and delineate a topographically-organized anatomical pathway via VGlut2-expressing, bursty neurons in the subiculum. Optogenetic stimulation or inhibition of bursty subicular cells induced or reduced responses in superficial gRSC, respectively. These results identify a specific path and underlying mechanisms by which the hippocampus can convey neuronal content to the neocortex during SPW-Rs.
Rtrack: a software package for reproducible automated water maze analysis
Authors: Overall Rupert W , Zocher Sara , Garthe Alexander , Kempermann Gerd 
Published: February 2020

SummaryRtrackis an open-source software package for the analysis of spatial exploration data from behavioural tests such as the Morris water maze. The software provides an easy-to-use interface for data import, analysis and visualisation. A parameter-free machine learning model allows rapid and reproducible classification of spatial search strategies. We also propose a standard export format to enable cross-platform data sharing for the first time in the field.
Genome-wide study identifies association between HLA-B*55:01 and penicillin allergy
Authors: Krebs Kristi , Bovijn Jonas , Lepamets Maarja , Censin Jenny C , Jürgenson Tuuli , Särg Dage , Luo Yang , Skotte Line , Geller Frank , Feenstra Bjarke , Wang Wei , Auton Adam ,   23andMe Research Team, Raychaudhuri Soumya , Esko Tõnu , Metspalu Andres , Laur Sven , Holmes Michael V , Lindgren Cecilia M , Mägi Reedik , Milani Lili , Fadista João 
Published: February 2020

AbstractBackgroundHypersensitivity reactions to drugs are often unpredictable and can be life-threatening, underscoring a need for understanding their underlying mechanisms and risk factors. The extent to which germline genetic variation influences the risk of commonly reported drug allergies such as penicillin allergy remains largely unknown.MethodsWe extracted data from the electronic health records of 52,000 Estonian and 500,000 UK biobank participants to study the role of genetic variation in the occurrence of penicillin hypersensitivity reactions. We used imputed SNP to HLA typing data from up to 22,554 and 488,377 individuals from the Estonian and UK cohorts, respectively, to further fine-map the human leukocyte antigen (HLA) association and replicated our results in two additional cohorts involving a total of 1.14 million individuals.ResultsGenome-wide meta-analysis of penicillin allergy revealed a significant association located in the HLA region on chromosome 6. The signal was further fine-mapped to the HLA-B*55:01 allele (OR 1.47 95% CI 1.37-1.58, P-value 4.63×10-26) and confirmed by independent replication in two cohorts. The meta-analysis of all four cohorts in the study revealed a strong association of HLA-B*55:01 allele with penicillin allergy (OR 1.33 95% CI 1.29-1.37, P-value 2.23×10-72).In silicofollow-up suggests a potential effect on T lymphocytes at HLA-B*55:01.ConclusionWe present the first robust evidence for the role of an allele of the major histocompatibility complex (MHC) I gene HLA-B in the occurrence of penicillin allergy.
Antarctic cryptoendolithic bacterial lineages of pre-Cambrian origin as proxy for Mars colonization
Authors: Albanese Davide , Coleine Claudia , Rota-Stabelli Omar , Onofri Silvano , Tringe Susannah G. , Stajich Jason E. , Selbmann Laura , Donati Claudio 
Published: February 2020

AbstractCryptoendolithic communities are microbial ecosystems dwelling inside porous rocks. They are able to persist at the edge of the biological potential for life in the ice-free areas of continental Antarctica. These areas include the McMurdo Dry Valleys, often cited as a Terrestrial analog of the Martian environment. Despite their interest as a model for the early colonization by living organisms of terrestrial ecosystems and for adaptation to extreme conditions of stress, little is known about the evolution, diversity and genetic makeup of bacterial species that reside in these environments. We performed metagenomic sequencing of 18 communities from rocks collected in Antarctic desert areas over a distance of about 350 km. A total of 469 draft bacterial genome sequences were assembled, and clustered into 269 candidate species that lack a representative genome in public databases. The majority of these new species belong to monophyletic bacterial clades that diverged from related taxa in a range from 1.2 billion to 410 Ma, much earlier than the glaciation of Antarctica, and that are functionally distinct from known related taxa. The hypothesis that Antarctic cryptoendolithic bacterial lineages were generated by the selection of pre-existing cold-tolerant organisms whose origin dates back to the Tonian glaciations gives new insights for the possibility of life on Mars.
Integrin-mediated adhesion in the unicellular holozoanCapsaspora owczarzaki
Authors: Parra-Acero Helena , Harcet Matija , Sánchez-Pons Núria , Casacuberta Elena , Brown Nicholas H. , Dudin Omaya , Ruiz-Trillo Iñaki 
Published: February 2020

AbstractIn animals, cell-matrix adhesion is mainly mediated by integrins and their associated proteins. Comparative genomic analyses have shown that core components of the integrin adhesome pre-date the emergence of animals, however, whether it mediates cell adhesion in non-metazoan taxa remains unknown. Here, we investigate cell-substrate adhesion inCapsaspora owczarzaki, the closest unicellular relative of animals with the most complete integrin adhesome. Using an adhesion assay, we show thatC. owczarzakiadheres to surfaces using actin-dependent filopodia. We show that integrin β2 and its associated protein vinculin localise as distinct patches in the filopodia. We also demonstrate that substrate adhesion and integrin localisation are enhanced by the ligand fibronectin. Finally, using a specific antibody for Integrin β2, we inhibited cell adhesion to a fibronectin-coated surface. Our results show that adhesion to the substrate inC. owczarzakiis mediated by integrins. This suggests that integrin-mediated adhesion pre-dates the emergence of animals.