bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of bottlenecks and inbreeding on the genome of the endangered Pyrenean desman
Authors: Escoda Lídia , Castresana Jose 
Published: July 2020

AbstractThe Pyrenean desman (Galemys pyrenaicus) is a small semiaquatic mammal endemic to the Iberian Peninsula. Despite its limited range, this species presents a strong genetic structure due to past isolation in glacial refugia and subsequent bottlenecks. Additionally, some populations are highly fragmented today as a consequence of river barriers, causing substantial levels of inbreeding. These features make the Pyrenean desman a unique model in which to study the genomic footprints of differentiation, bottlenecks and extreme isolation in an endangered species. The complete genome of the Pyrenean desman was assembled using a Bloom filter-based approach. An analysis of the 1.83 Gb reference genome and the sequencing of five additional individuals from different evolutionary units allowed us to detect its main genomic characteristics. The population differentiation of the species was reflected in highly distinctive demographic trajectories. A severe population bottleneck during the postglacial recolonization of the eastern Pyrenees created the lowest genomic heterozygosity ever recorded in a mammal. Moreover, isolation and inbreeding gave rise to a high proportion of runs of homozygosity (ROH). Despite these extremely low levels of genetic diversity, two key multigene families from an eco-evolutionary perspective that need to be genetically variable, the major histocompatibility complex and olfactory receptor genes, showed heterozygosity excess in the majority of individuals. Furthermore, these two classes of genes were significantly less abundant than expected within ROH. These results allow us to characterize important genomic health indicators for each individual, information that may be crucial for the conservation and management of the species.
Mapping social distancing measures to the reproduction number for COVID-19
Authors: Brooks-Pollock Ellen , Read Jonathan M. , McLean Angela R. , Keeling Matt J. , Danon Leon 
Published: July 2020

AbstractBackgroundIn the absence of a vaccine, SARS-CoV-2 transmission has been controlled by preventing person-to-person interactions via social distancing measures. In order to re-open parts of society, policy-makers need to consider how combinations of measures will affect transmission and understand the trade-offs between them.MethodsWe use age-specific social contact data, together with epidemiological data, to quantify the components of the COVID-19 reproduction number. We estimate the impact of social distancing policies on the reproduction number by turning contacts on and off based on context and age. We focus on the impact of re-opening schools against a background of wider social distancing measures.ResultsWe demonstrate that pre-collected social contact data can be used to provide a time-varying estimate of the reproduction number (R). We find that following lockdown (when R=0.7 (95% CI 0.6, 0.8)), opening primary schools as a modest impact on transmission (R = 0.89 (95%CI: 0.82 − 0.97)) as long as other social interactions are not increased. Opening secondary and primary schools is predicted to have a larger impact (R = 1.22, 95%CI: 1.02 − 1.53)). Contact tracing and COVID security can be used to mitigate the impact of increased social mixing to some extent, however social distancing measures are still required to control transmission.ConclusionsOur approach has been widely used by policy-makers to project the impact of social distancing measures and assess the trade-offs between them. Effective social distancing, contact tracing and COVID-security are required if all age groups are to return to school while controlling transmission.
Epidemiological investigation and prevention control analysis of longitudinal distribution of COVID-19 in Henan province, China
Authors: Yang Xianguang , Chen Xuelin , Ding Cuihong , Bai Zhibo , Zhu Jingyi , Sun Gege , Yu Guoying 
Published: July 2020

AbstractObjectiveTo analyze the vertical distribution of six cities in Henan Province,China from January 21, 2020 to June17, 2020: Xinyang City (including Gushi County), Nanyang City (including Dengzhou City), Zhumadian City (including XincaiCounty), Zhengzhou City (including Gongyi City), Puyang City and Anyang City (including Hua County) corona virus disease 2019(COVID-19) epidemiological characteristics and local prevention and control measures.MethodsData were collected and analyzed through the COVID-19 information published on the official websites of health commissions of Henan Province and six cities.ResultsAs of June 17, 2020, the cumulative incidence rate of COVID-19 in Henan province was 1.33/100,000, the cumulative cure rate was 98.27%, the cumulative mortality rate was 1.73%, the age range of diagnosed cases was 5days-85years old, and the male to female ratio was 1.09:1.The confirmed cases of COVID-19 in Henan province were mainly imported cases from Hubei, accounting for 87.74%, of which the highest number was 70.50% in Zhumadian. The contact cases and local cases increased in a fluctuating manner over time.SignificanceIn this paper, epidemiological characteristics of COVID-19 in Henan province from the outbreak to the effective control within 60 days were analyzed, and effective and distinctive prevention and control measures in various cities were summarized, so as to provide a favorable reference for the further formulation and implementation of epidemic prevention and control and a valuable theoretical basis for effectively avoiding the second outbreak.ImportanceEpidemic prevention and control in China has entered the normalized this new stage, this article analyze the epidemiological characteristics of COVID - 19 in henan province, and summarizes the prefecture level and effective disease prevention and control means and measures, the normalized private provide the theoretical reference to the prevention and control work, formulate and carry out, at the same time in other countries and regions of epidemic prevention and control work can also be used for reference.
Pathological uptake with 18-Fluorocholine versus 99mTc-MIBI in the location of the parathyroid glands in hyperparathyroidism. Systematic review and meta-analysis
Authors: Refoyo José Luis Pardal , Alonso Pilar Tamayo , Cendón Sofía Ferreira , Gómez Esther Martín 
Published: July 2020

SummaryIntroductionThe location of the pathological parathyroid glands in hyperparathyroidism is usually carried out by means of 99mTc-sestamibi scintigraphy, which increases its precision by adding the ultrasound examination. The non-localization of the parathyroid glands increases the difficulties for surgical removal. To increase the detection of pathological glands, other radioactive tracers are used, such as methionine, fluorocholine or 18F-flurpiridaz.ObjectiveTo establish if PET / CT with 18-Fluorocholine in patients with hyperparathyroidism increases the number of uptakes compared to the 99mTc-sestamibi scan.MethodSystematic review and meta-analysis. Two subgroups were analyzed. Subgroup 1: trials comparing both techniques as an initial exploration. Thirteen studies including 1131 examinations were selected (596 PET / CT with 18-Fluorocholine vs. 535 scintigraphy with 99mTc-sestamibi). Meta-analysis was performed following the random effects model and the odds ratio was calculated. Subgroup 2: studies that include 18-Fluorocholine as a rescue examination in patients with a previous negative study with a 99mTc-sestamibi scan. 17 articles including 412 examinations with 359 patients in which there was at least one uptake were selected. Meta-analysis of the prevalence of the number of patients in whom there was at least one uptake was performed using the random effects model.ResultsSubgroup 1: The number of patients in which at least one uptake occurs is significantly higher with the 18-Fluorocholine examinations (OR 4.264, 95% CI 2.400-7.577). The prevalence of uptake with 18-Fluorocholine is 0.91 [0.86, 0.95] and with sestamibi 0.68 [0.56, 0.80]. Subgroup 2: the prevalence of uptake among patients with previous negative MIBI studies was 0.90 [0.87, 0.94]. The probability of detection of both techniques in this group reaches 0.98. Publication bias in the meta-analyzes is low.Discussion18-Fluorocholine protocols provide higher precision, clearer images, with faster acquisition as well as being readily available for most PET / CT centers.ConclusionThe PET / CT study with 18-Fluorocholine can be recommended as a study for the location of pathological parathyroid glands after studies with negative MIBI.
An integrated, modular approach to data science education in the life sciences
Authors: Dill-McFarland Kimberly A , König Stephan G , Mazel Florent , Oliver David , McEwen Lisa M , Hong Kris Y , Hallam Steven J 
Published: July 2020

AbstractWe live in an increasingly data-driven world, where high-throughput sequencing and mass spectrometry platforms are transforming biology into an information science. This has shifted major challenges in biological research from data generation and processing to interpretation and knowledge translation. However, post-secondary training in bioinformatics, or more generally data science for life scientists, lags behind current demand. In particular, development of accessible, undergraduate data science curricula has potential to improve research and learning outcomes and better prepare students in the life sciences to thrive in public and private sector careers. Here, we describe the Experiential Data science for Undergraduate Cross-Disciplinary Education (EDUCE) initiative, which aims to progressively build data science competency across several years of integrated practice. Through EDUCE, students complete data science modules integrated into required and elective courses augmented with coordinated co-curricular activities. The EDUCE initiative draws on a community of practice consisting of teaching assistants, postdocs, instructors and research faculty from multiple disciplines to overcome several reported barriers to data science for life scientists, including instructor capacity, student prior knowledge, and relevance to discipline-specific problems. Preliminary survey results indicate that even a single module improves student self-reported interest and/or experience in bioinformatics and computer science. Thus, EDUCE provides a flexible and extensible active learning framework for integration of data science curriculum into undergraduate courses and programs across the life sciences.Availability and implementationThe EDUCE teaching and learning framework is accessible ateduce-ubc.github.io
Waking experience modulates sleep need in mice
Authors: Milinski Linus , Fisher Simon P. , Cui Nanyi , McKillop Laura E. , Blanco Duque Cristina , Ang Gauri , Yamagata Tomoko , Bannerman David M. , Vyazovskiy Vladyslav V. 
Published: July 2020

AbstractHomeostatic regulation of sleep is reflected in the maintenance of a daily balance between sleep and wake. Although numerous internal and external factors can influence sleep, it is unclear whether and to what extent the process that keeps track of time spent awake is determined by the content of the waking experience. We hypothesised that alterations in environmental conditions may elicit different types of wakefulness, which will in turn influence both the capacity to sustain continuous wakefulness as well the rates of accumulating sleep pressure. To address this, we performed two experiments, where we compared wakefulness dominated by novel object exploration with either (i) the effects of voluntary wheel running (Experiment 1) or (ii) performance in a simple touchscreen task (Experiment 2). We find that voluntary wheel running results in longer wake episodes, as compared with exploratory behaviour; yet it does not lead to higher levels of EEG slow wave activity (SWA) during subsequent sleep. On the other hand, engagement in a touchscreen task, motivated by a food reward, results in lower SWA during subsequent sleep, as compared to exploratory wakefulness, even though the total duration of wakefulness was similar. Overall, our study suggests that sleep-wake behaviour is highly flexible within an individual, and that the homeostatic process that keeps track of time spent awake is sensitive to the nature of the waking experience. We therefore conclude that sleep dynamics are determined, to a large degree, by the interaction between the organism and the environment.
Endocardial/endothelial angiocrines regulate cardiomyocyte development and maturation and induce features of ventricular non-compaction
Authors: Rhee Siyeon , Paik David T. , Yang Johnson Y. , Nagelberg Danielle , Williams Ian , Tian Lei , Roth Robert , Chandy Mark , Ban Jiyeon , Belbachir Nadjet , Kim Seokho , Zhang Hao , Phansalkar Ragini , Wong Ka Man , King Devin A. , Valdez Caroline , Winn Virginia D. , Morrison Ashby J. , Wu Joseph C. , Red-Horse Kristy 
Published: July 2020

AbstractNon-compaction cardiomyopathy is a devastating genetic disease caused by insufficient consolidation of ventricular wall muscle that can result in inadequate cardiac performance. Despite being the third most common cardiomyopathy, the mechanisms underlying the disease, including the cell types involved, are poorly understood. We have previously shown that endothelial cell-specific deletion of the chromatin remodeler geneIno80results in defective coronary vessel development that leads to ventricular noncompaction in embryonic mouse hearts. Here, we used single-cell RNA-sequencing to characterize endothelial and endocardial defects inIno80-deficient hearts. We observed a pathological endocardial cell population in the non-compacted hearts, and identified multiple dysregulated angiocrine factors that dramatically affected cardiomyocyte behavior. We identifiedCol15A1as a coronary vessel-secreted angiocrine factor, downregulated byIno80-deficiency, that functioned to promote cardiomyocyte proliferation. Furthermore, mutant endocardial and endothelial cells (ECs) upregulated expression of secreted factors, such asTgfbi, Igfbp3, Isg15, andAdm, which decreased cardiomyocyte proliferation and increased maturation. These findings support a model where coronary ECs normally promote myocardial compaction through secreted factors, but that endocardial and ECs can secrete factors that contribute to non-compaction under pathological conditions.
A unified atlas of CD8 T cell dysfunctional states in cancer and infection
Authors: Pritykin Yuri , van der Veeken Joris , Pine Allison , Zhong Yi , Sahin Merve , Mazutis Linas , Pe’er Dana , Rudensky Alexander , Leslie Christina 
Published: July 2020

ABSTRACTCD8 T cells play an essential role in defense against viral and bacterial infections and in tumor immunity. Deciphering T cell loss of functionality is complicated by the conspicuous heterogeneity of CD8 T cell states described across different experimental and clinical settings. By carrying out a unified analysis of over 300 ATAC-seq and RNA-seq experiments from twelve independent studies of CD8 T cell dysfunction in cancer and infection we defined a shared differentiation trajectory towards terminal dysfunction and its underlying transcriptional drivers and revealed a universal early bifurcation of functional and dysfunctional T cell activation states across models. Experimental dissection of acute and chronic viral infection using scATAC-seq and allele-specific scRNA-seq identified state-specific transcription factors and captured the early emergence of highly similar TCF1+progenitor-like populations at an early branch point, at which epigenetic features of functional and dysfunctional T cells diverge. Our atlas of CD8 T cell states will facilitate mechanistic studies of T cell immunity and translational efforts.
The metal cofactor zinc and interacting membranes modulate SOD1 conformation-aggregation landscape in anin vitroALS Model
Authors: Sannigrahi Achinta , Chowdhury Sourav , Das Bidisha , Banerjee Amrita , Halder Animesh , Naganathan Athi N. , Karmakar Sanat , Chattopadhyay Krishnananda 
Published: July 2020

AbstractAggregation of Cu-Zn superoxide dismutase (SOD1) is implicated in the motor neuron disease, ALS. Although more than 140 disease mutations of SOD1 are available, their stability or aggregation behaviors in membrane environment are not correlated with disease pathophysiology. Here, we use multiple mutational variants of SOD1 to show that the absence of Zn, and not Cu, significantly impacts membrane attachment of SOD1 through two loop regions facilitating aggregation driven by lipid induced conformational changes. These loop regions influence both the primary (through Cu intake) and the gain of function (through aggregation) of SOD1 presumably through a shared conformational landscape. Combining experimental and theoretical frameworks using representative ALS disease mutants, we develop a ‘co-factor derived membrane association model’ wherein mutational stress closer to the Zn (but not to the Cu) pocket is responsible for membrane association mediated toxic aggregation and survival time scale after ALS diagnosis.
Role for novel family of pathogen-induced cysteine-rich transmembrane proteins in disease resistance
Authors: Mendes Marciel Pereira , Hickman Richard , Van Verk Marcel C. , Nieuwendijk Nicole , Reinstädler Anja , Panstruga Ralph , Pieterse Corné M.J. , Van Wees Saskia C.M. 
Published: July 2020

ABSTRACTPlants possess a sophisticated immune system to protect themselves against pathogen attack. The defense hormone salicylic acid (SA) is an important player in the plant immune gene regulatory network. Using RNA-seq time series data ofArabidopsis thalianaleaves treated with SA, we identified a largely uncharacterized SA-responsive gene family of eight members that are all activated in response to various pathogens or their immune elicitors and encode small proteins with cysteine-rich transmembrane domains. Based on their nucleotide similarity and chromosomal position, the designatedPathogen-inducedCysteine-rich transMembrane protein (PCM) genes were subdivided into three subgroups consisting ofPCM1-3(subgroup I),PCM4-6(subgroup II), andPCM7-8 (subgroup III). Of thePCMgenes, onlyPCM4(also known asPCC1) has previously been implicated in plant immunity. Transient expression assays inNicotiana benthamianaindicated that most PCM proteins localize to the plasma membrane. Ectopic overexpression of thePCMsin Arabidopsis resulted in all eight cases in enhanced resistance against the biotrophic oomycete pathogenHyaloperonospora arabidopsidisNoco2. Additionally, overexpression ofPCMsubgroup I genes conferred enhanced resistance to the hemi-biotrophic bacterial pathogenPseudomonas syringaepv.tomatoDC3000. Ectopic overexpression of thePCMsalso affected the expression of genes related to light signaling and development, and accordingly PCM-overexpressing seedlings displayed elongated hypocotyl growth. These results point to a function of PCMs in both disease resistance and photomorphogenesis, connecting both biological processes, possibly via effects on membrane structure or activity of interacting proteins at the plasma membrane.
No evidence for basigin/CD147 as a direct SARS-CoV-2 spike binding receptor
Authors: Shilts Jarrod , Wright Gavin J. 
Published: July 2020

AbstractThe spike protein of SARS-CoV-2 is known to enable viral invasion into human cells through direct binding to host receptors including ACE2. An alternate entry receptor for the virus was recently proposed to be basigin/CD147. These early studies have already prompted a clinical trial and multiple published hypotheses of the role of this host receptor in viral infection and pathogenesis. We sought to independently characterize the basigin-spike protein interaction. After conducting several lines of experiments, we report that we are unable to find evidence supporting the role of basigin as a putative spike-binding receptor. Recombinant forms of both the entire ectodomain and S1 domain of the SARS-CoV-2 spike protein that directly bind ACE2 do not interact with basigin expressed on the surface of human cells. Using specialized assays tailored to detect receptor interactions as weak or weaker than the proposed basigin-spike binding, we report no evidence for direct binding of the viral spike to either of the two common isoforms of basigin. Given the pressing need for clarity on which targets of SARS-CoV-2 may lead to promising therapeutics, we present these findings to allow more informed decisions about the translational relevance of this putative mechanism in the race to understand and treat COVID-19.
The sleep-wake distribution contributes to the peripheral rhythms in PERIOD-2
Authors: Hoekstra Marieke M.B. , Jan Maxime , Emmenegger Yann , Franken Paul 
Published: July 2020

AbstractIn the mouse,Period-2(Per2) expression in tissues peripheral to the suprachiasmatic nuclei (SCN) increases during sleep deprivation and at times of the day when animals are predominantly awake spontaneously, suggesting that the circadian sleep-wake distribution directly contributes to the daily rhythms inPer2. We found support for this hypothesis by recording sleep-wake state alongside PER2 bioluminescence in freely behaving mice, demonstrating that PER2 increases during spontaneous waking and decreases during sleep. The temporary reinstatement of PER2 rhythmicity in behaviorally arrhythmic SCN-lesioned mice submitted to daily recurring sleep deprivations substantiates our hypothesis. Mathematical modelling revealed that PER2 dynamics can be described by a damped harmonic oscillator driven by two forces: a sleep-wake-dependent force and a SCN-independent circadian force. Our work underscores the notion that in peripheral tissues the clock gene circuitry integrates sleep-wake information and could thereby contribute to behavioral adaptability to respond to homeostatic requirements.
Optimal inaccuracy: estimating male fitness in the movement-assisted dichogamous speciesClerodendrum infortunatum
Authors: Mukhopadhyay Amritendu , Quader Suhel 
Published: July 2020

AbstractIn hermaphroditic species, sexual interference can drive the evolution of dichogamy, where sporophylls (reproductive parts) are separated in time. However, the separation of sporophylls can lead to pollination inaccuracy, especially in movement-assisted dichogamy, where sporophylls alter their position over time. Is pollination inaccuracy minimised by the second sporophyll taking the exact position of the first? Are the sporophylls optimally positioned and stable in their respective active phases? We address these questions inClerodendrum infortunatum, a protandrous, movement-assisted dichogamous species. We made predictions from optimality arguments, and tested these by measuring sporophyll angles over time, by experimentally manipulating flowers, and by estimating correlates of the resultant fitness, taking into account pollen export, pollination inaccuracy and the resultant total pollen delivered. Contrary to expectation, anthers do not have a fixed position in the male phase, and pollination inaccuracy is high. Further, when pollen load is highest, anthers are paradoxically not positioned at the pollen export peak. Also, pollen export and pollination accuracy peaks do not align. This seeming maladaptiveness of anther positioning nevertheless results in highest overall male fitness, measured as the total pollen delivered over the entire male phase. Instead of a simple positional exchange of sporophylls, stamens display a more complicated dynamic strategy which appears close to optimal even though naive measures of pollination inaccuracy are high. Such a strategy of maximising overall male fitness, integrating over the dynamics of stamen trajectory, could well be a general characteristic of protandrous movement-assisted dichogamy.