bluuebunny/crossref_metadata_2025_split huggingface dataset:
Seroprevalence of anti-SARS-CoV-2 IgG antibodies, risk factors for infection and associated symptoms in Geneva, Switzerland: a population-based study
Authors: Richard Aude , Wisniak Ania , Perez-Saez Javier , Garrison-Desany Henri , Petrovic Dusan , Piumatti Giovanni , Baysson Hélène , Picazio Attilio , Pennacchio Francesco , De Ridder David , Chappuis François , Vuilleumier Nicolas , Low Nicola , Hurst Samia , Eckerle Isabella , Flahault Antoine , Kaiser Laurent , Azman Andrew S , Guessous Idris , Stringhini Silvia ,   For the SEROCOV-POP study group
Published: December 2020

AbstractBackgroundPopulation-based serological surveys provide a means for assessing the immunologic landscape of a community, without the biases related to health-seeking behaviors and testing practices typically associated with rt-PCR testing. This study assesses SARS-CoV-2 seroprevalence over the first epidemic wave in Canton Geneva, Switzerland, as well as biological and socio-economic risk factors for infection and symptoms associated with IgG seropositivity.Methods and findingsBetween April 6 and June 30, 2020, former participants of a yearly representative cross-sectional survey of the 20-75-year-old population of the canton of Geneva were invited to participate in a seroprevalence study, along with household members five years and older. We collected blood and tested it for anti-SARS-CoV-2 immunoglobulins G (IgG). Questionnaires were self-administered. We estimated seroprevalence with a Bayesian model accounting for test performance and sampling design. We included 8344 participants (53.5% women, mean age 46.9 years). The population-level seroprevalence over the 12-week study period was 7.8 % (95% Credible Interval (CrI) 6.8-8.9), accounting for sex, age and household random effects. Seroprevalence was highest among 18-49 year olds (9.5%, 95%CrI 8.1-10.9), with young children (5-9 years) and those >65 years having significantly lower seroprevalence (4.3% and 4.7-5.4% respectively). Men were more likely to be seropositive than women (relative risk 1.2, 95%CrI 1.1-1.4). Odds of seropositivity were reduced for female retirees (0.46, 95%CI 0.23-0.93) and unemployed men (0.35, 95%CI 0.13-1.0) compared to employed individuals, and for current smokers (0.36, 95%CI 0.23-0.55) compared to never-smokers. We found no significant association between occupation, level of education, neighborhood income and the risk of being seropositive. Symptoms most strongly associated with seropositivity were anosmia/dysgeusia, loss of appetite, fever, fatigue and myalgia and/or arthralgia. Thirteen percent of seropositive participants reported no symptoms.ConclusionsOur results confirm a low population seroprevalence of anti-SARS-CoV-2 antibodies after the first wave in Geneva, a region hard hit by the COVID-19 pandemic. Socioeconomic factors were not associated with seropositivity in this sample. The elderly and young children were less frequently seropositive, though it is not clear how biology and behaviors shape these differences. These specificities should be considered when assessing the need for targeted public health measures.
Length–length and length–weight relationships for four small pelagic fishes in the Kuroshio–Oyashio current system
Authors: Furuichi Sho , Kamimura Yasuhiro , Yukami Ryuji 
Published: December 2020

SummaryLength–length relationships and length–weight relationships were estimated for four small pelagic fishes (Japanese sardineSardinops melanostictus, Japanese anchovyEngraulis japonicus, chub mackerelScomber japonicus, and spotted mackerelScomber australasicus) in the Kuroshio–Oyashio current system. Fish samples were collected from surface–midwater trawl surveys and commercial purse-seine fisheries between September and October of 2020 in the western North Pacific. Total length (TL), fork length (FL), and standard length (SL) were measured to 0.01 cm, and whole body weight (W) was measured to the nearest 0.01 g for each individual. All length–length relationships (TL–FL, TL–SL, and FL–SL) were highly significant (p< 0.0001), withr2> 0.98 in all species. Length–weight relationships (W–TL, W–FL, and W–SL) were also highly significant (p< 0.0001), withr2> 0.98 in all species. This study provides a useful reference for biological studies and stock assessments of these small pelagic fishes.
Activity flow underlying abnormalities in brain activations and cognition in schizophrenia
Authors: Hearne Luke J. , Mill Ravi D. , Keane Brian P. , Repovš Grega , Anticevic Alan , Cole Michael W. 
Published: December 2020

AbstractCognitive dysfunction is a core feature of many brain disorders such as schizophrenia (SZ), and has been linked to both aberrant brain functional connectivity (FC) and aberrant cognitive brain activations. We propose that aberrant network activity flow over FC pathways leads to altered cognitive activations that produce cognitive dysfunction in SZ. We tested this hypothesis using activity flow mapping – an approach that models the movement of task-related activity between brain regions as a function of FC. Using fMRI data from SZ individuals and healthy controls during a working memory task, we found that activity flow models accurately predict aberrant cognitive activations across multiple brain networks. Within the same framework, we simulated a connectivity-based clinical intervention, predicting specific treatments that normalized brain activations and behavior in independent patients. Our results suggest that dysfunctional task-evoked activity flow is a large-scale network mechanism contributing to the emergence of cognitive dysfunction in SZ.
Monitoring Reactivation of Latent HIV by Label-Free Gradient Light Interference Microscopy
Authors: Goswami Neha , Lu Yiyang , Kandel Mikhail E. , Fanous Michael J. , Bohn-Wippert Kathrin , Tevonian Erin N. , Dar Roy D. , Popescu Gabriel 
Published: December 2020

SummaryLatent human immunodeficiency virus (HIV) reservoirs in infected individuals present the largest barrier to a cure. The first step towards overcoming this challenge is to understand the science behind latency-reactivation interplay. Fluorescence imaging of GFP-tagged HIV has been the main method for studying reactivation of latent HIV in individually infected cells. In this paper, we report insights provided by label-free, gradient light interference microscopy (GLIM) about the changes in measures including dry mass, diameter, and dry mass density associated with infected cells that occur upon reactivation. We discovered that mean cell dry mass and mean diameter of latently infected cells treated with reactivating drug, TNF-α, are higher for cells with reactivated HIV as compared to those with latent disease. Results also indicate that cells with mean dry mass and diameter less than 10pg and 8µm, respectively, remain exclusively in the latent state. Also, cells with mean dry mass greater than 23pg and mean diameter greater than 11µm have a higher probability of reactivating. This study is significant as it presents a new label-free approach to quantify latent reactivation of a virus in single cells based on changes in cell morphology.
Error Rates in SARS-CoV-2 Testing Examined with Bayesian Inference
Authors: Bentley P. M. 
Published: December 2020

AbstractA literature review on SARS-CoV-2 reverse-transcription polymerase chain reaction (RT-PCR) is used to construct a clinical test confusion matrix. A simple correction method for bulk test results is then demonstrated with examples. The required sensitivity and specificity of a test are explored for societal needs and use cases, before a sequential analysis of common example scenarios is explored. The analysis suggests that many of the people with mild symptoms and positive test results are unlikely to be infected with SARS-CoV-2 in some regions. It is concluded that current and foreseen alternative tests can not be used to “clear” people as being non-infected. Recommendations are given that regional authorities must establish a programme to monitor operational test characteristics before launching large scale testing; and that large scale testing for tracing infection networks in some regions is not viable, but may be possible in a focused way that does not exceed the working capacity of the laboratories staffed by competent experts. RT-PCR tests can not be solely relied upon as the gold standard for SARS-CoV-2 diagnosis at scale, instead clinical assessment supported by a range of expert diagnostic tests should be used.
Classification of the infection status of COVID-19 in 190 countries
Authors: Odagaki Takashi , Suda Reiji 
Published: December 2020

AbstractWe propose a simple method to determine the infection rate from the time dependence of the daily confirmed new cases, in which the logarithm of the rate is fitted by piece-wise quadratic functions. Exploiting this method, we analyze the time dependence of the outbreak of COVID-19 in 190 countries around the world and determine the status of the outbreak in each country by the dependence of the infection rate on the number of new cases. We show that the infection status of each country can be completely classified into nine different states and that the infection status of countries succeeded in controlling COVID-19 implies the importance of the quarantine and/or self-isolation measure.
Capturing Human Trophoblast Development with Naïve Pluripotent Stem Cells In Vitro
Authors: Io Shingo , Kabata Mio , Iemura Yoshiki , Semi Katsunori , Morone Nobuhiro , Okamoto Ikuhiro , Nakamura Tomonori , Kojima Yoji , Iwatani Chizuru , Tsuchiya Hideaki , Kaswandy Belinda , Kondoh Eiji , Saitou Mitinori , Yamamoto Takuya , Mandai Masaki , Takashima Yasuhiro 
Published: December 2020

AbstractTrophoblast are extra-embryonic cells that are essential to maintain pregnancy. Human trophoblasts arise from the morula as trophectoderm (TE), which, after implantation, differentiates into cytotrophoblast (CT), syncytiotrophoblast (ST), and extravillous trophoblast (EVT) composing the placenta. Here we show that naïve, but not primed, human pluripotent stem cells (PSCs) recapitulate trophoblast development. Naïve PSC-derived TE and CT (nCT) recreated the human and monkey TE-to-CT transition. nCT self-renewed as CT stem cells and had the characteristics of proliferating villous CT and CT in the cell column of the first trimester. Notably, although primed PSCs differentiated into trophoblast-like cells (pBAP), pBAP were distinct from nCT and human placenta-derived CT stem cells, exhibiting properties consistent of the amnion. Our findings establish an authentic paradigm for human trophoblast development, demonstrating the invaluable properties of naïve human PSCs. Our system will provide a platform to study the molecular mechanisms underlying trophoblast development and related diseases.
Deregulation of epigenetic marks is correlated to differential exon usage of developmental genes
Authors: Trang Do Hoang Thu , Shanak Siba , Barghash Ahmad , Helms Volkhard 
Published: December 2020

ABSTRACTAlternative exon usage is known to affect a large portion of genes in mammalian genomes. Importantly, different splice forms sometimes lead to distinctly different protein functions. We analyzed data from the Human Epigenome Atlas (version 9) whereby we connected the differential usage of exons in various developmental stages of human cells/tissues to differential epigenetic modifications at the exon level. In total, we analyzed 19 human tissues, adult cells, and cultured cells that mimic early developmental stages. We found that the differential occurrence of protein isoforms across developmental stages was often associated with changes in histone marks at exon boundary regions. Many of the genes that are differentially regulated at the exon level were found to be functionally associated with development and metabolism.
Asymmetric chromatin capture and nuclear envelopes separate chromosomes in fused cells during mitosis
Authors: Sunchu Bharath , Lee Nicole , Segura Roberto Carlos , Roubinet Chantal , Cabernard Clemens 
Published: December 2020

AbstractHybrid cells derived through fertilization or somatic cell fusion recognize and separate chromosomes of different origin. The underlying mechanisms are unknown but could prevent aneuploidy and tumor formation. Here, we acutely induce fusion betweenDrosophilaneural stem cells (neuroblasts; Nbs) and differentiating ganglion mother cells (GMCs)in vivoto define how epigenetically distinct chromatin is recognized and segregated. We find that Nb-GMC hybrid cells align both endogenous (neuroblast-origin) and ectopic (GMC-origin) chromosomes at the metaphase plate through centrosome derived dual-spindles. Mixing of endogenous and ectopic chromatin is prevented through an asymmetric, microtubule-dependent chromatin capture mechanism during interphase and physical boundaries imposed by nuclear envelopes. Although hybrid cells fail to accurately segregate ectopic chromatin, hybrid cells neither reduce the lifespan nor form visible tumors in host flies. We propose that Nb-GMC derived hybrid cells utilize asymmetric centrosome activity in interphase and nuclear envelopes to physically separate epigenetically distinct chromatin.
Towards a unified theory of plant photosynthesis and hydraulics
Authors: Joshi Jaideep , Stocker Benjamin D. , Hofhansl Florian , Zhou Shuangxi , Dieckmann Ulf , Prentice Iain Colin 
Published: December 2020

AbstractThe global carbon and water cycles are governed by the coupling of CO2and water vapour exchanges through the leaves of terrestrial plants, controlled by plant adaptations to balance carbon gains and hydraulic risks. We introduce a trait-based optimality theory that unifies the treatment of stomatal responses and biochemical acclimation of plants to environments changing on multiple timescales. Tested with experimental data from 18 species, our model successfully predicts the simultaneous decline in carbon assimilation rate, stomatal conductance, and photosynthetic capacity during progressive soil drought. It also correctly predicts the dependencies of gas exchange on atmospheric vapour pressure deficit, temperature, and CO2. Model predictions are also consistent with widely observed empirical patterns, such as the distribution of hydraulic strategies. Our unified theory opens new avenues for reliably modelling the interactive effects of drying soil and rising atmospheric CO2on global photosynthesis and transpiration.
Divergent molecular signatures of regeneration and fibrosis during wound repair
Authors: Mascharak Shamik , desJardins-Park Heather E. , Januszyk Michael , Chen Kellen , Davitt Michael F. , Demeter Janos , Henn Dominic , Griffin Michelle , Bonham Clark A. , Foster Deshka S. , Mooney Nancie , Cheng Ran , Jackson Peter K. , Wan Derrick C. , Gurtner Geoffrey C. , Longaker Michael T. 
Published: December 2020

SummaryRegeneration is the “holy grail” of tissue repair, but skin injury typically yields fibrotic, non-functional scars. Developing pro-regenerative therapies requires rigorous understanding of the molecular progression from injury to fibrosis or regeneration. Here, we report the divergent molecular events driving skin wound cells toward either scarring or regenerative fates. We profile scarring versus YAP inhibition-induced wound regeneration at the transcriptional (single-cell RNA-sequencing), protein (timsTOF proteomics), and tissue (extracellular matrix ultrastructural analysis) levels. Using cell surface barcoding, we integrate these data to reveal fibrotic and regenerative “molecular trajectories” of healing. We show that disrupting YAP mechanical signaling yields regenerative repair orchestrated by fibroblasts with activated Trps1 and Wnt signaling. Our findings serve as a multimodal map of wound regeneration and could have therapeutic implications for pathologic fibroses.
ZIKV disrupts placental ultrastructure and drug transporter expression in mice
Authors: de Andrade Cherley Borba Vieira , de Siqueira Monteiro Victoria Regina , Coelho Sharton Vinicius Antunes , Gomes Hanailly Ribeiro , de Sousa Ronny Paiva Campos , de Oliveira Nascimento Veronica Muller , Bloise Flavia Fonseca , Matthews Stephen , Bloise Enrrico , de Arruda Luciana Barros , Ortiga-Carvalho Tania Maria 
Published: December 2020

AbstractCongenital Zika virus (ZIKV) infection can induce fetal brain abnormalities. Here, we investigated whether maternal ZIKV infection affects placental physiology and metabolic transport potential and impacts the fetal outcome, regardless of viral presence in the fetus at term. Low (103PFU-ZIKVPE243; low ZIKV) and high (5×107PFU-ZIKVPE243; high ZIKV) virus titers were injected into immunocompetent (ICompetent C57BL/6) and immunocompromised (ICompromised A129) mice at gestational day (GD) 12.5 for tissue collection at GD18.5 (term). High ZIKV elicited fetal death rates of 66% and 100%, whereas low ZIKV induced fetal death rates of 0% and 60% in C57BL/6 and A129 dams, respectively. All surviving fetuses exhibited intrauterine growth restriction (IUGR) and decreased placental efficiency. High-ZIKV infection in C57BL/6 and A129 mice resulted in virus detection in maternal spleens and placenta, but only A129 fetuses presented virus RNA in the brain. Nevertheless, pregnancies in both strains produced fetuses with decreased head sizes (p<0.05). Low-ZIKV-A129 dams had higher IL-6 and CXCL1 levels (p<0.05), and their placentas showed increased CCL-2 and CXCL-1 contents (p<0.05). In contrast, low-ZIKV-C57BL/6 dams had an elevated CCL2 serum level and increased type I and II IFN expression in the placenta. Notably, less abundant microvilli and mitochondrial degeneration were evidenced in the placental labyrinth zone (Lz) of ICompromised and high-ZIKV-ICompetent mice but not in low-ZIKV-C57BL/6 mice. In addition, decreased placental expression of the drug transporters P-glycoprotein (P-gp) and breast cancer resistance protein (Bcrp) and the lipid transporter Abca1 was detected in all ZIKV-infected groups, but Bcrp and Abca1 were only reduced in ICompromised and high-ZIKV ICompetent mice. Our data indicate that gestational ZIKV infection triggers specific proinflammatory responses and affects placental turnover and transporter expression in a manner dependent on virus concentration and maternal immune status. Placental damage may impair proper fetal-maternal exchange function and fetal growth/survival, likely contributing to congenital Zika syndrome.
Exosomal miR-224 contributes to hemolymph microbiota homeostasis during bacterial infection in crustacean
Authors: Gong Yi , Wei Xiaoyuan , Sun Wanwei , Ren Xin , Chen Jiao , Aweya Jude Juventus , Ma Hongyu , Chan Kok-Gan , Zhang Yueling , Li Shengkang 
Published: December 2020

AbstractThe modulation of hemolymph microbiota homeostasis is vital for the marine invertebrate innate immunity, while growing evidence shows that exosomes could serves as anti-bacterial immune factors, however, the relationship between exosomes and hemolymph microbiota homeostasis during pathogenic bacteria infection has not been addressed. Here, we determined that exosomes released fromVibrio parahaemolyticus-infectedScylla paramamosain(mud crabs) could reduce the mortality of the host during the infection by maintaining the homeostasis of hemolymph microbiota. We further confirmed that miR-224 was densely packaged in these exosomes and targeting to HSP70, which resulted in disruption of the HSP70-TRAF6 complex to release TRAF6 that allows it to interact with Ecsit. The interaction of TRAF6 with Ecsit regulates the production of mitochondrial ROS (mROS) and Anti-lipopolysaccharide factors (ALFs) expression in recipient hemocytes, which affects homeostasis of hemolymph microbiota in response to the pathogenic bacteria infection in mud crab. To the best of our knowledge, this is the first document that reports the role of exosome in the homeostasis of hemolymph microbiota during pathogen infection and a novel regulatory mechanism and crosstalk between exosomal miRNAs and innate immune response in crustaceans.Author summaryExosomes are small membrane vesicles of endocytic origin which are widely involved in the regulation of a variety of pathological processes in mammals. Yet, although the antibacterial function of exosomes has been discovered for many years, the relationship between exosomes and hemolymph microbiota homeostasis remains unknown. In the present study, we identified the miRNAs packaged by exosomes that were possibly involved inVibrio parahaemolyticusinfection by modulating hemolymph microbiota homeostasis in crustacean mud crabScylla paramamosain. Moreover, it was found that miR-224 was densely packaged in exosomes afterVibrio parahaemolyticuschallenge, resulting in the suppression of HSP70 and disruption of the HSP70-TRAF6 complex in recipient hemocytes, then the released TRAF6 was further interacted with Ecsit to regulate ROS and ALFs levels, which eventually affected hemolymph microbiota homeostasis to cope with pathogenic bacteria infection. Our finding is the first to reveal the relationship between exosomes and hemolymph microbiota homeostasis in animals, which shows a novel molecular mechanism of invertebrate resistance to pathogenic microbial infection.
Identifying mutant-specific multi-drug combinations using Comparative Network Reconstruction
Authors: Bosdriesz Evert , Fernandes Neto João M. , Sieber Anja , Bernards René , Blüthgen Nils , Wessels Lodewyk F.A. 
Published: December 2020

AbstractInhibition of aberrant signaling with target inhibitors is an important treatment strategy in cancer, but unfortunately responses are often short-lived. Multi-drug combinations have the potential to mitigate this, but to avoid toxicity such combinations must be selective and the dosage of the individual drugs should be as low as possible. Since the search space of multi-drug combinations is enormous, an efficient approach to identify the most promising drug combinations and dosages is needed.Here, we present a pipeline to prioritize promising multi-drug combinations. We performed a limited set of drug perturbations in an isogenic cell line pair with and without an activating PI3K mutation, and recorded their signaling states and cell viability. We used these data to reconstruct mutant specific signaling networks and map the short term signaling response to longer term changes in cell viability. The resulting models then allowed us to predict the effect of unseen multi-drug combinations, at arbitrary drug-concentrations, on cell viability. Our initial aim was to find combinations that selectively reduce the viability of the PI3K mutant cells, but our models indicated that such combinations do not exist for this cell line pair. However, we were able to validate 25 of the 30 low-dose multi-drug combinations that we predicted to be anti-selective. Our pipeline thus enables a powerful strategy to rapidly map the efficacy and possible selectivity of drug combinations, hence significantly speeding up the pace at which we can explore the vast space of combination therapies.