bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fibrous caps in atherosclerosis form by Notch-dependent mechanisms common to arterial media development
Authors: Martos Carlos J. , Albarrán-Juárez Julián , Morales-Cano Daniel , Caballero Ainoa , MacGrogan Donal , de la Pompa José Luis , Carramolino Laura , Bentzon Jacob F. 
Published: September 2020

AbstractRationaleThe rupture of the fibrous cap in atherosclerotic lesions is the underlying cause of most thrombi leading to heart attack and a frequent cause of stroke. Caps are produced by smooth muscle cells (SMCs) that are recruited to the subendothelial space. We hypothesized that the recruitment mechanisms are likely common to embryonic artery development, which relies prominently on Notch signaling to form the subendothelial layers of medial SMCs.ObjectiveTo analyze the causal roles of the Notch signaling pathway in SMCs for atherogenesis and cap formation.Methods and ResultsNotch elements involved in arterial media development were found expressed in regions of fibrous cap in mouse plaques. To assess the causal role of Notch signaling in cap formation, we studied atherosclerosis in mice in which the Notch pathway was inactivated specifically in SMCs by conditional knockout of the essential effector transcription factor RBPJ. No major effects were observed on plaque size, but the presence of cap SMCs was significantly reduced. Lineage tracing revealed that the accumulation of SMC-derived plaque cells in the cap region was unaltered but that Notch-defective cells failed to re-acquire the SMC phenotype in the cap. To analyze whether the accumulation of SMC-derived cells in atherogenesis requires down-regulation of Notch signaling, we studied atherosclerosis in mice with constitutive Notch signaling in SMCs achieved by conditional expression of the Notch intracellular domain. Forced Notch signaling inhibited the ability of medial SMCs to contribute to plaque cells, including both cap SMCs and osteochondrogenic cells, and significantly reduced atherosclerosis development.ConclusionsSequential loss and gain of Notch signaling is needed to build the cap SMC population. The shared mechanisms with embryonic arterial media assembly suggest that the fibrous cap forms as aneo-mediathat restores the connection between endothelium and stabilizing SMCs, which is transiently disrupted by atherogenesis.
Brain Connectivity and Behavioral Changes in a Spaceflight Analog Environment with Elevated CO2
Authors: McGregor Heather R. , Lee Jessica K. , Mulder Edwin R. , De Dios Yiri E. , Beltran Nichole E. , Kofman Igor S. , Bloomberg Jacob J. , Mulavara Ajitkumar P. , Seidler Rachael D. 
Published: October 2020

ABSTRACTAstronauts are exposed to microgravity and elevated CO2levels onboard the International Space Station. Little is known about how microgravity and elevated CO2combine to affect the brain and sensorimotor performance during and after spaceflight. Here we examined changes in resting-state functional connectivity (FC) and sensorimotor behavior associated with a spaceflight analog environment. Participants underwent 30 days of strict 6°head-down tilt bed rest with elevated ambient CO2(HDBR+CO2). Resting-state functional magnetic resonance imaging and sensorimotor assessments were collected 13 and 7 days prior to bed rest, on days 7 and 29 of bed rest, and 0, 5, 12, and 13 days following bed rest. We assessed the time course of FC changes from before, during, to after HDBR+CO2. We then compared the observed connectivity changes with those of a HDBR control group, which underwent HDBR in standard ambient air. Moreover, we assessed associations between post-HDBR+CO2FC changes and alterations in sensorimotor performance. HDBR+CO2was associated with significant changes in functional connectivity between vestibular, visual, somatosensory and motor brain areas. Several of these sensory and motor regions showed post-HDBR+CO2FC changes that were significantly associated with alterations in sensorimotor performance. We propose that these FC changes reflect multisensory reweighting associated with adaptation to the HDBR+CO2microgravity analog environment. This knowledge will further improve HDBR as a model of microgravity exposure and contribute to our knowledge of brain and performance changes during and after spaceflight.
Understanding the genetic diversity of the guayabillo (Psidium galapageium), an endemic plant of the Galapagos Islands
Authors: Urquia Diego , Pozo Gabriela , Gutierrez Bernardo , Rowntree Jennifer K. , de Lourdes Torres Maria 
Published: September 2020

ABSTRACTOceanic archipelagos are known to host a variety of endemic plant species. The genetic diversity and structure of these species is an important indicator of their evolutionary history and can inform appropriate conservation strategies that mitigate the risks to which they’re exposed, including invasive species and environmental disturbances. A comprehensive consideration of the role of their natural history, as well as the landscape features and the geological history of the islands themselves is required to adequately understand any emerging patterns. Such is the case for the guayabillo (Psidium galapageium), an understudied endemic plant from the Galapagos Islands with important ecological and economic roles. In this study we designed and evaluated 13 informative SSR markers and used them to investigate the genetic diversity, population structure and connectivity of the guayabillo populations from San Cristobal, Isabela and Santa Cruz islands. A total of 208 guayabillo individuals were analyzed, revealing a strong population structure between islands and two distinct genetic lineages for the Santa Cruz population. Overall, the guayabillo genetic diversity is relatively high, an unusual pattern for an insular endemic species which is possibly explained by its polyploidy and the geographical features of the islands. These include their broad altitudinal ranges and habitat heterogeneity. For populations displaying a lower genetic diversity such as San Cristobal, the history of human disturbance could be an important factor explaining these observations. Some similarities between individuals in Santa Cruz and the San Cristobal population could be explained by population differentiation or distinct natural histories of separate lineages. Our findings highlight the complex population dynamics that shape the genetic diversity of species like the guayabillo and emphasize the need to explore the currently unresolved questions about this Galapagos endemic plant.
Maximum Parsimony Inference of Phylogenetic Networks in the Presence of Polyploid Complexes
Authors: Yan Zhi , Cao Zhen , Liu Yushu , Nakhleh Luay 
Published: September 2020

AbstractPhylogenetic networks provide a powerful framework for modeling and analyzing reticulate evolutionary histories. While polyploidy has been shown to be prevalent not only in plants but also in other groups of eukaryotic species, most work done thus far on phylogenetic network inference assumes diploid hybridization. These inference methods have been applied, with varying degrees of success, to data sets with polyploid species, even though polyploidy violates the mathematical assumptions underlying these methods. Statistical methods were developed recently for handling specific types of polyploids and so were parsimony methods that could handle polyploidy more generally yet while excluding processes such as incomplete lineage sorting. In this paper, we introduce a new method for inferring most parsimonious phylogenetic networks on data that include polyploid species. Taking gene trees as input, the method seeks a phylogenetic network that minimizes deep coalescences while accounting for polyploidy. The method could also infer trees, thus potentially distinguishing between auto- and allo-polyploidy. We demonstrate the performance of the method on both simulated and biological data. The inference method as well as a method for evaluating given phylogenetic networks are implemented and publicly available in the PhyloNet software package.
SARS-CoV-2 D614G Variant Exhibits Enhanced Replicationex vivoand Earlier Transmissionin vivo
Authors: Hou Yixuan J. , Chiba Shiho , Halfmann Peter , Ehre Camille , Kuroda Makoto , Dinnon Kenneth H , Leist Sarah R. , Schäfer Alexandra , Nakajima Noriko , Takahashi Kenta , Lee Rhianna E. , Mascenik Teresa M. , Edwards Caitlin E. , Tse Longping V. , Boucher Richard C. , Randell Scott H. , Suzuki Tadaki , Gralinski Lisa E. , Kawaoka Yoshihiro , Baric Ralph S. 
Published: September 2020

AbstractThe D614G substitution in the S protein is most prevalent SARS-CoV-2 strain circulating globally, but its effects in viral pathogenesis and transmission remain unclear. We engineered SARS-CoV-2 variants harboring the D614G substitution with or without nanoluciferase. The D614G variant replicates more efficiency in primary human proximal airway epithelial cells and is more fit than wildtype (WT) virus in competition studies. With similar morphology to the WT virion, the D614G virus is also more sensitive to SARS-CoV-2 neutralizing antibodies. Infection of human ACE2 transgenic mice and Syrian hamsters with the WT or D614G viruses produced similar titers in respiratory tissue and pulmonary disease. However, the D614G variant exhibited significantly faster droplet transmission between hamsters than the WT virus, early after infection. Our study demonstrated the SARS-CoV2 D614G substitution enhances infectivity, replication fitness, and early transmission.
A synthetic small molecule stalls pre-mRNA splicing by promoting an early-stage U2AF2–RNA complex
Authors: Chatrikhi Rakesh , Feeney Callen F. , Pulvino Mary J. , Alachouzos Georgios , MacRae Andrew J. , Falls Zackary , Rai Sumit , Brennessel William W. , Jenkins Jermaine L. , Walter Matthew J. , Graubert Timothy A. , Samudrala Ram , Jurica Melissa S. , Frontier Alison J. , Kielkopf Clara L. 
Published: September 2020

AbstractDysregulated pre-mRNA splicing is an emerging Achilles heel of cancers and myelodysplasias. To expand the currently limited portfolio of small molecule drug leads, we screened for chemical modulators of the U2AF complex, which nucleates spliceosome assembly and is mutated in myelodysplasias. A hit compound specifically enhances RNA binding by a U2AF2 subunit. Remarkably, the compound inhibits splicing of representative substrates in cells and stalls spliceosome assembly at the stage of U2AF function. Computational docking, together with structure-guided mutagenesis, indicates that the compound bridges an active conformation of the U2AF2 RNA recognition motifsviahydrophobic and electrostatic moieties. Altogether, our results highlight the potential of trapping early spliceosome assembly as an effective pharmacological means to manipulate pre-mRNA splicing. By extension, we suggest that stabilizing inactive checkpoints may offer a breakthrough approach for small molecule inhibition of multi-stage macromolecular assemblies.
Global Analysis of the Mammalian MHC class I Immunopeptidome at the Organism-Wide Scale
Authors: Kubiniok Peter , Marcu Ana , Bichmann Leon , Kuchenbecker Leon , Schuster Heiko , Hamelin David , Despault Jérome , Kovalchik Kevin , Wessling Laura , Kohlbacher Oliver , Stevanovic Stefan , Rammensee Hans-Georg , Neidert Marian C. , Sirois Isabelle , Caron Etienne 
Published: September 2020

ABSTRACTUnderstanding the molecular principles that govern the composition of the mammalian MHC-I immunopeptidome (MHC-Ii) across different primary tissues is fundamentally important to predict how T cell respond in different contextsin vivo. Here, we performed a global analysis of the mammalian MHC-Ii from 29 and 19 primary human and mouse tissues, respectively. First, we observed that different HLA-A, -B and -C allotypes do not contribute evenly to the global composition of the MHC-Ii across multiple human tissues. Second, we found that peptides that are presented in a tissue-dependent and -independent manner share very distinct properties. Third, we discovered that proteins that are evolutionarily hyperconserved represent the primary source of the MHC-Ii at the organism-wide scale. Finally, we uncovered new components of the antigen processing and presentation network that may drive the high level of heterogeneity of the MHC-Ii across different tissues in mammals. This study opens up new avenues toward a system-wide understanding of antigen presentationin vivoand may serve as ground work to understand tissue-dependent T cell responses in autoimmunity, infectious diseases and cancer.
Discovery of genomic loci associated with sleep apnoea risk through multi-trait GWAS analysis with snoring
Authors: Campos Adrian I. , Ingold Nathan , Huang Yunru , Mitchell Brittany L. , Kho Pik-Fang , Han Xikun , García-Marín Luis M. , Ong Jue-Sheng ,   23andMe Research Team, Law Matthew H. , Yokoyama Jennifer S. , Martin Nicholas G. , Dong Xianjun , Cuellar-Partida Gabriel , MacGregor Stuart , Aslibekyan Stella , Rentería Miguel E. 
Published: October 2020

ABSTRACTBackgroundSleep apnoea is characterised by periods of halted breathing during sleep. Despite its association with severe health conditions, the aetiology of sleep apnoea remains understudied, and previous genetic analyses have not identified many robustly associated genetic risk variants.MethodsWe performed a genome-wide association study (GWAS) meta-analysis of sleep apnoea across five cohorts (NTotal=523,366), followed by a multi-trait analysis of GWAS (MTAG) to boost power, leveraging the high genetic correlation between sleep apnoea and snoring. We then adjusted our results for the genetic effects of body mass index (BMI) using multi-trait-based conditional & joint analysis (mtCOJO) and sought replication of lead hits in a large cohort of participants from 23andMe, Inc (NTotal=1,477,352; Ncases=175,522). We also explored genetic correlations with other complex traits and performed a phenome-wide screen for causally associated phenotypes using the latent causal variable method.ResultsOur MTAG analysis uncovered 49 significant independent loci associated with sleep apnoea risk. Twenty-nine variants were replicated in the 23andMe cohort. We observed genetic correlations with several complex traits, including multisite chronic pain, diabetes, eye disorders, high blood pressure, osteoarthritis, chronic obstructive pulmonary disease, and BMI-associated conditions.ConclusionsOur study uncovered multiple genetic loci associated with sleep apnoea risk, thus increasing our understanding of the aetiology of this condition and its relationship with other complex traits.
Neuroanatomical Considerations for Optimizing Thalamic Deep Brain Stimulation in Tourette Syndrome
Authors: Morishita Takashi , Sakai Yuki , Iida Hitoshi , Yoshimura Saki , Ishii Atsushi , Fujioka Shinsuke , Tanaka Saori C. , Inoue Tooru 
Published: October 2020

AbstractBackgroundDeep brain stimulation (DBS) of the centromedian (CM) thalamic nucleus has reportedly been used to treat severe Tourette syndrome (TS) with promising outcomes; however, it remains unclear how DBS electrode position and stimulation parameters modulate the specific area and related networks. We aimed to evaluate the relationships between the anatomical location of stimulation fields and clinical responses including therapeutic and side effects.MethodsWe collected data from eight TS patients treated with DBS. We evaluated the clinical outcomes using Yale Global Tic Severity Scale (YGTSS), Yale-Brown Obsessive Compulsive Scale (Y-BOCS), and Hamilton Depression Rating Scale (HAM-D). The DBS lead location was evaluated in the normalised brain space using a 3-D atlas. The volume of tissue activated (VTA) was determined, and the associated normative connective analyses were performed to link the stimulation field with the therapeutic and side effects.ResultsThe mean follow-up period was 10.9 ± 3.9 months. All clinical scale showed significant significant improvement. While the VTA associated with therapeutic effects covers the CM and ventrolateral nuclei and showed association with motor networks, those associated with paraesthesia and dizziness were associated with stimulation of the ventralis caudalis and red nucleus, respectively. Depressed mood was associated with the spread of stimulation current to the mediodorsal nucleus and showed association with limbic networks.ConclusionOur study addresses the importance of accurate implantation of DBS electrodes for obtaining standardised clinical outcomes and suggests that meticulous programming with careful monitoring of clinical symptoms may improve outcomes.
Seroprevalence of SARS-CoV-2 IgG antibodies, in Corsica (France), April and June 2020
Authors: Lisandru Capai , Nazli Ayhan , Shirley Masse , Jean Canarelli , Stéphane Priet , Helene Simeoni Marie , Remi Charrel , Xavier de Lamballerie , Alessandra Falchi 
Published: October 2020

AbstractOur aim was to assess the seroprevalence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection after the lockdown in a sample of the Corsican population. Between 16th April and 15th June 2020, 2,312 residual sera were collected from patients having carried out a blood analysis in one of the participating laboratories. Residual sera obtained from persons of all ages were tested for the presence of anti-SARS-CoV-2 IgG using the EUROIMMUN enzyme immunoassay kit for semiquantitative detection of IgG antibodies against S1 domain of viral spike protein (ELISA-S). Borderline and positive samples in ELISA-S were also tested with an in-house virus neutralization test (VNT). Prevalence values were adjusted for sex and age. A total of 1,973 residual sera samples were included in the study. The overall seroprevalence based on ELISA-S was 5.27% [95% confidence interval (CI) 4.33-6.35] and 5.46% [4.51-6.57] after adjustment. Gender was not associated with IgG detection. However, significant differences were observed between age groups (p-value = 1 E-5) and particularly for people being younger than 50 years of age (Odd ratio (OR) = 2.86 95% CI [1.80-4.53]; p-value <0.000001*). The prevalence of neutralizing antibody titers ≥40 was of 3% [2.28-3.84]. In conclusion the present study showed that a low seroprevalence for COVID-19 in Corsica in accordance with values reported for other French regions in which the impact of the pandemic was low.
Artificial intelligence to predict the risk of mortality from Covid-19: Insights from a Canadian Application
Authors: Snider Brett , Phillips Paige , MacLean Aryn , McBean Edward , Gadsden S. Andrew , Yawney John 
Published: October 2020

AbstractThe Severe Acute Respiratory Syndrome COVID-19 virus (SARS-CoV-2) has had enormous impacts, indicating need for non-pharmaceutical interventions (NPIs) using Artificial Intelligence (AI) modeling. Investigation of AI models and statistical models provides important insights within the province of Ontario as a case study application using patients’ physiological conditions, symptoms, and demographic information from datasets from Public Health Ontario (PHO) and the Public Health Agency of Canada (PHAC). The findings using XGBoost provide an accuracy of 0.9056 for PHO, and 0.935 for the PHAC datasets. Age is demonstrated to be the most important variable with the next two variables being Hospitalization and Occupation. Further, AI models demonstrate identify the importance of improved medical practice which evolved over the six months in treating COVID-19 virus during the pandemic, and that age is absolutely now the key factor, with much lower importance of other variables that were important to mortality near the beginning of the pandemic.An XGBoost model is shown to be fairly accurate when the training dataset surpasses 1000 cases, indicating that AI has definite potential to be a useful tool in the fight against COVID-19 even when caseload numbers needed for effective utilization of AI model are not large.
Virus evolution affected early COVID-19 spread
Authors: Corcoran Derek , Urban Mark C. , Wegrzyn Jill , Merow Cory 
Published: October 2020

AbstractAs the SARS-Cov-2 virus spreads around the world afflicting millions of people, it has undergone divergent genetic mutations. Although most of these mutations are expected to be inconsequential, some mutations in the spike protein structure have been hypothesized to affect the critical stage at which the virus invades human cells, which could affect transmission probability and disease expression. If true, then we expect an increased growth rate of reported COVID-19 cases in regions dominated by viruses with these altered proteins. We modeled early global infection dynamics based on clade assignment along with other demographic and meteorological factors previously found to be important. Clade, but not variant D614G which has been associated with increased viral load, enhanced our ability to describe early COVID-19 growth dynamics. Including clade identity in models significantly improved predictions over earlier work based only on weather and demographic variables. In particular, higher proportions of clade 19A and 19B were negatively correlated with COVID-19 growth rate, whereas higher proportions of 20A and 20C were positively correlated with growth rate. A strong interaction between the prevalence of clade 20C and relative humidity suggests that the impact of clade identity might be more important when coupled with certain weather conditions. In particular, 20C an 20A generate the highest growth rates when coupled with low humidity. Projections based on data through April 2020 suggest that, without intervention, COVID-19 has the potential to grow more quickly in regions dominated by the 20A and 20C clades, including most of South and North America.
Tracking private WhatsApp discourse about COVID-19: A longitudinal infodemiology study in Singapore
Authors: Tan Edina YQ , Wee Russell RE , Ern Saw Young , Heng Kylie JQ , Chin Joseph WE , Tong Eddie M.W. , Liu Jean CJ 
Published: September 2020

AbstractBackgroundWorldwide, social media traffic increased following the onset of the coronavirus disease (COVID-19) pandemic. Although the spread of COVID-19 content has been described for several social media platforms (e.g., Twitter, Facebook), little is known about how content is spread via private messaging platforms such as WhatsApp.ObjectiveIn this study, we documented: (i) how WhatsApp is used to transmit COVID-19 content; (ii) the characteristics of WhatsApp users based on their usage patterns; and (iii) how usage patterns link to well-being.MethodsWe used the experience sampling method to track day-to-day WhatsApp usage during the COVID-19 pandemic. For one week, participants reported each day the extent to which they had received, forwarded, or discussed COVID-19 content. The final dataset comprised 924 data points collected from 151 participants.ResultsDuring the week-long monitoring, most participants (143/151, 95%) reported at least one COVID-19-related use of WhatsApp. When a taxonomy was generated based on usage patterns, 1 in 10 participants (21/151, 14%) were found to have received and shared a high volume of forwarded COVID-19 content – akin to ‘super spreaders’ identified on other social media platforms. Finally, those who engaged with more COVID-19 content in their personal chats were more likely to report having COVID-19 thoughts throughout the day.ConclusionsThese findings provide a rare window into discourse on private messenger platforms. In turn, this can inform risk communication strategies during the pandemic.