bluuebunny/crossref_metadata_2025_split huggingface dataset:
OGP: A Repository of Experimentally Characterized O-Glycoproteins to Facilitate Studies on O-Glycosylation
Authors: Huang Jiang-Ming , Wu Meng-Xi , Zhang Yang , Kong Si-Yuan , Liu Ming-Qi , Jiang Bi-Yun , Yang Peng-Yuan , Cao Wei-Qian 
Published: March 2020

AbstractNumerous studies on cancer, biopharmaceuticals, and clinical trials have necessitated comprehensive and precise analysis of protein O-glycosylation. However, the lack of updated and convenient databases deters the storage and utilization of emerging O-glycoprotein data. To resolve this issue, an O-glycoprotein repository named OGP was established in this work. It was constructed with a collection of O-glycoprotein data from different sources. OGP contains 9354 O-glycosylation sites and 11,633 site-specific O-glycans mapping to 2133 O-glycoproteins, and it is the largest O-glycoprotein repository thus far. Based on the recorded O-glycosites, an O-glycosylation site prediction tool was developed. Moreover, an OGP-backed website is already available (http://www.oglyp.org/). The website comprises four specially designed and user-friendly modules: Statistic Analysis, Database Search, Site Prediction, and Data Submit. The first version of OGP repository and the website allow users to obtain vast O-glycoprotein related information, such as protein accession numbers, glycopeptides, site-specific glycan structures, experimental methods, and potential glycosylation sites. O-glycosylation data mining can be performed efficiently on this website, which can greatly facilitates O-glycosylation studies.
Coral accurately bridges paired-end RNA-seq reads alignment
Authors: Shi Qian , Shao Mingfu 
Published: March 2020

AbstractMotivationThe established high-throughput RNA-seq technologies usually produce paired-end reads. A challenging problem is therefore to computationally infer the alignment of entire fragments given the alignment of the two mate ends. Solving this problem essentially provide longer RNA-seq reads, and hence benefits downstream RNA-seq analysis.ResultsWe introduce Coral, a new tool that can accurately bridge paired-end RNA-seq reads. The core of Coral is a novel optimization formulation that can capture the most reliable bridging path while also filter out false paths. An efficient dynamic programming algorithm is designed to calculate the topNoptimum. Coral implements a consensus approach to select the best solution among theNcandidates by taking into account the distribution of fragment length. Coral is modular, can be easily incorporated into existing RNA-seq analysis pipeline. We show that Coral can improve transcript assembly by a large margin: on average over 2377 RNA-seq samples from GTEx, the improvement (measured with adjusted precision) is 7.5% and 11.2% when Coral is incorporated with StringTie and Scallop, respectively.AvailabilityCoral is open-source, freely available at GitHub (https://github.com/Shao-Group/coral) and Bioconda. Scripts, datasets and documentations that can reproduce all experimental results in this paper are available athttps://github.com/Shao-Group/coraltest.
Contrast-enhanced ultrasound measurement of pancreatic blood flow dynamics predicts type1 diabetes therapeutic reversal in preclinical models
Authors: Pham Vinh , Ramirez David G. , Benninger Richard K.P. 
Published: March 2020

AbstractIn type 1 diabetes (T1D) immune-cell infiltration into the islets of Langerhans (insulitis) and β-cell decline occurs many years before diabetes presents. Non-invasively detecting insulitis and β-cell decline would allow diagnosis of eventual diabetes and provide a means to monitor the efficacy of therapeutic intervention. However, there is a lack of validated clinical approaches for non-invasively imaging disease progression leading to T1D. Islets have a dense microvasculature that reorganizes during diabetes. We previously demonstrated contrast-enhanced ultrasound measurements of pancreatic blood-flow dynamics could predict disease progression in T1D pre-clinical models. Here we test whether these measurements can predict successful therapeutic prevention of T1D. We performed destruction-reperfusion measurements using a small-animal ultrasound machine and size-isolated microbubbles, in NOD-scid mice receiving an adoptive transfer of diabetogenic splenocytes (AT mice). Mice received vehicle control or either of the following treatments: 1) antiCD4 to deplete CD4+T cells; 2) antiCD3 to block T cell activation, 3) Verapamil to reduce β-cell apoptosis and 4) TUDCA to reduce ER stress. We compared measurements of pancreas blood-flow dynamics with subsequent progression to diabetes. In AT mice blood-flow dynamics were altered >2 weeks after splenocyte transfer. AntiCD4, antiCD3 and verapamil provided a significant delay in diabetes development. Treated AT mice with delayed or absent diabetes development showed significantly altered blood flow dynamics compared to untreated AT mice. Conversely, treated AT mice that developed diabetes, despite therapy, showed similar blood-flow dynamics to untreated AT mice. Thus, contrast-enhanced ultrasound measurement of pancreas blood-flow dynamics can predict the successful or unsuccessful delay or prevention of diabetes upon therapeutic treatments that target both immune activity or β-cell protection. This strategy may provide a clinically deployable predictive marker for disease progression and therapeutic reversal in asymptomatic T1D.
Where have all the spiders gone? Observations of a dramatic population density decline in the once very abundant garden spider,Araneus diadematus(Araneae: Araneidae), in the Swiss midland
Authors: Nyffeler Martin , Bonte Dries 
Published: March 2020

AbstractAerial web-spinning spiders (including large orb-weavers) depend, as a group of insectivores, completely on flying insects as a food source. The recent widespread loss of flying insects across large parts of western Europe, both in terms of diversity and biomass, can therefore be anticipated to have a drastic negative impact on survival and abundance of this type of spiders. To test the putative importance of such a to date neglected trophic cascade, a survey of population densities of the European garden spiderAraneus diadematus– a large orb-weaving spider – was conducted in late summer 2019 on twenty sites of the Swiss midland. The data from this survey were compared with published population densities for this species from the previous century. The study verifies above-mentioned hypothesis that this spider’s present-day overall mean population density has declined alarmly to densities much lower than can be expected from normal population fluctuations (0.7% of the historical densities). Review of other available records suggests this pattern is widespread and not restricted to this region. In conclusion, the here documented abundance decline of this once so abundant spider in the Swiss midland is evidently revealing a bottom-up trophic cascade in response to the widespread loss of flying insect prey in recent decades.
Case fatality risk of novel coronavirus diseases 2019 in China
Authors: Deng Xiaowei , Yang Juan , Wang Wei , Wang Xiling , Zhou Jiaxin , Chen Zhiyuan , Li Jing , Chen Yinzi , Yan Han , Zhang Juanjuan , Zhang Yongli , Wang Yan , Qiu Qi , Gong Hui , Wei Xianglin , Wang Lili , Sun Kaiyuan , Wu Peng , Ajelli Marco , Cowling Benjamin J. , Viboud Cecile , Yu Hongjie 
Published: March 2020

ABSTRACTObjectiveThe outbreak of novel coronavirus disease 2019 (COVID-19) imposed a substantial health burden in mainland China and remains a global epidemic threat. Our objectives are to assess the case fatality risk (CFR) among COVID-19 patients detected in mainland China, stratified by clinical category and age group.MethodsWe collected individual information on laboratory-confirmed COVID-19 cases from publicly available official sources from December 29, 2019 to February 23, 2020. We explored the risk factors associated with mortality. We used methods accounting for right-censoring and survival analyses to estimate the CFR among detected cases.ResultsOf 12,863 cases reported outside Hubei, we obtained individual records for 9,651 cases, including 62 deaths and 1,449 discharged cases. The deceased were significantly older than discharged cases (median age: 77 vs 39 years, p<0.001). 58% (36/62) were male. Older age (OR 1.18 per year; 95%CI: 1.14 to 1.22), being male (OR 2.02; 95%CI: 1.02 to 4.03), and being treated in less developed economic regions (e.g., West and Northeast vs. East, OR 3.93; 95%CI: 1.74 to 8.85) were mortality risk factors. The estimated CFR was 0.89-1.24% among all cases. The fatality risk among critical patients was 2-fold higher than that among severe and critical patients, and 24-fold higher than that among moderate, severe and critical patients.ConclusionsOur estimates of CFR based on laboratory-confirmed cases ascertained outside of Hubei suggest that COVID-19 is not as severe as severe acute respiratory syndrome and Middle East respiratory syndrome, but more similar to the mortality risk of 2009 H1N1 influenza pandemic in hospitalized patients. The fatality risk of COVID-19 is higher in males and increases with age. Our study improves the severity assessment of the ongoing epidemic and can inform the COVID-19 outbreak response in China and beyond.
Clinical characteristics of 101 COVID-19 nonsurvivors in Wuhan, China: a retrospective study
Authors: Shi Qiao , Zhao Kailiang , Yu Jia , Jiang Fang , Feng Jiarui , Zhao Kaiping , Zhang Xiaoyi , Chen Xiaoyan , Hu Peng , Hong Yupu , Li Man , Liu Fang , Chen Chen , Wang Weixing 
Published: March 2020

AbstractBackgroundThe outbreak of COVID-19 has aroused global concerns. We aimed to describe the clinical characteristics of COVID-19 nonsurvivors and analyze possible causes for the rapid disease progress to death.MethodsPatients with confirmed COVID-19 died in Renmin Hospital of Wuhan University before February 15, 2020, were identified. We obtained epidemiological, demographic, and clinical data from electronic medical records.ResultsAmong 101 nonsurvivors, the median age was 71.0 years (IQR, 59.0-80.0), 59.4% were male, 79.2% had one or more comorbidities including hypertension (58.4%), cardiovascular disease (22.8%), diabetes (20.8%) etc. The most common symptoms were fever (76.2%), cough (58.4%) and dyspnea (54.5%). Respiratory failure (99.0%), acute cardiac injury (52.5%), sepsis (40.6%) and acute kidney injury (23.8%) were most common complications. Compared with patients died after 3 days of admission, patients died within 3 days of admission had significantly higher white blood cell count (10.8 vs 6.7×109/L, P=0.001) and neutrophil count (8.9 vs 5.5×109/L, P=0.001), longer prothrombin time (13.2 vs 12.5 s, P=0.040), higher D-dimer concentration (7.64 vs 2.82, P=0.040), higher lactate level (2.9 vs 2.2 mmol/L, P=0.042), lower oxygen saturation (85.0% vs 91.0%, P=0.008), and were more likely to suffer sepsis (52.1% vs 30.2%, P=0.025).ConclusionsOlder patients with underlying comorbidities suffering COVID-19 were at high risk of death. Respiratory failure, acute cardiac injury and acute kidney injury played crucial roles in the death of COVID-19 patients. Early development of sepsis was associated with the rapid disease progress to death.
Genome sequencing combining prenatal ultrasound in the evaluation of fetal CNS structural anomalies
Authors: Yang Ying , Zhao Sheng , Sun Guoqiang , Chen Fang , Zhang Tongda , Song Jieping , Yang Wenzhong , Wang Lin , Zhan Nianji , Yang Xiaohong , Zhu Xia , Rao Bin , Yin Zhenzhen , Zhou Jing , Yan Haisheng , Huang Yushan , Ye Jingyu , Huang Hui , Cheng Chen , Zhu Shida , Guo Jian , Xu Xun , Chen Xinlin 
Published: March 2020

AbstractPurposeGenome sequencing (GS) is potentially the most suitable diagnostic tools for fetal CNS structural anomalies. However, its efficacy hasn’t been proved in large cohort of fetal CNS structural anomalies.MethodsPatients were enrolled by a multiple-level referral system when fetal CNS structure anomalies were found by ultrasonography. Samples from fetuses were subjected to GS.ResultsData of 162 fetuses with 11 frequent types of CNS anomalies was collected. The overall diagnosis yield of GS was 38.9%. 36(20.3%) fetuses were detected with chromosomal anomalies and pathogenic CNVs. Pathogenic or likely pathogenic single-gene variants and intragenic CNVs were found in 24 and three fetuses, contributing 14.8% and 1.9% diagnostic yield respectively. The diagnostic rate in 41 fetuses with CNS malformation combined with anomalies out of brain was as high as 73.3%. Malformations of the posterior cerebral fossa, abnormal neuronal proliferation and migration have the highest diagnostic rates. NTDs had the second lowest diagnostic rates of 14.7% and none pathogenic variants were found in ultrasound anomalies that suggested destructive cerebral lesions.ConclusionGS is an efficient genetic testing tool with the diagnostic power compared to current CMA plus ES procedure in fetal CNS anomalies evaluation.
Memory reconsolidation impairments in sign-tracking to an audiovisual compound stimulus
Authors: Drame Mohamed L. , Balaet Maria , Lee Jonathan L. C. 
Published: March 2020

AbstractStudies of memory reconsolidation of pavlovian memories have typically employed unimodal conditioned stimuli, despite the use of multimodal compound stimuli in other settings. Here we studied sign-tracking behaviour to a compound audiovisual stimulus. First, we observed not unexpectedly that sign-tracking was poorer to the audiovisual compound than to unimodal visual stimuli. Then, we showed that, depending on the parameters of compound stimulus re-exposure at memory reactivation, systemic MK-801 treatment either impaired extinction to improve signtracking at test, or disrupted reconsolidation to impair test behaviour. When memory reactivation consisted of re-exposure to only the auditory component of the compound stimulus, we observed sign-tracking impairments following MK-801 treatment, but only under certain test conditions. This was in contrast to the consistent impairment following reactivation with the full audiovisual compound. Moreover, the parameters of auditory stimulus presentation to enable MK-801-induced impairment at test varied depending on whether the stimulus was presented within or outside the training context. These findings suggest that behaviour under the control of appetitive pavlovian compound stimuli can be modulated by targeting both extinction and reconsolidation, and that it is not necessary to re-expose to the full compound stimulus in order to achieve a degree of modulation of behaviour.
Incorporating Prior Knowledge into Regularized Regression
Authors: Zeng Chubing , Thomas Duncan Campbell , Lewinger Juan Pablo 
Published: March 2020

AbstractMotivationAssociated with genomic features like gene expression, methylation, and genotypes, used in statistical modeling of health outcomes, there is a rich set of meta-features like functional annotations, pathway information, and knowledge from previous studies, that can be used post-hoc to facilitate the interpretation of a model. However, using this meta-feature information a-priori rather than post-hoc can yield improved prediction performance as well as enhanced model interpretation.ResultsWe propose a new penalized regression approach that allows a-priori integration of external meta-features. The method extends LASSO regression by incorporating individualized penalty parameters for each regression coefficient. The penalty parameters are in turn modeled as a log-linear function of the meta-features and are estimated from the data using an approximate empirical Bayes approach. Optimization of the marginal likelihood on which the empirical Bayes estimation is based is performed using a fast and stable majorization-minimization procedure. Through simulations, we show that the proposed regression with individualized penalties can outperform the standard LASSO in terms of both parameters estimation and prediction performance when the external data is informative. We further demonstrate our approach with applications to gene expression studies of bone density and breast cancer.Availability and implementationThe methods have been implemented in the R packagextunefreely available for download from CRAN.
A codon model for associating phenotypic traits with altered selective patterns of sequence evolution
Authors: Halabi Keren , Karin Eli Levy , Guéguen Laurent , Mayrose Itay 
Published: March 2020

AbstractChanges in complex phenotypes, such as pathogenicity levels, trophic lifestyle, and habitat shifts are brought on by multiple genomic changes: sub- and neofunctionalization, loss of function, and levels of gene expression. Thus, detecting the signature of selection in coding sequences and associating it with shifts in phenotypic state can unveil the genes underlying complex traits. Phylogenetic branch-site codon models are routinely applied to detect changes in selective patterns along specific branches of the phylogeny. These methods rely on a pre-specified partition of the phylogeny to branch categories, thus treating the course of trait evolution as fully resolved and assuming that transitions in phenotypic states have occurred only at speciation events. Here we present TraitRELAX, a new phylogenetic model that alleviates these strong assumptions by explicitly accounting for the uncertainty in the evolution of both trait and coding sequences. This joint statistical framework enables the detection of changes in selection intensity upon repeated trait transitions. We evaluated the performance of TraitRELAX using simulations and then applied it to two case studies. Using TraitRELAX, we found an intensification of selection in the SEMG2 gene in polygynandrous species of primates compared to species of other mating forms, as well as changes in the intensity of purifying selection operating on sixteen bacterial genes upon transitioning from free-living to an endosymbiotic lifestyle.
Evidence supporting an antimicrobial origin of targeting peptides to endosymbiotic organelles
Authors: Garrido Clotilde , Caspari Oliver D. , Choquet Yves , Wollman Francis-André , Lafontaine Ingrid 
Published: March 2020

AbstractMitochondria and chloroplasts emerged from primary endosymbiosis. Most proteins of the endosymbiont were subsequently expressed in the nucleo-cytosol of the host and organelle-targeted via the acquisition of N-terminal presequences, whose evolutionary origin remains enigmatic. Using a quantitative assessment of their physico-chemical properties, we show that organelle targeting peptides, which are distinct from signal peptides targeting other subcellular compartments, group with a subset of antimicrobial peptides. We demonstrate that extant antimicrobial peptides target a fluorescent reporter to either the mitochondria or the chloroplast in the green algaChlamydomonas reinhardtiiand, conversely, that extant targeting peptides still display antimicrobial activity. Thus, we provide strong computational and functional evidence for an evolutionary link between organelle-targeting and antimicrobial peptides. Our results support the view that resistance of bacterial progenitors of organelles to the attack of host antimicrobial peptides has been instrumental in eukaryogenesis and in emergence of photosynthetic eukaryotes.
IgG-aggregates rapidly up-regulate FcgRI expression at the surface of human neutrophils in a FcgRII-dependent fashion: A crucial role for FcgRI in the generation of reactive oxygen species
Authors: Huot Sandrine , Laflamme Cynthia , Fortin Paul R. , Boilard Eric , Pouliot Marc 
Published: March 2020

AbstractAutoimmune complexes are an important feature of several autoimmune diseases such as lupus, as they contribute to tissue damage through the activation of immune cells. Neutrophils, key players in lupus, interact with immune complexes through Fc gamma receptors (FcgR). Incubation of neutrophils with aggregated-IgGs caused degranulation and increased the surface expression of FcgRI within minutes in a concentration-dependent fashion. After 30 min, IgG aggregates (1 mg/ml) up-regulated FcgRI by 4.95 ± 0.45-fold. FcgRI-positive neutrophils reached 67.24% ± 6.88% on HA-IgGs stimulated neutrophils, from 3.12% ± 1.62% in non-stimulated cells, ranking IgG-aggregates among the most potent known agonists. FcgRIIa, and possibly FcgRIIIa, appeared to mediate this up-regulation. Also, FcgRI-dependent signaling proved necessary for reactive oxygen species (ROS) production in response to IgG-aggregates. Finally, combinations of bacterial materials with aggregates dramatically boosted ROS production. This work suggests FcgRI as an essential component in the response of human neutrophils to immune complexes leading to the production of ROS, which may help explain how neutrophils contribute to tissue damage associated with immune complex-associated diseases, such as lupus.
Cystathionine β-synthase deficiency impairs vision in the fruit fly,Drosophila melanogaster
Authors: Flores-Flores Marycruz , Moreno-García Leonardo , Ángeles Castro-Martínez Felipe , Nahmad Marcos 
Published: March 2020

PurposeIn humans, deficiency in Cystathionine β-Synthase (CBS) levels leads to an abnormal accumulation of homocysteine and results in classic homocystinuria, a multi-systemic disorder affecting connective tissue, muscles, the central nervous system and the eyes. However, the genetic and molecular mechanisms underlying vision problems in patients with homocystinuria are little understood.Materials and MethodsThe fruit fly,Drosophila melanogaster, is a useful experimental system to investigate the genetic basis of several human diseases, but no study to date has used Drosophila as model of homocystinuria. Here we use genetic tools to down-regulate CBS and classical behavioral assays to propose Drosophila as a model of homocystinuria to study vision problems.ResultsWe present evidence that CBS-deficient flies show an abnormal stereotypical behavior of attraction towards a luminous source or phototaxis, consistent with severe myopia in humans. We show that this behavior cannot be fully attributed to a motor or olfactory deficiency but most likely to an impaired vision. CBS-deficient flies are overall smaller, but smaller eyes do not explain their erratic phototactic response.ConclusionsWe propose Drosophila as a useful model to investigate ocular manifestations underlying homocystinuria.
Interrupting reactivation of immunological memory reprograms allergy and averts anaphylaxis
Authors: Bruton Kelly , Spill Paul , Vohra Shabana , Baribeau Owen , Manzoor Saba , Gadkar Siyon , Davidson Malcolm , Walker Tina D. , Ellenbogen Yosef , Florescu Alexandra , Wen Jianping , Chu Derek K. , Waserman Susan , Jiménez-Saiz Rodrigo , Epelman Slava , Robbins Clinton , Jordana Manel 
Published: March 2020

AbstractIgE production against innocuous antigens can lead to life-threatening reactions such as anaphylaxis. While IgE levels drastically decline with strict allergen avoidance, the ability to regenerate IgE can persist for a lifetime, as is the case for peanut allergy. The mechanism by which IgE regenerates remains unresolved. A novel culture system and application of single-cell RNA-sequencing, elucidated the transcriptomic signature of human peanut-reactive B and T cells and revealed IL-4/IL-13 as a signaling pathway critical for the IgE recall response. Indeed, interruption of this pathway not only prevented IgE production and anaphylaxis, but also reprogrammed the pathogenic response against peanut. This investigation advances our understanding of the mechanism that regenerates IgE in food allergy and spotlights IL-4/IL-13 blockade as a therapeutic with disease-transforming potential.One Sentence SummarySingle-cell transcriptomics of allergic memory responses reveals how to teach the immune system to forget.