bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hidden Transcriptome Signature in Autism Spectrum Disorder (ASD) is Attributed to the Interpatient Heterogeneity
Authors: Huang Yimei , Yang Yuqing , Qiu Chuchen , Sun Ting , Han Ruilin , Leung Chi Sum , Xie Songhong , Chen Dongjin 
Published: January 2021

AbstractRecent studies of ASD have mostly supported the existence of heterogeneity and genomic variation in ASD which have hindered and restrained development of any effective and targetable treatment for a long time. As numerous studies have shown, both genetic and phenotypic heterogeneity is presented in ASD, however, heterogeneity in genetic level is not fully understood which is the key challenges for the further research. Even dozens of ASD susceptibility genes have been discovered which is commonly accounting for 10 to 20 percent of ASD cases, the internal complex combination of mutated genes that determine the epigenetic factors of ASD is still not comprehensively recognized by the recent studies. First by discouraging the traditional method that have been applied in most of the current research of diseases, this research will then focus on dissecting the heterogeneity of polygenic diseases and analyzing with an unconventional approach for acquiring Differently Expressed Genes (DEGs) in Gupta’s Dataset that provided transcriptome of frontal cortex of ASD patients. Divide categories by using unsupervised learning strategy, the results yielded by analyzing within clusters of ASD have supported the feasibility of the attempts to use heterogeneity to reveal its underlying mechanism. This study puts forward the inference that the heterogeneity of polygenic diseases will obscure the molecular signals related to the disease, and at the same time attempts to use heterogeneity to reveal the underlying mechanism.
The functions of SARS-CoV-2 neutralizing and infection-enhancing antibodies in vitro and in mice and nonhuman primates
Authors: Li Dapeng , Edwards Robert J , Manne Kartik , Martinez David R. , Schäfer Alexandra , Alam S. Munir , Wiehe Kevin , Lu Xiaozhi , Parks Robert , Sutherland Laura L. , Oguin Thomas H. , McDanal Charlene , Perez Lautaro G. , Mansouri Katayoun , Gobeil Sophie M. C. , Janowska Katarzyna , Stalls Victoria , Kopp Megan , Cai Fangping , Lee Esther , Foulger Andrew , Hernandez Giovanna E. , Sanzone Aja , Tilahun Kedamawit , Jiang Chuancang , Tse Longping V. , Bock Kevin W. , Minai Mahnaz , Nagata Bianca M. , Cronin Kenneth , Gee-Lai Victoria , Deyton Margaret , Barr Maggie , Holle Tarra Von , Macintyre Andrew N. , Stover Erica , Feldman Jared , Hauser Blake M. , Caradonna Timothy M. , Scobey Trevor D. , Rountree Wes , Wang Yunfei , Moody M. Anthony , Cain Derek W. , DeMarco C. Todd , Denny ThomasN. , Woods Christopher W. , Petzold Elizabeth W. , Schmidt Aaron G. , Teng I-Ting , Zhou Tongqing , Kwong Peter D. , Mascola John R. , Graham Barney S. , Moore Ian N. , Seder Robert , Andersen Hanne , Lewis Mark G. , Montefiori David C. , Sempowski Gregory D. , Baric Ralph S. , Acharya Priyamvada , Haynes Barton F. , Saunders Kevin O. 
Published: January 2021

SummarySARS-CoV-2 neutralizing antibodies (NAbs) protect against COVID-19. A concern regarding SARS-CoV-2 antibodies is whether they mediate disease enhancement. Here, we isolated NAbs against the receptor-binding domain (RBD) and the N-terminal domain (NTD) of SARS-CoV-2 spike from individuals with acute or convalescent SARS-CoV-2 or a history of SARS-CoV-1 infection. Cryo-electron microscopy of RBD and NTD antibodies demonstrated function-specific modes of binding. Select RBD NAbs also demonstrated Fc receptor-γ (FcγR)-mediated enhancement of virus infectionin vitro, while five non-neutralizing NTD antibodies mediated FcγR-independentin vitroinfection enhancement. However, both types of infection-enhancing antibodies protected from SARS-CoV-2 replication in monkeys and mice. Nonetheless, three of 31 monkeys infused with enhancing antibodies had higher lung inflammation scores compared to controls. One monkey had alveolar edema and elevated bronchoalveolar lavage inflammatory cytokines. Thus, whilein vitroantibody-enhanced infection does not necessarily herald enhanced infectionin vivo, increased lung inflammation can occur in SARS-CoV-2 antibody-infused macaques.
Cas9-cleavage sequences in minimal plasmids enhance non-viral genome targeting of CARs in primary human T cells
Authors: Jing Ruirui , Jiao Peng , Chen Jiangqing , Meng Xianhui , Wu Xiaoyan , Duan Yanting , Shang Kai , Qian Liling , Huang Yanjie , Liu Junwei , Huang Tao , Jin Jin , Chen Wei , Zeng Xun , Yin Weiwei , Gao Xiaofei , Zhou Chun , Sadelain Michel , Sun Jie 
Published: January 2021

AbstractT cell genome editing holds great promise to advance a range of immunotherapies but is encumbered by the dependence on difficult-to-produce and expensive viral vectors. Here we have designed small double-stranded plasmid DNA modified to mediate high-efficiency homologous recombination. The resulting chimeric antigen receptor (CAR)-T cells display a similar phenotype, transcriptional profile andin vivopotency as CAR-T cells generated using adeno-associated viral (AAV) vector. This method should simplify and accelerate the use of precision engineering to produce edited T cells for research and clinical purposes.
Comprehensive analysis of the host-virus interactome of SARS-CoV-2
Authors: Chen Zhen , Wang Chao , Feng Xu , Nie Litong , Tang Mengfan , Zhang Huimin , Xiong Yun , Swisher Samuel K. , Srivastava Mrinal , Chen Junjie 
Published: January 2021

ABSTRACTHost-virus protein-protein interaction is the key component of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lifecycle. We conducted a comprehensive interactome study between the virus and host cells using tandem affinity purification and proximity labeling strategies and identified 437 human proteins as the high-confidence interacting proteins. Functional characterization and further validation of these interactions elucidated how distinct SARS-CoV-2 viral proteins participate in its lifecycle, and discovered potential drug targets to the treatment of COVID-19. The interactomes of two key SARS-CoV-2 encoded viral proteins, NSP1 and N protein, were compared with the interactomes of their counterparts in other human coronaviruses. These comparisons not only revealed common host pathways these viruses manipulate for their survival, but also showed divergent protein-protein interactions that may explain differences in disease pathology. This comprehensive interactome of coronavirus disease-2019 provides valuable resources for understanding and treating this disease.
Spatial and temporal dynamics of SAR11 marine bacteria sampled across a nearshore to offshore transect in the tropical Pacific Ocean
Authors: Tucker Sarah J. , Freel Kelle C. , Monaghan Elizabeth A. , Sullivan Clarisse E.S. , Ramfelt Oscar , Rii Yoshimi M. , Rappé Michael S. 
Published: January 2021

AbstractTime-series surveys of microbial communities coupled with contextual measures of the environment provide a useful approach to dissect the factors determining distributions of microorganisms across ecological niches. Here, monthly time-series samples of surface seawater along a transect spanning the nearshore coastal environment within Kāne‘ohe Bay on the island of O‘ahu, Hawai‘i, and the adjacent offshore environment were collected to investigate the diversity and abundance of SAR11 marine bacteria over a two-year time period. Using 16S ribosomal RNA gene amplicon sequencing, the spatiotemporal distributions of major SAR11 subclades and individual amplicon sequence variants (ASVs) were evaluated. On average, 77% of the SAR11 community was compromised of a small number of ASVs (7 of 106 in total), which were ubiquitously distributed across all samples collected from one or both of the end-member environments sampled in this study (coastal or offshore). SAR11 ASVs were more often restricted spatially to coastal or offshore environments (64 of 106 ASVs) than they were shared among coastal, transition, and offshore environments (39 of 106 ASVs). Overall, offshore SAR11 communities contained a higher diversity of SAR11 ASVs than their nearshore counterparts. This study reveals ecological differentiation of SAR11 marine bacteria across a short physiochemical gradient, further increasing our understanding of how SAR11 genetic diversity partitions into distinct ecological units.
Sequencing of Sars-CoV-2 genome using different Nanopore chemistries
Authors: González-Recio Oscar , Gutiérrez-Rivas Mónica , Peiró-Pastor Ramón , Aguilera-Sepúlveda Pilar , Cano-Gómez Cristina , Jiménez-Clavero Miguel Ángel , Fernández-Pinero Jovita 
Published: January 2021

ABSTRACTNanopore sequencing has emerged as a rapid and cost-efficient tool for diagnostic and epidemiological surveillance of SARS-CoV-2 during the COVID-19 pandemic. This study compared results from sequencing the SARS-CoV-2 genome using R9 vs R10 flow cells and Rapid Barcoding Kit (RBK) vs Ligation Sequencing Kit (LSK). The R9 chemistry provided a lower error rate (3.5%) than R10 chemistry (7%). The SARS-CoV-2 genome includes few homopolymeric regions. Longest homopolymers were composed of 7 (TTTTTTT) and 6 (AAAAAA) nucleotides. The R10 chemistry resulted in a lower rate of deletions in timine and adenine homopolymeric regions than R9, at expenses of a larger rate (~10%) of mismatches in these regions.The LSK had a larger yield than RBK, and provided longer reads than RBK. It also resulted in a larger percentage of aligned reads (99% vs 93%) and also in a complete consensus genome.The results from this study suggest that the LSK used on a R9 flow cell could maximize the yield and accuracy of the consensus sequence when used in epidemiological surveillance of SARS-CoV-2.KeypointsSequencing SARS-CoV-2 genome is of great importance for the pandemic surveillanceNanopore offers a low cost and accurate method to sequence SARS-CoV-2 genomeLigation sequencing is preferred rather than the rapid kit using transposases
An RNAi screen inC. elegansfor genes that play a role in secretion and cleavage of VAPB MSP domain
Authors: Zein-Sabatto Hala , Collawn Jim , Chang Chenbei , Miller Michael A. 
Published: January 2021

AbstractVAPB (VPR-1 inC. elegans) is a type-II ER transmembrane protein whose N-terminal Major Sperm Protein domain (MSPd) is cleaved and secreted. Mutations in the MSPd of human VAPB cause impaired secretion and are associated with Amyotrophic Lateral Sclerosis (ALS). InC. elegans, the secreted MSPd signals non-cell-autonomously to regulate striated muscle mitochondrial morphology and gonad development. As VAPB/VPR-1 does not have a signal peptide and its MSPd extends into the cytosol, it is unclear how the protein is proteolytically cleaved and secreted. To identify genes that are involved in VPR-1 cleavage and unconventional secretion, we performed an RNA interference (RNAi) screen inC. elegans. Worms null forvpr-1are sterile and have striated muscle mitochondrial abnormalities. These defects can be rescued byvpr-1expression in the neurons, germline, or intestine, implying that these three tissues share a common machinery to cleave and secrete the MSPd. Examination of shared gene expression in these tissues revealed a list of 422 genes, which we targeted with RNAi.vpr-1null worms expressingvpr-1from intestine were used in the screen, and the brood size of these worms after RNAi knockdown was scored. Disruption of factors involved in VPR-1 MSPd processing and/or secretion should revert fertility phenotypes in these worms. We identified many genes that induce compromised fertility when knocked down in these but not wild type worms, including a V-SNARE, several proteasome components, stress response molecules, and mitochondrial genes. Our screen thus identified many potential players involved in MSPd processing and/or secretion.SummaryThe MSP domain (MSPd) of a type-II ER transmembrane protein called VAPB is cleaved and secreted to function as a non-cell-autonomous signal. The topology of VAPB positions MSPd in the cytosol. It is thus unclear how MSPd is cleaved from VAPB and released extracellularly. UsingC. elegans, we screened 422 genes by RNAi to identify potential candidates regulating MSPd cleaving and secretion. We identified the Golgi v-SNARE YKT-6 and several components of the 20S and 19S proteasome that may mediate MSPd trafficking and cleaving, respectively. These results have promising implications in advancing our understanding of MSPd signaling.
Translational control of lipogenesis links protein synthesis and phosphoinositide signaling with nuclear division
Authors: Maitra Nairita , Hammer Staci , Kjerfve Clara , Bankaitis Vytas A. , Polymenis Michael 
Published: January 2021

ABSTRACTContinuously dividing cells coordinate their growth and division. How fast cells grow in mass determines how fast they will multiply. Yet, there are few, if any, examples of a metabolic pathway that actively drives a cell cycle event instead of just being required for it. Here, we show that translational upregulation of lipogenic enzymes in yeast increased the abundance of lipids and accelerated nuclear elongation and division. De-repressing translation of acetyl CoA carboxylase and fatty acid synthase also suppressed cell cycle-related phenotypes, including delayed nuclear division, associated with Sec14p phosphatidylinositol transfer protein deficiencies, and the irregular nuclear morphologies of mutants defective in phosphatidylinositol 4-OH kinase activities. Our results show that increased lipogenesis drives a critical cell cycle landmark and report a phosphoinositide signaling axis in control of nuclear division. The broad conservation of these lipid metabolic and signaling pathways raises the possibility these activities similarly govern nuclear division in mammals.
Current status and perspectives on the role of polyamines in plant immunity
Authors: Gonzalez María E. , Jasso‐Robles Francisco I. , Flores‐Hernández Emmanuel , Rodríguez‐Kessler Margarita , Pieckenstain Fernando L. 
Published: January 2021

AbstractPolyamines are low molecular weight amines, with versatile and essential functions during the lifespan of prokaryotes and eukaryotes. Modulation of polyamine metabolism under biotic stress has attracted a great deal of interest; however, the precise functions of these amines in plant defence responses to pathogen attack are still poorly understood. Herein we summarise and review important aspects of the regulation of polyamine biosynthesis, catabolism and conjugation under biotic stress that might contribute to improve present‐day knowledge about these compounds in plant immunity. Particular attention is paid to the intracellular localisation of the proteins/enzymes associated to polyamine metabolism, as well as the impact of pathogen effector proteins on the control of plant polyamine metabolism is discussed.
Soil properties and bamboo cover drive the structure of the woody plant community along a forest–savanna gradient
Authors: Gonçalves Lorrayne Aparecida , Abadia Ana Clara , Vilar Cesar Crispim , Silvério Divino Vicente , Colli Guarino Rinaldi , Martins Jhany , Maracahipes‐Santos Leonardo , Ushiwata Silvio Yoshiharu , Lenza Eddie 
Published: January 2021

AbstractUnderstanding the role of environmental conditions and geographic space on species distributions is a major goal of ecological studies. Here, we investigate the effects of soil properties, a native bamboo (Actinocladum verticillatum (Nees) McClure ex Soderstr) ground cover and geographic distance on species richness and turnover in the Brazilian Cerrado. We established three transects along a forest–savanna gradient (14°41′S and 52°20′W), from the lowland next to a stream to the top of a hill, where we sampled the woody plant community (DBH ≥ 3 cm), soil properties and ground cover of A. verticillatum. We evaluated changes in species composition with a principal coordinates analysis, and the effects of the environmental predictors on species richness using generalised linear models and on species turnover using generalised dissimilarity modelling. We found that species richness increases with K concentration in the soil and decreases with Zn concentration in the soil and bamboo cover. The predictors explained 62% of species turnover, with environmental parameters (soil properties, bamboo cover and altitude) having the most significant contribution (80%), followed by the spatially structured environmental variation (20%). The most important environmental predictors of woody species turnover were soil concentration of Zn, P and K, altitude, and bamboo cover. Changes in species richness and composition in the studied gradient were strongly associated with plot height, bamboo cover and soil content of K, Zn and P. Our findings indicate that nutrient availability and competition with bamboo explain vegetation structure and composition in this region.
Rethinking third trimester ultrasound measurements and risk of adverse neonatal outcomes in pregnancies complicated by hyperglycaemia: A retrospective study
Authors: McLean Anna , Katz Melissa , Oats Jeremy , Wang Zhiqiang , Barr Elizabeth , Maple‐Brown Louise 
Published: January 2021

BackgroundAntenatal ultrasound is used frequently in pregnancies complicated by hyperglycaemia; however, it is unclear which measurements have the greatest association with adverse neonatal outcomes.AimTo assess the association between third trimester ultrasound parameters with adverse neonatal outcomes in pregnancies complicated by hyperglycaemia.MethodAll pregnant women with gestational or type 2 diabetes who birthed in a regional hospital over 12 months were included. A composite adverse neonatal outcome was defined by one or more: admission to special care nursery, acidosis, hypoglycaemia, jaundice, shoulder dystocia, respiratory distress syndrome or 5‐minute Apgar score < 5. Logistic regression was used to determine odds ratios (OR) for an adverse neonatal outcome, according to pre‐specified cut points in both lower and upper percentiles of abdominal circumference (AC) and estimated fetal weight (EFW).ResultsOf 275 births an adverse outcome occurred in 122 (44%). Unadjusted OR (95% CI) for AC ≤30th was 3.2 (1.1–8.8) and >95th percentile was 3.1 (1.5–6.0) compared with the reference group of 31–70th percentile. Unadjusted OR for EFW ≤30th was 1.5 (0.7–3.1) and >95th percentile was 3.0 (1.4–6.3). After adjusting for maternal age, body mass index, diabetes type, ethnicity, gravidity, mode of delivery and gestation at birth the OR (95% CI) were as follows: AC ≤30th percentile, 3.7 (1.1–12.4); AC >95th, 2.2 (1.1–4.8); EFW ≤30th, 2.6 (1.1–6.1); EFW >95th, 2.5 (1.1–6.1).ConclusionAn AC and EFW up to the 30th percentile may pose just as great a risk to the fetus as an AC or EFW >95th percentile in pregnancies complicated by hyperglycaemia.
Intravitreal anti‐VEGF therapy is not associated with a higher risk of all‐cause mortality in patients with macular oedema caused by posterior segment vascular diseases
Authors: Loukovaara Sirpa , Haukka Jari 
Published: January 2021

AbstractPurposeTo examine whether real‐world clinical patients with macular oedema (MO) receiving intravitreal antivascular endothelial growth factor (VEGF) therapy have a higher mortality compared with a matched reference population.MethodsA population‐based, retrospective cohort study of 26 386 patients from Finland, from January 1, 2001, to December 31, 2017. Index patients were identified through the Caring Epidemiology Project database, receiving at least one intravitreal anti‐VEGF injection for wet age‐related macular degeneration (AMD, n = 2243, 48.61%), diabetic MO (n = 744, 16.12%), MO due to retinal vascular occlusion (n = 589, 12.77%), or other MO (n = 1038, 22.5%). For each individual treated with intravitreal injection (n = 4614), five age‐ , sex‐ , calendar year‐ and hospital district‐ matched control individuals (n = 21 772) were chosen. Baseline data of chronic conditions were available. All‐cause and cause‐specific mortality was analysed using Cox´s proportional hazards model.ResultsIn general, the anti‐VEGF treated patients had a higher prevalence of systemic conditions, including diabetes (60.1% vs. 46.8%, p < 0.001), chronic hypertension (38.4% vs. 34.6%, p < 0.001), in hospital‐treated ischaemic heart disease (23.1% vs. 21.5%, p = 0.014), and glaucoma (11.1% vs. 6.3%, p < 0.001) than controls. There was no difference in all‐cause mortality between the anti‐VEGF treated patients and matched controls (p = 0.62). In unadjusted Kaplan–Meier analysis of wet AMD subgroup, all‐cause mortality was lower in anti‐VEGF treated patients than matched controls (p = 0.015), but adjusted Cox´s proportional hazards model showed no difference in the risk of all‐cause mortality (HR 0.85, 95% CI 0.66–1.09).ConclusionsIntravitreal anti‐VEGF therapy was not associated with an increase in the risk of mortality in patients with MO compared with age‐ and sex‐matched controls.
Bioethics and the argumentative legacy of atrocities in medical history: Reflections on a complex relationship
Authors: Schicktanz Silke , Michl Susanne , Stoff Heiko 
Published: January 2021

AbstractSlippery slope‐, taboo‐breaking‐ or Nazi‐analogy‐arguments are common, but not uncontroversial examples of the complex relationship between bioethics and the various ways of using historical arguments in these debates. In our analysis we examine first the relationship between bioethics and medical history both as separate disciplines and as argumentative practices. Secondly, we then analyse six common types of historical arguments in bioethics (slippery slope‐, analogy‐, continuity‐, knockout/taboo‐, ethical progress‐ and accomplice‐arguments), some as arguments within the academic debate of bioethics, others as arguments within political and public debates over bioethical issues. We conclude by suggesting to bioethicists to better understand historical arguments as socially and culturally embedded practices of critical reflection of power, medical and government paternalism and possible future scenarios. More interdisciplinarity between ethicists and medical historians is needed to appropriately rationalize and understand the different legacies.
Categorizing Smells: A Localist Approach
Authors: Jraissati Yasmina , Deroy Ophelia 
Published: January 2021

AbstractHumans are poorer at identifying smells and communicating about them, compared to other sensory domains. They also cannot easily organize odor sensations in a general conceptual space, where geometric distance could represent how similar or different all odors are. These two generalities are more or less accepted by psychologists, and they are often seen as connected: If there is no conceptual space for odors, then olfactory identification should indeed be poor. We propose here an important revision to this conclusion: We believe that the claim that there is no odor space is true only if by odor space, one means a conceptual space representing all possible odor sensations, in the paradigmatic sense used for instance for color. However, in a less paradigmatic sense, local conceptual spaces representing a given subset of odors do exist. Thus the absence of a global odor space does not warrant the conclusion that there is no olfactory conceptual map at all. Here we show how a localist account provides a new interpretation of experts and cross‐cultural categorization studies: Rather than being exceptions to the poor olfactory identification and communication usually seen elsewhere, experts and cross‐cultural categorization are here taken to corroborate the existence of local conceptual spaces.