bluuebunny/crossref_metadata_2025_split huggingface dataset:
UPhyloplot2: Visualizing Phylogenetic Trees from Single-Cell RNA-seq Data
Authors: Kurtenbach Stefan , Rodriguez Daniel A. , Durante Michael A. , Harbour J. William 
Published: May 2020

AbstractRecent advances in single cell sequencing technologies allow for greater resolution in assessing tumor clonality using chromosome copy number variations (CNVs), which can be inferred from single cell RNA-seq (scRNA-seq) data using applications such as inferCNV. Inferences regarding tumor clonality are frequently visualized using phylogenetic plots, which previously required time-consuming and tedious manual analysis. Here, we present UPhyloplot2, a python script that generates phylogenetic plots directly from inferCNV output files. The tool is publicly available athttps://github.com/harbourlab/UPhyloplot2/.
14-3-3 shuttles Activity-dependent neuroprotective protein to the cytoplasm to promote appropriate neuronal morphogenesis, cortical connectivity and calcium signaling
Authors: Bennison Sarah A. , Blazejewski Sara M. , Liu Xiaonan , Toyo-oka Kazuhito 
Published: May 2020

AbstractNeurite formation is the earliest stage of neuronal morphogenesis, where primitive dendrites and the primitive axon emerge from a spherical neuron and begin to elongate. Defective neuritogenesis is a contributing pathogenic mechanism behind a variety of neurodevelopmental disorders. Activity-dependent neuroprotective protein (Adnp) is essential to embryonic and postnatal brain development, and mutations inADNPare among the most frequent underlying autism spectrum disorder (ASD). We found that knockdown of Adnpin vitroandin vivoin mouse layer 2/3 pyramidal neurons leads to increased neurite initiation and defective neurite elongation, suggesting that Adnp has distinct roles in each.In vivoanalysis revealed that deficits begin at P0 and are sustained throughout development, the most notable of which include increased neurite stabilization, disrupted angle of the apical dendrite, increased basal dendrite number, and increased axon length. Because small changes in neuronal morphology can have large-scale effects on neuronal function and connectivity, we performedex vivocalcium imaging to assess spontaneous function of layer 2/3 pyramidal neurons deficient in Adnp. This revealed that Adnp deficient neurons had a greater spontaneous calcium influx and a higher proportion of cells firing action potentials. Next, we utilized GRAPHIC, a novel synaptic tracing technology, to assess interhemispheric cortical connectivity. We found increased interhemispheric excitatory connectivity between Adnp deficient layer 2/3 pyramidal neurons. Because Adnp is a multifunctional protein with both transcription factor and cytoskeletal activity, we performed localization analysis of Adnp as neurons underwent neurite formation to probe the mechanism of our morphological defects. We found that Adnp is shuttled from the nucleus to the cytoplasm upon differentiation and this shuttling can be blocked via application of a global 14-3-3 inhibitor, difopein. Furthermore, we found that Adnp binds nuclear-cytoplasmic shuttle 14-3-3ε. We conclude that Adnp is shuttled from the nucleus to the cytoplasm by 14-3-3ε, where it regulates neuronal morphology, maturation, cortical connectivity, and calcium signaling.
Genetic, lifestyle and environmental risk factors for chronic pain revealed through GWAS
Authors: Lundberg Mischa , Campos Adrian I. , Farrell Scott F. , Wang Geng , Sterling Michele , Renteria Miguel E. , Ngo Trung Thanh , Cuellar-Partida Gabriel 
Published: May 2020

AbstractChronic pain (CP) is a leading cause of disability worldwide with complex aetiologies that remain elusive. Here we addressed this issue by performing a GWAS on a large UK Biobank sample (N=188,352 cases & N=69,627 controls) which identified two independent loci associated with CP nearADAMTS6andLEMD2. Gene-based tests revealed additional CP-associated genes (DCAKD, NMT1, MLN, IP6K3). Across 1328 complex traits, 548 (41%) were genetically correlated with CP, of which 175 (13%) showed genetic causal relationships using the latent causal variable approach and Mendelian randomization. In particular, major depressive disorder, anxiety, smoking, body fat & BMI were found to increase the risk of CP, whereas diet, walking for pleasure & higher educational attainment were associated with a reduced risk (i.e., protective effect). This data-driven hypothesis-free approach has uncovered several specific risk factors that warrant further examination in longitudinal trials to help deliver effective early screening & management strategies for CP.
Different pattern of pre-existing SARS-COV-2 specific T cell immunity in SARS-recovered and uninfected individuals
Authors: Bert Nina Le , Tan Anthony T , Kunasegaran Kamini , Tham Christine Y L , Hafezi Morteza , Chia Adeline , Chng Melissa , Lin Meiyin , Tan Nicole , Linster Martin , Chia Wan Ni , Chen Mark I-Cheng , Wang Lin-Fa , Ooi Eng Eong , Kalimuddin Shirin , Tambyah Paul Anantharajal , Low Jenny Guek-Hong , Tan Yee-Joo , Bertoletti Antonio 
Published: May 2020

AbstractMemory T cells induced by previous infections can influence the course of new viral infections. Little is known about the pattern of SARS-CoV-2 specific pre-existing memory T cells in human. Here, we first studied T cell responses to structural (nucleocapsid protein, NP) and non-structural (NSP-7 and NSP13 of ORF1) regions of SARS-CoV-2 in convalescent from COVID-19 (n=24). In all of them we demonstrated the presence of CD4 and CD8 T cells recognizing multiple regions of the NP protein. We then show that SARS-recovered patients (n=23), 17 years after the 2003 outbreak, still possess long-lasting memory T cells reactive to SARS-NP, which displayed robust cross-reactivity to SARS-CoV-2 NP. Surprisingly, we observed a differential pattern of SARS-CoV-2 specific T cell immunodominance in individuals with no history of SARS, COVID-19 or contact with SARS/COVID-19 patients (n=18). Half of them (9/18) possess T cells targeting the ORF-1 coded proteins NSP7 and 13, which were rarely detected in COVID-19- and SARS-recovered patients. Epitope characterization of NSP7-specific T cells showed recognition of protein fragments with low homology to “common cold” human coronaviruses but conserved among animal betacoranaviruses.Thus, infection with betacoronaviruses induces strong and long-lasting T cell immunity to the structural protein NP. Understanding how pre-existing ORF-1-specific T cells present in the general population impact susceptibility and pathogenesis of SARS-CoV-2 infection is of paramount importance for the management of the current COVID-19 pandemic.
Structure and reconstitution of a MCU-EMRE mitochondrial Ca2+uniporter complex
Authors: Wang Chongyuan , Baradaran Rozbeh , Long Stephen Barstow 
Published: May 2020

AbstractThe proteins MCU and EMRE form the minimal functional unit of the mitochondrial calcium uniporter complex in metazoans, a highly selective and tightly controlled Ca2+channel of the inner mitochondrial membrane that regulates cellular metabolism. Here we present functional reconstitution of an MCU-EMRE complex from the red flour beetle,Tribolium castaneum, and a cryo-EM structure of the complex at 3.5 Å resolution. Robust Ca2+uptake is observed into proteoliposomes containing the purified complex and is dependent on EMRE. The structure reveals a tetrameric channel with a single ion pore. EMRE is located at the periphery of the transmembrane domain and associates primarily with the first transmembrane helix of MCU. Coiled coil and juxtamembrane domains within the matrix portion of the complex adopt markedly different conformations than in a structure of a human MCU-EMRE complex, suggesting that the structures represent different conformations of these functionally similar metazoan channels.
Assessment of sample pooling for clinical SARS-CoV-2 testing
Authors: Griesemer Sara B , Van Slyke Greta , St. George Kirsten 
Published: May 2020

AbstractAccommodating large increases in sample workloads has presented one of the biggest challenges to clinical laboratories during the COVID-19 pandemic. Despite the implementation of new automated detection systems, and previous efficiencies such as barcoding, electronic data transfer and extensive robotics, throughput capacities have struggled to meet the demand. Sample pooling has been suggested as an additional strategy to further address this need. The greatest concern with this approach in a clinical setting is the potential for reduced sensitivity, particularly the risk of false negative results when weak positive samples are pooled. To investigate this possibility, detection rates in pooled samples were evaluated, with extensive assessment of pools containing weak positive specimens. Additionally, the frequency of occurrence of weak positive samples across ten weeks of the pandemic were reviewed. Weak positive specimens were detected in all five-sample pools but failed to be detected in four of the 24 nine-sample pools tested. Weak positive samples comprised an average 16.5% of the positive specimens tested during the pandemic thus far, slightly increasing in frequency during later weeks. Other aspects of the testing process should be considered, however, such as accessioning and reporting, which are not streamlined and may be complicated by pooling procedures. Therefore, the impact on the entire laboratory process needs to be carefully assessed prior to implementing such a strategy.
High Resolution CHEST CT(HRCT) Evaluation in Patients Hospitalized with COVID-19 Infection
Authors: Patel Maulin , Chowdhury Junad , Zheng Matthew , Abramian Osheen , Verga Steven , Zhao Huaqing , Patlakh Nicole , Montecalvo Nicholas , Fleece David , Cohen Gary , Kumaran Maruti , Dass Chandra , Criner Gerard J. ,   for the Temple University COVID-19 Research Group
Published: May 2020

AbstractIntroductionCurrently the main diagnostic modality for COVID-19 (Coronavirus disease-2019) is reverse transcriptase polymerase chain reaction (RT-PCR) via nasopharyngeal swab which has high false negative rates. We evaluated the performance of high-resolution computed tomography (HRCT) imaging in the diagnosis of suspected COVID-19 infection compared to RT-PCR nasopharyngeal swab alone in patients hospitalized for suspected COVID-19 infection.MethodsThis was a retrospective analysis of 324 consecutive patients admitted to Temple University Hospital. All hospitalized patients who had RT-PCR testing and HRCT were included in the study. HRCTs were classified as Category 1, 2 or 3. Patients were then divided into four groups based on HRCT category and RT-PCR swab results for analysis.ResultsThe average age of patients was 59.4 (±15.2) years and 123 (38.9%) were female. Predominant ethnicity was African American 148 (46.11%). 161 patients tested positive by RT-PCR, while 41 tested positive by HRCT. 167 (52.02%) had category 1 scan, 63 (19.63%) had category 2 scan and 91 (28.35%) had category 3 HRCT scans. There was substantial agreement between our radiologists for HRCT classification (κ = 0.64). Sensitivity and specificity of HRCT classification system was 77.6 and 73.7 respectively. Ferritin, LDH, AST and ALT were higher in Group 1 and D-dimers levels was higher in Group 3; differences however were not statistically significant.ConclusionDue to its high infectivity and asymptomatic transmission, until a highly sensitive and specific COVID-19 test is developed, HRCT should be incorporated into the assessment of patients who are hospitalized with suspected COVID-19.Key PointsKey QuestionCan High Resolution CT chest (HRCT) improve diagnostic accuracy of current Nasopharyngeal swab in suspected COVID-19 patients?Bottom LineIn this retrospective analysis, our novel HRCT classification identified 20% of all COVID-19 patients who had negative nasopharyngeal reverse transcriptase polymerase chain reaction (RT-PCR) tests but had HRCT findings consistent with COVID-19 pneumonia. These patients were ruled out for other infections and laboratory markers were similar to other RT-PCR positive patientsWhy Read onOur new HRCT classification when combined with RT-PCR can improve diagnostic accuracy while promptly improving triaging in COVID-19 patients.
Gut microbiota predict Enterococcus expansion but not Vancomycin-resistant Enterococcus acquisition
Authors: Chanderraj Rishi , Brown Christopher A. , Hinkle Kevin , Falkowski Nicole , Ranjan Piyush , Dickson Robert P. , Woods Robert J. 
Published: May 2020

ABSTRACTBACKGROUNDVancomycin-resistant Enterococcus (VRE) is a leading cause of hospital-acquired infections, and continues to spread despite widespread implementation of pathogen-targeted control guidelines. Commensal gut microbiota provide colonization resistance to VRE, but the role of gut microbiota in VRE acquisition in at-risk patients is unknown.METHODSWe performed a case-control study of gut microbiota in hospitalized patients who did (cases) and did not (controls) acquire VRE. We matched case subjects to control subjects by known risk factors and “time at risk,” defined as the time elapsed between admission until positive VRE screen. We characterized gut bacterial communities using 16S rRNA gene amplicon sequencing of rectal swab specimens.RESULTSWe analyzed 236 samples from 59 matched case-control pairs. At baseline, case and control subjects did not differ in gut microbiota when measured by community diversity (p=0.33) or composition (p=0.30). After hospitalization, gut communities of cases and controls differed only in the abundance of the Enterococcus containing operational taxonomic unit (OTU), with the gut microbiota of case subjects having more of this OTU than time-matched control subjects (p=0.01). Otherwise, case and control communities after the time at risk did not differ in diversity (p=.33) or community structure (p=0.12). Among patients who became VRE colonized, those having the Blautia containing OTU on admission had lower Enterococcus relative abundance once colonized (p =0.004).CONCLUSIONSThe 16S profile of the gut microbiome does not predict VRE acquisition in hospitalized patients, likely due to rapid and profound microbiota change. The gut microbiome does not predict VRE acquisition, but may be associated with Enterococcus expansion, suggesting that these should be considered as two distinct processes.Summary16S profile of the gut microbiome does not predict VRE acquisition in hospitalized patients, likely due to the rapid and profound microbiota change in this) opulation. VRE expansion and VRE acquisition may be two distinct processes.
Blood donor variability is a modulatory factor forP. falciparuminvasion phenotyping assays
Authors: Thiam Laty G. , Nyarko Prince B. , Kusi Kwadwo A. , Niang Makhtar , Aniweh Yaw , Awandare Gordon A. 
Published: May 2020

AbstractHuman erythrocytes are indispensable forPlasmodium falciparumdevelopment. Unlike other eukaryotic cells, there is no existing erythroid cell line capable of supporting long-termP. falciparum in vitroexperiments. Consequently, invasion phenotyping experiments rely on erythrocytes of different backgrounds. However, the contribution of the erythrocytes variation in influencing invasion rates remains unknown, which presents a challenge for conducting large-scale comparative studies. Here, we used erythrocytes of different blood groups harboring different hemoglobin genotypes to assess the relative contribution of blood donor variability inP. falciparuminvasion phenotyping assays. For each donor, we investigated the relationship between parasite invasion phenotypes and erythrocyte phenotypic characteristics, including; the expression levels of surface receptors (e.g. the human glycophorins A and C, the complement receptor 1 and decay accelerating factor), blood groups (e.g. ABO/Rh system), and hemoglobin genotypes (e.g. AA, AS and AC). Across all donors, there were significant differences in invasion efficiency following treatment with either neuraminidase, trypsin or chymotrypsin relative to the control erythrocytes. Primarily, we showed that the levels of key erythrocyte surface receptors and their sensitivity to enzyme treatment, significantly differed across donors. However, invasion efficiency correlated neither with susceptibility to enzyme treatment nor with the levels of the selected erythrocyte surface receptors. Upon further analysis, we found no relationship betweenP. falciparuminvasion phenotype and blood group or hemoglobin genotype.ImportanceAssays to decipherP. falciparuminvasion phenotypes are of great importance in the quest for an efficient malaria vaccine. Malaria associated mortality is mainly attributed to the blood stage of the parasite’s life cycle, a major focus of vaccine development strategies. Further, testing and validating blood stage vaccines necessitates conducting large-scale studies in endemic countries. However, comparing results from such studies is challenged by the lack of standard assays. As human erythrocytes play a pivotal role inP. falciparuminvasion assays, the need to investigate the effect of blood donor variability in the outcome of such assays is apparent. The significance of our study is in reporting the absence of relationship betweenP. falciparuminvasion efficiency and commonly shared erythrocyte features across different erythrocyte donors, therefore emphasizing the need to consider erythrocyte donor uniformity and to anticipate challenges associated to blood donor variability in early stages of large-scale study design.
Extracellular Vesicles Hijack the Autophagic Pathway to Induce Tau Accumulation in Endolysosomes
Authors: Pedrioli Giona , Barberis Marialuisa , Molinari Maurizio , Morone Diego , Papin Stéphanie , Paganetti Paolo 
Published: May 2020

AbstractClinical progression of tauopathies is reflected by the transcellular propagation of pathogenic Tau seeds with the possible involvement of extracellular vesicles as transport vectors. However, the mechanism regulating extracellular vesicle cargo delivery to recipient cells is poorly understood. We established a cell model for investigating extracellular vesicle-delivery of membranes and proteins. In this model, extracellular vesicles are readily internalized and accumulate in endolysosomes. For the first time, we show that in this acidic compartment of recipient cells, extracellular vesicle-delivered Tau seeds cause the accumulation and abnormal folding of normal Tau by a process that requires the participation of autophagy. Endolysomes represent thus a cross-road where Tau seeds released from extracellular vesicles propagate on cellular Tau on its route for autophagy-mediated degradation, ultimately driving its accumulation, endolysosomal stress and cytotoxicity. Whilst, autophagy stimulation is considered as a viable solution to protect neurons from harmful cytosolic protein inclusions, our data suggest that this approach may favour the aberrant accumulation of neurodegeneration-associated proteins induced by exogenous pathogenic protein forms, with possible implications in the spreading of the disease.
Glycyrrhizin inhibits LPS-induced inflammatory responses in goat ruminal epithelial cellsin vitro
Authors: Pu Xuanxuan , Mullahred Pattygouri , Liu Junfeng , Guo Xuefeng , Gao Jian , Zhang Xiuping , Jiang Chenyu , Zhang Sujiang 
Published: May 2020

AbstractA long-term of high concentration feeding in ruminants can bring huge economic profits, but it also impose ruminants into great threat of suffering subacute ruminal acidosis (SARA). SARA is a kind of disease which attenuate the health, feed intake and production of ruminants, and when ruminants suffer SARA, the concentration of lipopolysaccharide (LPS) increase largely. Glycyrrhizin is reported to have anti-inflammation effects, and the study was conducted to investigate effects of glycyrrhizin on LPS-induced goat ruminal epithelial cells (GRECs) to provide evidence for using glycyrrhizin as a treatment for SARA. Effects of LPS, and glycyrrhizin on cell viability of GRECs were investigated, respectively. Then GRECs were stimulated with LPS (50 mg/L) for 2 h, and glycyrrhizin were added at the concentration of 0, 50, 75, 100 and 125 mg/L for 24 h to investigate the expression of inflammatory cytokines (by Elisa kits), the mRNA expression of NF-κB and inflammatory cytokines (by qRT-PCR), the distribution of Zo-1 and Occludin (by immunofluorescence staining), the expression of Occludin (by Western blot analysis), and the morphology of GRECs. The results showed that: (1) Glycyrrhizin at the concentration of 50, 75, 100, and 125 mg/L had no cytotoxic effects on GRECs, and LPS at the concentration of 50 mg/L significantly decreased the cell viability of GRECs. (2) Glycyrrhizin attenuated the expression and relative mRNA expression of TNF-α, IL-1β, IL-6, IL-8 and IL-12 by a dose-dependent manner, and significantly attenuated the relative mRNA expression of NF-κB. (3) Immunofluorescence staining and Western blot analysis showed that the quantity of Zo-1 and Occludin, and the expression of Occludin all increased with the treatment of glycyrrhizin. (4) Glycyrrhizin attenuated LPS-induced autophagy and protected the structural integrity of GRECs. In conclusion, glycyrrhizin significantly inhibited the inflammatory response in LPS-stimulated GRECs, and it may be used as a potential agent for the treatment of SARA.
Neuronal circuitry underlying female aggression inDrosophila
Authors: Schretter Catherine E. , Aso Yoshinori , Dreher Marisa , Robie Alice A. , Dolan Michael-John , Chen Nan , Ito Masayoshi , Yang Tansy , Parekh Ruchi , Rubin Gerald M. 
Published: May 2020

AbstractAggressive social interactions are used to compete for limited resources and are regulated by complex sensory cues and the organism’s internal state. While both sexes exhibit aggression, its neuronal underpinnings are understudied in females. Here, we describe a set of connected neurons in the adultDrosophila melanogastercentral brain that drive female aggression. We identified a population of sexually dimorphic aIPg neurons whose optogenetic activation increased, and genetic inactivation reduced, female aggression. Analysis of GAL4 lines identified in an unbiased screen for increased female chasing behavior revealed the involvement of another sexually dimorphic neuron, pC1d, and implicated pC1d and aIPg neurons as core nodes regulating female aggression. pC1d activation increased female aggression and electron microscopy (EM) connectomic analysis demonstrated that aIPg neurons and pC1d have strong reciprocal connections. Our work reveals important regulatory components of the neuronal circuitry that underlies female aggressive social interactions and provides tools for their manipulation.
Metabolic cooperation among commensal bacteria supportsDrosophilajuvenile growth under nutritional stress
Authors: Consuegra Jessika , Grenier Théodore , Akherraz Houssam , Rahioui Isabelle , Gervais Hugo , da Silva Pedro , Leulier François 
Published: May 2020

SUMMARYThe gut microbiota shapes animal growth trajectory in stressful nutritional environments, but the molecular mechanisms behind such physiological benefits remain poorly understood. The gut microbiota is mostly composed of bacteria, which construct metabolic networks among themselves and with the host. Until now, how the metabolic activities of the microbiota contribute to host juvenile growth remains unknown. Here, usingDrosophilaas a host model, we report that two of its major bacterial partners,Lactobacillus plantarumandAcetobacter pomorumengage in a beneficial metabolic dialogue that boosts host juvenile growth despite nutritional stress. We pinpoint that lactate, produced byL. plantarum, is utilized byA. pomorumas an additional carbon source, andA. pomorumprovides essential amino-acids and vitamins toL. plantarum. Such bacterial cross-feeding provisions a set of anabolic metabolites to the host, which may foster host systemic growth despite poor nutrition.GRAPHICAL ABSTRACTHIGHLIGHTSL. plantarumfeeds lactate toA. pomorumA. pomorumsupplies essential amino acids and vitamins toL. plantarumMicrobiota metabolic dialogue boosts Drosophila’s larval growthLactate utilization byAcetobacterreleases anabolic metabolites to larvae