bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low prevalence of COVID-19 Exposure is Coincident with Self-reported Compliance with Public Health Guidelines among Essential Employees at an Institute of Higher Education
Authors: Nelson Tracy L. , Fosdick Bailey , Biela Laurie M. , Schoenberg Hayden , Mast Sarah , McGinnis Emma , Young Michael C. , Lynn Lori , Fahrner Scott , Nolt Laura , Dihle Tina , Quicke Kendra , Gallichotte Emily N. , Fitzmeyer Emily , Ebel Greg D. , Pabilonia Kristy , Ehrhart Nicole , VandeWoude Sue 
Published: March 2021

AbstractImportanceDetailed analysis of infection rates paired with behavioral and employee reported risk factors are vital to understanding how COVID-19 transmission may be inflamed or mitigated in the workplace. Institutes of Higher Education are heterogeneous work units that supported continued in person employment during COVID-19, providing an excellent test site for occupational health evaluation.ObjectiveTo evaluate self-reported behaviors and SARS-CoV-2 among essential in-person employees during the first six months of the COVID-19 pandemic.DesignCross-sectional, conducted from July 13-September 2, 2020.SettingInstitute of Higher Education in Fort Collins, Colorado.ParticipantsEmployees identified to be an essential in-person employee during the first six months of the pandemic (1,522 invited, 1,507 qualified, 603 (40%) completed the survey). Of those completing the survey, 84.2% (508) elected to participate in blood and nasal swab sample collection to assess active SARS-CoV-2 infection via qRT-PCR, and past infection by serology (overall completion rate of 33.7%). Eligibility included > 18 years old, able to read and understand English, not currently experiencing cough, shortness of breath or difficulty breathing, fever >100.4F (38C), chills/shaking with chills, muscle pain, new or worsening headaches, sore throat or new loss of sense of taste/smell.ExposureSelf-reported COVID-19 protective behaviorsMain Outcome(s) and Measure(s)Current SARS-CoV-2 infection detected by qRT-PCR or previous SARS-CoV-2 infection detected by IgG SARS-CoV-2 testing platform.ResultsThere were no qRT-PCR positive tests, and only 2 (0.39%) contained seroreactive IgG antibodies. Participants were 60% female, 90% non-Hispanic white, mean age 41 years (18-70 years). Handwashing and mask wearing were reported frequently both at work (98% and 94% respectively) and outside work (91% and 95% respectively) while social distancing was reported less frequently at work (79%) then outside of work (92%) [p < .001]. Participants were more highly motivated to avoid exposures out of concern for spreading to others (83%) than for personal implications (63%) [p < .001].Conclusions and RelevanceThis is one of the first reports to document that complex work environments can be operated safely during the COVID-19 pandemic when employees report compliance with public health practices both at and outside work.
The absence of islet autoantibodies in clinically diagnosed older-adult onset type 1 diabetes suggests an alternative pathology, advocating for routine testing in this age group
Authors: Thomas Nicholas J , Walkey Helen C , Kaur Akaal , Misra Shivani , Oliver Nick S , Colclough Kevin , Weedon Michael N , Johnston Desmond G , Hattersley Andrew T , Patel Kashyap A 
Published: March 2021

AbstractObjectiveIslet autoantibodies at diagnosis are not well studied in older-adult onset (>30years) type 1 diabetes due to difficulties of accurate diagnosis. We used a type 1 diabetes genetic risk score (T1DGRS) to identify type 1 diabetes aiming to evaluate the prevalence and pattern of autoantibodies in older-adult onset type 1 diabetes.MethodsWe used a 30 variant T1DGRS in 1866 white-European individuals to genetically confirm a clinical diagnosis of new onset type 1 diabetes. We then assessed the prevalence and pattern of GADA, IA2A and ZnT8A within genetically consistent type 1 diabetes across three age groups (<18years (n=702), 18-30years (n=524) and >30years (n=588)).FindingsIn autoantibody positive cases T1DGRS was consistent with 100% type 1 diabetes in each age group. Conversely in autoantibody negative cases, T1DGRS was consistent with 93%(56/60) of <18years, 55%(37/67) of 18-30years and just 23%(34/151) of >30years having type 1 diabetes. Restricting analysis to genetically consistent type 1 diabetes showed similar proportions of positive autoantibodies across age groups (92% <18years, 92% 18-30years, 93% >30years)[p=0.87]. GADA was the most common autoantibody in older-adult onset type 1 diabetes, identifying 95% of autoantibody positive cases versus 72% in those <18years.InterpretationOlder adult-onset type 1 diabetes has identical rates but different patterns of positive autoantibodies to childhood onset. In clinically suspected type 1 diabetes in older-adults, absence of autoantibodies strongly suggests non-autoimmune diabetes. Our findings suggest the need to change guidelines from measuring islet autoantibodies where there is diagnostic uncertainty to measuring at least GADA in all suspected adult type 1 diabetes cases.
Inhibition of Tau seeding by targeting Tau nucleation core within neurons with a single domain antibody fragment
Authors: Danis Clément , Dupré Elian , Zejneli Orgeta , Caillierez Raphaëlle , Arrial Alexis , Bégard Séverine , Loyens Anne , Mortelecque Justine , Cantrelle François-Xavier , Hanoulle Xavier , Rain Jean-Christophe , Colin Morvane , Buée Luc , Landrieu Isabelle 
Published: March 2021

AbstractTau proteins aggregate into filaments in brain cells in Alzheimer’s disease and related disorders referred to as tauopathies. Here, we used fragments of camelid heavy-chain-only antibodies (VHHs or single domain antibody fragments) targeting Tau as immuno-modulators of its pathologic seeding. A VHH issued from the screen against Tau of a synthetic phage-display library of humanized VHHs was selected for its capacity to bind Tau microtubule-binding domain, composing the core of Tau fibrils. This lead VHH was optimized to improve its biochemical properties and to act in the intracellular compartment, resulting in VHH Z70. VHH Z70 was more efficient than the lead to inhibitin vitroTau aggregation in heparin-induced assays. Expression of VHH Z70 in a cellular model of Tau seeding also decreased the fluorescence-reported aggregation. Finally, intracellular expression of VHH Z70 in the brain of an established tauopathy mouse seeding model demonstrated its capacity to mitigate accumulation of pathological Tau. VHH Z70, by targeting Tau inside brain neurons, where most of the pathological Tau resides, provides a new tool to explore the optimal strategies of immunotherapy in tauopathies.
DrosoPhyla: genomic resources for drosophilid phylogeny and systematics
Authors: Finet Cédric , Kassner Victoria A. , Carvalho Antonio B. , Chung Henry , Day Jonathan P. , Day Stephanie , Delaney Emily K. , De Ré Francine C. , Dufour Héloïse D. , Dupim Eduardo , Izumitani Hiroyuki F. , Gautério Thaísa B. , Justen Jessa , Katoh Toru , Kopp Artyom , Koshikawa Shigeyuki , Longdon Ben , Loreto Elgion L. , Nunes Maria D. S. , Raja Komal K. B. , Rebeiz Mark , Ritchie Michael G. , Saakyan Gayane , Sneddon Tanya , Teramoto Machiko , Tyukmaeva Venera , Vanderlinde Thyago , Wey Emily E. , Werner Thomas , Williams Thomas M. , Robe Lizandra J. , Toda Masanori J. , Marlétaz Ferdinand 
Published: March 2021

AbstractThe vinegar flyDrosophila melanogasteris a pivotal model for invertebrate development, genetics, physiology, neuroscience, and disease. The whole family Drosophilidae, which contains over 4000 species, offers a plethora of cases for comparative and evolutionary studies. Despite a long history of phylogenetic inference, many relationships remain unresolved among the groups and genera in the Drosophilidae. To clarify these relationships, we first developed a set of new genomic markers and assembled a multilocus data set of 17 genes from 704 species of Drosophilidae. We then inferred well-supported group and species trees for this family. Additionally, we were able to determine the phylogenetic position of some previously unplaced species. These results establish a new framework for investigating the evolution of traits in fruit flies, as well as valuable resources for systematics.
Robustness of Collective Scenting in the Presence of Physical Obstacles
Authors: Nguyen Dieu My T. , Fard Golnar Gharooni , Iuzzolino Michael , Peleg Orit 
Published: March 2021

AbstractHoney bees (Apis melliferaL.) aggregate around the queen by collectively organizing a communication network to propagate volatile pheromone signals. Our previous study shows that individual bees “scent” to emit pheromones and fan their wings to direct the signal flow, creating an efficient search and aggregation process. In this work, we introduce environmental stressors in the form of physical obstacles that partially block pheromone signals and prevent a wide open path to the queen. We employ machine learning methods to extract data from the experimental recordings, and show that in the presence of an obstacle that blocks most of the path to the queen, the bees need more time but can still effectively employ the collective scenting strategy to overcome the obstacle and aggregate around the queen. Further, we increase the complexity of the environment by presenting the bees with a maze to navigate to the queen. The bees require more time and exploration to form a more populated communication network. Overall, we show that given volatile pheromone signals and only local communication, the bees can collectively solve the swarming process in a complex unstructured environment with physical obstacles.
Rice MEL2 regulates the timing of meiotic transition as a component of cytoplasmic RNA granules
Authors: Mimura Manaki , Ono Seijiro , Nonomura Ken-Ichi 
Published: March 2021

AbstractCytoplasmic RNA granules play important roles in gene expression at the post-transcriptional level. In this study, we found that the rice RNA-binding protein MEIOSIS ARRESTED AT LEPTOTENE2 (MEL2), which contributes to the control of meiotic entry timing, was a constituent of RNA granules, frequently associating with processing bodies and stress granules in the cytoplasm of premeiotic spore mother cells. MEL2 has four conserved domains and a large intrinsically disordered region, which is often responsible for formation and maintenance of granular structures. MEL2-like proteins with diverse domain structures are widely conserved in land plants and charophyte algae. In basal land plants, MEL2-like proteins are exclusively expressed in the sporophyte, which expresses meiotic genes, suggesting the functional conservation of MEL2 among land plant species. We propose here that MEL2 participates in post-transcriptional regulation of meiotic genes as a component of RNA granules to ensure proper timing of the meiotic transition.
circMRPS35 promotes malignant progression and cisplatin resistance in hepatocellular cancer
Authors: Li Peng , Song Runjie , Liu Huijiao , Liu Mei , Yin Fan , Ma Shuoqian , Jia Xiaomeng , Lu Xiaohui , Zhong Yuting , Li Xiru , Li Xiangdong 
Published: March 2021

AbstractHepatocellular carcinoma (HCC), a common malignant tumor, is one of the main causes of cancer-related deaths worldwide. Circular RNAs (circRNAs), a novel class of non-coding RNA, have been reported to be involved in the etiology of various malignancy. However, the functions of circRNAs in HCC remain unclear. In this study, through mining the RNA sequencing databases from GEO datasets and subsequent experimental verification, we identified that hsa_circ_0000384 (circMRPS35) was highly expressed in HCC. Knockdown of circMRPS35 suppressed the proliferation, migration, invasion, clone formation and cell cycle of HCC cell lines both in vitro and in a xenograft mouse model. Mechanically, circMRPS35 sponged microRNA-148a-3p (miR-148a), which in turn regulated STX3-PTEN axis. Surprisingly, we detected a peptide encoded by circMRPS35 (circMRPS35-168aa), which was significantly induced by chemotherapeutic drugs and promoted cisplatin resistance in HCC cells. These results demonstrated that circMRPS35 might be a novel factor in HCC progress, and has a great potential as a new diagnosis and therapeutic target for treatment of HCC.
Human eosinophil cationic protein manifests alarmin activity through its basicity and ribonuclease activity
Authors: Attery Ayush , Saha Irene , Tailor Prafullakumar , Batra Janendra K. 
Published: March 2021

ABSTRACTEosinophil cationic protein (ECP), eosinophil derived neurotoxin (EDN), and human pancreatic ribonuclease (HPR) are members of the RNase A superfamily having similar catalytic residues and diverse functions. Alarmins are the endogenous mediators of innate immunity which activate or alarm the adaptive immune system by activating antigen presenting cells (APCs). EDN acts as an alarmin molecule and plays an important role in innate as well as adaptive immunity. EDN displays chemotactic activity for dendritic cells (DCs) and activates them, has antiviral and antiparasitic activities, and is rapidly released from immune cells. HPR only displays chemotactic activity while no such activity has been reported for ECP. In this study we show that ECP displays the chemotactic activity comparable to that of HPR and EDN. ECP also interacts with TLR-2 to activate NF-κB/AP-1 expression like EDN. The RNase activity of ECP, EDN and HPR, and basicity of ECP were found to be crucial determinants for their chemotactic activity for APCs, however for the DC maturation activity, RNase activity was not found to be essential. Bovine RNase A did not show any chemotactic activity despite having a very high RNase activity indicating that other determinants in addition to the RNase activity are involved in the chemotactic activity of ECP, EDN and HPR. The current study establishes that ECP also can act like an alarmin.
BacterialPxRdl2dsRNA increased the insecticidal activities of GABAR-targeting compounds againstPlutella xylostella
Authors: Li Ben-Jie , Wang Kun-Kun , Yu Ye , Wei Jia-Qi , Zhu Jian , Wang Jia-Li , Lin Fei , Xu Han-Hong 
Published: March 2021

AbstractThe utilization of RNA interference (RNAi) for pest management has garnered global interest. The bioassay results suggested the knockout ofPxRdl2significantly increased the insecticidal activities of theγ-aminobutyric acid receptor (GABAR) targeting compounds (Fipronil, two pyrazoloquinazolines and two isoxazolines), thereby presenting a viable target gene for RNAi-mediated pest control. Consequently, we suggest enhancing the insecticidal activities of GABAR-targeting compounds by knockdown the transcript level ofPxRdl2. Furthermore,PxRdl2dsRNA was expressed in HT115Escherichia colito reduce costs and protect dsRNA against degradation. In comparison toin vitrosynthesized dsRNA, the recombinant bacteria (ds-B) exhibited superior interference efficiencies and greater stability when exposed to UV irradiation. Collectively, our results provide a new strategy of insecticide spray which combined synergistically with insecticidal activities by suppressingPxRdl2using ds-B, and may be beneficial for reducing the usage of insecticide and slowing pest resistance.
A new chemoenzymatic semisynthetic approach provides novel insight into the role of phosphorylation beyond exon1 of Huntingtin and reveals N-terminal fragment length-dependent distinct mechanisms of aggregation
Authors: Kolla Rajasekhar , Gopinath Pushparathinam , Ricci Jonathan , Reif Andreas , Rostami Iman , Lashuel Hilal A. 
Published: March 2021

AbstractHuntington’s disease is a neurodegenerative disorder caused by the expansion of a polyglutamine (poly Q) repeat (>36Q) in the N-terminal domain of the huntingtin protein (Htt), which renders the protein or fragments thereof more prone to aggregate and form inclusions. Although several Htt N-terminal fragments of different lengths have been identified within Htt inclusions, most studies on the mechanisms, sequence, and structural determinants of Htt aggregation have focused on the Htt exon1 (Httex1). Herein, we investigated the aggregation properties of mutant N-terminal Htt fragments of various lengths (Htt171, Htt140, and Htt104) in comparison to mutant Httex1. We also present a new chemoenzymatic semisynthetic strategy that enables site-specific phosphorylation of Htt beyond Httex1. These advances yielded novel insights into how PTMs and structured domains beyond Httex1 influence aggregation mechanisms, kinetics, and fibril morphology of longer N-terminal Htt fragments. We demonstrate that phosphorylation at T107 significantly slowed its aggregation, whereases phosphorylation at T107 and S116 accelerated the aggregation of Htt171, underscoring the importance of crosstalk between different PTMs. We demonstrate that mutant Htt171 proteins aggregate via a different mechanism and form oligomers and fibrillar aggregates with morphological properties that are distinct from that of mutant Httex1. These observations suggest that different N-terminal fragments could have distinct mechanisms of aggregation and that a single polyQ-targeting anti-aggregation strategy may not effectively inhibit the aggregation of all N-terminal Htt fragments. Finally, our results underscore the importance of further studies to investigate the aggregation mechanisms of Htt fragments and how the various fragments interact with each other and influence Htt toxicity, pathology formation, and disease progression.Table of content
Genome-wide molecular recording using Live-seq
Authors: Chen Wanze , Guillaume-Gentil Orane , Dainese Riccardo , Rainer Pernille Yde , Zachara Magda , Gäbelein Christoph G. , Vorholt Julia A. , Deplancke Bart 
Published: March 2021

AbstractSingle-cell transcriptomics (scRNA-seq) has greatly advanced our ability to characterize cellular heterogeneity in health and disease. However, scRNA-seq requires lysing cells, which makes it impossible to link the individual cells to downstream molecular and phenotypic states. Here, we established Live-seq, an approach for single-cell transcriptome profiling that preserves cell viability during RNA extraction using fluidic force microscopy. Based on cell division, functional responses and whole-cell transcriptome read-outs, we show that Live-seq does not induce major cellular perturbations and therefore can function as a transcriptomic recorder. We demonstrate this recording capacity by preregistering the transcriptomes of individual macrophage-like RAW 264.7 cells that were subsequently subjected to time-lapse imaging after lipopolysaccharide (LPS) exposure. This enabled the unsupervised, genome-wide ranking of genes based on their ability to impact macrophage LPS response heterogeneity, revealing basalNFKBIAexpression level and cell cycle state as major phenotypic determinants. Furthermore, we show that Live-seq can be used to sequentially profile the transcriptomes of individual macrophages before and after stimulation with LPS, thus enabling the direct mapping of a cell’s trajectory. Live-seq can address a broad range of biological questions by transforming scRNA-seq from an end-point to a temporal analysis approach.
High Mobility Group Box 1 enhances ADP-mediated platelet activation by increasing platelet surface P2Y12localization
Authors: Nolfi-Donegan Deirdre , Annarapu Gowtham K , Maurer Lisa M , Hillery Cheryl A , Shiva Sruti 
Published: March 2021

AbstractThrombosis and inflammation are intimately linked and synergistically contribute to the pathogenesis of a number of vascular diseases. On a cellular level, while the platelet is central to thrombus formation as well as an active mediator of inflammation, the molecular mechanisms of cross-talk between thrombosis and inflammation remain elusive. High-Mobility Group Box 1 protein (HMGB1) is an inflammatory regulator that also stimulates platelet activation through its interaction with toll-like receptor 4 (TLR4). However, it remains unclear whether cross-talk between HMGB1 and traditional thrombotic agonists exists to modulate platelet activation. Using isolated human platelets, we tested whether HMGB1 treatment affects platelet activation mediated by traditional agonists. We found that HMGB1 enhances ADP-mediated platelet activation, but not platelet activation stimulated by thrombin or collagen. Further, inhibition of the canonical ADP purinergic P2Y12receptor attenuates HMGB1-dependent platelet activation. Mechanistically, we discovered that HMGB1 activates platelet surface TLR4 to release ADP from the platelet and concomitantly increase the localization of P2Y12on the platelet membrane. These data demonstrate that ADP-dependent P2Y12activation contributes to HMGB1 mediated platelet activation, while HMGB1 primes platelets for an enhanced activation response to ADP. These novel findings further our understanding of thrombo-inflammatory signaling and provide new insight for therapeutic P2Y12inhibition.Key PointsHMGB1 enhances ADP-mediated platelet activation but not platelet activation stimulated by collagen or thrombin.HMGB1 stimulates platelet ADP release and increases platelet surface localization of P2y12 receptors via TLR4-dependent mechanism(s).Visual AbstractCaption:HMGB1 activates TLR4 to activate platelets, release platelet ADP, and upregulate P2Y12at the platelet surface.
The capacity to produce hydrogen sulfide (H2S) via cysteine degradation is ubiquitous in the human gut microbiome
Authors: Braccia Domenick J. , Jiang Xiaofang , Pop Mihai , Hall A. Brantley 
Published: March 2021

AbstractAs one of the three mammalian gasotransmitters, hydrogen sulfide (H2S) plays a major role in maintaining physiological homeostasis. Endogenously produced H2S plays numerous beneficial roles including mediating vasodilation and conferring neuroprotection. Due to its high membrane permeability, exogenously produced H2S originating from the gut microbiota can also influence human physiology and is implicated in reducing intestinal mucosal integrity and potentiating genotoxicity and is therefore a potential target for therapeutic interventions. Gut microbial H2S production is often attributed to dissimilatory sulfate reducers such as Desulfovibrio and Bilophila species. However, an alternative source for H2S production, cysteine degradation, is present in gut microbes, but the genes responsible for cysteine degradation have not been systematically annotated in gut microbes. To better understand the potential for H2S production via cysteine degradation by the human gut microbiome, we performed a comprehensive search for genes encoding cysteine-degrading genes in 4,644 bacterial genomes from the Unified Human Gastrointestinal Genome (UHGG) catalogue. We identified 407 gut bacterial species as putative cysteine degrading bacteria, 328 of which have not been previously implicated in H2S production. We identified the presence of at least one putative cysteine degrading bacteria in metagenomic data of 100% of 6,644 healthy subjects and the expression of cysteine-degrading genes in metatranscriptomics data of 100% of 59 samples. Additionally, putative cysteine-degrading bacteria are more abundant than sulfate reducing bacteria (p<2.2e-16). Overall, this study improves our understanding of the capacity for H2S production by the human gut microbiome and may help to inform interventions to therapeutically modulate gut microbial H2S production.