bluuebunny/crossref_metadata_2025_split huggingface dataset:
Socio-demographic determinants associated with Blastocystis infection in Arequipa, Peru
Authors: Salazar-Sánchez Renzo S. , Ascuña-Durand Kasandra , Cartillo-Neyra Ricardo , Vásquez-Huerta Victor , Martínez-Barrios Elí , Ballón-Echegaray Jorge 
Published: June 2020

AbstractBlastocystis is one of the most common protozoa in the human gut and is a zoonotic parasite related to unhealthy living conditions. This parasite shows a broad distribution, unclear symptomatology, and undefined pathogenicity. In Peru, studies report the presence of Blastocystis in many regions, but the highest prevalence levels are reported in Arequipa. The aim of this study was to link Blastocystis infection with social determinants of health. We recruited and survey 232 participants from infected and uninfected homes. All samples were analyzed by direct microscopy and confirmed with methylene-stained stool smear. We found a human Blastocystis prevalence of 51.3% in the study sample. We also found statistical associations between Blastocystis infection and the use of alternative non-domiciliary water supplies as well as the use of latrine for body-waste disposal, suggesting these are risk factors for human Blastocystis infection.
Model-based prediction of muscarinic receptor function from auditory mismatch negativity responses
Authors: Schöbi Dario , Jung Fabienne , Frässle Stefan , Endepols Heike , Moran Rosalyn J. , Friston Karl J. , Tittgemeyer Marc , Heinzle Jakob , Stephan Klaas Enno 
Published: June 2020

AbstractDrugs affecting neuromodulation, for example by dopamine or acetylcholine, take centre stage among therapeutic strategies in psychiatry. These neuromodulators can change both neuronal gain and synaptic plasticity and therefore affect electrophysiological measures. An important goal for clinical diagnostics is to exploit this effect in the reverse direction, i.e., to infer the status of specific neuromodulatory systems from electrophysiological measures.In this study, we provide proof-of-concept that the functional status of cholinergic (specifically muscarinic) receptors can be inferred from electrophysiological data using generative (dynamic causal) models. To this end, we used epidural EEG recordings over two auditory cortical regions during a mismatch negativity (MMN) paradigm in rats. All animals were treated, across sessions, with muscarinic receptor agonists and antagonists at different doses. Together with a placebo condition, this resulted in five levels of muscarinic receptor status. Using a dynamic causal model - embodying a small network of coupled cortical microcircuits - we estimated synaptic parameters and their change across pharmacological conditions. The ensuing parameter estimates associated with (the neuromodulation of) synaptic efficacy showed both graded muscarinic effects and predictive validity between agonistic and antagonistic pharmacological conditions.This finding illustrates the potential utility of generative models of electrophysiological data as computational assays of muscarinic function. In application to EEG data of patients from heterogeneous spectrum diseases, e.g. schizophrenia, such models might help identify subgroups of patients that respond differentially to cholinergic treatments.SignificanceStatementIn psychiatry, the vast majority of pharmacological treatments affect actions of neuromodulatory transmitters, e.g. dopamine or acetylcholine. As treatment is largely trial-and-error based, one of the goals for computational psychiatry is to construct mathematical models that can serve as “computational assays” and infer the status of specific neuromodulatory systems in individual patients. This neuro-modelling strategy has great promise for electrophysiological data in particular but requires careful validation. The present study demonstrates that the functional status of cholinergic (muscarinic) receptors can be inferred from electrophysiological data using dynamic causal models of neural circuits. While accuracy needs to be enhanced and our results must be replicated in larger samples, our current results provide proof-of-concept for computational assays of muscarinic function using EEG.
Hitchhiking on condensed chromatin promotes plasmid persistence in yeast without perturbing chromosome function
Authors: Prajapati Hemant Kumar , Kumar Deepanshu , Yang Xian-Mei , Ma Chien-Hui , Mittal Priyanka , Jayaram Makkuni , Ghosh Santanu K. 
Published: June 2020

AbstractEquipartitioning by chromosome hitchhiking and copy number correction by DNA amplification are at the heart of the evolutionary success of the selfish yeast 2-micron plasmid. The present analysis reveals plasmid presence near centromeres and telomeres in mitotic cells, with a preference towards the latter. The observed correlation of plasmid missegregation with non-disjunction of rDNA and telomeres under Cdc14 inactivation, higher plasmid missegregation upon induced missegregation of chromosome XII but not chromosome III, requirement of condensin for plasmid stability and the interaction of the condensin subunit Brn1 with the plasmid partitioning system lend functional credence to condensed chromatin being favored for plasmid tethering. By homing to condensed/quiescent chromosome locales, and not over-perturbing genome homeostasis, the plasmid may minimize fitness conflicts with its host. Analogous persistence strategies may be utilized by other extrachromosomal selfish genomes, for example, episomes of mammalian viruses that also hitchhike on host chromosomes for their stable maintenance.
SUMO orchestrates multiple alternative DNA-protein crosslink repair pathways
Authors: Serbyn Nataliia , Bagdiul Ivona , Michel Agnès H. , Suhandynata Raymond T. , Zhou Huilin , Kornmann Benoît , Stutz Françoise 
Published: June 2020

SUMMARYSeveral endogenous metabolites, environmental agents, and therapeutic drugs promote formation of covalent DNA-protein crosslinks (DPCs). Persistent DPCs pose a serious threat to genome integrity and are eliminated by multiple repair pathways. Aberrant Top1 crosslinks to DNA, or Top1ccs, are processed by Tdp1 and Wss1 functioning in parallel pathways inSaccharomyces cerevisiae.It remains obscure how cells choose between these diverse mechanisms of DPC repair. Here we show that several SUMO biogenesis factors - Ulp1, Siz2, Slx5, Slx8 - control repair of Top1cc or an analogous DPC lesion. Genetic analysis reveals that SUMO promotes Top1cc processing in the absence of Tdp1 but has an inhibitory role if cells additionally lack Wss1. In thetdp1Δ wss1Δmutant, the E3 SUMO ligase Siz2 stimulates sumoylation in the vicinity of the DPC, but not SUMO conjugation to Top1. This Siz2-dependent sumoylation delays DPC repair when cells progress through S and G2 phases. Our findings suggest that SUMO tunes available repair pathways to facilitate faithful DPC repair.
Neuromodulation Exerts Feedback and Feedforward Control of Action Selection
Authors: Diao Fengqiu , Peabody Nathan , White Benjamin H. 
Published: June 2020

SummaryTo be effective, behavioral choices must result in actions that are appropriate to an animal’s needs and environmental circumstances. In addition, the actions must be ones the animal can sustain until its needs are met. This aligning of goals, action, and motivation requires the coordinated activity of multiple brain circuits, but how such coordination is achieved is poorly understood. Here, we show how the insect hormone Bursicon coordinates the selection and sustains execution of a behavior in newly emerged adultDrosophila.Such flies must expand and harden their wings after metamorphosis, but they choose to delay expansion in confined conditions. We show that the decision to expand is mediated by an environmentally-sensitive, positive feedback loop in which Bursicon promotes its own sustained release. Released Bursicon then modulates motor neurons to promote wing expansion behavior. Bursicon thus exerts feedforward and feedback control to coordinately select and motivate a goal-directed action.
Effective Inhibition of SARS-CoV-2 Entry by Heparin and Enoxaparin Derivatives
Authors: Tandon Ritesh , Sharp Joshua S. , Zhang Fuming , Pomin Vitor H. , Ashpole Nicole M. , Mitra Dipanwita , Jin Weihua , Liu Hao , Sharma Poonam , Linhardt Robert J. 
Published: June 2020

AbstractSevere acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) has caused a pandemic of historic proportions and continues to spread globally, with enormous consequences to human health. Currently there is no vaccine, effective therapeutic or prophylactic. Like other betacoronaviruses, attachment and entry of SARS-CoV-2 is mediated by the spike glycoprotein (SGP). In addition to its well-documented interaction with its receptor, human angiotensin converting enzyme 2 (hACE2), SGP has been found to bind to glycosaminoglycans like heparan sulfate, which is found on the surface of virtually all mammalian cells. Here, we pseudotyped SARS-CoV-2 SGP on a third generation lentiviral (pLV) vector and tested the impact of various sulfated polysaccharides on transduction efficiency in mammalian cells. The pLV vector pseudotyped SGP efficiently and produced high titers on HEK293T cells. Various sulfated polysaccharides potently neutralized pLV-S pseudotyped virus with clear structure-based differences in anti-viral activity and affinity to SGP. Concentration-response curves showed that pLV-S particles were efficiently neutralized by a range of concentrations of unfractionated heparin (UFH), enoxaparin, 6-O-desulfated UFH and 6-O-desulfated enoxaparin with an IC50of 5.99 µg/L, 1.08 mg/L, 1.77 µg/L, and 5.86 mg/L respectively. The low serum bioavailability of intranasally administered UFH, along with data suggesting that the nasal epithelium is a portal for initial infection and transmission, suggest that intranasal administration of UFH may be an effective and safe prophylactic treatment.
Rhythmic coordination of hippocampal-prefrontal ensembles for odor-place associative memory and decision making
Authors: Symanski Claire A. , Bladon John H. , Kullberg Emi T. , Miller Paul , Jadhav Shantanu P. 
Published: June 2020

ABSTRACTMemory-guided decision making involves long-range coordination across sensory and cognitive brain networks, with key roles for the hippocampus and prefrontal cortex (PFC). To investigate these coordination mechanisms, we monitored activity in hippocampus (CA1), PFC, and olfactory bulb in rats performing an odor-place associative memory guided decision task on a T-maze. During odor sampling, the beta (20-30 Hz) and respiratory (7-8 Hz) rhythms (RR) were prominent across the three regions, with CA1-PFC beta and RR coherence enhanced during the odor-cued decision making period. Beta phase modulation of CA1 and PFC neuronal activity during this period was linked to accurate decisions, suggesting that this temporal modulation influences sensory-cued decision making. Single neurons and ensembles in both CA1 and PFC encoded and predicted animals’ upcoming choices. Our findings indicate that rhythmic coordination within the hippocampal-prefrontal network supports utilization of odor cues for memory-guided decision making.
A single N6-methyladenosine site in lncRNA HOTAIR regulates its function in breast cancer cells
Authors: Porman Allison M. , Roberts Justin T. , Duncan Emily D. , Chrupcala Madeline L. , Levine Ariel A. , Kennedy Michelle A. , Williams Michelle M. , Richer Jennifer K. , Johnson Aaron M. 
Published: June 2020

AbstractN6-methyladenosine (m6A) modification of RNA plays important roles in normal and cancer biology, but knowledge of its function on long noncoding RNAs (lncRNAs) remains limited. Here, we investigate whether m6A regulates the function of the human HOTAIR lncRNA, which contributes to multiple pro-tumor phenotypes in triple-negative breast cancer (TNBC) cells. We identify at least 8 individual m6A sites within HOTAIR, with a single site (A783) consistently methylated. Mutation of A783 impairs cellular proliferation and invasion in HOTAIR-overexpressing TNBC cells. m6A at A783 regulates HOTAIR’s ability to localize to chromatin and induce gene pathways that affect tumor progression. In contrast, A783U mutant HOTAIR demonstrates loss-of-function and antimorph behaviors by impairing gene expression changes induced by WT HOTAIR and, in some cases, inducing opposite changes in gene expression. HOTAIR interacts with nuclear m6A reader YTHDC1 and high HOTAIR is significantly associated with shorter overall patient survival, particularly in the context of highYTHDC1. At the molecular level, YTHDC1-HOTAIR interactions are required for chromatin localization and regulation of gene repression. Our work demonstrates how modification of one base in a lncRNA can elicit a distinct gene regulation mechanism and drive disease-associated phenotypic changes such as proliferation and invasion.
Context sensitivity across multiple time scales with a flexible frequency bandwidth
Authors: Regev Tamar I. , Markusfeld Geffen , Deouell Leon Y. , Nelken Israel 
Published: June 2020

ABSTRACTEveryday auditory streams are complex, including spectro-temporal content that varies at multiple time scales. Using EEG, we investigate the sensitivity of human auditory cortex to the content of past stimulation in unattended sequences of equiprobable tones. In 3 experiments including 82 participants overall, we found that neural responses measured at different latencies after stimulus onset were sensitive to frequency intervals computed over distinct time scales. Importantly, early responses were sensitive to a longer history of stimulation than later responses. To account for these results, we tested a model consisting of neural populations with frequency-specific but broad tuning that undergo adaptation with exponential recovery. We found that the coexistence of neural populations with distinct recovery rates can explain our results. Furthermore, the adaptation bandwidth of these populations depended on spectral context – it was wider when the stimulation sequence had a wider frequency range. Our results provide electrophysiological evidence as well as a possible mechanistic explanation for dynamic and multi-scale context-dependent auditory processing in the human cortex.SIGNIFICANCE STATEMENTIt has become clear that brain processing of sensory stimuli depends on their temporal context, but context can be construed at time scales from the recent millisecond to life-long. How do different contextual time scales affect sensory processing? We show that auditory context is integrated across at least two separate time scales, and that at both of these time scales responses dynamically adapt to a varying frequency stimulation range. Using computational modeling, we develop a rigorous methodology to estimate the time and frequency scales of context integration for separate response components. Our robust results replicated across 3 EEG experiments, and contribute to the understanding of neural mechanisms supporting complex and dynamic context integration.
Convergence of distinct subpopulations of mechanosensory neurons onto a neural circuit that elicits grooming
Authors: Hampel Stefanie , Eichler Katharina , Yamada Daichi , Kim Hyunsoo , Horigome Mihoko , Franconville Romain , Bock Davi D. , Kamikouchi Azusa , Seeds Andrew M. 
Published: June 2020

AbstractDiverse subpopulations of mechanosensory neurons detect different mechanical forces and influence behavior. How these subpopulations connect with central circuits to influence behavior remains an important area of study. We previously discovered a neural circuit that elicits grooming of theDrosophila melanogasterantennae that is activated by an antennal mechanosensory chordotonal organ, the Johnston’s organ (JO) (Hampel et al., 2015). Here, we describe anatomically and physiologically distinct JO mechanosensory neuron subpopulations and define how they interface with the circuit that elicits antennal grooming. We show that the subpopulations project to distinct zones in the brain and differ in their responses to mechanical stimulation of the antennae. Each subpopulation elicits grooming through direct synaptic connections with a single interneuron in the circuit, the dendrites of which span the different mechanosensory afferent projection zones. Thus, distinct JO subpopulations converge onto the same neural circuit to elicit a common behavioral response.
Adverse Outcomes and Mortality in Users of Non-Steroidal Anti-Inflammatory Drugs tested positive for SARS-CoV-2: A Danish Nationwide Cohort Study
Authors: Lund Lars Christian , Kristensen Kasper Bruun , Reilev Mette , Christensen Steffen , Thomsen Reimar W. , Christiansen Christian F. , Støvring Henrik , Johansen Nanna Borup , Brun Nikolai , Hallas Jesper , Pottegård Anton 
Published: June 2020

AbstractBackgroundConcerns over the safety of non-steroidal anti-inflammatory drug (NSAID) use during SARS-CoV-2 infection have been raised.ObjectivesTo study whether use of NSAIDs is associated with adverse outcomes and mortality during SARS-CoV-2 infection.DesignPopulation based cohort studySettingDanish administrative and health registries.Participants Individuals tested positive for SARS-CoV-2 during Feb 27, 2020 to Apr 29, 2020. Treated individuals (defined as a filled NSAID prescription up to 30 days before the SARS-CoV-2 test) were matched to up to 4 non-treated individuals on propensity scores based on age, sex, relevant comorbidities and prescription fills.Outcome measuresThe main outcome was 30-day mortality and treated individuals were compared to untreated individuals using risk ratios (RR) and risk differences (RD). Secondary outcomes included hospitalisation, intensive care unit (ICU) admission, mechanical ventilation and acute renal replacement therapy.ResultsA total of 9236 SARS-CoV-2 PCR positive individuals were eligible for inclusion. Of these, 248 (2.7%) had filled a prescription for NSAIDs and 535 (5.8%) died within 30 days. In the matched analyses, treatment with NSAIDs was not associated with 30-day mortality (RR 1.02, 95% CI 0.57 to 1.82; RD 0.1%, −3.5% to 3.7%), increased risk of hospitalisation (RR 1.16, 0.87 to 1.53; RD 3.3%, −3.4% to 10%), ICU-admission (RR 1.04, 0.54 to 2.02; RD 0.2%, −3.0% to 3.4%), mechanical ventilation (RR 1.14, 0.56 to 2.30; RD 0.5%, - 2.5% to 3.6%), or renal replacement therapy (RR 0.86, 0.24 to 3.09; RD −0.2%, −2.0% to 1.6%).ConclusionUse of NSAIDs was not associated with 30-day mortality, hospitalisation, ICU-admission, mechanical ventilation or renal replacement therapy in Danish individuals tested positive for SARS-CoV-2.RegistrationThe European Union electronic Register of Post-Authorisation Studies, EUPAS-34734 (http://www.encepp.eu/encepp/viewResource.htm?id=34735)
Longitudinal Characterization of the Tumoral Microbiome during Radiotherapy in HPV-associated Oropharynx Cancer
Authors: Bahig Houda , Fuller Clifton D , Mitra Aparna , Solley Travis , Ng Sweet Ping , Abu-Gheida Ibrahim , Elgohari Baher , Delgado Andrea , Rosenthal David I , Garden Adam S , Frank Steven J , Reddy Jay P , Colbert Lauren , Klopp Ann 
Published: June 2020

ABSTRACTPurposeTo describe the baseline and serial tumor microbiome in HPV-associated oropharynx cancer (OPC) over the course of radiotherapy (RT).MethodsPatients with newly diagnosed HPV-associated OPC treated with definitive radiotherapy +/- concurrent chemotherapy were enrolled in this prospective study. Using 16S rRNA gene sequencing, dynamic changes in tumor microbiome during RT were investigated. Surface tumor samples were obtained before RT and at week 1, 3 and 5 of RT. Radiological primary tumor response at mid-treatment was categorized as complete (CR) or partial (PR).ResultsTen patients were enrolled. Mean age was 63 years (range: 51-71). As per AJCC 8th Ed, 50%, 20% and 30% of patients had stage I, II and III, respectively. At 4-weeks, 7 patients had CR and 3 patients had PR; at follow-up imaging post treatment, all patients had CR. Baseline diversity of tumoral and buccal microbiomes was not statistically different. For the entire cohort, alpha diversity was significantly decreased over the course of treatment (p=0.02). There was a significant alteration in the bacterial community within the first week of radiation. Baseline tumor alpha diversity of patients with CR was significantly higher than those with PR (p=0.03). While patients with CR had significant reduction in diversity over the course of radiation (p=0.02), the diversity remained unchanged in patients with PR. Patients with history of smoking had significantly increased abundance of Granulicatella (p=0.04), and Kingella (0.05) and lower abundance of Alloprevotella (p=0.04) compared to never smokers.ConclusionsThe tumor microbiome of HPV-associated OPC exhibits reduced alpha diversity and altered taxa abundance over the course of radiotherapy. The baseline bacterial profiles of smokers vs. non-smokers were inherently different. Baseline tumor alpha diversity of patients with CR was higher than patients with PR, suggesting that the microbiome as a biomarker of radiation response deserves further investigation.
Weather variables impact on COVID-19 incidence
Authors: Corripio Javier G. , Raso Lorna 
Published: June 2020

AbstractWe test the hypothesis of COVID-19 contagion being influenced by meteorological parameters such as temperature or humidity. We analysed data at high spatial resolution (regions in Italy and counties in the USA) and found that while at low resolution this might seem the case, at higher resolution no correlation is found. Our results are consistent with a poor outdoors transmission of the disease. However, a possible indirect correlation between good weather and a decrease in disease spread may occur, as people spend longer time outdoors.
Temporal evolution of COVID-19 in the states of India using SIQR Model
Authors: Tiwari Alok 
Published: June 2020

ABSTRACTCOVID 19 entered during the last week of April 2020 in India has caused 3,546 deaths with 1,13,321 number of reported cases. Indian government has taken many proactive steps, including strict lockdown of the entire nation for more than 50 days, identification of hotspots, app-based tracking of citizens to track infected. This paper investigated the evolution of COVID 19 in five states of India (Maharashtra, UP, Gujrat, Tamil Nadu, and Delhi) from 1st April 2020 to 20th May 2020. Variation of doubling rate and reproduction number (from SIQR) with time is used to analyse the performance of the majorly affected Indian states. It has been determined that Uttar Pradesh is one of the best performers among five states with the doubling rate crossing 18 days as of 20th May. Tamil Nadu has witnessed the second wave of infections during the second week of May. Maharashtra is continuously improving at a steady rate with its doubling rate reaching to 12.67 days. Also these two states are performing below the national average in terms of infection doubling rate. Gujrat and Delhi have reported the doubling rate of 16.42 days and 15.49 days respectively. Comparison of these states has also been performed based on time-dependent reproduction number. Recovery rate of India has reached to 40 % as the day paper is written.