bluuebunny/crossref_metadata_2025_split huggingface dataset:
RNA secondary structure packages evaluated and improved by high-throughput experiments
Authors: Wayment-Steele Hannah K. , Kladwang Wipapat , Strom Alexandra I. , Lee Jeehyung , Treuille Adrien ,   Eterna Participants, Das Rhiju 
Published: May 2020

AbstractThe computer-aided study and design of RNA molecules is increasingly prevalent across a range of disciplines, yet little is known about the accuracy of commonly used structure modeling packages in tasks sensitive to ensemble properties of RNA. Here, we demonstrate that the EternaBench dataset, a set of over 20,000 synthetic RNA constructs designed in iterative cycles on the RNA design platform Eterna, provides incisive discriminative power in evaluating current packages in ensemble-oriented structure prediction tasks. We find that CONTRAfold and RNAsoft, packages with parameters derived through statistical learning, achieve consistently higher accuracy than more widely used packages in their standard settings, which derive parameters primarily from thermodynamic experiments. Motivated by these results, we develop a multitask-learning-based model, EternaFold, which demonstrates improved performance that generalizes to diverse external datasets, including complete mRNAs and viral genomes probed in human cells and synthetic designs modeling mRNA vaccines.
Retina-specific targeting of pericytes reveals structural diversity and enables control of capillary blood flow
Authors: Ivanova Elena , Corona Carlo , Eleftheriou Cyril G. , Bianchimano Paola , Sagdullaev Botir T. 
Published: May 2020

AbstractPericytes are a unique class of mural cells essential for angiogenesis, maintenance of the vasculature and are key players in microvascular pathology. However, their diversity and specific roles are poorly understood, limiting our insight into vascular physiology and the ability to develop effective therapies. Here, in the mouse retina, a tractable model of the CNS, we evaluated distinct classes of mural cells along the vascular tree for both structural characterization and physiological manipulation of blood flow. To accomplish this, we first tested three inducible mural cell-specific mouse lines using a sensitive Ai14 reporter and tamoxifen application either by a systemic injection, or by local administration in the form of eye drops. Across three lines, under either the PDGFRb or NG2 promoter, the specificity and pattern of Cre activation varied significantly. In particular, a mouse line with Cre under the NG2 promoter resulted in sparse TdTomato labeling of mural cells, allowing for an unambiguous characterization of anatomical features of individual sphincter cells and capillary pericytes. Furthermore, in one PDGFRb line, we found that focal eye drop application of tamoxifen led to an exclusive Cre-activation in pericytes, without affecting arterial mural cells. We then used this approach to boost capillary blood flow by selective expression of Halorhodopsin, a highly precise hyperpolarizing optogenetic actuator. The ability to exclusively target capillary pericytes may prove a precise and potentially powerful tool to treat microcirculation deficit, a common pathology in numerous diseases.
Predicting subsurface sonar observations with satellite-derived ocean surface data in the California Current Ecosystem
Authors: Gadeken Kellie R. , Joseph Maxwell B. , McGlinchy Joseph , Karnauskas Kristopher B. , Wall Carrie C. 
Published: May 2020

AbstractVessel-based sonar systems that focus on the water column provide valuable information on the distribution of underwater marine organisms, but such data are expensive to collect and limited in their spatiotemporal coverage. Satellite data, however, are widely available across large regions and provide information on surface ocean conditions. If satellite data can be linked to subsurface sonar measurements, it may be possible to predict marine life over broader spatial regions with higher frequency using satellite observations. Here, we use random forest models to evaluate the potential for predicting a sonar-derived proxy for subsurface biomass as a function of satellite imagery in the California Current Ecosystem. We find that satellite data may be useful for prediction under some circumstances, but across a range of sonar frequencies and depths, overall predictive performance was low. Performance in spatial interpolation tasks exceeded performance in spatial and temporal extrapolation, suggesting that this approach is not yet reliable for forecasting or spatial extrapolation. We conclude with some potential limitations and extensions of this work.
Preferential Pharmacological Inhibition of Nav1.6, but not Nav1.1, Abolishes Epileptiform Activity Induced by 4-AP in Mouse Cortical Slices
Authors: Patel Reesha R. , Ping Xingjie , Patel Shaun R. , McDermott Jeff S. , Krajewski Jeffrey L. , Chi Xian Xuan , Nisenbaum Eric S. , Jin Xiaoming , Cummins Theodore R. 
Published: May 2020

ABSTRACTBrain isoforms of voltage-gated sodium channels (VGSCs) have distinct cellular and subcellular expression patterns as well as functional roles that are critical for normal physiology as aberrations in their expression or activity lead to pathophysiological conditions. In this study, we asked how inhibition of select isoforms of VGSCs alters epileptiform activity to further parse out the roles of VGSCs in the brain. We first determined the relative selectivity of recently discovered small molecule, aryl sulfonamide, inhibitors (ICA-121431 and Compound 801) against Nav1.1, Nav1.2, and Nav1.6 activity using whole-cell patch clamp recordings obtained from HEK293 cells. To test the effects of these inhibitors on epileptiform activity, we obtained multielectrode array (MEA) recordings from mouse cortical slices in the presence of 4-aminopyridine (4-AP) to induce epileptiform activity. We found that the ICA-121431 and Compound 801 compounds are relatively selective for Nav1.1 and Nav1.6, respectively. From the MEA recordings, we found that inhibition of Nav1.6 and Nav1.2 with 500nM of the Compound 801 compound completely abolishes ictal local field potentials induced by 4-AP, whereas inhibition of Nav1.1 with 500nM of the ICA-121431 compound had minimal effect on epileptiform activity induced by 4-AP. Due to the prominent expression of Nav1.1 in inhibitory neurons, we asked whether inhibition of Nav1.1 alone alters activity. We found that, indeed, inhibition of Nav1.1 with the ICA-121431 compound increased basal activity in the absence of 4-AP. These findings expand our current understanding of the roles of VGSC isoforms in the brain and suggest that selective targeting of Nav1.6 may be a more efficacious treatment strategy for epileptic syndromes.
Adaptive optics two-photon endomicroscopy enables deep brain imaging at synaptic resolution over large volumes
Authors: Qin Zhongya , Chen Congping , He Sicong , Wang Ye , Tam Kam Fai , Ip Nancy Y. , Qu Jianan Y. 
Published: May 2020

AbstractOptical deep brain imaging in vivo at high resolution has remained a great challenge over the decades. Two-photon endomicroscopy provides a minimally invasive approach to image buried brain structures, once it is integrated with a gradient refractive index (GRIN) lens embedded in the brain. However, its imaging resolution and field of view are compromised by the intrinsic aberrations of the GRIN lens. Here, we develop a two-photon endomicroscopy by adding adaptive optics based on the direct wavefront sensing, which enables recovery of diffraction-limited resolution in deep brain imaging. A new precompensation strategy plays a critical role to correct aberrations over large volumes and achieve rapid random-access multiplane imaging. We investigate the neuronal plasticity in the hippocampus, a critical deep brain structure, and reveal the relationship between the somatic and dendritic activity of pyramidal neurons.
CellMeSH: Probabilistic Cell-Type Identification Using Indexed Literature
Authors: Mao Shunfu , Zhang Yue , Seelig Georg , Kannan Sreeram 
Published: May 2020

AbstractSingle-cell RNA sequencing (scRNA-seq) is widely used for analyzing gene expression in multi-cellular systems and provides unprecedented access to cellular heterogeneity. scRNA-seq experiments aim to identify and quantify all cell types present in a sample. Measured single-cell transcriptomes are grouped by similarity and the resulting clusters are mapped to cell types based on cluster-specific gene expression patterns. While the process of generating clusters has become largely automated, annotation remains a laborious ad-hoc effort that requires expert biological knowledge. Here, we introduce CellMeSH - a new automated approach to identifying cell types based on prior literature. CellMeSH combines a database of gene-cell type associations with a probabilistic method for database querying. The database is constructed by automatically linking gene and cell type information from millions of publications using existing indexed literature resources. Compared to manually constructed databases, CellMeSH is more comprehensive and scales automatically. The probabilistic query method enables reliable information retrieval even though the gene-cell type associations extracted from the literature are necessarily noisy. CellMeSH achieves up to 60% top-1 accuracy and 90% top-3 accuracy in annotating the cell types on a human dataset, and up to 58.8% top-1 accuracy and 88.2% top-3 accuracy on three mouse datasets, which is consistently better than existing approaches.AvailabilityWeb server:https://uncurl.cs.washington.edu/db_queryand API:https://github.com/shunfumao/cellmesh
Validation and Performance Comparison of Three SARS-CoV-2 Antibody Assays
Authors: Paiva Kimberly J , Grisson Ricky D , Chan Philip A , Lonks John R. , King Ewa , Huard Richard C , Pytel-Parenteau Diane L , Nam Ga Hie , Yakirevich Evgeny , Lu Shaolei 
Published: May 2020

AbstractSerology testing of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is increasingly being used during the current pandemic of Coronavirus Disease 2019 (COVID-19). The clinical and epidemiologic utilities of antibody-based SARS-CoV-2 testing are under debate. Characterizing these assays helps to understand the disease and provides scientific basis for deciding how to best use these assays. The study assessed one chemiluminescent assay (Abbott COVID-2 IgG) and two lateral flow assays (STANDARD Q [SQ] IgM/IgG Duo and Wondfo Total Antibody Test). Validation included 113 blood samples from 71 PCR-confirmed COVID-19 patients and 1182 samples from negative controls with potential interferences/cross-reactions, including 1063 pre-pandemic samples. IgM antibodies against SARS-CoV-2 were detected as early as post-symptom onset days 3-4. IgG antibodies were first detected post-onset days 5-6 by SQ assays. The detection rates increased gradually, and SQ IgG, Abbott IgG and Wondfo Total detected antibodies from all the PCR-confirmed patients 14 days after symptom onset. Overall agreements between SQ IgM/IgG and Wondfo Total was 88.5% and between SQ IgG and Abbott IgG was 94.6% (Kappa = 0.75, 0.89). No cross-reaction with other endemic coronavirus infections were identified. Viral hepatitis and autoimmune samples were the main cross-reactions observed. However, the interferences/cross-reactions were low. The specificities were 100% for SQ IgG and Wondfo Total and 99.62% for Abbott IgG and 98.87% for SQ IgM. These findings demonstrate high sensitivity and specificity of appropriately validated antibody-based SARS-CoV-2 assays with implications for clinical use and epidemiological seroprevalence studies.
Structural neuroplastic responses preserve functional connectivity and neurobehavioural outcomes in children born without corpus callosum
Authors: Siffredi Vanessa , Preti Maria G. , Kebets Valeria , Obertino Silvia , Leventer Richard J. , McIlroy Alissandra , Wood Amanda G. , Anderson Vicki , Spencer-Smith Megan M. , Van De Ville Dimitri 
Published: May 2020

AbstractBackgroundThe corpus callosum is the largest white matter pathway in the brain connecting the left and the right hemispheres. Developmental absence of the corpus callosum is a model disease for exploring disrupted connectivity and in turn understanding plasticity of the human brain, with atypically developing structure and function resulting in a highly heterogeneous clinical and cognitive profile. A proposed candidate for neuroplastic response in the context of this brain malformation is strengthening of intra-hemispheric pathways.MethodsTo test this hypothesis, we assessed structural and functional connectivity at the whole-brain and regional level in a uniquely large cohort of children with agenesis of the corpus callosum (AgCC, n = 20) compared with typically developing controls (TDC, n = 29), and then examined associations with neurobehavioural outcomes using a multivariate data-driven approach.ResultsFor structural connectivity, children with AgCC showed a significant increase in intrahemispheric connectivity in addition to a significant decrease in inter-hemispheric connectivity compared with TDC. In contrast, for functional connectivity, children with AgCC and TDC showed a similar pattern of intra-hemispheric and inter-hemispheric connectivity. In AgCC, structural strengthening of the intra-hemispheric pathway was uniquely associated with verbal learning and memory, attention and executive measures.ConclusionsWe observed structural strengthening of intra-hemispheric pathways in children born without corpus callosum, which seems to allow for functional connectivity comparable to a typically developing brain, and were relevant to explain neurobehavioural outcomes in this population. This neuroplasticity might be relevant to other disorders of axonal guidance, and developmental disorders in which corpus callosum alteration is observed.
Use of community-based intervention to promote Family Planning use among Pastoralist women in Ethiopia: Cluster randomized controlled trial
Authors: Alemayehu Mussie , Medhanyie Araya Abrha , Reed Elizabeth , Bezabih Afework Mulugeta 
Published: May 2020

AbstractObjectiveWe assessed the effect of a community-based intervention for promoting FP use and intention among pastoralist communities of Afar region state, Ethiopia.MethodsThe design was parallel, cluster randomized controlled trial (CRT) recruiting married women. It had three arms: 1) women’s FP education, 2) male involvement and 3) control with one to one ratio. A total of 33 kebeles were randomized and allocated. Data were collected through an open data kit. Women’s FP education and male involvement in FP service were the interventions. It was implemented with the assistance of a faema leader using a separate group meeting for males and women and disseminates video recorded messages on FP. The intervention was given for a total of 9 months. FP use and intentions were measured. Cluster level summaries considering a cluster effect analysis was performed. The result was presented with adjusted risks and 95% CI. A p-value < 0.05 was used to declare statistically significant.ResultsThere was a positive change in the proportion of married women who use FP in the women’s FP education arm, absolute risk (AR) of 0.13(95% CI,0.08,0.17) and male involvement arm with AR of 0.29 (95% CI, 0.23,0.34) as compared to the control arm. In the control arm, the proportion of FP use was 4.3%, whereas it was 17.5% with women who receive FP education and 34% in the male involvement arm. Furthermore, the proportion of married women who had high intention to use FP was high in arms of women’s FP education and male involvement with AR = 3.4(95% CI: 2.48,4.91) and AR = 2.1 (95% CI: 1.5,2.95), respectively as compared with the control arm.ConclusionThe community-based intervention (male involvement and women’s education about FP use) brings a significant change in increasing FP users and promotes the intention to use FP.
Alpha globin gene deletions in amelioration of clinical severity in beta haemoglobinopathy subjects with the β0/β+ genotype
Authors: Saha Dipankar , Chowdhury Prosanto Kumar , Panja Amrita , Pal Debashis , Chakraborty Sharmistha , Nayek Kaustav , Chakraborty Gispati , Sharma Prashant , Das Reena , Basu Surupa , Chatterjee Raghunath , Basu Anupam 
Published: May 2020

AbstractThalassemia is the commonest inherited hemoglobinopathy worldwide. Variation of clinical symptoms entail differences in disease-onset and transfusion requirements. Our objective was to investigate the role of alpha gene deletions in modulating the clinical heterogeneity of thalassemia syndromes. A total of 214 individuals with diagnosed beta-thalassemia major/intermedia were included in the study. Beta globin mutations were determined and categorized as β+ and β0. Eight common alpha globin gene deletions were detected by multiplex GAP-PCR. Out of the 17 individuals with β+/β+, 16 did not harbour alpha deletions (αα/αα), and most of them were non-severe. On the other hand, out of 46 individuals with β0/β0, 30 did not reveal alpha deletions, whereas 16 possessed one or more alpha deletion(s). Accordingly, most of them presented as clinically severe. Out of the 151 β0/β+ individuals, 119 were negative for alpha deletion, whereas 32 possessed alpha deletions. It was observed that, only in this last category, alpha deletions made a significant contribution (P< 0.0001) in modulation of clinical non severity in this genotype. In conclusion, alpha globin gene deletions play a role to help in ameliorating the phenotype in the β+/β0 genotype. However, they may have only minor/no role in patients with β+/β+ or β0/β0 genotype.
How Efficacious Must a COVID-19 Coronavirus Vaccine be to Prevent or Stop an Epidemic by Itself
Authors: Bartsch Sarah M. , O’Shea Kelly J. , Ferguson Marie C. , Bottazzi Maria Elena , Cox Sarah N. , Strych Ulrich , McKinnell James A. , Wedlock Patrick T. , Siegmund Sheryl S. , Hotez Peter J. , Lee Bruce Y. 
Published: May 2020

AbstractBackgroundGiven the continuing coronavirus disease 2019 (COVID-19) pandemic and much of the U.S. implementing social distancing due to the lack of alternatives, there has been a push to develop a vaccine to eliminate the need for social distancing.MethodsIn 2020, we developed a computational model of the U.S. simulating the spread of COVID-19 coronavirus and vaccination.ResultsSimulation experiments revealed that when vaccine efficacy exceeded 70%, coverage exceeded 60%, and vaccination occurred on day 1, the attack rate dropped to 22% with daily cases not exceeding 3.2 million (reproductive rate, R0, 2.5). When R0 was 3.5, the attack rate dropped to 41% with daily cases not exceeding 14.4 million. Increasing coverage to 75% when vaccination occurred by day 90 resulted in 5% attack rate and daily cases not exceeding 258,029when R0 was 2.5 and a 26% attack rate and maximum daily cases of 22.6 million when R0 was 3.5. When vaccination did not occur until day 180, coverage (i.e., those vaccinated plus those otherwise immune) had to reach 100%. A vaccine with an efficacy between 40% and 70% could still obviate the need for other measures under certain circumstances such as much higher, and in some cases, potentially unachievable, vaccination coverages.ConclusionOur study found that to either prevent or largely extinguish an epidemic without any other measures (e.g., social distancing), the vaccine has to have an efficacy of at least 70%.
Mendelian randomization analysis to characterize causal association between coronary artery disease and COVID-19
Authors: Wu Lang , Zhu Jingjing , Wu Chong 
Published: May 2020

AbstractObservational studies have suggested that having coronary artery disease increases the risk of Coronavirus disease 2019 (COVID-19) susceptibility and severity, but it remains unclear if this association is causal. Inferring causation is critical to facilitate the development of appropriate policies and/or individual decisions to reduce the incidence and burden of COVID-19. We applied Two-sample Mendelian randomization analysis and found that genetically predicted CAD was significantly associated with higher risk of COVID-19: the odds ratio was 1.29 (95% confidence interval 1.11 to 1.49; P = 0.001) per unit higher log odds of having CAD.
Escape of TLR5 Recognition byLeptospira spp: A Rationale for Atypical Endoflagella
Authors: Holzapfel Marion , Bonhomme Delphine , Cagliero Julie , Vernel-Pauillac Frédérique , d’Andon Martine Fanton , Bortolussi Sophia , Fiette Laurence , Goarant Cyrille , Wunder Elsio A. , Picardeau Mathieu , Ko Albert I. , Werling Dirk , Matsui Mariko , Boneca Ivo G. , Werts Catherine 
Published: May 2020

AbstractLeptospira interrogansare invasive bacteria responsible for leptospirosis, a worldwide zoonosis. They possess two periplasmic endoflagella that allow their motility.L. interrogansare stealth pathogens that escape the innate immune responses of the NOD-like receptors NOD1/2, and the human Toll-like receptor (TLR)4, sensing peptidoglycan and lipopolysaccharide (LPS), respectively. TLR5 is another receptor of bacterial cell wall components, recognizing flagellin subunits.To study the contribution of TLR5 in the host defense against leptospires, we infected WT and TLR5 deficient mice with pathogenicL. interrogansand tracked the infection byin vivolive imaging of bioluminescent bacteria or by q-PCR. We did not identify any protective or inflammatory role of murine TLR5 to control pathogenicLeptospira. Likewise, subsequentin vitroexperiments showed that infections with different live strains ofL. interrogansandL. biflexadid not trigger TLR5. However, unexpectedly, heat-killed bacteria stimulated human and bovine TLR5, although barely mouse TLR5. Abolition of TLR5 recognition required extensive boiling time of the bacteria or proteinase K treatment, showing an unusual high stability of the leptospiral flagellins. Interestingly, using antimicrobial peptides to destabilize live leptospires, we detected some TLR5 activity, suggesting that TLR5 could participate in the fight against leptospires in humans or cattle. Using differentLeptospirastrains with mutations in flagellin proteins, we further showed that neither FlaAs nor Fcps participated in the recognition by TLR5, suggesting a role for the FlaBs. These have structural homology toSalmonellaFliC, and conserved residues important for TLR5 activation, as shown byin silicoanalyses. Accordingly, we found that leptospires regulate the expression of FlaB mRNA according to the growth phasein vitro, and that infection withL. interrogansin hamsters and in mice downregulated the expression of the FlaBs but not the FlaAs subunits.Altogether, in contrast to different bacteria that modify their flagellin sequences to escape TLR5 recognition, our study suggests that the peculiar central localization and stability of the FlaB monomers in the periplasmic endoflagella, associated with the downregulation of FlaB subunits in hosts, constitute an efficient strategy of leptospires to escape TLR5 recognition and the immune response.