bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Ecological Structure of Mosquito Population Seasonal Dynamics
Authors: Whittaker Charles , Winskill Peter , Sinka Marianne , Pironon Samuel , Massey Claire , Weiss Daniel J , Nguyen Michele , Gething Peter W , Kumar Ashwani , Ghani Azra , Bhatt Samir 
Published: January 2021

AbstractUnderstanding the temporal dynamics of mosquito populations underlying malaria transmission is key to optimising control strategies. We collate mosquito time-series catch data spanning 40 years and 117 locations across India to understand the factors driving these dynamics. Our analyses reveal pronounced variation in dynamics across locations and between species. Many mosquito populations lacked the often-assumed positive relationship with rainfall, instead displaying patterns of abundance that were only weakly or even negatively correlated with precipitation and highlighting the role of temperature, proximity to perennial bodies of water and patterns of land use in shaping the dynamics and seasonality of mosquito populations. We show that these diverse dynamics can be clustered into “dynamical archetypes”, each characterised by distinct temporal properties and driven by a largely unique set of environmental factors. These results highlight that a complex interplay of factors, rather than rainfall alone, shape the timing and extent of mosquito population seasonality.
24-Nor-Ursodeoxycholic acid reshapes immunometabolism in CD8+T cells and alleviates hepatic inflammation
Authors: Zhu Ci , Boucheron Nicole , Müller André C. , Májek Peter , Claudel Thierry , Halilbasic Emina , Baazim Hatoon , Lercher Alexander , Viczenczova Csilla , Hainberger Daniela , Preglej Teresa , Sandner Lisa , Alteneder Marlis , Gülich Alexandra F. , Khan Matarr , Hamminger Patricia , Remetic Jelena , Ohradanova-Repic Anna , Schatzlmaier Philipp , Donner Clemens , Fuchs Claudia D. , Stojakovic Tatjana , Scharnagl Hubert , Sakaguchi Shinya , Weichhart Thomas , Bergthaler Andreas , Stockinger Hannes , Ellmeier Wilfried , Trauner Michael 
Published: January 2021

AbstractBackground & Aims24-NorUrsodeoxycholic acid (NorUDCA) is novel therapy for immune-mediated liver diseases such as primary sclerosing cholangitis (PSC) where dysregulated T cells including CD8+T cells cause liver immunopathology. We hypothesized that NorUDCA may directly modulate CD8+T cell effector function thus contributing to its therapeutic efficacy independent of anti-cholestatic effects.MethodsNorUDCA effects on CD8+T cell functionin vivowere investigated in a hepatic injury model system induced by excessive CD8+T cell immune response upon non-cytolytic lymphocytic choriomeningitis virus (LCMV) infection. Mechanistic studies included molecular and biochemical approaches, flow cytometry and metabolic assays in mouse CD8+T cellsin vitro. Mass spectrometry (MS) was used to identify potential targets modulated by NorUDCA in CD8+T cells. NorUDCA signaling effects observed in murine systems were validated in peripheral T cells from healthy volunteers and PSC patients.ResultsIn vivoNorUDCA ameliorated hepatic injury and systemic inflammation upon LCMV infection. Mechanistically, NorUDCA demonstrated a strong immunomodulatory efficacy in CD8+T cells affecting lymphoblastogenesis, mTORC1 signaling and glycolysis of CD8+T cells. With MS, we identified that NorUDCA regulates CD8+T cells via targeting mTORC1. NorUDCA’s impact on mTORC1 signaling was further confirmed in circulating human CD8+T cells.ConclusionsNorUDCA possesses a yet-unrecognized direct modulatory potency on CD8+T cells and attenuates excessive CD8+T cell hepatic immunopathology. These findings may be relevant for treatment of immune-mediated liver diseases such as PSC and beyond.
Epidemiological impact of prioritizing SARS-CoV-2 vaccination by antibody status: Mathematical modeling analyses
Authors: Ayoub Houssein H. , Chemaitelly Hiam , Makhoul Monia , Kanaani Zaina Al , Kuwari Einas Al , Butt Adeel A. , Coyle Peter , Jeremijenko Andrew , Kaleeckal Anvar Hassan , Latif Ali Nizar , Shaik Riyazuddin Mohammad , Rahim Hanan F. Abdul , Nasrallah Gheyath K. , Yassine Hadi M. , Kuwari Mohamed G. Al , Romaihi Hamad Eid Al , Al-Thani Mohamed H. , Bertollini Roberto , Khal Abdullatif Al , Raddad Laith J. Abu 
Published: January 2021

AbstractBackgroundVaccines against SARS-CoV-2 have been developed, but their availability falls far short of global needs. This study aimed to investigate the impact of prioritizing available doses on the basis of recipient antibody status, that is by exposure status, using Qatar as an example.MethodsVaccination impact was assessed under different scale-up scenarios using a deterministic meta-population mathematical model describing SARS-CoV-2 transmission and disease progression in the presence of vaccination.ResultsFor a vaccine that protects against infection with an efficacy of 95%, half as many vaccinations were needed to avert one infection, disease outcome, or death by prioritizing antibody-negative individuals for vaccination. Prioritization by antibody status reduced incidence at a faster rate and led to faster elimination of infection and return to normalcy. Further prioritization by age group amplified the gains of prioritization by antibody status. Gains from prioritization by antibody status were largest in settings where the proportion of the population already infected at the commencement of vaccination was 30-60%, which is perhaps where most countries will be by the time vaccination programs are up and running. For a vaccine that only protects against disease and not infection, vaccine impact was reduced by half, whether this impact was measured in terms of averted infections or disease outcomes, but the relative gains from using antibody status to prioritize vaccination recipients were similar.ConclusionsMajor health, societal, and economic gains can be achieved more quickly by prioritizing those who are antibody-negative while doses of the vaccine remain in short supply.
The hyperlipidaemic drug fenofibrate significantly reduces infection by SARS-CoV-2 in cell culture models
Authors: Davies Scott P. , Mycroft-West Courtney J. , Pagani Isabel , Hill Harriet J. , Chen Yen-Hsi , Karlsson Richard , Bagdonaite Ieva , Guimond Scott E. , Stamataki Zania , De Lima Marcelo Andrade , Turnbull Jeremy E. , Yang Zhang , Vicenzi Elisa , Skidmore Mark A. , Khanim Farhat , Richardson Alan 
Published: January 2021

AbstractThe SARS-CoV-2 pandemic has caused a significant number of fatalities and worldwide disruption. To identify drugs to repurpose to treat SARS-CoV-2 infections, we established a screen to measure dimerization of ACE2, the primary receptor for the virus. This screen identified fenofibric acid, the active metabolite of fenofibrate. Fenofibric acid also destabilized the receptor binding domain (RBD) of the viral spike protein and inhibited RBD binding to ACE2 in ELISA and whole cell binding assays. Fenofibrate and fenofibric acid were tested by two independent laboratories measuring infection of cultured Vero cells using two different SARS-CoV-2 isolates. In both settings at drug concentrations which are clinically achievable, fenofibrate and fenofibric acid reduced viral infection by up to 70%. Together with its extensive history of clinical use and its relatively good safety profile, these studies identify fenofibrate as a potential therapeutic agent requiring urgent clinical evaluation to treat SARS-CoV-2 infection.TeaserThe approved drug fenofibrate inhibits infection by SARS-COV-2
Characterization of cephalic and non-cephalic sensory cell types provides insight into joint photo- and mechanoreceptor evolution
Authors: Revilla-i-Domingo Roger , Veedin Rajan Vinoth Babu , Waldherr Monika , Prohaczka Günther , Musset Hugo , Orel Lukas , Gerrard Elliot , Smolka Moritz , Farlik Matthias , Lucas Robert J. , Raible Florian , Tessmar-Raible Kristin 
Published: January 2021

ABSTRACTRhabdomeric Opsins (r-Opsins) are light-sensors in cephalic eye photoreceptors, but also function in additional sensory organs. This has prompted questions on the evolutionary relationship of these cell types, and if ancient r-Opsins cells were non-photosensory. Our profiling of cephalic and non-cephalic r-opsin1-expressing cells of the marine bristlewormPlatynereis dumeriliireveals shared and distinct features. Non-cephalic cells possess a full set of phototransduction components, but also a mechanosensory signature. We determine that Pdu-r-Opsin1 is a Gαq-coupled blue-light receptor. Profiling of cells fromr-opsin1mutants versus wild-types, and a comparison under different light conditions reveals that in the non-cephalic cells, light – mediated by r-Opsin1 – adjusts the expression level of a calcium transporter relevant for auditory mechanosensation in vertebrates. We establish a deep learning-based quantitative behavioral analysis for animal trunk movements, and identify a light-and r-Opsin-1-dependent fine-tuning of the worm’s undulatory movements in headless trunks, which are known to require mechanosensory feedback.Our results suggest an evolutionary concept in which r-Opsins act as ancient, light-dependent modulators of mechanosensation, and suggest that light-independent mechanosensory roles of r-Opsins likely evolved secondarily.
Biophysical investigation of the dual binding surfaces of human transcription factors FOXO4 and p53
Authors: Kim Jinwoo , Ahn Dabin , Park Chin-Ju 
Published: January 2021

AbstractCellular senescence is protective against external oncogenic stress, but its accumulation causes aging-related diseases. Forkhead box O4 (FOXO4) and p53 are human transcription factors known to promote senescence by interacting each other and activating p21 transcription. Inhibition of the interaction is a strategy for inducing apoptosis of senescent cells, but the binding surfaces that mediate the FOXO4-p53 interaction remain elusive. Here, we investigated two binding sites involved in the interaction between FOXO4 and p53 by NMR spectroscopy. NMR chemical shift perturbation analysis showed that the binding between FOXO4’s forkhead domain (FHD) and p53’s transactivation domain (TAD), and between FOXO4’s C-terminal transactivation domain (CR3) and p53’s DNA binding domain (DBD), mediate the FOXO4-p53 interaction. Isothermal titration calorimetry data showed that both interactions have micromolar Kdvalues, and FOXO4 FHD-p53 TAD interaction has a higher binding affinity. Also, we showed that the FOXO4 CR3-binding surface of FOXO4 FHD interacts with p53 TAD2, and FOXO4 CR3 interacts with the DNA/p53 TAD-binding surface of p53 DBD, suggesting a network of potentially competitive and/or coordinated interactions. Based on the results, we propose that the dual interaction contributes to two TF’s proper location on the p21 promoter site and consequently promotes p21 transcription and cell senescence. This work provides structural information at the molecular level that is key to understanding the interplay of two proteins responsible for cellular senescence.Conflicts of interestNone
High-content single-cell combinatorial indexing
Authors: Mulqueen Ryan M. , Pokholok Dmitry , O’Connell Brendan L. , Thornton Casey A. , Zhang Fan , O’Roak Brian J. , Link Jason , Yardmici Galip Gurkan , Sears Rosalie C. , Steemers Frank J. , Adey Andrew C. 
Published: January 2021

AbstractSingle-cell genomics assays have emerged as a dominant platform for interrogating complex biological systems. Methods to capture various properties at the single-cell level typically suffer a tradeoff between cell count and information content, which is defined by the number of unique and usable reads acquired per cell. We and others have described workflows that utilize single-cell combinatorial indexing (sci)1, leveraging transposase-based library construction2to assess a variety of genomic properties in high throughput; however, these techniques often produce sparse coverage for the property of interest. Here, we describe a novel adaptor-switching strategy, ‘s3’, capable of producing one-to-two order-of-magnitude improvements in usable reads obtained per cell for chromatin accessibility (s3-ATAC), whole genome sequencing (s3-WGS), and whole genome plus chromatin conformation (s3-GCC), while retaining the same high-throughput capabilities of predecessor ‘sci’ technologies. We apply s3 to produce high-coverage single-cell ATAC-seq profiles of mouse brain and human cortex tissue; and whole genome and chromatin contact maps for two low-passage patient-derived cell lines from a primary pancreatic tumor.
Toward Optimized and Predictive Connectomics at Scale
Authors: Moon Joseph Y. , Mukherjee Pratik , Madduri Ravi K. , Markowitz Amy J. , Palacios Eva M. , Manley Geoffrey T. , Bremer Peer-Timo 
Published: January 2021

AbstractProbabilistic MRI diffusion tractography is a sophisticated technique to investigate structural connectomes, but its steep computational cost prevents application to broader research and clinical settings. Major speedup can be achieved by reducing the number of tractography streamlines. To ensure this does not degrade connectome quality, we calculate the identifiability of connectomes between test and retest MRI as a proxy for information content. We find that reducing streamline count by up to two orders of magnitude from prevailing levels in literature has no significant impact on identifiability. Incidentally, we also observe that Jaccard similarity is more effective than Pearson correlation in achieving identifiability.This document was prepared as an account of work sponsored by an agency of the United States government. Neither the United States government nor Lawrence Livermore National Security, LLC, nor any of their employees makes any warranty, expressed or implied, or assumes any legal liability or responsibility for the accuracy, completeness, or usefulness of any information, apparatus, product, or process disclosed, or represents that its use would not infringe privately owned rights. Reference herein to any specific commercial product, process, or service by trade name, trademark, manufacturer, or otherwise does not necessarily constitute or imply its endorsement, recommendation, or favoring by the United States government or Lawrence Livermore National Security, LLC. The views and opinions of authors expressed herein do not necessarily state or reflect those of the United States government or Lawrence Livermore National Security, LLC, and shall not be used for advertising or product endorsement purposes.
Spatial Transcriptomics to define transcriptional patterns of zonation and structural components in the liver
Authors: Hildebrandt Franziska , Andersson Alma , Saarenpää Sami , Larsson Ludvig , Van Hul Noémi , Kanatani Sachie , Masek Jan , Ellis Ewa , Barragan Antonio , Mollbrink Annelie , Andersson Emma R. , Lundeberg Joakim , Ankarklev Johan 
Published: January 2021

ABSTRACTReconstruction of heterogeneity through single-cell transcriptional profiling has greatly advanced our understanding of the spatial liver transcriptome in recent years. However, global transcriptional differences across lobular units remain elusive in physical space. Here, we implement Spatial Transcriptomics to perform transcriptomic analysis across sectioned liver tissue. We confirm that the heterogeneity in this complex tissue is predominantly determined by lobular zonation. By introducing novel computational approaches, we enable transcriptional gradient measurements between tissue structures, including several lobules in a variety of orientations. Further, our data suggests the presence of previously transcriptionally uncharacterized structures within liver tissue, contributing to the overall spatial heterogeneity of the organ. This study demonstrates how comprehensive spatial transcriptomic technologies can be used to delineate extensive spatial gene expression patterns in the liver, indicating its future impact for studies of liver function, development and regeneration as well as its potential in pre-clinical and clinical pathology.
Low oxygen arrestsBabesia duncanischizonts and leads to increased drug susceptibilities in hamster erythrocytes
Authors: Zhang Yumin , Alvarez-Manzo Hector , Zhang Ying 
Published: January 2021

AbstractWe studied the effect of oxygen concentrations on the in vitro growth and drug susceptibility ofBabesia duncani. We found that the growth ofB. duncanirequired high level oxygen and the culture condition at ambient aerobic condition (21% O2) was optimal. Compared with ambient air, our results further showed that low oxygen (6-16%) could arrestB. duncanischizonts and lead to high susceptibilities to antiparasitic drugs atovaquone, pyrimethamine, quinine, and chloroquine at certain concentrations in vitro. Drug susceptibilities of otherBabesiaspp impacted by O2levels need to be studied in the future, and this study indicates that culturing conditions ofBabesiaspp should be considered and reestablished for generating more comparable and reliable results in drug research in the future.Graphical abstractHighlightsThe in vitro growth ofB. duncanirequires high level oxygen and the culture condition of 5% CO2ambient air is optimalLow level oxygen resultsB. duncaniin low growth rate and high schizont ratio in vitroCompared with 5% CO2ambient air, in vitro drug susceptibilities ofB. duncanican be significantly increased when cultured in microaerobic condition
A Simple Parametric Representation of the Hodgkin-Huxley Model
Authors: Rodríguez-Collado Alejandro , Rueda Cristina 
Published: January 2021

AbstractThe Hodgkin-Huxley model, decades after its first presentation, is still a reference model in neuroscience as it has successfully reproduced the electrophysiological activity of many organisms. The primary signal in the model represents the membrane potential of a neuron. A parametric and simple representation of this signal is presented in this paper.The new proposal is an adapted Frequency Modulated Möbius multicomponent model defined as a flexible decomposition in waves that describe the signal morphology. A specific feature of the new model is that the parameters are subject to interpretable restrictions.A broad simulation experiment is conducted to show the new model accurately represents the simulated Hodgkin-Huxley signal. Moreover, the model potential to predict the neuron’s relevant characteristics, described with parameters of the Hodgkin Huxley model, is shown using different Machine Learning methods. The proposed model is also validated with real data from Squid Giant Axons. The comparison of the parameter configuration between the simulated and real data demonstrated the flexibility of the model as well as interesting differences.Author summaryAlejandro Rodríguez-Collado. I received the double degree in Statistics and Computer Engineering and the Master’s degree in Business Intelligence and Big Data from the Universidad de Valladolid in 2019 and 2020, respectively. I work as researcher and Professor for the Department of Statistics and Operational Research at the Universidad de Valladolid. My main research interests include oscillatory signal processing, neuroscience, multivariate data analysis and supervised learning.Cristina Rueda. I received the BS degree in mathematics from the Universidad de Valladolid in 1987 and the PhD degree in statistical science from the Universidad de Valladolid in 1989. I am currently Professor in the Department of Statistics and Operational Research at the Universidad de Valladolid. My main research interests include statistical inference methods under restrictions, circular data, computational biology, and statistical methods for signal analysis.
A flexible micro-piston device for mechanical cell stimulation and compression in microfluidic settings
Authors: Onal Sevgi , Alkaisi Maan M. , Nock Volker 
Published: January 2021

AbstractEvidence continues to emerge that cancer is not only a disease of genetic mutations, but also of altered mechanobiological profiles of the cells and microenvironment. This mutation-independent element might be a key factor in promoting development and spread of cancer. Biomechanical forces regulate tumor microenvironment by solid stress, matrix mechanics, interstitial pressure and flow. Compressive stress by tumor growth and stromal tissue alters the cell deformation, and recapitulates the biophysical properties of cells to grow, differentiate, spread or invade. Such a solid stress can be introduced externally to change the cell response and to mechanically induce cell lysis by dynamic compression. In this work we report a microfluidic cell-culture platform with an integrated, actively-modulated actuator for the application of compressive forces on cancer cells. Our platform is composed of a control microchannel in a top layer for introducing external force and a polydimethylsiloxane (PDMS) membrane with monolithically integrated actuators. The integrated actuator, herein called micro-piston, was used to apply compression on SKOV-3 ovarian cancer cells in a dynamic and controlled manner by modulating applied gas pressure, localization, shape and size of the micro-piston. We report fabrication of the platform, characterization of the mechanical actuator experimentally and computationally, as well as cell loading and culture in the device. We further show use of the actuator to perform both, repeated dynamic cell compression at physiological pressure levels, and end-point mechanical cell lysis, demonstrating suitability for mechanical stimulation to study the role of compressive forces in cancer microenvironments.
COVID-19 Severity Is Associated with Differential Antibody Fc-mediated Innate Immune Functions
Authors: Adeniji Opeyemi S. , Giron Leila B. , Zilberstein Netanel F , Shaikh Maliha W. , Balk Robert A , Moy James N , Forsyth Christopher B. , Keshavarzian Ali , Landay Alan , Abdel-Mohsen Mohamed 
Published: January 2021

ABSTRACTBeyond neutralization, antibodies elicit several innate immune functions including complement deposition (ADCD), phagocytosis (ADCP), and cytotoxicity (ADCC). These functions can be both beneficial (by clearing pathogens) and/or detrimental (by inducing inflammation). We tested the possibility that qualitative differences in SARS-CoV-2 specific antibody-mediated innate immune functions contribute to Coronavirus disease 2019 (COVID-19) severity. We found that antibodies from hospitalized COVID-19 patients elicited higher ADCD but lower ADCP compared to antibodies from non-hospitalized COVID-19 patients. Consistently, higher ADCD was associated with higher systemic inflammation during COVID-19. Our study points to qualitative, differential features of anti-SARS-CoV-2 antibodies as potential contributors to COVID-19 severity.