bluuebunny/crossref_metadata_2025_split huggingface dataset:
Studying the course of Covid-19 by a recursive delay approach
Authors: Kreck Matthias , Scholz Erhard 
Published: January 2021

AbstractIn an earlier paper we proposed a recursive model for epidemics; in the present paper we generalize this model to include the asymptomatic or unrecorded symptomatic people, which we call dark people (dark sector). We call this the SEPARd-model. A delay differential equation version of the model is added; it allows a better comparison to other models. We carry this out by a comparison with the classical SIR model and indicate why we believe that the SEPARd model may work better for Covid-19 than other approaches.In the second part of the paper we explain how to deal with the data provided by the JHU, in particular we explain how to derive central model parameters from the data. Other parameters, like the size of the dark sector, are less accessible and have to be estimated more roughly, at best by results of representative serological studies which are accessible, however, only for a few countries. We start our country studies with Switzerland where such data are available. Then we apply the model to a collection of other countries, three European ones (Germany, France, Sweden), the three most stricken countries from three other continents (USA, Brazil, India). Finally we show that even the aggregated world data can be well represented by our approach.At the end of the paper we discuss the use of the model. Perhaps the most striking application is that it allows a quantitative analysis of the influence of the time until people are sent to quarantine or hospital. This suggests that imposing means to shorten this time is a powerful tool to flatten the curves.
Impact of Public Health Education Program on the Novel Coronavirus Outbreak in the United States
Authors: Iboi Enahoro A. , Richardson Ariana , Ruffin Rachel , Ingram DeAndrea , Clark Jailyn , Hawkins Jala , McKinney Maati , Horne Nianza , Ponder Reyla , Denton Zoe , Agusto Folashade B. , Oduro Bismark , Akinyemi Lanre 
Published: January 2021

AbstractThe coronavirus outbreak in the United States continues to pose a serious threat to human lives. Public health measures to slow down the spread of the virus involve using a face mask, social-distancing, and frequent hand washing. Since the beginning of the pandemic, there has been a global campaign on the use of non-pharmaceutical interventions (NPIs) to curtail the spread of the virus. However, the number of cases, mortality, and hospitalization continue to rise globally, including in the United States. We developed a mathematical model to assess the impact of a public health education program on the coronavirus outbreak in the US. Our simulation showed the prospect of an effective public health education program in reducing both the cumulative and daily mortality of the novel coronavirus. Finally, our result suggests the need to obey public health measures as loss of willingness would increase the cumulative and daily mortality in the US.
Immune Markers Are Associated with Cognitive Performance in a Multiethnic Cohort: the Northern Manhattan Study
Authors: Elkind Mitchell S. V. , Moon Michelle , Rundek Tatjana , Wright Clinton B. , Cheung Ken , Sacco Ralph L. , Hornig Mady 
Published: January 2021

OBJECTIVETo determine whether immune protein panels add significant information to correlates of cognition.BACKGROUNDImmune mechanisms in vascular cognitive impairment and dementia are incompletely characterized.DESIGN/METHODSA subsample of the prospective Northern Manhattan Study underwent detailed neuropsychological testing. Cognitive scores were converted into Z-scores and categorized into four domains (memory, language, processing speed, and executive function) based on factor analysis. Blood samples were analyzed using a 60-plex immunoassay. We used least absolute shrinkage and selection operator (LASSO) procedures to select markers and their interactions independently associated with cognitive scores. Linear regression models assessed cross-sectional associations of known correlates of cognition with cognitive scores, and assessed model fit before and after addition of LASSO-selected immune markers.RESULTSAmong 1179 participants (mean age 70±8.9 years, 60% women, 68% Hispanic), inclusion of LASSO-selected immune markers improved model fit above age, education, and other risk factors (p for likelihood ratio test<0.005 for all domains). C-C Motif Chemokine Ligand 11 (CCL 11, eotaxin), C-X-C Motif Chemokine Ligand 9 (CXCL9), hepatocyte growth factor (HGF), and serpin E1 (plasminogen activator inhibitor-1) were associated with each of the domains and with overall cognitive function. Immune marker effects were comparable to conventional risk factors: for executive function, each standard deviation (SD) increase in CCL11 was associated with an effect equivalent to aging three years; for memory, HGF had twice the effect of aging.CONCLUSIONSImmune markers associate with cognitive function in a multi-ethnic cohort. Further work is needed to validate these findings and determine optimal treatment targets.
The impacts of COVID-19 vaccine timing, number of doses, and risk prioritization on mortality in the US
Authors: Wang Xutong , Du Zhanwei , Johnson Kaitlyn E. , Pasco Remy F. , Fox Spencer J. , Lachmann Michael , McLellan Jason S. , Meyers Lauren Ancel 
Published: January 2021

AbstractAs COVID-19 vaccination begins worldwide, policymakers face critical trade-offs. Using a mathematical model of COVID-19 transmission, we find that timing of the rollout is expected to have a substantially greater impact on mortality than risk-based prioritization and uptake and that prioritizing first doses over second doses may be life saving.
Loss of C3aR induces immune infiltration and inflammatory microbiota in a new spontaneous model of colon cancer
Authors: Krieg Carsten , Weber Lukas M. , Fosso Bruno , Hardiman Gary , Mileti Erika , Aidy Sahar El , Marzano Marinella , Robinson Mark D. , Guglietta Silvia 
Published: January 2021

ABSTRACTSeveral lines of evidence suggest that inflammation plays a pivotal role in the development and progression of colorectal cancer (CRC) and can be unleashed by the loss of innate immunosurveillance. The complement system is a well characterized first line of defense against pathogens and a central component of the immune response. Emerging evidence suggests that complement anaphylatoxin C3a produced upon complement activation and acting via its receptor (C3aR) may play a role in intestinal homeostasis. However, to date, it is unknown whether and how the C3a/C3aR axis can affect CRC. By mining publicly available datasets, we found that CpG island methylation ofc3ar1occurs in CRC patients and is associated with significant downregulation of C3aR. By reverse-translating this finding we were able to shift in APCMin/+mice the tumorigenesis from the small intestine to the colon therefore generating a novel mouse model, which more closely mirrors the CRC in humans. Transcriptomic analysis on colorectal polyps from our newly developed genetic mouse model revealed a significant increase in innate and adaptive immune signatures in absence of C3aR. Furthermore, loss of C3aR significantly impacted the fecal and tumor-associated microbiota and supported the blooming of pro-inflammatory bacterial species as confirmed by experiments of fecal microbiota transplantation.Future studies will elucidate whether loss of C3aR can be exploited as a biomarker for sub-groups of CRC and whether the C3a/C3aR axis may be exploited for the generation of more effective therapeutic interventions.
Structural and functional characterization of a putativede novogene inDrosophila
Authors: Lange Andreas , Patel Prajal H. , Heames Brennen , Damry Adam M. , Saenger Thorsten , Jackson Colin J. , Findlay Geoffrey D. , Bornberg-Bauer Erich 
Published: January 2021

AbstractComparative genomic studies have repeatedly shown that new protein-coding genes can emergede novofrom non-coding DNA. Still unknown is how and when the structures of encodedde novoproteins emerge and evolve. Combining biochemical, genetic and evolutionary analyses, we elucidate the function and structure ofgoddard, a gene which appears to have evolvedde novoat least 50 million years ago within theDrosophilagenus.Previous studies found thatgoddardis required for male fertility. Here, we show that Goddard protein localizes to elongating sperm axonemes and that in its absence, elongated spermatids fail to undergo individualization. Combining modelling, NMR and CD data, we show that Goddard protein contains a large central α-helix, but is otherwise partially disordered. We find similar results for Goddard’s orthologs from divergent fly species and their reconstructed ancestral sequences. Accordingly, Goddard’s structure appears to have been maintained with only minor changes over millions of years.
The molecular basis of coupling between poly(A)-tail length and translational efficiency
Authors: Xiang Kehui , Bartel David P. 
Published: January 2021

AbstractIn animal oocytes and early embryos, mRNA poly(A)-tail length strongly influences translational efficiency (TE), but later in development this coupling between tail length and TE disappears. Here, we elucidate how this coupling is first established and why it disappears. Overexpressing cytoplasmic poly(A)-binding protein (PABPC) in frog oocytes specifically improved translation of short-tailed mRNAs, thereby diminishing coupling between tail length and TE. Thus, coupling requires limiting PABPC, implying that in coupled systems longer-tail mRNAs better compete for limiting PABPC. In addition to expressing excess PABPC, post-embryonic cells had two other properties that prevented strong coupling: terminal-uridylation-dependent destabilization of mRNAs lacking bound PABPC, and a regulatory regime wherein PABPC contributes minimally to TE. Thus, these results revealed three fundamental mechanistic requirements for coupling and defined the context-dependent functions for PABPC, in which this protein promotes TE but not mRNA stability in coupled systems and mRNA stability but not TE in uncoupled systems.
Hypoxic Preconditioning Promotes Survivals of Human Adipocyte Mesenchymal Stem Cell via Expression of Prosurvival and Proangiogenic Biomarkers
Authors: Suryawan I Gde Rurus , Pikir Budi Susetyo , Rantam Fedik Abdul , Ratri Anudya Kartika , Nugraha Ricardo Adrian 
Published: January 2021

AbstractBackgroundContributing factors for improved survival of human adipocytes mesenchymal stem cells (h-AMSCs) cultured through hypoxia preconditioning, in example apoptosis inhibition involving BCL2 and HSP27 expression, trigger signal expression (VEGF), SCF expression, OCT-4 expression, and CD44+ expression.ObjectiveTo explain the mechanism and role of hypoxic preconditioning and the optimal duration of hypoxic preconditioning exposure to improve survival of h-AMSCs so that could it could be used as a benchmark for h-AMSCs culture strategy before transplantation.MethodsThis study was an experimental laboratory explorative study (in vitro study) with hypoxic preconditioning in human-adipose mesenchymal stem cells (h-AMSCs) cultures. This research was conducted through 4 stages ;First, Isolation and h-AMSCs culture from adipose tissue of patient (human). Second is the characterization of h-AMSCs from adipose tissue by phenotype (Flowcytometry) through CD44+, CD90+ and CD45-expression before being pre-conditioned for hypoxic treatment. Third, the hypoxic preconditioning in h-AMSCs culture (in vitro) was performed with an oxygen concentration of 1% for 24, 48 and 72 hours. Fourth, observation of survival from h-AMSCs culture was tested on the role of CD44 +, VEGF, SCF, OCT-4, BCL2, HSP27 with Flowcytometry method and apoptotic inhibition by Tunnel Assay method.ResultsThe result of regression test showed that time difference had an effect on VEGF expression (p=0,000;β=−0,482) and hypoxia condition also influenced VEGF expression (p= 0,000;β=0,774). The result of path analysis showed that SCF had an effect on OCT-4 expression (p=0,000;β=0,985). The regression test results showed that time effects on HSP27 expression (p=0.000;β=0.398) and hypoxia precondition also affects HSP27 expression (p=0.000;β=0.847). Pathway analysis showed that BCL2 expression inhibited apoptosis (p=0.030;β=−0.442) and HSP27 expression also inhibited apoptosis (p=0,000;β=−0.487).ConclusionIn conclusion, hypoxic preconditioning of h-AMSC culture has proven to increase the expression of VEGF, SCF, OCT-4, and BCL2 and HSP27. This study demonstrated and explained the existence of a new mechanism of increased h-AMSC survival in cultures with hypoxic preconditioning (O2 1%) via VEGF, SCF, OCT-4, BCL2, and HSP 27. But CD 44+ did not play a role in the mechanism of survival improvement of human AMSC survival.
Fluorescence-based 3D targeting of FIB-SEM acquisition of small volumes in large samples
Authors: Ronchi Paolo , Machado Pedro , D’Imprima Edoardo , Mizzon Giulia , Best Benedikt T. , Cassella Lucia , Schnorrenberg Sebastian , Montero Marta G. , Jechlinger Martin , Ephrussi Anne , Leptin Maria , Mahamid Julia , Schwab Yannick 
Published: January 2021

AbstractCells are three dimensional objects. Therefore, 3D electron microscopy is often crucial for correct interpretation of ultrastructural data. Today samples are frequently imaged in 3D at ultrastructural resolution using volume Scanning Electron Microscopy (SEM) methods such as Focused Ion Beam (FIB) SEM and Serial Block face SEM. While these imaging modalities allow for automated data acquisition, precise targeting of (small) volumes of interest within a large sample remains challenging. Here, we provide an easy and reliable approach to target FIB-SEM acquisition of fluorescently labelled cells or subcellular structures with micrometer precision. The strategy relies on fluorescence preservation during sample preparation and targeting based on confocal acquisition of the fluorescence signal in the resin block. Targeted trimming of the block exposes the cell of interest and laser branding of the surface after trimming creates landmarks to precisely position the FIB-SEM acquisition. Using this method, we acquired volumes of specific single cells within large tissues such as a 3D culture of mouse primary mammary gland organoids, tracheal terminal cells inDrosophila melanogasterlarvae and ovarian follicular cells in adultDrosophila, discovering ultrastructural details that could not be appreciated before.SummaryRonchi et al. present a workflow to facilitate the precise targeting of three-dimensional (3D) Electron Microscopy acquisitions, guided by fluorescence. This method allows ultrastructural visualization of single cells within a millimeter-range large specimen, based on molecular identity characterized by fluorescence.
All-optical electrophysiology in hiPSC-derived neurons with synthetic voltage sensors
Authors: Puppo Francesca , Sadegh Sanaz , Trujillo Cleber A. , Thunemann Martin , Campbell Evan , Vandenberghe Matthieu , Shan Xiwei , Akkouh Ibrahim A , Miller Evan W. , Bloodgood Brenda L. , Silva Gabriel A. , Dale Anders M. , Einevoll Gaute T. , Djurovic Srdjan , Andreassen Ole A. , Muotri Alysson R. , Devor Anna 
Published: January 2021

AbstractVoltage imaging and “all-optical electrophysiology” in human induced pluripotent stem cell (hiPSC)-derived neurons have opened unprecedented opportunities for high-throughput phenotyping of activity in neurons possessing unique genetic backgrounds of individual patients. While prior all-optical electrophysiology studies relied on genetically encoded voltage indicators, viral transduction of human neurons with large or multiple expression vectors can impact cell function and often lead to massive cell death. Here, we demonstrate an alternative protocol using a synthetic voltage sensor and genetically encoded optogenetic actuator that generate robust and reproducible results. We demonstrate the functionality of this method by measuring spontaneous and evoked activity in three independent hiPSC-derived neuronal cell lines with distinct genetic backgrounds.
Analysis of phloem trajectory links tissue maturation to cell specialization
Authors: Roszak Pawel , Heo Jung-ok , Blob Bernhard , Toyokura Koichi , de Luis Balaguer Maria Angels , Lau Winnie W. Y. , Hamey Fiona , Cirrone Jacopo , Wang Xin , Ursache Robertas , Tavares Hugo , Verstaen Kevin , Wendrich Jos , Melnyk Charles W. , Shasha Dennis , Ahnert Sebastian E. , Saeys Yvan , De Rybel Bert , Heidstra Renze , Scheres Ben , Mähönen Ari Pekka , Göttgens Berthold , Sozzani Rosangela , Birnbaum Kenneth D. , Helariutta Yrjö 
Published: January 2021

AbstractThe mechanisms that allow cells in the plant meristem to coordinate tissue-wide maturation gradients with specialized cell networks are critical for indeterminate growth. Here, we reconstructed the protophloem developmental trajectory of 19 cells from cell birth to terminal differentiation at single cell resolution in the Arabidopsis root. We found that cellular specification is mediated near the stem cell niche by PHLOEM EARLY DOF (PEAR) transcription factors. However, the PEAR dependent differentiation program is repressed by a broad gradient of PLETHORA (PLT) transcription factors, which directly inhibit PEARs’ own direct targetALTERED PHLOEM DEVELOPMENT (APL). The dissipation of PLT gradient around 7 cells from the stem cell activates APL expression, and a subsequent transitional network that results in a “seesaw” pattern of mutual inhibition over developmental time. Together, we provide a mechanistic understanding of how morphogen-like maturation gradients interface with cell-type specific transcriptional regulators to stage cellular differentiation.
The chromatin, topological and regulatory properties of pluripotency-associated poised enhancers are conservedin vivo
Authors: Crispatzu Giuliano , Rehimi Rizwan , Pachano Tomas , Bleckwehl Tore , de la Cruz Molina Sara , Xiao Cally , Mahabir-Brenner Esther , Bazzi Hisham , Rada-Iglesias Alvaro 
Published: January 2021

AbstractPoised enhancers (PEs) represent a limited and genetically distinct set of distal regulatory elements that control the induction of developmental genes in a hierarchical and non-redundant manner. Before becoming activated in differentiating cells, PEs are already bookmarked in pluripotent cells with unique chromatin and topological features that could contribute to their privileged regulatory properties. However, since PEs were originally identified and subsequently characterized using embryonic stem cells (ESC) as anin vitrodifferentiation system, it is currently unknown whether PEs are functionally conservedin vivo. Here, we generate and mine various types of genomic data to show that the chromatin and 3D structural features of PEs are conserved among mouse pluripotent cells bothin vitroandin vivo. We also uncovered that, in mouse pluripotent cells, the interactions between PEs and their bivalent target genes are globally controlled by the combined action of Polycomb, Trithorax and architectural proteins. Moreover, distal regulatory sequences located close to developmental genes and displaying the typical genetic (i.e. proximity to CpG islands) and chromatin (i.e. high accessibility and H3K27me3 levels) features of PEs are commonly found across vertebrates. These putative PEs show high sequence conservation, preferentially within specific vertebrate clades, with only a small subset being evolutionary conserved across all vertebrates. Lastly, by genetically disrupting evolutionary conserved PEs in mouse and chicken embryos, we demonstrate that these regulatory elements play essential and non-redundant roles during the induction of major developmental genesin vivo.
Potent but transient immunosuppression of T-cells is a general feature of CD71+erythroid cells
Authors: Grzywa Tomasz M. , Sosnowska Anna , Rydzynska Zuzanna , Lazniewski Michal , Plewczynski Dariusz , Klicka Klaudia , Malecka-Gieldowska Milena , Rodziewicz-Lurzynska Anna , Ciepiela Olga , Justyniarska Magdalena , Pomper Paulina , Grzybowski Marcin M. , Blaszczyk Roman , Wegrzynowicz Michal , Tomaszewska Agnieszka , Basak Grzegorz , Golab Jakub , Nowis Dominika 
Published: January 2021

AbstractCD71+erythroid cells (CECs) have been recently recognized in both neonates and cancer patients as potent immunoregulatory cells. Here, we show that in mice early-stage CECs expand in anemia, have high levels of arginase 2 (ARG2) and reactive oxygen species (ROS). In the spleens of anemic mice, CECs expansion-inducedL-arginine depletion suppresses T-cell responses. In humans with anemia, CECs expand and express ARG1 and ARG2 that suppress T-cells IFN-γ production. Moreover, bone marrow CECs from healthy human donors suppress T-cells proliferation. CECs differentiated from peripheral blood mononuclear cells potently suppress T-cell activation, proliferation, and IFN-γ production in an ARG- and ROS-dependent manner. These effects are the most prominent for early-stage CECs (CD71highCD235adimcells). The suppressive properties disappear during erythroid differentiation as more differentiated CECs and mature erythrocytes lack significant immunoregulatory properties. Our studies provide a novel insight into the role of CECs in the immune response regulation.
Development and validation of an LC-MS/MS method for determination of B vitamins and some its derivatives in whole blood
Authors: Kahoun David , Fojtíková Pavla , Vácha František , Nováková Eva , Hypša Václav 
Published: January 2021

AbstractObligate symbiotic bacteria associated with the insects feeding exclusively on vertebrate blood are supposed to complement B vitamins presumably lacking in their diet, vertebrate blood. Recent genomic analyses revealed considerable differences in biosynthetic capacities across different symbionts, indicating that levels of B vitamins vary across different vertebrate hosts. However, a rigorous determination of B vitamins content in blood of various vertebrates has not yet been approached. A reliable analytical method focused on B vitamin complex in blood and hemolymph can provide valuable informative background and understanding of general principles of insect symbiosis.In this work chromatographic separation of a mixture of eight B vitamins (B1 – thiamine, B2 – riboflavin, B3 – niacin, B5 – pantothenic acid, B6 – pyridoxine, B7 – biotin, B9 – folic acid and B12 – cyanocobalamine), four B vitamin derivatives (B3 – niacinamide, B6 – pyridoxal-5-phosphate, B6 – 4-pyridoxic acid and B9 – tetrahydrofolic acid) and 3 stable isotope labelled internal standards (B3 – niacin-13C6, B5 – pantothenic acid (di-β-alanine-13C6,15N2) and B7 – biotin-(ring-6,6-d2)) on C30 column was developed. Detection was carried out using dual-pressure linear ion trap mass spectrometer in FullScan MS/MS and SIM mode. Matching internal standards with analytes was done according to the results of linearity, accuracy and precision. Except for vitamin B9 (tetrahydrofolic acid) instrument quantitation limits of all analytes were ranging from 0.42 to 5.0 μg/L, correlation coefficients from 0.9997 to 1.0000 and QC coefficients from 0.53 to 3.2 %.Optimization of whole blood sample preparation step was focused especially on evaluation of two types of protein-precipitation agents: trichloroacetic acid and zinc sulphate in methanol. Samples of whole blood prepared in six independent replicates were spiked at 10 μg/L and 100 μg/L level. The best results were obtained for zinc sulphate in methanol, but only nine analytes (B1 – thiamine, B2 – riboflavin, B3 – niacin, B3 – niacinamide, B5 – pantothenic acid, B6 – pyridoxine, B6 – 4-pyridoxic acid, B7 – biotin and B12 – cyanocobalamine) were successfully validated. Accuracy of the procedure using this protein-precipitating agent was ranging from 89 to 120 %, precision from 0.5 to 13 % and process efficiency from 65 to 108 %.HighlightsLC-MS/MS method for quantitation of eight B vitamins and four B vitamin derivatives was developed.Deproteinization agents trichloroacetic acid and ZnSO4/methanol were tested for protein precipitation of whole blood.Accuracy, precision and process efficiency were evaluated.Successful method validation for seven B vitamins and two B vitamin derivatives in whole blood.