bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influence of delayed density and ultraviolet radiation on caterpillar baculovirus infection and mortality
Authors: Pepi Adam , Pan Vincent , Rutkowski Danielle , Mase Vinay , Karban Richard 
Published: March 2021

AbstractInfectious disease is an important potential driver of population cycles, but this must occur through delayed density-dependent infection and resulting fitness effects. Delayed density-dependent infection by baculoviruses can be caused by environmental persistence of viral occlusion bodies, which can be influenced by environmental factors. In particular, ultraviolet radiation is potentially important in reducing the environmental persistence of viruses by inactivating viral occlusion bodies.Delayed density-dependent viral infection has rarely been observed empirically at the population level although theory predicts that it is necessary for these pathogens to drive population cycles. Similarly, field studies have not examined the potential effects of ultraviolet radiation on viral infection rates in natural animal populations. We tested if viral infection is delayed density-dependent with the potential to drive cyclic dynamics and if ultraviolet radiation influences viral infection levels.We censused 18 Ranchman’s tiger moth (Arctia virginalis) populations across nearly 9° of latitude over two years and quantified the effects of direct and delayed density and ultraviolet radiation on baculovirus infection rates, infection severity, and survival to adulthood. Caterpillars were collected from each population in the field and reared in the laboratory. Baculovirus has not previously been described infectingArctia virginalis, and we used genetic methods to confirm the identity of the virus.We found that infection rate, infection severity, and survival to adulthood exhibited delayed density-dependence. Ultraviolet radiation in the previous summer decreased infection severity, and increased survival probability of the virus. Structural equation modelling indicated that the effect of lagged density on moth survival was mediated through infection rate and infection severity, and was 2.5 fold stronger than the effect of ultraviolet radiation on survival through infection severity. We successfully amplified polh, lef-8, and lef-9 viral genes from caterpillar samples, and BLAST search results confirmed that the virus was a nucleopolyhedrovirus.Our findings provide clear evidence that delayed density dependence can arise through viral infection rate and severity in insects, which supports the role of viral disease as a potential mechanism, among others, that may drive insect population cycles. Furthermore, our findings support predictions that ultraviolet radiation can modify viral disease dynamics in insect populations, most likely through attenuating viral persistence in the environment.
The cryo-EM structure of the bacterial type I DNA segregation ATPase filament reveals its conformational plasticity upon DNA binding
Authors: Parker AV , Mann D , Tzokov SB , Hwang LC , Bergeron JRC 
Published: March 2021

AbstractThe efficient segregation of replicated genetic material is an essential step for cell division. In eukaryotic cells, sister chromatids are separated via the mitotic spindles. In contrast, bacterial cells use several evolutionarily-distinct genome segregation systems. The most common of these is the Type I Par system. It consists of an adapter protein, ParB, that binds to the DNA cargo via interaction with the parS DNA sequence; and an ATPase, ParA, that binds nonspecific DNA and mediates cargo transport. However, the molecular details of how this system functions are not well understood.Here, we report the cryo-EM structure of a ParA filament bound to its DNA template, using the chromosome 2 (Chr2) ofVibrio choleraeas a model system. We also report the crystal structures of this protein in various nucleotide states, which collectively offer insight into its conformational changes from dimerization through to DNA binding and filament assembly. Specifically, we show that the ParA dimer is stabilized by nucleotide binding, and forms a left-handed filament using DNA as a scaffold. Our structural analyses also reveal dramatic structural rearrangements upon DNA binding and filament assembly. Finally, we show that filament formation is controlled by nucleotide hydrolysis. Collectively, our data provide the structural basis for ParA’s cooperative binding to DNA and the formation of high ParA density regions on the nucleoid, and suggest a role for its filament formation.
Encapsulation and recovery of murine hematopoietic stem and progenitor cells in a thiol-crosslinked maleimide-functionalized gelatin hydrogel
Authors: Gilchrist Aidan E. , Serrano Julio F. , Ngo Mai T. , Hrnjak Zona , Kim Sanha , Harley Brendan A.C. 
Published: March 2021

AbstractBiomaterial platforms are an integral part of stem cell biomanufacturing protocols. The collective biophysical, biochemical, and cellular cues of the stem cell niche microenvironment play an important role in regulating stem cell fate decisions. Three-dimensional (3D) culture of stem cells within biomaterials provides a route to present biophysical and biochemical stimuli such as cell-matrix interactions and cell-cell interactions via secreted biomolecules. Herein, we describe a maleimide-functionalized gelatin (GelMAL) hydrogel that can be crosslinked via thiol-Michael addition click reaction for the encapsulation of sensitive stem cell populations. The maleimide functional units along the gelatin backbone enables gelation via the addition of a dithiol crosslinker without requiring external stimuli (e.g., UV light, photoinitiator), reducing reactive oxide species generation. Additionally, the versatility of crosslinker selection enables easy insertion of thiol-containing bioactive or bioinert motifs. Hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs) were encapsulated in GelMAL, with mechanical properties tuned to mimic thein vivobone marrow niche. We report insertion of a cleavable peptide crosslinker that can be degraded by the proteolytic action of SortaseA, a mammalian-inert enzyme. Notably, SortaseA exposure preserves stem cell surface markers, an essential metric of hematopoietic activity used in immunophenotyping. This novel GelMAL system enables a route to producing artificial stem cell niches with tunable biophysical properties with intrinsic cell-interaction motifs and orthogonal addition of bioactive crosslinks.
TCF-1 in CD4 T cells regulates GVHD severity and persistence
Authors: Harris Rebecca , Mammadli Mahinbanu , May Adriana , Yang Qi , Fung Ivan Ting Hin , Sen Jyoti Misra , Karimi Mobin 
Published: March 2021

AbstractGraft-versus-host disease (GVHD) is a leading cause of mortality following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Mature donor T cells in the graft mediate graft-versus-leukemia (GVL) responses against residual tumor cells, which may persist after pre-transplant conditioning regimens. Importantly, the same mature T cells also mediate GVHD. The transcription factor T Cell Factor-1 (TCF-1) is critical for T cell development in the thymus. Using a unique mouse model of allo-HSCT leading to GVHD, we investigated the role of TCF-1 in alloactivated T cell functioning and in GVHD. Here, we report that loss of TCF-1 in mature CD4 T cells reduces GVHD severity and persistence, improving survival of recipient mice. This was due to reduced proliferation, survival, and cytokine production of T cells, as well as increased exhaustion. Gene pathways involved in cytokine response, immune signaling, chemokine signaling, cell cycle, and T cell differentiation were altered by loss of TCF-1 in donor cells. Our companion paper shows that regulation of alloactivated CD4 T cells by TCF-1 differs from regulation of CD8 T cells, suggesting that TCF-1 plays a unique role in each subset. Therefore, targeting of TCF-1 or downstream signaling pathways may be an effective strategy for reducing GVHD following allo-HSCT.
TCF-7is dispensable for anti-tumor response but required for persistent function of mature CD8 T cells
Authors: Harris Rebecca , Mammadli Mahinbanu , Hiner Shannon , Suo Liye , Yang Qi , Sen Jyoti Misra , Karimi Mobin 
Published: March 2021

AbstractT Cell Factor-1, encoded byTCF-7,is a transcription factor that plays an essential role during T cell development and differentiation. In this manuscript we utilized a pre-clinical model provided evidence thatTCF-7is dispensable for the anti-tumor response, and thatTCF-7suppresses key transcriptional factors Eomes and T-bet and molecules responsible for peripheral CD8 T cell cytolytic function. We discovered thatTCF-7regulates NKG2D expression on naïve and activated mouse CD8 T cells, and that peripheral CD8 T cells fromTCF-7cKO utilize NKG2D to clear tumor cells.We also provide evidence thatTCF-7regulates key signaling molecules, including LCK, LAT, ITK, PLC-γ1, P65, ERKI/II, and JAK/STATs required for peripheral CD8 T cell persistent function. Our data transcriptomic and protein data uncovered the mechanism of howTCF-7impacting peripheral CD8 T cell inflammatory cytokine production, CD8 T cell activation, and apoptosis. Our pre-clinical model showed that CD8 T cells fromTCF-7cKO mice did not cause GVHD, but effectively cleared primary tumor cells.
VICTOR: A visual analytics web application for comparing cluster sets
Authors: Karatzas Evangelos , Gkonta Maria , Hotova Joana , Baltoumas Fotis A. , Kontou Panagiota I. , Bobotsis Christopher J. , Bagos Pantelis G. , Pavlopoulos Georgios A. 
Published: March 2021

ABSTRACTClustering is the process of grouping together different data objects based on similar properties. Clustering has applications in various case studies from several fields such as graph theory, image analysis, pattern recognition, statistics and others. Nowadays, there are numerous algorithms and tools able to generate clustering results. However, different algorithms or parameterization may result in very different clusters. This way, the user is often forced to manually filter and compare these results in order to decide which of them produce the ideal clusters. To automate this process, in this study, we present VICTOR, the first fully interactive and dependency-free visual analytics web application which allows the comparison and visualization of various clustering algorithms. VICTOR can handle multiple clustering results simultaneously and compare them using ten different metrics. Clustering results can be filtered and compared to each other with the use of interactive heatmaps, bar plots, correlation networks, sankey and circos plots. We demonstrate VICTOR’s functionality using three examples. In the first case, we compare five different algorithms on a protein-protein interaction dataset whereas in the second example, we test four different parameters of the same clustering algorithm applied on the same dataset. Finally, as a third example, we compare four different meta-analyses with hierarchically clustered differentially expressed genes found to be involved in myocardial infarction. VICTOR is available athttp://bib.fleming.gr:3838/VICTOR.
HiCBin: Binning metagenomic contigs and recovering metagenome-assembled genomes using Hi-C contact maps
Authors: Du Yuxuan , Sun Fengzhu 
Published: March 2021

AbstractRecovering high-quality metagenome-assembled genomes (MAGs) from complex microbial ecosystems remains challenging. Conventional shotgun-based binning approaches may encounter barriers when multiple samples are scarce. Recently, high-throughput chromosome conformation capture (Hi-C) has been applied to simultaneously study multiple genomes in natural microbial communities. Several Hi-C-based binning pipelines have been put forward and yielded state-of-the-art results using a single sample. We conclude that normalization and clustering are two vital steps in the Hi-C-based binning analyses, and develop HiCBin, a novel open-source pipeline, to resolve high-quality MAGs utilizing Hi-C contact maps. HiCBin employs the HiCzin normalization method and the Leiden community detection algorithm based on the Potts spin-glass model and includes the spurious contact detection into binning pipelines for the first time. Using the metagenomic yeast sample with a perfect ground truth of contigs’ species identity, we comprehensively evaluate the impacts on the binning performance of different normalization methods and clustering algorithms from the HiCBin and other available metagenomic Hi-C analysis pipelines, demonstrate that the HiCzin and the Leiden algorithm achieve the best binning accuracy, and show that the spurious contact detection can improve the retrieval performance. We also validate our method and compare the capability to recover high-quality MAGs of HiCBin against other state-of-the-art Hi-C-based binning tools including ProxiMeta, bin3C, and MetaTOR, and one popular shotgun-based binning software MetaBAT2 on a human gut sample and a wastewater sample. HiCBin provides the best performance and applicability in resolving MAGs and is available athttps://github.com/dyxstat/HiCBin.
The Prolyl-tRNA Synthetase Inhibitor Halofuginone Inhibits SARS-CoV-2 Infection
Authors: Sandoval Daniel R. , Clausen Thomas Mandel , Nora Chelsea , Cribbs Adam P. , Denardo Andrea , Clark Alex E. , Garretson Aaron F. , Coker Joanna K.C. , Narayanan Anoop , Majowicz Sydney A. , Philpott Martin , Johansson Catrine , Dunford James E. , Spliid Charlotte B. , Golden Gregory J. , Payne N. Connor , Tye Mark A. , Nowell Cameron J. , Griffis Eric R. , Piermatteo Ann , Grunddal Kaare V. , Alle Thibault , Magida Jason A. , Hauser Blake M. , Feldman Jared , Caradonna Timothy M. , Pu Yuan , Yin Xin , McVicar Rachael N. , Kwong Elizabeth M. , Weiss Ryan J. , Downes Michael , Tsimikas Sotirios , Smidt Aaron G. , Ballatore Carlo , Zengler Karsten , Evans Ron M. , Chanda Sumit K. , Croker Ben A. , Leibel Sandra L. , Jose Joyce , Mazitschek Ralph , Oppermann Udo , Esko Jeffrey D. , Carlin Aaron F. , Gordts Philip L.S.M. 
Published: March 2021

Summary ParagraphWe identify the prolyl-tRNA synthetase (PRS) inhibitor halofuginone1, a compound in clinical trials for anti-fibrotic and anti-inflammatory applications2, as a potent inhibitor of SARS-CoV-2 infection and replication. The interaction of SARS-CoV-2 spike protein with cell surface heparan sulfate (HS) promotes viral entry3. We find that halofuginone reduces HS biosynthesis, thereby reducing spike protein binding, SARS-CoV-2 pseudotyped virus, and authentic SARS-CoV-2 infection. Halofuginone also potently suppresses SARS-CoV-2 replication post-entry and is 1,000-fold more potent than Remdesivir4. Inhibition of HS biosynthesis and SARS-CoV-2 infection depends on specific inhibition of PRS, possibly due to translational suppression of proline-rich proteins. We find that pp1a and pp1ab polyproteins of SARS-CoV-2, as well as several HS proteoglycans, are proline-rich, which may make them particularly vulnerable to halofuginone’s translational suppression. Halofuginone is orally bioavailable, has been evaluated in a phase I clinical trial in humans and distributes to SARS-CoV-2 target organs, including the lung, making it a near-term clinical trial candidate for the treatment of COVID-19.
Analysis of immune subtypes across the epithelial-mesenchymal plasticity spectrum
Authors: Chakraborty Priyanka , Chen Emily , McMullens Isabelle , Armstrong Andrew J. , Jolly Mohit Kumar , Somarelli Jason A. 
Published: March 2021

AbstractEpithelial-mesenchymal plasticity plays a critical role in many solid tumor types as a mediator of metastatic dissemination and treatment resistance. In addition, there is also a growing appreciation that the epithelial/mesenchymal status of a tumor plays a role in immune evasion and immune suppression. A deeper understanding of the immunological features of different tumor types has been facilitated by the availability of large gene expression datasets and the development of methods to deconvolute bulk RNA-Seq data. These resources have generated powerful new ways of characterizing tumors, including classification of immune subtypes based on differential expression of immunological genes. In the present work, we combine scoring algorithms to quantify epithelial-mesenchymal plasticity with immune subtype analysis to understand the relationship between epithelial plasticity and immune subtype across cancers. We find heterogeneity of epithelial-mesenchymal transition (EMT) status both within and between cancer types, with greater heterogeneity in the expression of EMT-related factors than of MET-related factors. We also find that specific immune subtypes have associated EMT scores and differential expression of immune checkpoint markers.
Moonlighting adenylyl cyclases in plants – anArabidopsis thaliana9-cis-epoxycarotenoid dioxygenase as point in case
Authors: Al-Younis Inas , Wong Aloysius , Moosa Basem , Kwiatkowski Mateusz , Jaworski Krzysztof , Gehring Chris 
Published: March 2021

AbstractAdenylyl cyclases (ACs) and their catalytic product cAMP are regulatory components of plant responses. AC domains are intrinsic components of complex molecules with multiple functions, some of which are co-regulated by cAMP. Here we used an amino acid search motif based on annotated ACs in organisms across species to identify 12 uniqueArabidopsis thalianacandidate ACs, four of which have a role in the biosynthesis of the stress hormone abscisic acid (ABA). One of these, the 9-cis-epoxycarotenoid dioxygenase (NCED3, At3g14440), was identified by sequence and structural analysis as a putative AC and then tested experimentally for activity. We show that an NCED3 AC fragment can complement an AC deficientE. colimutant and this rescue is nullified when key amino acids in the AC motif are mutated. AC activity was also confirmed by tandem liquid chromatography mass spectrometry (LC-MS/MS). Our results are consistent with a moonlighting role for mononucleotide cyclases in multi-domain proteins that have at least one other distinct molecular function such as catalysis or ion channel activation and promise to yield new insights into tuning mechanisms of ABA dependent plant responses. Finally, our search method can also be applied to discover ACs in other species includingHomo sapiens.HighlightsAn adenylyl cyclase (AC) catalytic center motif identifies novel ACs in plantsACs can moonlight in complex proteins with other enzymatic domainsA 9-cis-epoxycarotenoid dioxygenase essential for abscisic acid synthesis contains an ACThis finding implicates cAMP in abscisic acid synthesis and signaling
Genome-wide decoupling of H2Aub and H3K27me3 in early mouse development
Authors: Zhu Yezhang , Yu Jiali , Rong Yan , Wu Yun-Wen , Fan Heng-Yu , Shen Li 
Published: March 2021

AbstractPolycomb group (PcG) proteins are crucial chromatin regulators during development. H2Aub and H3K27me3 are catalyzed by Polycomb-repressive Complex 1 and 2 (PRC1/2) respectively, and largely overlap in the genome due to mutual recruitment of the two complexes. However, whether PRC1/H2Aub and PRC2/H3K27me3 can function independently remains obscure. Here we uncovered a genome-wide decoupling of H2Aub and H3K27me3 in preimplantation mouse embryos, at both canonical PcG targets and broad distal domains. H2Aub represses future bivalent genes without H3K27me3 but does not contribute to maintenance of H3K27me3-dependent non-canonical imprinting. Our study thus revealed their distinct and independent functions in early mammalian development.
A novel type of IRES having variable numbers of eIF4E-binding site and synergistic effect in RNA2 of WYMV isolates
Authors: Guowei Geng , Chengming Yu , Xiangdong Li , Kerong Shi , Xuefeng Yuan 
Published: March 2021

AbstractSome viral proteins were translated in cap-independent manner via internal ribosome entry site (IRES), which ever maintained conservative characteristic among different isolates of same species of virus. However, IRES activity presented 7-fold of variance in RNA2 of wheat yellow mosaic virus (WYMV) HC and LYJN isolates. Based on RNA structure probing and mutagenesis assay, the loosened middle stem of H1 and hepta-nucleotide top loop of H2 in LYJN isolate synergistically ensured the higher IRES activity than that in HC isolate. In addition, the conserved top loop of H1 ensured basic IRES activity in HC and LYJN isolates. RNA2 5′-UTR specifically interacted with the wheat eIF4E, which was accomplished by the top loop of H1 in HC isolate or the top loop of H1 and H2 in LYJN isolate. Different IRES activity of WYMV RNA2 was regulated by different numbers of eIF4E-binding site and their synergistic effect, which was accomplished by the proximity of H1 and H2 due to the flexibility of middle stem in H1. It is represented a novel evolution pattern of IRES.
Dry Swab Method of sample collection for SARS-CoV2 testing can be used for culturing virus
Authors: Ram Sushma , Enayathullah M. Ghalib , Parekh Yash , Tallapaka Karthik Bharadwaj , Mishra Rakesh K , Bokara Kiran Kumar 
Published: March 2021

AbstractBack groundEarlier studies suggested the use of dry swab method for SARS-CoV-2 detection as it does not need VTM and subsequent RNA extraction step making the process cheaper, safer and faster. In this study we explore whether the virus in the dry swab is viable and can be cultured and propagated.MethodSwabs were spiked with SARS-CoV-2 and stored in three different conditions: a) as dry swab (SD, eluted in 1 mL DMEM), b) in 1 mL of Viral Transport Medium (SVTM), and c) in 1 mL of Tris-EDTA buffer (STE). The sample groups were stored either at room temperature (RT, 25°C±1°C) or at 4°C for 1, 4, 8, 12, 24, 48 and 72 hours before being used as viral inoculums for the propagation studies in Vero cells.ResultsThe RT-qPCR data suggests that SDincubated both at RT and 4°C harbors viral particles that are viable and culturable at par with SVTMand STE.ConclusionThe dry swab method, in addition to its advantages in detection of the virus, also renders viable viral particles that can be cultured and propagated.
Biophysical demonstration of co-packaging of glutamate and GABA in individual synaptic vesicles in the central nervous system
Authors: Kim SeulAh , Wallace Michael L. , El-Rifai Mahmoud , Knudsen Alexa R. , Sabatini Bernardo L. 
Published: March 2021

SummaryMany mammalian neurons release multiple neurotransmitters to activate diverse classes of ionotropic receptors on their postsynaptic targets. Entopeduncular nucleus somatostatin (EPSst+) neurons that project to the lateral habenula (LHb) release both glutamate and GABA, but it is unclear if these are packaged into the same or segregated pools of synaptic vesicles. Here we describe a novel method combining electrophysiology, spatially-patterned optogenetics, and computational modeling designed to analyze the mechanism of glutamate/GABA corelease. We find that the properties of PSCs elicited in LHb neurons by optogenetic activation of EPSst+terminals are only consistent with co-packaging of glutamate and GABA into individual vesicles. Furthermore, serotonin, which acts presynaptically to weaken EPSst+to LHb synapses, does so by altering the release probability of vesicles containing both transmitters. Our approach is broadly applicable to the study of multi-transmitter neurons throughout the brain and our results constrain mechanisms of neuromodulation in LHb.