bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genomes of the Autonomous Parvovirus Minute Virus of Mice Induce Replication Stress Through RPA Exhaustion
Authors: Haubold MegAnn K. , Aquino Jessica N. Pita , Rubin Sarah R. , Jones Isabella K. , Pham Edward , Majumder Kinjal 
Published: February 2023

ABSTRACTThe oncolytic autonomous parvovirus Minute Virus of Mice (MVM) establishes infection in the nuclear environment by usurping host DNA Damage Response (DDRs) in the vicinity of cellular DNA break sites. MVM replication induces a global cellular DDR that is dependent on signaling by the ATM kinase and inactivates the cellular ATR-kinase pathway. However, the mechanism of how MVM generates cellular DNA breaks remains unknown. Using single molecule DNA Fiber Analysis, we have discovered that MVM infection leads to a shortening of host replication forks as infection progresses, as well as induction of replication stress prior to the initiation of virus replication. Ectopically expressed viral non-structural proteins NS1 and NS2 are sufficient to cause host-cell replication stress, as is the presence of UV-inactivated non-replicative MVM genomes. The host single-stranded DNA binding protein Replication Protein A (RPA) associates with the UV-inactivated MVM genomes, suggesting MVM genomes might serve as a sink for cellular stores of RPA. Overexpressing RPA in host cells prior to UV-MVM infection rescues DNA fiber lengths and increases MVM replication, confirming that MVM genomes deplete RPA stores to cause replication stress. Together, these results indicate that the presence of ssDNA in the nucleus generated by MVM genomes and viral proteins induces replication stress in the host cell through RPA exhaustion, rendering the host genome vulnerable to additional DNA breaks.AUTHOR SUMMARYParvoviruses are used in the clinic to design recombinant gene therapy vectors and as oncolytic agents. The autonomous parvovirus MVM utilizes the host cell’s DNA damage response machinery to replicate in host cells and cause additional DNA breaks. However, the mechanism of MVM-induced DNA damage remains unknown. We have discovered that MVM sequesters the host DNA repair protein RPA, which normally associates with single stranded DNA in the nucleus, rendering the host genome susceptible to replication stress. Our study provides insights into the mechanisms utilized by single-stranded DNA viruses to amplify host-cell DNA damage.
Predicting hearing help-seeking: What features are important for a profiling module within a hearing mHealth application?
Authors: Angonese Giulia , Buhl Mareike , Kuhlmann Inka , Kollmeier Birger , Hildebrandt Andrea 
Published: February 2023

AbstractBackgroundMobile health care solutions can improve quality, accessibility and equity of health services, fostering early rehabilitation. For people suffering from hearing loss, mobile applications might be designed to support the decision-making processes in auditory diagnostics and to provide treatment recommendations to the user (e.g., hearing aid need). For some individuals, such mobile app might be the first contact with a hearing diagnostic service and should motivate users with hearing loss to seek professional help.ObjectiveThis study aims at characterizing individuals who are more or less prone to seek professional help after the repeated use of an app-based hearing test. The goal is to develop a profiling module building upon hearing related traits and personality characteristics to secure personalized treatment recommendations in hearing mHealth solutions.MethodsN=185 (106 females) non-aided older individuals (Mage=63.8,SDage=6.6) with subjective hearing loss participated in a comprehensive online study. We collected cross-sectional and longitudinal data on several hearing-related and psychological features that were previously found to predict hearing help-seeking. Readiness to seek help was assessed as outcome variable at study-end and after two months. Participants were classified into help-seekers and non-seekers with several supervised machine learning algorithms (Random Forest, Naïve Bayes and Support Vector Machine). The most relevant features for prediction were identified with feature importance analysis.ResultsThe algorithms correctly predicted action to seek help at study-end in 66 to 70% of cases, reaching 75% classification accuracy at follow-up. Among the most important features for classifications were the degree of hearing loss and its perceived consequences in daily life, attitude towards hearing aids, and the personality traits neuroticism and conscientiousness.ConclusionsThis study contributes to the identification of individual characteristics that predict help-seeking in older individuals with self-perceived hearing loss. Suggestions for the implementation of an individual profiling algorithm and for targeted recommendations in hearing mHealth applications are derived.
Optimal Delivery Management for the Prevention of Early Neonatal SARS-CoV-2 Infection: Systematic review and Meta-analysis
Authors: Chan Christina S , Kong Juin Yee , Sultana Rehena , Mundra Vatsala , Babata Kikelomo L , Mazzarella Kelly , Adhikari Emily H , Yeo Kee Thai , Hascoët Jean-Michel , Brion Luc P 
Published: February 2023

ABSTRACTObjectiveReview how specific delivery management interventions (DMI) are associated with early neonatal SARS-CoV-2 infection (ENI) and neonatal death <28 days of life (ND).DesignSystematic review and meta-analysis of individual patient-specific data from articles published 1 January 2020 - 31 December 2021 from Cochrane review databases, Medline and Google Scholar.SettingInternational publications specifying DMI, ENI, and ND.PatientsPregnant women infected with SARS-CoV-2 and their infantsMain outcome measuresArticle inclusion criteria: 1) mothers with SARS-CoV-2 PCR positive status within 10 days before delivery or symptomatic at delivery with a positive test within 48 hours after delivery, 2) delivery method described, 3) infant SARS-CoV-2 PCR result reported. Primary outcomes were 1) ENI confirmed by positive neonatal PCR and 2) ND.ResultsAmong 11,075 screened publications, 117 publications containing data for 244 infants and 230 mothers were included. Maternal and infant characteristics were pooled using DerSimonian-Laird inverse variance method. Primary outcome analyses were completed using logit transformation and random effect. Heterogeneity of included studies was evaluated with I2statistics.No routine care was described so comparison of DMI combinations to routine care was not possible. Sample size for each combination was too small to conduct any valid comparison of different DMI combinations.ConclusionSupport for specific DMI in SARS-CoV-2 infected mothers is lacking. This review highlights the need for rigorous and multinational studies on the guidelines best suited to prevent transmission from mother to neonate.KEY MESSAGESWhat is already known on this topicSeveral specific delivery management interventions (DMI) have been recommended for women with active SARS-CoV-2 to prevent early neonatal SARS-CoV-2 infection.What this study addsThis systematic review shows that support for specific DMI in SARS-CoV-2 infected mothers is lacking.How this study might affect research, practice or policyThis review highlights the need for rigorous and multinational studies on the guidelines best suited to prevent transmission from mother to neonate.
Translatome analysis reveals microglia and astrocytes to be distinct regulators of inflammation in the hyperacute and acute phases after stroke
Authors: Hernandez Victoria G. , Lechtenberg Kendra J. , Peterson Todd C. , Zhu Li , Lucas Tawaun A. , Owah Justice O. , Dorsey Alanna I. , Gentles Andrew J. , Buckwalter Marion S. 
Published: February 2023

AbstractNeuroinflammation is a hallmark of ischemic stroke, which is a leading cause of death and long-term disability. Understanding the exact cellular signaling pathways that initiate and propagate neuroinflammation after stroke will be critical for developing immunomodulatory stroke therapies. In particular, the precise mechanisms of inflammatory signaling in the clinically relevant hyperacute period, hours after stroke, have not been elucidated. We used the RiboTag technique to obtain astrocyte and microglia-derived mRNA transcripts in a hyperacute (4 hours) and acute (3 days) period after stroke, as these two cell types are key modulators of acute neuroinflammation. Microglia initiated a rapid response to stroke at 4 hours by adopting an inflammatory profile associated with the recruitment of immune cells. The hyperacute astrocyte profile was marked by stress response genes and transcription factors, such asFosandJun, involved in pro-inflammatory pathways such as TNF-α. By 3 days, microglia shift to a proliferative state and astrocytes strengthen their inflammatory response. The astrocyte pro-inflammatory response at 3 days is partially driven by the upregulation of the transcription factorsC/EBPβ, Spi1, andRel, which comprise 25% of upregulated transcription factor-target interactions. Surprisingly, few sex differences across all groups were observed. Expression and log2fold data for all sequenced genes are available on a user-friendly website for researchers to examine gene changes and generate hypotheses for stroke targets. Taken together our data comprehensively describe the astrocyte and microglia-specific translatome response in the hyperacute and acute period after stroke and identify pathways critical for initiating neuroinflammation.
Automatic identification of scientific publications describing digital reconstructions of neural morphology
Authors: Maraver Patricia , Tecuatl Carolina , Ascoli Giorgio A. 
Published: February 2023

AbstractMotivationThe increasing number of peer-reviewed publications constitutes a challenge for biocuration. For example, NeuroMorpho.Org, a sharing platform for digital reconstructions of neural morphology, must evaluate more than 6000 potentially relevant articles per year to identify data of interest. Here, we describe a tool that uses natural language processing and deep learning to assess the likelihood of a publication to be relevant for the project.ResultsThe tool automatically identifies articles describing digitally reconstructed neural morphologies with high accuracy. Its processing rate of 900 publications per hour is not only amply sufficient to autonomously track new research, but also allowed the successful evaluation of older publications backlogged due to limited human resources. The number of bio-entities found since launching the tool almost doubled while greatly reducing manual labor. The classification tool is open source, configurable, and simple to use, making it extensible to other biocuration projects.Availabilityhttps://github.com/Joindbre/TextRelevancyContactascoli@gmu.eduSupplementary informationSupplementary information, tool installation, and API usage are available athttps://docs.joindbre.com
Genetic control of cell layer interactions in plants via tissue mechanics
Authors: Kelly-Bellow Robert , Lee Karen , Kennaway Richard , Barclay Elaine , Whibley Annabel , Bushell Claire , Spooner Jamie , Yu Man , Brett Paul , Kular Baldeep , Cheng Shujing , Chu Jinfang , Xu Ting , Lane Brendan , Fitzsimons James , Xue Yongbiao , Smith Richard , Whitewoods Christopher D. , Coen Enrico 
Published: February 2023

AbstractPlant development depends on coordination of growth between different cell layers. Coordination may be mediated by molecular signalling or mechanical connectivity between cells, but evidence for genetic control via direct mechanics has been lacking. We show that a brassinosteroid-deficient dwarf mutant of the aquatic plantUtricularia gibbahas twisted internal tissue, likely caused by a mechanical constraint from a slow-growing epidermis creating tissue stresses. This conclusion is supported by showing that inhibition of brassinosteroid action in anArabidopsismutant compromised for cell adhesion, enhances epidermal crack formation, an indicator of increased tissue tension. Thus, genes driving brassinosteroid synthesis can promote growth of internal tissue by reducing mechanical epidermal constraint, showing that tissue mechanics plays a key role in coordinating growth between cell layers.One-Sentence SummaryInternal twists in a mutant carnivorous plant reveal how genes control growth via tissue mechanics.
Stimulus novelty uncovers coding diversity in survey of visual cortex
Authors: Garrett Marina , Groblewski Peter , Piet Alex , Ollerenshaw Doug , Najafi Farzaneh , Yavorska Iryna , Amster Adam , Bennett Corbett , Buice Michael , Caldejon Shiella , Casal Linzy , D’Orazi Florence , Daniel Scott , de Vries Saskia EJ , Kapner Daniel , Kiggins Justin , Lecoq Jerome , Ledochowitsch Peter , Manavi Sahar , Mei Nicholas , Morrison Christopher B. , Naylor Sarah , Orlova Natalia , Perkins Jed , Ponvert Nick , Roll Clark , Seid Sam , Williams Derric , Williford Allison , Ahmed Ruweida , Amine Daniel , Billeh Yazan , Bowman Chris , Cain Nicholas , Cho Andrew , Dawe Tim , Departee Max , Desoto Marie , Feng David , Gale Sam , Gelfand Emily , Gradis Nile , Grasso Conor , Hancock Nicole , Hu Brian , Hytnen Ross , Jia Xiaoxuan , Johnson Tye , Kato India , Kivikas Sara , Kuan Leonard , L’Heureux Quinn , Lambert Sophie , Leon Arielle , Liang Elizabeth , Long Fuhui , Mace Kyla , de Abril Ildefons Magrans , Mochizuki Chris , Nayan Chelsea , North Katherine , Ng Lydia , Ocker Gabriel Koch , Oliver Michael , Rhoads Paul , Ronellenfitch Kara , Schelonka Kathryn , Sevigny Josh , Sullivan David , Sutton Ben , Swapp Jackie , Nguyen Thuyanh K , Waughman Xana , Wilkes Joshua , Wang Michael , Farrell Colin , Wakeman Wayne , Zeng Hongkui , Phillips John , Mihalas Stefan , Arkhipov Anton , Koch Christof , Olsen Shawn R 
Published: February 2023

AbstractDetecting novel stimuli in the environment is critical for learning and survival, yet the neural basis of novelty processing is not understood. To characterize cell type-specific novelty processing, we surveyed the activity of ∼15,000 excitatory and inhibitory neurons in mice performing a visual task with novel and familiar stimuli. Clustering revealed a dozen functional neuron types defined by experience-dependent encoding. Vasoactive-intestinal-peptide (Vip) expressing inhibitory neurons were diverse, encoding novel stimuli, omissions of familiar stimuli, or behavioral features. Distinct Somatostatin (Sst) expressing inhibitory neurons encoded either familiar or novel stimuli. Subsets of excitatory neurons co-clustered with specific Vip or Sst subpopulations, while Sst and Vip inhibitory clusters were non-overlapping. This study establishes that novelty processing is mediated by diverse functional neuron types in the visual cortex.
Nearly (?) sterile avian egg in a passerine bird
Authors: Těšický Martin , Schmiedová Lucie , Krajzingrová Tereza , Gomez Samblas Mercedes , Bauerová Petra , Kreisinger Jakub , Vinkler Michal 
Published: February 2023

AbstractDuring early ontogeny, microbiome affects development of the gastrointestinal tract, immunity and survival in vertebrates. Bird egg has been suggested to be either (1) initially sterile (Sterile egg hypothesis) and (2) colonized throughhorizontal trans-shell migrationafter egg laying, or (3) initially seeded with bacteria throughvertical transferfrom mother’ ss oviduct. Little empirical data illuminate so far the contribution of these mechanisms to gut microbiota formation in avian embryos. We evaluated microbiome of the egg content (day 0; E0-egg), embryonic gut at day 13 (E13) and female faeces in a free-living passerine, the great tit (Parus major), using a methodologically advanced procedure combining16S rRNAgene sequencing and microbe-specific qPCR assays. Our metabarcoding revealed that avian egg is (nearly)sterile, barely distinguishable in microbial composition from negative controls. Of the three potentially pathogenic bacteria targeted by qPCR, onlyDietziawas found in E0-egg (yet also in controls), E13 gut and female samples, which might indicate its possiblevertical transfer. Unlike in poultry, we have shown in passerines that major bacterial colonisation of the gut does not occur before chick’s hatching. We stress that protocols carefully checking for environmental contamination are critically important in studies using samples with low bacterial biomass.
Long-term survival and induction of operational tolerance to murine islet allografts through the co-transplantation of cyclosporine A eluting microparticles
Authors: Kuppan Purushothaman , Wong Jordan , Kelly Sandra , Lin Jiaxin , Worton Jessica , Castro Chelsea , Paramor Joy , Seeberger Karen , Anderson Colin C. , Korbutt Gregory S. , Pepper Andrew R. 
Published: February 2023

AbstractOne strategy to prevent islet rejection, is to create a favorable immune-protective local environment at the transplant site. Herein, we utilize localized cyclosporine A (CsA) delivery to islet grafts via poly(lactic-co-glycolic acid) (PLGA) microparticles to attenuate allograft rejection. CsA microparticles alone significantly delayed islet allograft rejection compared to islets alone (p<0.05). Over 50% (6/11) of recipients receiving CsA microparticles and short-term cytotoxic T lymphocyte-associated antigen 4-Ig (CTLA4-Ig) therapy displayed prolonged allograft survival for 214 days, compared to 25% (2/8) receiving CTLA4-Ig alone (p>0.05). CsA microparticles + CTLA4-Ig islet allografts exhibited reduced T-cell (CD4+and CD8+cells) and macrophage (CD68+cells) infiltration compared to islets alone. We observed reduced mRNA expression of proinflammatory cytokines (IL-6, IL-10, INF-γ & TNF-α; p<0.05) and chemokines (CCL2, CCL5, CCL22, and CXCL10; p<0.05) in CsA microparticles + CTLA4-Ig allografts compared to islets alone. Long-term islet allografts contained insulin+and intra-graft FoxP3+T regulatory cells. Rapid rejection of third-party skin grafts (C3H) in islet allograft recipients suggested that CsA microparticles + CTLA4-Ig therapy induced donor specific operational tolerance. This study demonstrates that localized CsA drug delivery plus short-course systemic immunosuppression promotes an immune protective transplant niche for allogeneic islets.Article HighlightsSystemic immunosuppression limits patient inclusion for beta cell replacement therapiesLocalized islet graft immunosuppression may reduce drug toxicity and improve graft survivalCyclosporine eluting microparticles + CTLA4-Ig therapy induced donor specific operational toleranceGraft localized drug delivery can create an immune protective transplant niche
Human gene regulatory evolution is driven by the divergence of regulatory element function in bothcisandtrans
Authors: Hansen Tyler , Fong Sarah , Capra John A. , Hodges Emily 
Published: February 2023

SUMMARYGene regulatory divergence between species can result fromcis-acting local changes to regulatory element DNA sequences or globaltrans-acting changes to the regulatory environment. Understanding how these mechanisms drive regulatory evolution has been limited by challenges in identifyingtrans-acting changes. We present a comprehensive approach to directly identifycis-andtrans-divergent regulatory elements between human and rhesus macaque lymphoblastoid cells using ATAC-STARR-seq. In addition to thousands ofcischanges, we discover an unexpected number (~10,000) oftranschanges and show thatcisandtranselements exhibit distinct patterns of sequence divergence and function. We further identify differentially expressed transcription factors that underlie >50% oftransdifferences and trace howcischanges can produce cascades oftranschanges. Overall, we find that most divergent elements (67%) experienced changes in bothcisandtrans, revealing a substantial role fortransdivergence—alone and together withcischanges—to regulatory differences between species.
A Brighter picALuc Generated Through the Loss of a Salt Bridge Interaction
Authors: Biswas Kabir H 
Published: February 2023

AbstractRecently, a miniaturized variant of an artificial luciferase (ALuc), named picALuc, with a molecular weight of 13 kDa and thus, the smallest luciferase, was reported. While picALuc was found to be as active as the ALuc, questions remained on the structural organization and residue-residue interactions in the protein. Here, combining structural modeling, molecular dynamics (MD) simulations and mutational analysis, we show that the loss of a salt bridge interaction formed by Glu50 (E50) residue results in an increased enzymatic activity of picALuc. Specifically, we generated a model of picALuc using the available structure of theGaussialuciferase (GLuc) and performed a 1 μs long Gaussian accelerated molecular dynamics (GaMD) simulation which revealed a general compaction of the protein structure as well as residue level interactions in the protein. Given that picALuc contains a number of charged residues, we focused our attention to salt bridge interactions and decided to mutate E10, E50 and D94 that were found to form a fluctuating, stable or a new salt bridge interaction, respectively. Live cell assays showed an enhanced bioluminescence in cells expressing the E50A mutant picALuc while in vitro assays revealed an increasedVmaxof the E50A mutant without affecting its thermal stability. Dynamic cross-correlation and principal component analyses of the GaMD simulation trajectories revealed altered collective dynamics in the protein, in which residue E50 contributed substantially. Finally, we developed a protein fragment complementation assay using picALuc that allows monitoring protein-protein interaction in live cells. We envisage that the brighter variant of picALuc and the protein fragment complementation assay reported here will find a general applicability in developing bioluminescence-based assays and the strategy developed here will pave the way for further engineering of brighter variants of picALuc.