bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impaired antigen-specific memory B cell and plasma cell responses including lack of specific IgG upon SARS-CoV-2 BNT162b2 vaccination among Kidney Transplant and Dialysis patients
Authors: Rincon-Arevalo Hector , Choi Mira , Stefanski Ana-Luisa , Halleck Fabian , Weber Ulrike , Szelinski Franziska , Jahrsdörfer Bernd , Schrezenmeier Hubert , Ludwig Carolin , Sattler Arne , Kotsch Katja , Potekhin Alexander , Chen Yidan , Burmester Gerd R. , Eckardt Kai-Uwe , Guerra Gabriela Maria , Durek Pawel , Heinrich Frederik , Ferreira-Gomes Marta , Radbruch Andreas , Budde Klemens , Lino Andreia C. , Mashreghi Mir-Farzin , Schrezenmeier Eva , Dörner Thomas 
Published: April 2021

AbstractPatients with kidney failure are at increased risk during the COVID-19 pandemic and effective vaccinations are needed. It is not known how efficient mRNA vaccines mount B and plasma cell responses in dialysis patients (DP) or kidney transplant recipients (KTR) compared to healthy controls (HC). We studied humoral and B cell responses of 25 HC, 44 DP and 40 KTR. Markedly impaired anti-BNT162b2 responses were identified among KTR and DP compared to 100% seroconversion in HC. In DP, the response was delayed (3-4 weeks after boost) and reduced with anti-S1 IgG positivity in 31 (70.5%) and anti-S1 IgA in 30 (68.2%) of 44, respectively. In contrast, KTR did not develop IgG response except one patient who had prior unrecognized infection and developed anti-S1 IgG. The majority of antigen-specific B cells (RBD+) were identified in the plasmablast or post-switch memory B cell compartments in HC, whereas these RBD+ B cells were enriched among pre-switch and naïve B cells from DP and KTR. Single cell transcriptome and CITE-seq analyses found reduced frequencies of plasmablasts, TCF7+CD27+GZMK+ T cells and proliferating MKI67-expressing lymphocytes among KTR non-responders. Importantly, the frequency and absolute number of antigen-specific circulating plasmablasts in the whole cohort correlated with the Ig response, a characteristic not reported for other vaccinations. In conclusion, this data indicate that lack of T cell help related to immunosuppression results in impaired germinal center differentiation of B and plasma cell memory. There is an urgent need to improve vaccination protocols in patients after kidney transplantation or on chronic dialysis.One Sentence SummaryKidney transplant recipients and dialysis patients show a markedly diminished humoral response and impaired molecular B cell memory formation upon vaccination with BNT162b2.
Patient-Specific Connectomic Models Correlate With, But Do Not Predict, Outcomes in Deep Brain Stimulation for Obsessive-Compulsive Disorder
Authors: Widge Alik S. , Zhang Fan , Gosai Aishwarya , Papadimitrou George , Wilson-Braun Peter , Tsintou Magdalini , Palanivelu Senthil , Noecker Angela M. , McIntyre Cameron C. , O’Donnell Lauren , McLaughlin Nicole C.R. , Greenberg Benjamin D. , Makris Nikolaos , Dougherty Darin D. , Rathi Yogesh 
Published: April 2021

AbstractBackgroundDeep brain stimulation (DBS) of the ventral internal capsule/ventral striatum (VCVS) is an emerging treatment for obsessive-compulsive disorder (OCD). Recently, multiple studies using normative connectomes have correlated DBS outcomes to stimulation of specific white matter tracts. Those studies did not test whether these correlations are clinically predictive, and did not apply cross-validation approaches that are necessary for biomarker development. Further, they did not account for the possibility of systematic differences between DBS patients and the non-diagnosed controls used in normative connectomes.MethodsWe performed patient-specific diffusion imaging in 8 patients who underwent VCVS DBS for OCD. We delineated tracts connecting thalamus and subthalamic nucleus (STN) to prefrontal cortex via VCVS. We then calculated which tracts were likely activated by individual patients’ DBS settings. We fit multiple statistical models to predict both OCD and depression outcomes from tract activation. We further attempted to predict hypomania, a VCVS DBS complication. We assessed all models’ performance on held-out test sets.ResultsNo model predicted OCD response, depression response, or hypomania above chance. Coefficient inspection partly supported prior reports, in that capture of tracts projecting to cingulate cortex was associated with both YBOCS and MADRS response. In contrast to prior reports, however, tracts connected to STN were not reliably correlated with response.ConclusionsPatient-specific imaging and a guideline-adherent analysis were unable to identify a tractographic target with sufficient effect size to drive clinical decision-making or predict individual outcomes. These findings suggest caution in interpreting the results of normative connectome studies.
Asymptomatic or mild symptomatic SARS-CoV-2 infection elicits durable neutralizing antibody responses in children and adolescents
Authors: Garrido Carolina , Hurst Jillian H. , Lorang Cynthia G. , Aquino Jhoanna N. , Rodriguez Javier , Pfeiffer Trevor S. , Singh Tulika , Semmes Eleanor C. , Lugo Debra J. , Rotta Alexandre T. , Turner Nicholas A. , Burke Thomas W. , McClain Micah T. , Petzold Elizabeth A. , Permar Sallie R. , Moody M. Anthony , Woods Christopher W. , Kelly Matthew. S. , Fouda Genevieve G. 
Published: April 2021

ABSTRACTAs SARS-CoV-2 continues to spread globally, questions have emerged regarding the strength and durability of immune responses in specific populations. In this study, we evaluated humoral immune responses in 69 children and adolescents with asymptomatic or mild symptomatic SARS-CoV-2 infection. We detected robust IgM, IgG, and IgA antibody responses to a broad array of SARS-CoV-2 antigens at the time of acute infection and 2 and 4 months after acute infection in all participants. Notably, these antibody responses were associated with virus neutralizing activity that was still detectable 4 months after acute infection in 94% of children. Moreover, antibody responses and neutralizing activity in sera from children and adolescents were comparable or superior to those observed in sera from 24 adults with mild symptomatic infection. Taken together, these findings indicate children and adolescents with mild or asymptomatic SARS-CoV-2 infection generate robust and durable humoral immune responses that are likely to protect from reinfection.
TheDrosophilaDCP2 is evolutionarily conserved in sequence and structure – insights fromin silicostudies of DmDCP2 orthologs and paralogs
Authors: Kunar Rohit , Roy Jagat Kumar 
Published: April 2021

AbstractThe mRNA decapping proteins (DCPs) function to hydrolyze the 7-methylguanosine cap at the 5’ end of mRNAs thereby, exposing the transcript for degradation by the exonuclease(s) and hence, play a pioneering role in the mRNA decay pathway. InDrosophila melanogaster, the mRNA decapping protein 2 (DCP2) is the only catalytically active mRNA decapping enzyme present. Despite its presence being reported across diverse species in the phylogenetic tree, a quantitative approach to the index of its conservation in terms of its sequence has not been reported so far. With structural and mechanistic insights being explored in the yeasts, the insect DCP2 has never been explored in the perspectives of structure and the indices of the conservation of its sequence and/or structurevis-à-vistopological facets. Being an evolutionarily conserved protein, the present endeavor aimed at deciphering the evolutionary relationship(s) and the pattern of conservation of the sequence of DCP2 across the phylogenetic tree as well as in sibling species ofD. melanogasterthrough a semi-quantitative approach relying on multiple sequence alignment and analyses of percentage identity matrices. Since NUDIX proteins are functionally diverse, an attempt to identify the other NUDIX proteins (or, DCP2 paralogs) inD. melanogasterand compare and align their structural features with that of DCP2 throughin silicoapproaches was endeavored in parallel. Our observations provide quantitative and structural bases for the observed evolutionary conservation of DCP2 across the diverse phyla and also, identify and reinforce the structural conservation of the NUDIX family inD. melanogaster.
Systematic discovery and perturbation of regulatory genes in human T cells reveals the architecture of immune networks
Authors: Freimer Jacob W. , Shaked Oren , Naqvi Sahin , Sinnott-Armstrong Nasa , Kathiria Arwa , Chen Amy F. , Cortez Jessica T. , Greenleaf William J. , Pritchard Jonathan K. , Marson Alexander 
Published: April 2021

SummaryComplex gene regulatory networks ensure that important genes are expressed at precise levels. When gene expression is sufficiently perturbed it can lead to disease. To understand how gene expression disruptions percolate through a network, we must first map connections between regulatory genes and their downstream targets. However, we lack comprehensive knowledge of the upstream regulators of most genes. Here we developed an approach for systematic discovery of upstream regulators of critical immune factors – IL2RA, IL-2, and CTLA4 – in primary human T cells. Then, we mapped the network of these regulators’ target genes and enhancers using CRISPR perturbations, RNA-Seq, and ATAC-Seq. These regulators form densely interconnected networks with extensive feedback loops. Furthermore, this network is highly enriched for immune-associated disease variants and genes. These results provide insight into how immune-associated disease genes are regulated in T cells and broader principles about the structure of human gene regulatory networks.HighlightsA systematic approach to identify upstream regulators of key immune genes in primary human cellsComprehensive RNA-Seq and ATAC-Seq perturbation maps after KO of individual discovered regulatorsAnalysis uncovers a highly interconnected regulatory network of enhancers and genes in T cellsThis network is highly enriched for immune disease variants and genes shedding light on the trans-regulatory connections among key immune genes in health and disease
ChIP-AP – An Integrated ChIP-Seq Analysis Pipeline
Authors: Suryatenggara Jeremiah , Yong Kol Jia , Tenen Danielle E. , Tenen Daniel G. , Bassal Mahmoud A. 
Published: April 2021

AbstractChIP-Seq is a technique used to analyse protein-DNA interactions. The protein-DNA complex is pulled down using a protein antibody, after which sequencing and analysis of the bound DNA fragments is performed. A key bioinformatics analysis step is “peak” calling - identifying regions of enrichment. Benchmarking studies have consistently shown that no optimal peak caller exists. Peak callers have distinct selectivity and specificity characteristics which are often not additive and seldom completely overlap in many scenarios. In the absence of a universal peak caller, we rationalized one ought to utilize multiple peak-callers to 1) gauge peak confidence as determined through detection by multiple algorithms, and 2) more thoroughly survey the protein-bound landscape by capturing peaks not detected by individual peak callers owing to algorithmic limitations and biases. We therefore developed an integrated ChIP-Seq Analysis Pipeline (ChIP-AP) which performs all analysis steps from raw fastq files to final result, and utilizes four commonly used peak callers to more thoroughly and comprehensively analyse datasets. Results are integrated and presented in a single file enabling users to apply selectivity and sensitivity thresholds to select the consensus peak set, the union peak set, or any sub-set in-between to more confidently and comprehensively explore the protein-bound landscape. (https://github.com/JSuryatenggara/ChIP-AP).
Aberrant Activation of the Mentalizing Brain System During Eye Gaze Discrimination in Bipolar Disorder
Authors: Tso Ivy F. , Burton Cynthia Z. , Lasagna Carly A. , Rutherford Saige , Yao Beier , Peltier Scott J. , Johnson Timothy D. , McInnis Melvin G. , Taylor Stephan F. 
Published: April 2021

AbstractBipolar disorder (BD) is associated with a range of social cognitive deficits. This study investigated the functioning of the mentalizing brain system in BD probed by an eye gaze perception task during fMRI. Compared with healthy controls (n = 21), BD participants (n = 14) showed reduced preferential activation for self-directed gaze discrimination in the medial prefrontal cortex (mPFC) and temporo-parietal junction (TPJ), which was associated with poorer cognitive and social functioning. Aberrant functions of the mentalizing system should be further investigated as marker of social dysfunction and treatment targets.HighlightsSocial dysfunction in bipolar disorder (BD) may be due to altered mentalizing.Individuals with BD showed reduced activation in the mentalizing brain system.Aberrant activity of the mentalizing system was associated with poorer functioning.
The Mental Health Under the COVID-19 Crisis in Africa: A Systematic Review and Meta-Analysis
Authors: Chen Jiyao , Farah Nusrat , Dong Rebecca Kechen , Chen Richard Z. , Xu Wen , Yin Allen , Chen Bryan Z. , Delios Andrew , Miller Saylor , Wan Xue , Zhang Stephen X. 
Published: April 2021

ABSTRACTObjectiveIn this paper, we aim to provide a systematic review and meta-analysis on the prevalence rates of mental health symptoms of anxiety, depression, and insomnia among the major populations during the COVID-19 pandemic in Africa.DesignA systematic review and meta-analysis.Data sourcesWe search and include articles using PubMed, Embase, Web of Science, PsycINFO, and medRxiv databases between Feb 202 and Feb 6th, 2021.Eligibility criteria and data analysisThe meta-analysis targets the prevalence rates of mental health symptoms of major populations including frontline/general healthcare workers (HCWs), the general adult population, and medical students during the COVID-19 pandemic in Africa. To estimate the prevalence rates of anxiety, depression, and insomnia, we pooled data using random-effects meta-analyses.ResultsIn this meta-analysis, we identify and include 28 studies and 32 independent samples from 12 countries with a total of 15,072 participants in Africa. Ethiopia (7) and Egypt (6) had the largest number of studies. While many countries including, but not limited to, Algeria, Kenya, and Ghana had a high number of COVID-19 cases, as many as three quarters of African countries have no studies. The pooled prevalence of anxiety in 27 studies was 37% (95%CI: 31-43%,I2= 99.0%) and that of depression in 24 studies was 45% (95%CI: 36-51%,I2= 99.5%) and that of insomnia in 9 studies was 28% (95%CI: 20-41%,I2= 99.2%). The pooled prevalence rates of anxiety, depression, and insomnia in North Africa (44%, 55%, and 31%, respectively) are higher than the rates in Sub-Saharan Africa (31%, 30%, and 24%, respectively). Our analysis indicated high heterogeneity and varying prevalence rates of mental health symptoms during the COVID-19 pandemic in Africa.DiscussionWe discuss our findings that a) a scarcity of studies in several African countries with a high number of COVID-19 cases, b) high heterogeneity among the studies, c) the extent of prevalence of mental health symptoms in Africa to be high, and d) the pattern of mental health symptoms in Africa differs from elsewhere, i.e., more African adults suffer from depression rather than anxiety and insomnia during COVID 19 compared to adult population in other countries or regions. Hence, our findings carry crucial implications for healthcare organizations and future research to enable evidence-based medicine in Africa. Our findings also call for increased scholarly attention on Africa, the least studied continent with a limited amount of research on mental health symptoms under the COVID 19 pandemic.Trial registrationCRD42020224458
Babytwins Study Sweden (BATSS): A multi-method infant twin study of genetic and environmental factors influencing infant brain and behavioral development
Authors: Falck-Ytter Terje , Hamrefors Linnea , Sanchez Monica Siqueiros , Portugal Ana Maria , Taylor Mark , Li Danyang , Viktorsson Charlotte , Hardiansyah Irzam , Myers Lynnea , Westberg Lars , Bölte Sven , Tammimies Kristiina , Ronald Angelica 
Published: April 2021

ABSTRACTTwin studies can help us understand the relative contributions of genes and environment to phenotypic trait variation including attentional and brain activation measures. In terms of applying methodologies like electroencephalography (EEG) and eye tracking, which are key methods in developmental neuroscience, infant twin studies are almost non-existent. Here we describe the Babytwins Study Sweden (BATSS), a multi-method longitudinal twin study of 177 MZ and 134 DZ twin pairs (i.e. 622 individual infants) covering the 5 - 36 month time period. The study includes EEG, eye tracking and genetics, together with more traditional measures based on in-person testing, direct observation and questionnaires. The results show that interest in participation in research among twin parents is high, despite the comprehensive protocol. DNA analysis from saliva samples was possible in virtually all participants, allowing for both zygosity confirmation and polygenic score analyses. Combining a longitudinal twin design with advanced technologies in developmental cognitive neuroscience and genomics, BATSS represents a new approach in infancy research, which we hope to have impact across multiple disciplines in the coming years.
Cytoskeletal vimentin regulates cell size and autophagy through mTORC1 signaling
Authors: Mohanasundaram Ponnuswamy , Rato Leila S Coelho , Modi Mayank , Urbanska Marta , Lautenschläger Franziska , Cheng Fang , Eriksson John E 
Published: April 2021

AbstractThe nutrient-activated mTORC1 (mechanistic target of rapamycin kinase complex 1) signaling pathway determines cell size by controlling mRNA translation, ribosome biogenesis, protein synthesis, and autophagy. Here we show that vimentin, a cytoskeletal intermediate filament protein that we know to be important for wound healing and cancer progression, determines cell size through mTORC1 signaling, an effect that is also manifested at the organism level in mice. We found that vimentin maintains normal cell size by supporting mTORC1 activation and through inhibition of autophagic flux. This regulation is manifested at all levels of downstream target activation and regulation of protein synthesis. We show that vimentin controls mTORC1 mobility by allowing access to lysosomes. Vimentin inhibits the autophagic flux in normal fibroblasts even under starved conditions, indicating a growth factor-independent inhibition of autophagy at the level of mTORC1. Our findings demonstrate that vimentin couples cell size signaling and autophagy with the biomechanic, sensing, and kinetic functions of the cytoskeleton.
The association between Hfq and RNase E in long-term nitrogen starvedEscherichia coli
Authors: McQuail Josh , Carpousis Agamemnon J. , Wigneshweraraj Sivaramesh 
Published: April 2021

AbstractUnder conditions of nutrient adversity, bacteria adjust metabolism to minimise cellular energy usage. This is often achieved by controlling the synthesis and degradation of RNA. InEscherichia coli, RNase E is the central enzyme involved in RNA degradation and serves as a scaffold for the assembly of the multiprotein complex known as the RNA degradosome. The activity of RNase E against specific mRNAs can also be regulated by the action of small RNAs (sRNA). In this case, the ubiquitous bacterial chaperone Hfq bound to sRNAs can interact with the RNA degradosome for the sRNA guided degradation of target RNAs. The RNA degradosome and Hfq have never been visualised together in live bacteria. We now show that in long-term nitrogen starvedE. coli, both RNase E and Hfq co-localise in a single, large focus. This subcellular assembly, which we refer to as the H-body, forms by a liquid-liquid phase separation type mechanism and includes components of the RNA degradosome, namely, the helicase RhlB and the exoribonuclease polynucleotide phosphorylase. The results support the existence of an hitherto unreported subcellular compartmentalisation of a process(s) associated with RNA management in stressed bacteria.
Flexible Simultaneous Mesoscale Two-Photon Imaging Of Neural Activity at High Speeds
Authors: Clough Mitchell , Chen Ichun Anderson , Park Seong-Wook , Ahrens Allison M. , Stirman Jeffrey N. , Smith Spencer L. , Chen Jerry L. 
Published: April 2021

ABSTRACTUnderstanding brain function requires monitoring local and global brain dynamics. Two-photon imaging of the brain across mesoscopic scales has presented trade-offs between imaging area and acquisition speed. We describe a flexible cellular resolution two-photon microscope capable of simultaneous video rate acquisition of four independently targetable brain regions spanning an approximate five-millimeter field of view. With this system, we demonstrate the ability to measure calcium activity across mouse sensorimotor cortex at behaviorally relevant timescales.
Evolutionary transcriptomics implicates new genes and pathways in human pregnancy and adverse pregnancy outcomes
Authors: Mika Katie , Marinić Mirna , Singh Manvendra , Lynch Vincent J. 
Published: April 2021

AbstractEvolutionary changes in the anatomy and physiology of the female reproductive system underlie the origins and diversification of pregnancy in Eutherian (“Placental”) mammals. This developmental and evolutionary history constrains normal physiological functions and biases the ways in which dysfunction contributes to reproductive trait diseases and adverse pregnancy outcomes. Here, we show that gene expression changes in the human endometrium during pregnancy are associated with the evolution of human-specific traits and pathologies of pregnancy. We found that hundreds of genes gained or lost endometrial expression in the human lineage. Among these are genes that may contribute to human-specific maternal-fetal communication (HTR2B) and maternal-fetal immunotolerance (PDCD1LG2) systems, as well as vascular remodeling and deep placental invasion (CORIN). These data suggest that explicit evolutionary studies of anatomical systems complement traditional methods for characterizing the genetic architecture of disease. We also anticipate our results will advance the emerging synthesis of evolution and medicine (“evolutionary medicine”) and be a starting point for more sophisticated studies of the maternal-fetal interface. Furthermore, the gene expression changes we identified may contribute to the development of diagnostics and interventions for adverse pregnancy outcomes.
Predicting Individual Task Contrasts From Resting-state Functional Connectivity using a Surface-based Convolutional Network
Authors: Ngo Gia H. , Khosla Meenakshi , Jamison Keith , Kuceyeski Amy , Sabuncu Mert R. 
Published: April 2021

AbstractTask-based and resting-state represent the two most common experimental paradigms of functional neuroimaging. While resting-state offers a flexible and scalable approach for characterizing brain function, task-based techniques provide superior localization. In this paper, we build on recent deep learning methods to create a model that predicts task-based contrast maps from resting-state fMRI scans. Specifically, we propose BrainSurfCNN, a surface-based fully-convolutional neural network model that works with a representation of the brain’s cortical sheet. Our model achieves state of the art predictive accuracy on independent test data from the Human Connectome Project and yields individual-level predicted maps that are on par with the target-repeat reliability of the measured contrast maps. We also demonstrate that BrainSurfCNN can generalize remarkably well to novel domains with limited training data.