bluuebunny/crossref_metadata_2025_split huggingface dataset:
VEGF subtype A and B Gene Expression, Clues to a Temporal Signature in Kawasaki Disease, Implications for Coronary Pathogenesis through a Secondary analysis of Clinical Datasets
Authors: Rashid Asrar , Toufiq M. , Khilnani Praveen , Malik Zainab A. , Sharief Javed , Kadwa Raziya , Brusletto Berit S. , Sarpal Amrita , Chaussabel Damien , Malik Rayaz , Quraishi Nasir , Benakatti Govind , Zaki Syed A. , Ogrodzki Pauline , Zaher Walid , Zouhbi Mouhamad Al , Saleh Husam , Khayer Ahmad Al , Nadeem M. Rashid , Shaikh Guftar , Hussain Shazia , Tariq Mishal , Al-Dubai Ahmed , Hussain Amir 
Published: August 2022

Background and AimAn essential issue for Kawasaki Disease (KD) is the development of coronary artery disease. We decided to investigate (VEGF) subtype gene expression in KD due to the proangiogenic nature of Vasoactive Endothelial Growth Factor A (VEGF). VEGF-A is a known angiogenic molecule with pro-inflammatory effects, whereas the role of VEGFB has been less defined.MethodKD Microarray and RNA-seq datasets were selected using a comprehensive search strategy of the NCBI GEO Dataset, which resulted in eight studies from whole blood. This included three extensive studies in KD (KD1-KD3). Further, one study dataset from coronary artery tissue, the Coronary Artery Dataset (CAD), was also included to appreciate end-stage KD.ResultsIn CAD, cases of KD versus controls, VEGF-B was up-regulated (p = 4.932e-02). KD1, KD Acute versus convalescent samples, VEGF-A is up-regulated (p=1.258e-07) and VEGF-B was down-regulated (p=1.42e-28). Similar up regulation of VEGF-A and down regulation of VEGF-B was seen in KD2 (p=1.140e-04; p=1.746e-02) and KD3 (p=1.140e-04; p=1.746e-02), both are KD Versus Controls. VEGF-A up-regulated (p=1.140e-04), VEGF-B down-regulated (p=1.746e-02).KD3, KD versus Control; VEGF-A up-regulated (p=1.140e-04), VEGF-B down regulated (p=1.746e-02).ConclusionsIn acute KD VEGF-A up-regulation, with VEGFB being down-regulated, the reverse being true of the convalescent situation. This suggests a temporal inverse relationship between VEGF-A and VEGF-B may have biomarker implications. Moreover, a dual therapeutic strategy, enhancing VEGFB while minimizing VEGFA effects, could be a possible advancement over current KD related-therapies. Further work defining the relationship of VEGF-A to VEGF-B in KD-related angiogenesis is suggested.
Uremic toxin indoxyl sulfate induces trained immunityviathe AhR-dependent arachidonic acid pathway in end-stage renal disease (ESRD)
Authors: Kim Hee Young , Kang Yeon Jun , Kim Dong Hyun , Jang Jiyeon , Lee Su Jeong , Kim Gwanghun , Koh Hee Byung , Ko Ye Eun , Shin Hyun Mu , Lee Hajeong , Yoo Tae-Hyun , Lee Won-Woo 
Published: August 2022

AbstractTrained immunity is the long-term functional reprogramming of innate immune cells, which results in altered responses toward a secondary challenge. Despite indoxyl sulfate (IS) being a potent stimulus associated with chronic kidney disease (CKD)-related inflammation, its impact on trained immunity has not been explored. Here, we demonstrate that IS induces trained immunity in monocytesviaepigenetic and metabolic reprogramming, resulting in augmented cytokine production. Mechanistically, the aryl hydrocarbon receptor (AhR) contributes to IS-trained immunity by enhancing the expression of arachidonic acid (AA) metabolism-related genes such as Arachidonate 5-Lipoxygenase (ALOX5) and ALOX5 Activating Protein (ALOX5AP). Inhibition of AhR during IS training suppresses the induction of IS-trained immunity. Monocytes from end-stage renal disease (ESRD) patients have increased ALOX5 expression and after 6-day training, they exhibit enhanced TNF-α and IL-6 production to LPS. Furthermore, healthy control-derived monocytes trained with uremic sera from ESRD patients exhibit increased production of TNF-α and IL-6. Consistently, IS-trained mice and their splenic myeloid cells had increased production of TNF-α afterin vivoandex vivoLPS stimulation compared to that of control mice. These results provide insight into the role of IS in the induction of trained immunity, which is critical during inflammatory immune responses in CKD patients.
Spiking burstiness and working memory in the human medial temporal lobe
Authors: Cocina Francesco , Vitalis Andreas , Caflisch Amedeo 
Published: August 2022

AbstractPersistent activity has commonly been considered to be a hallmark of working memory (WM). Recent evidence indicates that neuronal discharges in the medial temporal lobe (MTL) are compatible with WM neural patterns observed in cortical areas. However, the characterization of this activity rarely consists of measurements other than firing rates of single neurons. Moreover, a varied repertoire of firing dynamics has been reported in the MTL regions, which motivate the more detailed examination of the relationships between WM processes and discharge patterns undertaken here. Specifically, we investigate at different resolution levels firing irregularities in electrode recordings from the hippocampus, amygdala, and the entorhinal cortex of epileptic patients during a WM task. We show that some types of (ir)regularities predict response times of the patients depending on the trial periods under consideration. Prominent burst activity at the population level is observed in the amygdala and entorhinal cortex during memory retrieval. In general, regular and bursty neurons contribute to the decoding of the memory load, yet they display important differences across the three anatomical areas. Our results suggest that non-random (non-Poisson) patterns are relevant for WM, which calls for the development and use of statistics complementary to mere spike counts.
Defining the separation landscape of topological domains for decoding consensus domain organization of 3D genome
Authors: Dang Dachang , Zhang Shao-Wu , Duan Ran , Zhang Shihua 
Published: August 2022

SummaryTopologically associating domains (TADs) have emerged as basic structural and functional units of genome organization, and have been determined by many computational methods from Hi-C contact maps. However, the TADs obtained by different methods vary greatly, which makes the accurate determination of TADs a challenging issue and hinders subsequent biological analyses about their organization and functions. Obvious inconsistencies among the TADs identified by different methods indeed make the statistical and biological properties of TADs overly depend on the method we chose rather than on the data. To this end, we employ the consensus structural information captured by these methods to define the TAD separation landscape for decoding consensus domain organization of the 3D genome. We demonstrate that the TAD separation landscape could be used to compare domain boundaries across multiple cell types for discovering conserved and divergent topological structures, decipher three types of boundary regions with diverse biological features, and identify Consensus Topological Associating Domains (ConsTADs). We illustrate that these analyses could deepen our understanding of the relationships between the topological domains and chromatin states, gene expression, and DNA replication timing. In short, we provide an alternative solution to deal with the serious inconsistencies of TADs obtained via different methods by defining the TAD separation landscape and ConsTAD.
Isotope effects on radical pair performance in cryptochrome: a new hypothesis for the evolution of animal migration
Authors: Galván Ismael , Hassasfar Abbas , Adams Betony , Petruccione Francesco 
Published: August 2022

AbstractMechanisms occurring at the atomic level are now known to drive processes essential for life, as revealed by quantum effects on biochemical reactions. Some macroscopic characteristics of organisms may thus show an atomic imprint, which may be transferred across organisms and affect their evolution. This possibility is considered here for the first time, with the aim of elucidating the appearance of an animal innovation with an unclear evolutionary origin: migratory behaviour. This trait may be mediated by a radical pair (RP) mechanism in the retinal flavoprotein cryptochrome, providing essential magnetic orientation for migration. Isotopes may affect the performance of quantum processes through their nuclear spin. Here, we consider a simple model and then apply the standard open quantum system approach to the spin dynamics of cryptochrome RP. We changed the spin quantum number (I) and g-factor of hydrogen and nitrogen isotopes to investigate their effect on RP’s yield and magnetic sensitivity. Strong differences arose between isotopes withI=1 andI=1/2 in their contribution to cryptochrome magnetic sensitivity, particularly regarding Earth’s magnetic field strengths (25-65 µT). In most cases, isotopic substitution improved RP’s magnetic sensitivity. Migratory behaviour may thus have been favoured in animals with certain isotopic compositions of cryptochrome.
Taking shortcuts: Great for travel, but not for reproducible methods sections
Authors: Standvoss Kai , Kazezian Vartan , Lewke Britta R. , Bastian Kathleen , Chidambaram Shambhavi , Arafat Subhi , Alsharif Ubai , Herrera-Melendez Ana , Knipper Anna-Delia , Seco Bruna M. S. , Soto Nina Nitzan , Rakitzis Orestis , Steinecker Isa , Till Philipp van Kronenberg , Zarebidaki Fereshteh , Weissgerber Tracey L. 
Published: August 2022

AbstractMethods sections are often missing critical details needed to reproduce an experiment. Methodological shortcut citations, in which authors cite previous papers instead of describing the method in detail, may contribute to this problem. This meta-research study used three approaches to systematically examine the use of shortcut citations in neuroscience, biology and psychiatry. First, we examined papers to determine why authors use citations in the methods section and to assess how often shortcut citations were used. Common reasons for using citations in the methods section included explaining how something was done by citing a previous resource that used the method (methodological shortcut citation), giving credit or specifying what was used (who or what citation), and providing context or a justification (why citation). Next, we reviewed 15 papers to determine what can happen when readers follow shortcut citations to find methodological details. While shortcut citations can be used effectively, problems encountered included difficulty identifying or accessing the cited materials, missing or insufficient descriptions of the cited method, and chains of shortcut citations. Third, we examined journal policies. Fewer than one quarter of journals had policies describing how authors should report methods that have been described previously or asking authors to explain modifications of previously described methods. We propose that methodological shortcut citations should meet three criteria; cited resources should describe a method very similar to the authors’ method, provide enough detail to allow others to implement the method, and be open access. We outline actions that authors and journals can take to use shortcut citations responsibly, while fostering a culture of open and reproducible methods reporting.
Loss of EED in the oocyte causes initial fetal growth restriction followed by placental hyperplasia and offspring overgrowth
Authors: Oberin Ruby , Petautschnig Sigrid , Tsai Tesha , Jarred Ellen G. , Qu Zhipeng , Youngson Neil A. , Bildsoe Heidi , Truong Thi T. , Fernando Dilini , van den Buuse Maarten , Gardner David K. , Sims Natalie A. , Adelson David L. , Western Patrick S. 
Published: August 2022

AbstractGermline epigenetic programming, including genomic imprinting, substantially influences offspring development. Polycomb Repressive Complex 2 (PRC2) plays an important role in Histone 3 Lysine 27 trimethylation (H3K27me3)-dependent imprinting, loss of which leads to placental hyperplasia in mammalian offspring generated by somatic cell nuclear transfer (SCNT). In this study, we show that offspring from mouse oocytes lacking the Polycomb protein Embryonic Ectoderm Development (EED) were initially growth restricted, characterised by low blastocyst cell counts and substantial mid-gestational developmental delay. This initial developmental delay was followed by striking late-gestational placental hyperplasia, fetal catch-up growth and extended gestational length that culminated in offspring overgrowth. This involved remodelling of the placenta, including expansion of fetal and maternal tissues and conspicuous expansion of the glycogen enriched cell population in the junctional zone that was associated with a delay in parturition. Despite this remodelling and offspring catchup growth, fetal/placental weight ratio and fetal blood glucose levels were low indicating low placental efficiency. Genome-wide analyses identified extensive transcriptional dysregulation in affected placentas, including a range of imprinted and non-imprinted genes and increased expression of the H3K27me3-imprinted geneSlc38a4,which regulates transport of essential amino acids in the placenta. Our data provide an explanation for apparently opposing observations of growth restriction and overgrowth of offspring derived fromEed-nulloocytes and demonstrate that PRC2-dependent programming in the oocyte regulates fetal and placental growth and developmental outcomes.
Exploring the adaptability and robustness of the central carbon metabolism of Mycoplasma pneumoniae
Authors: Zondervan Niels A. , Yus Eva , Sévin Daniel C. , Martinez Sira , Gallo Carolina , Schaap Peter J. , Lluch-Senar Maria , Serrano Luis , Martins dos Santos Vitor A. P. , Suarez-Diez Maria 
Published: August 2022

AbstractIn this study we explored the adaptability and robustness of glycolysis and pyruvate metabolism of Mycoplasma pneumoniae (MPN). We used a dual approach, we analysed metabolomics data collected for a large number of OE and KO mutants and perturbation samples. Furthermore, we trained a dynamic model of central carbon metabolism and tested the model’s capacity to predict these mutants and perturbation samples as well as identify key controlling factors in central carbon metabolism. Our analysis of metabolite data as well as our model analysis indicate MPN metabolism is inherently robust against perturbations due to its network structure. Two key control hubs of central carbon metabolism were identified.
WITCH-NG: Efficient and Accurate Alignment of Datasets with Sequence Length Heterogeneity
Authors: Liu Baqiao , Warnow Tandy 
Published: August 2022

AbstractMultiple sequence alignment (MSA) is a basic part of many bioinformatics pipelines, including in phylogeny estimation, prediction of structure for both RNAs and proteins, and metagenomic sequence analysis. Yet many sequence datasets exhibit substantial sequence length heterogeneity, both because of large insertions and deletions (indels) in the evolutionary history of the sequences and the inclusion of sequencing reads or incompletely assembled sequences in the input. A few methods have been developed that can be highly accurate in aligning datasets with sequence length heterogeneity, with UPP (Nguyen et al., 2015) one of the first methods to achieve good accuracy, and WITCH (Shen et al., Bioinformatics 2021) an improvement on UPP for accuracy, In this paper, we show how we can speed up WITCH. Our improvement includes replacing a critical step in WITCH (currently performed using a heuristic search) by a polynomial time exact algorithm using Smith-Waterman. Our new method, WITCH-NG (i.e., “next generation WITCH”, pronounced “witching”) achieves the same accuracy but is substantially faster. WITCH-NG is available in open source form at https://github.com/RuneBlaze/WITCH-NG.
Counting is Almost All You Need
Authors: Akerman Ofek , Isakov Haim , Levi Reut , Psevkin Vladimir , Louzoun Yoram 
Published: August 2022

AbstractThe immune memory repertoire encodes the history of present and past infections and immunological attributes of the individual. As such, multiple methods were proposed to use T-cell receptor (TCR) repertoires to detect disease history. We here show that the counting method outperforms all existing algorithms. We then show that the counting can be further improved using a novel attention model to weight the different TCRs. The attention model is based on the projection of TCRs using a Variational AutoEncoder (VAE). Both counting and attention algorithms predict better than any current algorithm whether the host had CMV and its HLA alleles. As an intermediate solution between the complex attention model and the very simple counting model, we propose a new Graph Convolutional Network approach that obtains the accuracy of the attention model and the simplicity of the counting model. The code for the models used in the paper are provided in:https://github.com/louzounlab/CountingIsAlmostAllYouNeed
Phosphorylation at Ser65 modulates ubiquitin conformational dynamics
Authors: Yovanno Remy A. , Yu Alvin , Wied Tyler J. , Lau Albert Y. 
Published: August 2022

SUMMARYPhosphorylation of ubiquitin at Ser65 increases the population of a rare C-terminally retracted (CR) conformation. Transition between the CR and the Major ubiquitin conformations is critical for promoting mitochondrial degradation. The mechanisms by which the Major and CR conformations of Ser65-phosphorylated (pSer65) ubiquitin interconvert, however, have not yet been revealed. Here, we perform all-atom molecular dynamics simulations using the string method with swarms of trajectories to calculate the lowest free-energy path between these two conformers. Our analysis reveals the existence of a Bent intermediate in which the C-terminal residues of the β5 strand shift to resemble the CR conformation, while pSer65 retains contacts resembling the Major conformation. This stable intermediate was reproduced in well-tempered metadynamics calculations, with the exception of a Gln2Ala mutant that disrupts contacts with pSer65. Lastly, dynamical network modelling reveals that the transition from the Major to CR conformations involves a decoupling of residues near pSer65 from the adjacent β1 strand.
A Shape Sensing Mechanism driven by Arp2/3 and cPLA2licenses Dendritic Cells for Migration to Lymph Nodes in Homeostasis
Authors: Alraies Zahraa , Rivera Claudia A. , Delgado Maria-Graciela , Sanséau Doriane , Maurin Mathieu , Amadio Roberto , Piperno Giulia Maria , Dunsmore Garett , Yatim Aline , Mariano Livia Lacerda , Sáez Pablo J. , Gratia Matthieu , Lamiable Olivier , Moreau Aurélie , Williart Alice , Albaud Benoit , Legoix Patricia , Nakano Hideki , Cook Donald N , Lawrence Toby , Manel Nicolas , Benvenuti Federica , Ginhoux Florent , Moreau Hélène D. , Nader Guilherme P.F. , Piel Matthieu , Lennon-Duménil Ana-Maria 
Published: August 2022

AbstractMotile cells such as immune and cancer cells experience large deformation events that result from the physical constraints they encounter while migrating within tissues or circulating between organs. It has become increasingly clear that these cells can survive and adapt to these changes in cell shape using dedicated shape sensing pathways. However, how shape sensing impacts their function and fate remains largely unknown. Here we identify a shape sensing mechanism that couples cell motility to expression of CCR7, the chemokine receptor that guides immune cells to lymph nodes. We found that this mechanism is controlled by the lipid metabolism enzyme cPLA2, requires an intact nuclear envelop and exhibits an exquisitely sensitive activation threshold tuned by ARP2/3 and its inhibitor Arpin. We further show that shape sensing through the ARP2/3-cPLA2axis controls Ikkβ-NFκB-dependent transcriptional reprogramming of dendritic cells, which instructs them to migrate to lymph nodes in an immunoregulatory state compatible with their homeostatic tolerogenic function. These results highlight that the cell shape changes experienced by motile cells evolving within the complex environment of tissues can dictate their behavior and fate.
Comparison and benchmark of long-read based structural variant detection strategies
Authors: Lin Jiadong , Jia Peng , Wang Songbo , Ye Kai 
Published: August 2022

AbstractBackgroundRecent advances in long-read callers and assembly methods have greatly facilitated structural variants (SV) detection via read-based and assembly-based detection strategies. However, the lack of comparison studies, especially for SVs at complex genomic regions, complicates the selection of proper detection strategy for ever-increasing demand of SV analysis.ResultsIn this study, we compared the two most widely-used strategies with six long-read datasets of HG002 genome and benchmarked them with well curated SVs at genomic regions of different complexity. First of all, our results suggest that SVs detected by assembly-based strategy are slightly affected by assemblers on HiFi datasets, especially for its breakpoint identity. Comparably, though read-based strategy is more versatile to different sequencing settings, aligners greatly affect SV breakpoints and type. Furthermore, our comparison reveals that 70% of the assembly-based calls are also detectable by read-based strategy and it even reaches 90% for SVs at high confident regions. While 60% of the assembly-based calls that are totally missed by read-based callers is largely due to the challenges of clustering ambiguous SV signature reads. Lastly, benchmarking with SVs at complex genomic regions, our results show that assembly-based approach outperforms read-based calling with at least 20X coverage, while read-based strategy could achieve 90% recall even with 5X coverage.ConclusionsTaken together, with sufficient sequencing coverage, assembly-based strategy is able to detect SVs more consistently than read-based strategy under different settings. However, read-based strategy could detect SVs at complex regions with high sensitivity and specificity but low coverage, thereby suggesting its great potential in clinical application.