bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of analytical variability in estimating EEG-based functional connectivity
Authors: Allouch Sahar , Kabbara Aya , Duprez Joan , Paban Véronique , Khalil Mohamad , Modolo Julien , Hassan Mahmoud 
Published: August 2023

AbstractThe significant degree of variability and flexibility in neuroimaging analysis approaches has recently raised concerns. When running any neuroimaging study, the researcher is faced with a large number of methodological choices, often made arbitrarily. This can produce substantial variability in the results, ultimately hindering research replicability, and thus, robust conclusions. Here, we addressed the analytical variability in the EEG source connectivity pipeline and its effects on outcomes consistency. Like most neuroimaging analyses, the EEG source connectivity analysis involves the processing of high-dimensional data and is characterized by a complex workflow that leads to high analytical variability. In this study, we focused on source functional connectivity variability induced by three key factors along the analysis pipeline: 1) number of EEG electrodes, 2) inverse solution algorithms, and 3) functional connectivity metrics. Outcomes variability was assessed in terms of group-level consistency, inter-, and intra-subjects similarity, using resting-state EEG data (n = 88). As expected, our results showed that different choices related to the number of electrodes, source reconstruction algorithm, and functional connectivity measure substantially affect group-level consistency, between-, and within-subjects similarity. We believe that the significant impact of such methodological variability represents a critical issue for neuroimaging studies that should be prioritized.HighlightsThe significant impact of methodological variability is a recognized critical priority issue for neuroimaging studies.Analytical variability related to the number of electrodes, source reconstruction algorithm, and functional connectivity measure is a prominent issue in the EEG source connectivity analysis.Group-level consistency, between-, and within-subjects similarity are substantially affected by analytical variability in the EEG source connectivity analysis.
A fluorescence-based sensor screen identifies MED12 as a potential microsatellite instability regulator in colon cancer
Authors: Neto João M. Fernandes , Venkatesan Subramanian , Dias Matheus , Lieftink Cor , Morris Ben , Bresser Kaspar , Vecchione Loredana , Evers Bastiaan , Scheeren Ferenc , Schumacher Ton , Beijersbergen Roderick L. , Bernards René 
Published: August 2023

AbstractInactivation of the DNA mismatch repair (MMR) system, due to (epi)genetic alterations of MMR genes, increases the frequency of mutations across the genome, creating a phenotype known as microsatellite instability (MSI). Cancers with this phenotype have been associated with a better prognosis for some time, but only since recently it has been recognised as a predictive biomarker of response to immunotherapy. Because MSI tumours accumulate more insertions and/or deletions in coding regions of the genome containing microsatellites, there is an increase in neoantigens resulting from reading frame shifts, which promotes immunogenicity. To investigate if additional genes exist that can cause an MSI phenotype, we developed a fluorescence-based sensor to identify genes whose inactivation increases the rate of frameshift mutations on microsatellite sequences in cancer cells. Using genome-scale CRISPR/Cas9 screens, we identifiedMED12as a potential new regulator of microsatellite instability. Consistent with this, we found thatMED12mutant colon cancers that lack mutations in the known MMR genes are more likely to be of the MSI phenotype.
“Important enough to show the world”: Using Authentic Research Opportunities and Micropublications to Build Students’ Science Identities
Authors: Rubenstein Lisa DaVia , Woodruff Kelsey A. , Taylor April M. , Olesen James B. , Smaldino Philip J. , Rubenstein Eric M. 
Published: August 2023

ABSTRACTPrimarily undergraduate institutions (PUIs) often struggle to provide authentic research opportunities that culminate in peer-reviewed publications due to “recipe-driven” lab courses and the comprehensive body of work necessary for traditional scientific publication. However, the advent of short-form, single-figure “micropublications” has created novel opportunities for early-career scientists to make and publish authentic scientific contributions on a scale and in a timespan compatible with their training periods. The purpose of this qualitative case study is to explore the benefits accrued by eight undergraduate and master’s students who participated in authentic, small-scale research projects and disseminated their work as coauthors of peer-reviewed micropublications at a PUI. In these interviews, students reported that through the process of conducting and publishing their research, they developed specific competencies: reading scientific literature, proposing experiments, and collecting/interpreting publication-worthy data. Further, they reported this process enabled them to identify as contributing members of the greater scientific community.
“Identifying and characterizing scene representations relevant for categorization behavior”
Authors: Singer Johannes J.D. , Karapetian Agnessa , Hebart Martin N. , Cichy Radoslaw M. 
Published: August 2023

1.AbstractScene recognition is a core sensory capacity that enables humans to adaptively interact with their environment. Despite substantial progress in the understanding of the neural representations underlying scene recognition, the relevance of these representations for behavior given varying task demands remains unknown. To address this, we aimed to identify behaviorally relevant scene representations, to characterize them in terms of their underlying visual features, and to reveal how they vary across different tasks. We recorded fMRI data while human participants viewed scenes and linked brain responses to behavior in three tasks acquired in separate sessions: manmade/natural categorization, basic-level categorization, and fixation color discrimination. We found correlations between categorization response times and scene-specific brain responses, quantified as the distance to a hyperplane derived from a multivariate classifier. Across tasks, these effects were found in largely distinct parts of the ventral visual stream. This suggests that different scene representations are relevant for behavior depending on the task. Next, using deep neural networks as a proxy for visual feature representations, we found that early/intermediate layers mediated the relationship between scene representations and behavior for both categorization tasks, indicating a contribution of low-/mid-level visual features to these representations. Finally, we observed opposite patterns of brain-behavior correlations in the manmade/natural and the fixation task, indicating interference of representations with behavior for task demands that do not align with the content of representations. Together, these results reveal the spatial extent, content, and task-dependence of the visual representations that mediate behavior in complex scenes.
Massively Parallel Reporter Assay Confirms Regulatory Potential of hQTLs and Reveals Important Variants in Lupus and Other Autoimmune Diseases
Authors: Fu Yao , Kelly Jennifer A. , Gopalakrishnan Jaanam , Pelikan Richard C. , Tessneer Kandice L. , Pasula Satish , Grundahl Kiely , Murphy David A. , Gaffney Patrick M. 
Published: August 2023

AbstractObjectiveTo systematically characterize the potential for histone post-translational modifications, i.e., histone quantitative trait loci (hQTLs), expression QTLs (eQTLs), and variants on systemic lupus erythematosus (SLE) and autoimmune (AI) disease risk haplotypes to modulate gene expression in an allele dependent manner.MethodsWe designed a massively parallel reporter assay (MPRA) containing ∼32K variants and transfected it into an Epstein-Barr virus transformed B cell line generated from an SLE case.ResultsOur study expands our understanding of hQTLs, illustrating that epigenetic QTLs are more likely to contribute to functional mechanisms than eQTLs and other variant types, and a large proportion of hQTLs overlap transcription start sites (TSS) of noncoding RNAs. In addition, we nominate 17 variants (including 11 novel) as putative causal variants for SLE and another 14 for various other AI diseases, prioritizing these variants for future functional studies primary and immortalized B cells.ConclusionWe uncover important insights into the mechanistic relationships between genotype, epigenetics, gene expression, and SLE and AI disease phenotypes.
Identification andin vitrocharacterization of UDP-GlcNAc-RNA cap-modifying and decapping enzymes
Authors: Weber Frederik , Motzkus Nikolas Alexander , Brandl Leona , Möhler Marvin , Jäschke Andres 
Published: August 2023

ABSTRACTIn recent years, several noncanonical RNA caps derived from cofactors and metabolites have been identified. Purine-containing RNA caps have been extensively studied, with multiple decapping enzymes identified and efficient capture and sequencing protocols developed for nicotinamide adenine dinucleotide (NAD)-RNA, which allowed for a stepwise elucidation of capping functions. Despite being identified as an abundant noncanonical RNA-cap, UDP-sugar-capped RNA remains poorly understood, which is partly due to its complexin vitropreparation. Here, we describe a scalable synthesis of sugar-capped uridine-guanosine dinucleotides from readily available protected building blocks and their enzymatic conversion into several cell wall precursor-capped dinucleotides. We employed these capped dinucleotides in T7 RNA polymerase-catalyzedin vitrotranscription reactions to efficiently generate RNAs capped with uridine diphosphateN-acetylglucosamine (UDP-GlcNAc), itsN-azidoacetyl derivative UDP-GlcNAz, and various cell wall precursors. We furthermore identified four enzymes capable of processing UDP-GlcNAc-capped RNAin vitro: MurA, MurB and MurC fromEscherichia colican sequentially modify the sugar-cap structure and were used to introduce a bioorthogonal, clickable moiety, and the human Nudix hydrolase Nudt5 was shown to efficiently decap UDP-GlcNAc-RNA. Our findings underscore the importance of efficient synthetic methods for capped model RNAs and provide useful enzymatic tools for the potential use in and development of UDP-GlcNAc capture and sequencing protocols.
Chromatin-associated cohesin turns over extensively and forms new cohesive linkages during meiotic prophase
Authors: Haseeb Muhammad A. , Weng Katherine A. , Bickel Sharon E. 
Published: August 2023

SUMMARYIn dividing cells, accurate chromosome segregation depends on sister chromatid cohesion, protein linkages that are established during DNA replication. Faithful chromosome segregation in oocytes requires that cohesion, first established in S phase, remain intact for days to decades, depending on the organism. Premature loss of meiotic cohesion in oocytes leads to the production of aneuploid gametes and contributes to the increased incidence of meiotic segregation errors as women age (maternal age effect). The prevailing model is that cohesive linkages do not turn over in mammalian oocytes. However, we have previously reported that cohesion-related defects arise in Drosophila oocytes when individual cohesin subunits or cohesin regulators are knocked down after meiotic S phase. Here we use two strategies to express a tagged cohesin subunit exclusively during mid-prophase in Drosophila oocytes and demonstrate that newly expressed cohesin is used to formde novolinkages after meiotic S phase. Moreover, nearly complete turnover of chromosome-associated cohesin occurs during meiotic prophase, with faster replacement on the arms than at the centromeres. Unlike S-phase cohesion establishment, the formation of new cohesive linkages during meiotic prophase does not require acetylation of conserved lysines within the Smc3 head. Our findings indicate that maintenance of cohesion between S phase and chromosome segregation in Drosophila oocytes requires an active cohesion rejuvenation program that generates new cohesive linkages during meiotic prophase.
Thrombospondin-1 promotes fibro-adipogenic stromal expansion and contractile dysfunction of the diaphragm in obesity
Authors: Buras Eric D. , Woo Moon-Sook , Verma Romil Kaul , Kondisetti Sri Harshita , Davis Carol S. , Claflin Dennis R. , Baran Kimber Converso , Michele Daniel E. , Brooks Susan V. , Chun Tae-Hwa 
Published: August 2023

ABSTRACTPulmonary disorders impact 40-80% of individuals with obesity. Respiratory muscle dysfunction is linked to these conditions; however, its pathophysiology remains largely undefined. Mice subjected to diet-induced obesity (DIO) develop diaphragmatic weakness. Increased intra-diaphragmatic adiposity and extracellular matrix (ECM) content correlate with reductions in contractile force. Thrombospondin-1 (THBS1) is an obesity-associated matricellular protein linked with muscular damage in genetic myopathies. THBS1 induces proliferation of fibro-adipogenic progenitors (FAPs)—mesenchymal cells that differentiate into adipocytes and fibroblasts. We hypothesized that THBS1 drives FAP-mediated diaphragm remodeling and contractile dysfunction in DIO. We tested this by comparing effects of dietary challenge on diaphragms of wild-type (WT) andThbs1knockout (Thbs1-/-) mice. Bulk and single-cell transcriptomics demonstrated DIO-induced stromal expansion in WT diaphragms. Diaphragm FAPs displayed upregulation of ECM and TGFβ-related expression signatures, and augmentation of aThy1-expressing sub-population previously linked to type 2 diabetes. Despite similar weight gain,Thbs1-/-mice were protected from these transcriptomic changes, and from obesity-induced increases in diaphragm adiposity and ECM deposition. Unlike WT controls,Thbs1-/-diaphragms maintained normal contractile force and motion after DIO challenge. These findings establish THBS1 as a necessary mediator of diaphragm stromal remodeling and contractile dysfunction in overnutrition, and potential therapeutic target in obesity-associated respiratory dysfunction.
Co-Occurrence Network Analysis Reveals The Alterations Of The Skin Microbiome And Metabolome In Atopic Dermatitis Patients
Authors: Gomes Paulo Wender P. , Mannochio-Russo Helena , Mao Junhong , Zhao Haoqi Nina , Tipton Craig D. , Ancira Jacob , Dorrestein Pieter C. , Li Min 
Published: August 2023

AbstractSkin microbiome can be altered in patients with Atopic Dermatitis (AD). An understanding of the changes from healthy to atopic skin can help develop new targets for better treatments and identify specific microbial or molecular biomarkers. This study investigates the skin microbiome and metabolome of healthy subjects and lesion (ADL) and non-lesion (ADNL) of AD patients by 16S rRNA gene sequencing and mass spectrometry, respectively. Samples from AD patients showed alterations in the diversity and composition of the skin microbiome.Staphylococcusspecies, especiallyS. aureus, were significantly increased in the ADL group. Metabolomic profiles were also different between the groups. Dipeptide-derived are more abundant in ADL, which may be related to skin inflammation. Co-occurrence network analysis was applied to integrate the microbiome and metabolomics data and revealed higher co-occurrence of metabolites and bacteria in healthy and ADNL compared to ADL.S. aureusco-occurred with dipeptide-derived in ADL, while phytosphingosine-derived compounds showed co-occurrences with commensal bacteria,e.g. Paracoccussp.,Pseudomonassp.,Prevotella bivia, Lactobacillus iners, Anaerococcussp.,Micrococcussp.,Corynebacterium ureicelerivorans, Corynebacterium massiliense, Streptococcus thermophilus, andRoseomonas mucosa, in healthy and ADNL groups. Therefore, these findings provide valuable insights into how AD affects the human skin metabolome and microbiome.ImportanceThis study provides valuable insight into changes in the skin microbiome and associated metabolomic profiles. It also identifies new therapeutic targets that may be useful for developing personalized treatments for individuals with atopic dermatitis based on their unique skin microbiome and metabolic profiles.
Pneumatic Nano-Sieve for CRISPR-based Detection of Drug-resistant Bacteria
Authors: Peng Ruonan , Chen Xinye , Xu Fengjun , Hailstone Richard , Men Yujie , Du Ke 
Published: August 2023

AbstractThe increasing prevalence of antibiotic-resistant bacterial infections, particularly methicillin-resistant Staphylococcus aureus (MRSA), presents a significant public health concern. Timely detection of MRSA is crucial to enable prompt medical intervention, limit its spread, and reduce antimicrobial resistance. Here, we introduce a miniaturized nano-sieve device featuring a pneumatically-regulated chamber for highly efficient MRSA purification from human plasma samples. By using packed magnetic beads as a filter and leveraging the deformability of the nano-sieve channel, we achieve an on-chip concentration factor of 15 for MRSA. We integrated this device with recombinase polymerase amplification (RPA) and clustered regularly interspaced short palindromic repeats (CRISPR)-Cas detection system, resulting in an on-chip limit of detection (LOD) of approximately 100 CFU/mL. This developed approach provides a rapid, precise, and centrifuge-free solution suitable for point-of-care diagnostics, with the potential to significantly improve patient outcomes in resource-limited medical conditions.
Perturbation of the insomniaWDR90GWAS locus pinpoints rs3752495 as a causal variant influencing distal expression of neighboring gene,PIG-Q
Authors: Sonti Shilpa , Littleton Sheridan H. , Pahl Matthew C. , Zimmerman Amber J. , Chesi Alessandra , Palermo Justin , Lasconi Chiara , Brown Elizabeth B. , Pippin James A. , Wells Andrew D. , Doldur-Balli Fusun , Pack Allan I. , Gehrman Phillip R. , Keene Alex C. , Grant S.F.A. 
Published: August 2023

ABSTRACTAlthough genome wide association studies (GWAS) have been crucial for the identification of loci associated with sleep traits and disorders, the method itself does not directly uncover the underlying causal variants and corresponding effector genes. The overwhelming majority of such variants reside in non-coding regions and are therefore presumed to impact the activity ofcis-regulatory elements, such as enhancers. Our previously reported ‘variant-to-gene mapping’ effort in human induced pluripotent stem cell (iPSC)-derived neural progenitor cells (NPCs), combined with validation in bothDrosophilaand zebrafish, implicatedPIG-Qas a functionally relevant gene at the insomnia ‘WDR90’ locus. However, importantly that effort did not characterize the corresponding underlying causal variant at this GWAS signal. Specifically, our genome-wide ATAC-seq and high-resolution promoter-focused Capture C datasets generated in this cell setting brought our attention to a shortlist of three tightly neighboring single nucleotide polymorphisms (SNPs) in strong linkage disequilibrium in a candidate intronic enhancer region ofWDR90that contacted the openPIG-Qpromoter. The objective of this study was to investigate the influence of the proxy SNPs collectively and then individually onPIG-Qmodulation and to pinpoint the causal “regulatory” variant among the three SNPs. Starting at a gross level perturbation, deletion of the entire region harboring all three SNPs in human iPSC-derived neural progenitor cells via CRISPR-Cas9 editing and subsequent RNA sequencing revealed expression changes in specificPIG-Qtranscripts. Results from more refined individual luciferase reporter assays for each of the three SNPs in iPSCs revealed that the intronic region with the rs3752495 risk allele induced a ∼2.5-fold increase in luciferase expression (n=10). Importantly, rs3752495 also exhibited an allele specific effect, with the risk allele increasing the luciferase expression by ∼2-fold compared to the non-risk allele. In conclusion, our variant-to-function approach and subsequentin vitrovalidation implicates rs3752495 as a causal insomnia risk variant embedded at theWDR90-PIG-Qlocus.
Structural polymorphism of the nucleic acids in pentanucleotide repeats associated with CANVAS
Authors: Kudo Kenta , Hori Karin , Asamitsu Sefan , Maeda Kohei , Aida Yukari , Hokimoto Mei , Matsuo Kazuya , Yabuki Yasushi , Shioda Norifumi 
Published: August 2023

AbstractShort tandem repeats are highly unstable, depending on repeat length, and the expansion of the repeat length in the human genome is responsible for repeat expansion disorders. Pentanucleotide AAGGG and ACAGG repeat expansions in intron 2 of the gene encoding replication factor C subunit 1 (RFC1) cause cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS) and other phenotypes of late-onset cerebellar ataxia. Herein, we reveal the structural polymorphism of theRFC1repeat sequences associated with CANVASin vitro. Single-stranded AAGGG repeat DNA formed a hybrid-type G-quadruplex, whereas its RNA formed a parallel-type G-quadruplex with three layers. The RNA of the ACAGG repeat sequence formed double helical hairpin structures comprising C-G and G-C base pairs with A:A and GA:AG mismatched repeats. Furthermore, both pathogenic repeat RNAs formed more rigid structures than those of the non-pathogenic sequences. These findings provide novel insights into the structural polymorphism of theRFC1repeat sequences, which may be closely related to the disease mechanism of CANVAS.
Purine biosynthesis pathways are required for myogenesis inXenopus laevis
Authors: Duperray Maëlle , Henriet Elodie , Saint-Marc Christelle , Boué-Grabot Eric , Daignan-Fornier Bertrand , Massé Karine , Pinson Benoît 
Published: August 2023

AbstractPurines are required for fundamental biological processes and alterations in their metabolism lead to severe genetic diseases associated with developmental defects whose etiology remains unclear. Here, we studied the developmental requirements for purine metabolism using the amphibianXenopus laevisas a vertebrate model. We provide the first functional characterization of purine pathway-genes and show that these genes are mostly expressed in nervous and muscular embryonic tissues. Morphants were generated to decipher the functions of these genes, with a focus on the adenylosuccinate lyase (ADSL), an enzyme required for both salvage andde novopurine pathways.adsl.Lknock-down leads to severe reduction in the expression of the Myogenic Regulatory Factors (MRFs: Myod1, Myf5 and Myogenin), thus resulting in defects in somitogenesis and in the formation and/or migration of both craniofacial and hypaxial muscle progenitors. Similar alterations were observed upon reduced expression ofhprt1.Landppat, two genes specific to the salvage and thede novopathways, respectively. In conclusion, our data shows for the first time thatde novoand recycling purine pathways are essential for myogenesis and highlight new mechanisms in the regulation of MRFs gene expression.