bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanical transapical coupling of endometrial epithelial cells during implantation
Authors: Sakurai Jun , Kinoshita Noriyuki , Otani Tetsuhisa , Koyama Hiroshi , Furuse Mikio , Fujimori Toshihiko 
Published: December 2023

AbstractEpithelial cells lining the lumen of organs have an apical-basal polarity, and mechanical cell contacts are located in the lateral and basal regions. During early pregnancy in rodents, the luminal space of the uterus is closed, and opposing epithelial cells attach to each other at apical–apical surfaces. Here, we show that cells are mechanically coupled at the apical cell–cell contacts. The apical plasma membrane was intricately intertwined between opposing cells. Extracellular matrix and tight junction molecules were localized at apical contacts. Claudin inhibition resulted in impaired luminal closure, suggesting a functional requirement of claudins for the establishment of transapical coupling. The present results demonstrate a mechanical cell–cell interaction that occurs between apical–apical surfaces in addition to lateral and basal cell junctions.One Sentence SummariesTransapical coupling of epithelial cells mediated by extracellular matrix and tight junction molecules
Using twin-pairs to assess potential bias in polygenic prediction of externalising behaviours across development
Authors: Bright Joanna K. , Rayner Christopher , Freeman Ze , Zavos Helena M.S. , Ahmadzadeh Yasmin I. , Viding Essi , McAdams Tom A. 
Published: December 2023

AbstractPrediction from polygenic scores may be confounded sources of passive gene-environment correlation (rGE; e.g. population stratification, assortative mating, and environmentally mediated effects of parental genotype on child phenotype). Using genomic data from 10,000 twin pairs, we asked whether polygenic scores from the recent externalising genome-wide association study predicted conduct problems, ADHD symptomology and callous-unemotional traits, and whether these predictions are biased by rGE. We ran regression models including within-family and between-family polygenic scores, to separate the direct genetic influence on a trait from environmental influences that correlate with genes (indirect genetic effects). Findings suggested that this externalising polygenic score is a good index of direct genetic influence on conduct and ADHD-related symptoms across development, with minimal bias from rGE, although the polygenic score predicted less variance in CU traits. Post-hoc analyses showed some indirect genetic effects acting on a common factor indexing stability of conduct problems across time and contexts.
DBF4, not DRF1, is the crucial regulator of CDC7 kinase at replication forks
Authors: Göder Anja , Maric Chrystelle , Rainey Michael D. , Cazzaniga Chiara , Shamavu Daniel , Cadoret Jean-Charles , Santocanale Corrado 
Published: December 2023

SummaryIn eukaryotes, CDC7 kinase is crucial for DNA replication initiation and has been involved in fork processing and replication stress response. Human CDC7 requires the binding of either one of two regulatory subunits, DBF4 and DRF1, for its activity. However, it is unclear whether the two regulatory subunits target CDC7 to a specific set of substrates, thus having different biological functions, or if they act redundantly.Using genome editing technology, we generated an isogenic set of cell lines deficient in either one of the two CDC7-activating subunits: these cells are viable but present signs of genomic instability, indicating that both DBF4 and DRF1 can independently support CDC7 for bulk DNA replication. Nonetheless, DBF4-deficient cells show altered replication efficiency, including partial deficiency in MCM helicase phosphorylation and alterations in the replication timing of discrete genomic regions. Notably, we find that CDC7 function at replication forks is entirely dependent on DBF4 and not DRF1. Thus, DBF4 is the primary regulator of CDC7 activity, likely mediating most of its functions in unperturbed DNA replication and during replication fork processing upon replication interference.
IIHP: Intelligent Incident Hypertension Prediction in Obstructive Sleep Apnea
Authors: Halimi Milani Omid , Cetin Ahmet Enis , Prasad Bharati 
Published: December 2023

AbstractThe Obstructive sleep apnea (OSA) increases the risk of hypertension, mainly attributed to intermittent hypoxia and sleep fragmentation. Given the multifaceted pathogenesis of hypertension, accurately predicting incident hypertension in individuals with OSA has posed a considerable challenge. In this study, we leveraged Machine Learning (ML) techniques to develop a predictive model for incident hypertension up to five years after OSA diagnosis by polysomnography. We used data from the Sleep Heart Health Study (SHHS), which included 4,797 participants diagnosed with OSA. After excluding those with pre-existing hypertension and Apnea Hypopnea Index (AHI) values below 21 per hour, we had 671 participants with five-year follow-up data. We adopted two distinct methodologies. We first implemented adaptive convolution layers to extract features from the signals and combined them into a 2D array. The 2D array was further processed by a 2D pre-trained neural network to take advantage of transfer learning. Subsequently, we delved into feature extraction from full-length signals across various temporal frames, resulting in a 2D feature array. We studied the use of various 2D networks such as MobileNet, EfficientNet, and a family of RESNETs. The best algorithm achieved an average area under the curve of 72%. These results suggest a promising approach for predicting the risk of incident hypertension in individuals with OSA, providing tools for practice and public health initiatives.
Profile of tetralogy of Fallot at the cardiology clinic of Saint-Damien hospital from January 2019 to December 2021
Authors: Désir Naïka Paulemie , Isaac Julien Adonaï Aly , Alexandre Richcard , Fevry Joanne , Brice Taina , Noisette Alexandra 
Published: December 2023

AbstractObjectiveOur work aimed to study the epidemiological and clinical aspects of Tetralogy of Fallot (TF) in the cardiology unit of the Saint-Damien Nos Petits Frères et Sœurs hospital in Haiti.MethodologyThis is a retrospective study of patients aged 0 to 18 years with Tetralogy of Fallot confirmed by echocardiography. Data were entered using an elaborated form and analyzed with Epi Info software version 7.2.2.16 and Microsoft Excel 2013.ResultsFrom January 2019 to December 2021, we identified 102 patients aged 0 to 18 years with TF. A male predominance was noted with a sex ratio M/F of 1.55. The average age of discovery of our cohort was 3 years and 7 months [0-16 years; standard deviation: 9.9]. The clinical signs were dominated by a systolic murmur (91.18%) followed by cyanosis (39.22%) and dyspnea (33.33%). On echocardiography, the regular form (76.47%) associated with the severe stenosis (83.33%) was remarkable. 20.59% of patients were able to benefit from surgery and the mortality rate was 14.94%. Patients were presenting at an advanced stage where they mostly needed surgical treatment to survive.ConclusionThis study shows that the prevalence of TF is also high in developing countries. The heart murmur at the pulmonary focus and the cyanosis were more present on physical examination. Patients were presenting at an advanced stage where they mostly needed surgical treatment to survive. Preventive measures are needed to reduce the mortality rate.
PVT in patients presenting with post-acute sequelae of COVID-19
Authors: Chakrabarti Shinjon , Krishnan Kamini , Galioto Rachel 
Published: December 2023

ABSTRACTWe investigated performance validity tests (PVTs) in patients presenting with new onset cognitive complaints associated with post-acute sequelae of COVID-19 infection (PASC). Retrospective data were obtained from IRB-approved registries. All patients completed the Victoria Symptom Validity Test (VSVT) in conjunction with a neuropsychological evaluation. A sub-analysis included 7 other PVT measures. The PASC sample was compared to an analogous multiple sclerosis (MS) sample with known PVT failure rates. The PASC sample consisted of 177 patients (49.4 ± 11.2 years), educated (14.7 ± 2.3 years), predominantly female (81.4%), and white, non-Hispanic (85.3%) patients. Seven percent of the PASC sample scored below the established VSVT hard item cut-off, and of those with invalid VSVT over 50% failed 3 or more additional PVTs. In comparison to a MS sample, the PASC sample reported comparable psychological symptoms, but were significantly less likely to produce invalid VSVT scores and seek disability benefits. This study provides a profile of PVTs in patients presenting with PASC. The general infrequence of invalid responding in this PASC sample (7%) is noteworthy compared to an MS sample and highlights the role of additional factors in non-credible response such as elevated psychological symptoms or pursuit of disability.
Exploring the application of deep learning methods for polygenic risk score estimation
Authors: Squires Steven , Weedon Michael N. , Oram Richard A. 
Published: December 2023

AbstractBackgroundPolygenic risk scores (PRS) summarise genetic information into a single number with multiple clinical and research uses. Machine learning (ML) has revolutionised a diverse set of fields, however, the impact of ML on genomics in general, and PRSs in particular, has been less significant. We explore how ML can improve the generation of PRSs.MethodsWe train ML models on known PRSs using UK Biobank data. We explore whether the models can recreate human programmed PRSs, including using a single model to generate multiple PRSs, and the difficulty in using ML for PRS generation. We also investigate how ML can compensate for missing data and the constraints on performance.ResultsWe demonstrate almost perfect generation of PRSs, including when using one model to predict multiple scores, and with little loss of performance with reduced quantity of training data. For an example set of missing SNPs the MLP produces predictions that enable separation of cases from population samples with an area under the receiver operating characteristic curve of 0.847 (95% CI: 0.828-0.864) compared to 0.798 (95% CI: 0.779-0.818) for the PRS. We provide evidence that input information is the limiting factor of further improvement.ConclusionsML can accurately generate PRSs, including with one model for multiple PRSs. The models are transferable and have high longevity. With certain missing SNPs the ML models can statistically significantly improve on normal PRS generation. Models trained are probably at the edge of performance and further improvements likely require use of additional input data.Code is available athttps://github.com/stevensquires/
Gain efficiency with streamlined and automated data processing: Examples from high-throughput monoclonal antibody production
Authors: Kotowicz Malwina , Fengler Sven , Kurkowsky Birgit , Meyer-Berhorn Anja , Moretti Elisa , Blersch Josephine , Shumanska Magdalena , Schmidt Gisela , Kreye Jakob , van Hoof Scott , Sánchez-Sendín Elisa , Reincke S. Momsen , Krüger Lars , Prüss Harald , Denner Philip , Fava Eugenio , Stappert Dominik 
Published: December 2023

AbstractData management and sample tracking in complex biological workflows are essential steps to ensure necessary documentation and guarantee the reusability of data and metadata. Currently, these steps pose challenges related to correct annotation and labeling, error detection, and safeguarding the quality of documentation. With growing acquisition of biological data and the expanding automatization of laboratory workflows, manual processing of samples is no longer favorable, as it is time- and resource-consuming, is prone to biases and errors, and lacks scalability and standardization. Thus, managing heterogeneous biological data calls for efficient and tailored systems, especially in laboratories run by biologists with limited computational expertise. Here, we showcase how to meet these challenges with a modular pipeline for data processing, facilitating the complex production of monoclonal antibodies from single B-cells. We present best practices for development of data processing pipelines concerned with extensive acquisition of biological data that undergoes continuous manipulation and analysis. Moreover, we assess the versatility of proposed design principles through a proof-of-concept data processing pipeline for automated induced pluripotent stem cell culture and differentiation. We show that our approach streamlines data management operations, speeds up experimental cycles and leads to enhanced reproducibility. Finally, adhering to the presented guidelines will promote compliance with FAIR principles upon publishing.
Structural basis ofS-adenosylmethionine-dependent Allosteric Transition from Active to Inactive States in Methylenetetrahydrofolate Reductase
Authors: Yamada Kazuhiro , Mendoza Johnny , Koutmos Markos 
Published: December 2023

AbstractMethylenetetrahydrofolate reductase (MTHFR) is a pivotal flavoprotein connecting the folate and methionine methyl cycles, catalyzing the conversion of methylenetetrahydrofolate to methyltetrahydrofolate. Human MTHFR (hMTHFR) undergoes elaborate allosteric regulation involving protein phosphorylation and AdoMet-dependent inhibition, though other factors such as subunit orientation and FAD status remain understudied due to the lack of a functional structural model. Here, we report crystal structures ofChaetomium thermophilumMTHFR (cMTHFR) in both active (R) and inhibited (T) states. We reveal FAD occlusion by Tyr361 in the T-state, which prevents substrate interaction. Remarkably, the inhibited form ofcMTHFR accommodates two AdoMet molecules per subunit. In addition, we conducted a detailed investigation of the phosphorylation sites inhMTHFR, three of which are novel. Based on the structural framework provided by ourcMTHFR model, we propose a possible mechanism to explain the allosteric structural transition of MTHFR, including the impact of phosphorylation on AdoMet-dependent inhibition.
Imputation approaches and quality standards for single-cell epigenetic age predictions
Authors: Liu Zian , Samee Md Abul Hassan 
Published: December 2023

AbstractDNA methylation describes the addition of methyl groups, often between CpG dinucleotides. Single-cell bisulfite sequencing technologies allow the measurement of DNA methylation levels within individual cells. Epigenetic clocks are statistical models for computing biological age from DNA methylation levels, and have been used for detecting age variations in various disease contexts. However, there have been no attempts to apply epigenetic clocks to single-cell methylation data in humans. Thus, we questioned whether pre-built epigenetic clocks could be applied to single-cell methylation data; if so, how can we perform data quality control and imputation. We concluded that 1) linear regression-based epigenetic clocks can be applied to bisulfite-sequencing data, 2) data quality control can be used to reach the desired level of prediction accuracy, 3) first-principle imputation strategies could be used for missing data on selected CpG methylation sites, and 4) machine learning-based imputation tools could be used for accuracy-based age predictions. We built the first training-free, reference data-free framework for estimating epigenetic age in human single-cells, which would provide a foundation for future single-cell methylation-based age analyses.
Fructose-1-kinase has pleiotropic roles inEscherichia coli
Authors: Weeramange Chamitha , Menjivar Cindy , O’Neil Pierce T. , Qaidi Samir El , Harrison Kelly S. , Meinhardt Sarah , Bird Cole L. , Sreenivasan Shwetha , Hardwidge Philip R. , Fenton Aron W. , Hefty P. Scott , Bose Jeffrey L. , Swint-Kruse Liskin 
Published: December 2023

AbstractInEscherichia coli, the master transcription regulator Catabolite Repressor Activator (Cra) regulates >100 genes in central metabolism. Cra binding to DNA is allosterically regulated by binding to fructose-1-phosphate (F-1-P), but the only documented source of F-1-P is from the concurrent import and phosphorylation of exogenous fructose. Thus, many have proposed that fructose-1,6-bisphosphate (F-1,6-BP) is also a physiological regulatory ligand. However, the role of F-1,6-BP has been widely debated. Here, we report that theE. colienzyme fructose-1-kinase (FruK) can carry out its “reverse” reaction under physiological substrate concentrations to generate F-1-P from F-1,6-BP. We further show that FruK directly binds Cra with nanomolar affinity and forms higher order, heterocomplexes. Growth assays with a ΔfruKstrain andfruKcomplementation show that FruK has a broader role in metabolism than fructose catabolism. The ΔfruKstrain also alters biofilm formation. SincefruKitself is repressed by Cra, these newly-reported events add layers to the dynamic regulation ofE. colicentral metabolism that occur in response to changing nutrients. These findings might have wide-spread relevance to other γ-proteobacteria, which conserve both Cra and FruK.
RNA-guided RNA silencing by an Asgard archaeal Argonaute
Authors: Bastiaanssen Carolien , Ugarte Pilar Bobadilla , Kim Kijun , Feng Yanlei , Finocchio Giada , Anzelon Todd A. , Köstlbacher Stephan , Tamarit Daniel , Ettema Thijs J. G. , Jinek Martin , MacRae Ian J. , Joo Chirlmin , Swarts Daan C. , Wu Fabai 
Published: December 2023

AbstractEukaryotic Argonaute proteins achieve gene repression and defense against viruses and transposons by RNA-guided RNA silencing. By contrast, known prokaryotic Argonautes adopt single-stranded DNA as guides and/or targets, leaving the evolutionary origin of RNA-guided RNA silencing elusive. Here, we show an evolutionary expansion of Asgard archaeal Argonautes (asAgos), including the discovery of HrAgo1 from the Lokiarchaeon ‘CandidatusHarpocratesius repetitus’ that shares a common origin with eukaryotic PIWI proteins. HrAgo1 exhibits RNA-guided RNA cleavagein vitroand RNA silencing in human cells. The cryo-EM structure of HrAgo1 combined with quantitative single-molecule experiments reveals that HrAgo1 possesses hybrid structural features and target binding modes bridging those of the eukaryotic AGO and PIWI clades. Finally, genomic evidence suggests that eukaryotic Dicer-like processing of double-stranded RNA likely emerged as a mechanism of generating guide RNA for asAgos prior to eukaryogenesis. Our study provides new insights into the evolutionary origin and plasticity of Argonaute-based RNA silencing.
A proteolytic AAA+ machine poised to unfold a protein substrate
Authors: Ghanbarpour Alireza , Sauer Robert T. , Davis Joseph H. 
Published: December 2023

ABSTRACTAAA+ proteolytic machines unfold proteins prior to degradation. Cryo-EM of a ClpXP-substrate complex reveals a postulated but heretofore unseen intermediate in substrate unfolding/degradation. The natively folded substrate is drawn tightly against the ClpX channel by interactions between axial pore loops and the substrate degron tail, and by contacts with the native substrate that are, in part, enabled by movement of one ClpX subunit out of the typically observed hexameric spiral.
Clouds, oases for airborne microbes – Differential metagenomics/ metatranscriptomics analyses of cloudy and clear atmospheric situations
Authors: Péguilhan Raphaëlle , Rossi Florent , Joly Muriel , Nasr Engy , Batut Bérénice , Enault François , Ervens Barbara , Amato Pierre 
Published: December 2023

AbstractBacteria cells and fungal spores can aerosolize and remain suspended in the atmosphere for several days, exposed to water limitation, oxidation, and lack of nutrients. Using comparative metagenomics/metatranscriptomics, we show that clouds are associated with the activation of numerous metabolic functions in airborne microorganisms, including fungal spore germination. The whole phenomenon mirrors the rapid recovery of microbial activity in soils after rewetting by rain, known as the “Birch effect”. Insufficient nutrient resources in cloud droplets cause a famine that recycling cellular structures could alleviate. The recovery of metabolic activity by microorganisms in clouds could favor surface invasion upon deposition, but it may also compromise further survival upon cloud evaporation. In any case, clouds appear as floating biologically active aquatic systems.One-Sentence SummaryClouds activate metabolic processes in airborne microorganisms
Assessing adverse effects and unspecific effects of transcutaneous spinal direct current stimulation (tsDCS)
Authors: Zhao Hongyan , Horn Ulrike , Freund Melanie , Bujanow Anna , Gundlach Christopher , Hartwigsen Gesa , Eippert Falk 
Published: December 2023

AbstractBackgroundTranscutaneous spinal direct current stimulation (tsDCS) is a relatively recent method for non-invasively modulating neuronal activity in the human spinal cord. Despite its growing prominence, comprehensive studies addressing its potential adverse effects (AEs) and unspecific effects (UEs) are lacking.ObjectiveIn this study, we conducted a systematic investigation into the potential AEs and UEs of tsDCS in healthy volunteers.MethodsWe used a randomized double-blind within-participant design, employing anodal, cathodal and sham tsDCS of the thoracolumbar spinal cord. Our approach involved a newly-developed structured questionnaire (to assess subjectively-reported AEs) in combination with tsDCS-concurrent recording of skin conductance, cardiac and respiratory activity (to assess UEs in bodily state).ResultsThe most frequently participant-reported AEs were sensations of burning, tingling, and itching, although they were largely described as mild; skin redness (experimenter-reported) occurred even more frequently. Importantly, when comparing AEs between active and sham tsDCS via frequentist and Bayesian analysis approaches, the results were largely in favour of no difference between conditions (with the exception of skin redness). A similar picture emerged for most UE metrics, suggesting that tsDCS does not induce changes in bodily state, at least as measured by our autonomic nervous system metrics.ConclusionWe believe that the strategy employed here could serve as a starting point for a systematic AE and UE assessment in clinical populations, longitudinal designs and when stimulating different spinal sites. Taken together, our results contribute to assessing the tolerability, safety and specificity of tsDCS, in order to further the investigation of spinal cord function in health and disease.
Split GFP assay to show chloroplast targeting ofAgrobacteriumVirD2 protein
Authors: Matsuoka Aki , Ferranti Julia L. , Maliga Pal 
Published: December 2023

AbstractRegenerating fertileArabidopsis thalianaplants from tissue culture cells with transformed plastid genomes is difficult, because of somaclonal variation in tissue culture cells. For nuclear gene transformation, tissue culture limitations were overcome in Arabidopsis by direct transformation of the female gametes using the floral dip protocol and identification of transgenic events in the seed progeny. DuringAgrobacteriumtransformation the VirD2 protein guides the T-complex, consisting of single stranded transferred-DNA (T-DNA) coated with VirE2 proteins, to the plant nucleus. To enable floral dip transformation of the plastid DNA, we retargeted VirD2 to chloroplasts. We show plastid targeting of VirD2 in a split GFP assay, where VirD2-GFP11complements GFP1-10in chloroplasts. Floral dip transformation of plastids will avoid tissue culture altogether, making plastid transformation readily available for the research community.