bluuebunny/crossref_metadata_2025_split huggingface dataset:
Individual patterns of functional connectivity in neonates as revealed by surface-based Bayesian modeling
Authors: Derman Diego , Pham Damon D. , Mejia Amanda F. , Ferradal Silvina L. 
Published: July 2023

ABSTRACTResting-state functional connectivity is a widely used approach to study the functional brain network organization during early brain development. However, the estimation of functional connectivity networks in individual infants has been rather elusive due to the unique challenges involved with functional magnetic resonance imaging (fMRI) data from young populations. Here, we use fMRI data from the developing Human Connectome Project (dHCP) database to characterize individual variability in a large cohort of term-born infants (N = 289) using a novel data-driven Bayesian framework. To enhance alignment across individuals, the analysis was conducted exclusively on the cortical surface, employing surface-based registration guided by age-matched neonatal atlases. Using 10 minutes of resting-state fMRI data, we successfully estimated subject-level maps for fourteen brain networks/subnetworks along with individual functional parcellation maps that revealed differences between subjects. We also found a significant relationship between age and mean connectivity strength in all brain regions, including previously unreported findings in higher-order networks. These results illustrate the advantages of surface-based methods and Bayesian statistical approaches in uncovering individual variability within very young populations.
SparrKULee: A Speech-evoked Auditory Response Repository of the KU Leuven, containing EEG of 85 participants
Authors: Accou Bernd , Bollens Lies , Gillis Marlies , Verheijen Wendy , Van hamme Hugo , Francart Tom 
Published: July 2023

ABSTRACTResearchers investigating the neural mechanisms underlying speech perception often employ electroencephalography (EEG) to record brain activity while participants listen to spoken language. The high temporal resolution of EEG enables the study of neural responses to fast and dynamic speech signals. Previous studies have successfully extracted speech characteristics from EEG data and, conversely, predicted EEG activity from speech features.Machine learning techniques are generally employed to construct encoding and decoding models, which necessitate a substantial amount of data. We present SparrKULee: A Speech-evoked Auditory Repository of EEG, measured at KU Leuven, comprising 64-channel EEG recordings from 85 young individuals with normal hearing, each of whom listened to 90-150 minutes of natural speech. This dataset is more extensive than any currently available dataset in terms of both the number of participants and the amount of data per participant. It is suitable for training larger machine learning models. We evaluate the dataset using linear and state-of-the-art non-linear models in a speech encoding/decoding and match/mismatch paradigm, providing benchmark scores for future research.
A Novel Milli-fluidic Liver Tissue Chip with Continuous Recirculation for Predictive Pharmacokinetics Applications
Authors: Priya Rajan Shiny Amala , Sherfey Jason , Ohri Shivam , Nichols Lauren , Smith J. Tyler , Parekh Paarth , Kadar Eugene P. , Clark Frances , George Billy T. , Gregory Lauren , Tess David , Gosset James R. , Liras Jennifer , Geishecker Emily , Obach R. Scott , Cirit Murat 
Published: July 2023

AbstractA crucial step in lead selection during drug development is accurate estimation and optimization of hepatic clearance usingin vitromethods. However, current methods are limited by factors such as lack of physiological relevance, short culture/incubation times that are not consistent with drug exposure patterns in patients, use of drug absorbing materials, and evaporation during long-term incubation. To address these technological needs, we developed a novel milli-fluidic human liver tissue chip (LTC) that was designed with continuous media recirculation and optimized for hepatic cultures using human primary hepatocytes. Here, we characterized the LTC using a series of physiologically relevant metrics and test compounds to demonstrate that we could accurately predict the PK of both low and high clearance compounds. The non-biological characterization indicated that the cyclic olefin copolymer (COC)-based LTC exhibited negligible evaporation and minimal non-specific binding of drugs of varying ionic states and lipophilicity. Biologically, the LTC exhibited functional and polarized hepatic culture with sustained metabolic CYP activity for at least 15 days. This long-term culture was then used for drug clearance studies for low and high-clearance compounds for at least 12 days and clearance was estimated for a range of compounds with high in vitro in vivo correlation (IVIVC). We also demonstrated that LTC can be induced by rifampicin, and the culture age had insignificant effect on depletion kinetic and predicted clearance value. Thus, we used advances in bioengineering to develop a novel purpose-built platform with high reproducibility and minimal variability to address unmet needs for PK applications.
Physical Chemistry of Drug Permeation through the Cell Membrane with Atomistic Detail
Authors: Paulikat Mirko , Piccini GiovanniMaria , Ippoliti Emiliano , Rossetti Giulia , Arnesano Fabio , Carloni Paolo 
Published: July 2023

AbstractWe provide a molecular-level description of the thermodynamics and mechanistic aspects of drug permeation through the cell membrane. As a case study, we considered the anti-malaria, FDA approved drug chloroquine. Molecular dynamics simulations of the molecule (in its neutral and protonated form) were performed in the presence of different lipid bilayers, with the aim of uncovering key aspects of the permeation process, a fundamental step for drug’s action. Free energy values obtained by well-tempered metadynamics simulations suggest that the neutral form is the only permeating protomer, consistent with experimental data. H-bond interactions of the drug with water molecules and membrane headgroups play a crucial role for permeation. The presence of the transmembrane potential, investigated here for the first time in a drug permeation study, does not qualitatively affect these conclusions.TOC Graphic
Learning high-dimensional reaction coordinates of fast-folding proteins using State Predictive information bottleneck and Bias Exchange Metadynamics
Authors: Pomarici Nancy D. , Mehdi Shams , Quoika Patrick K. , Lee Suemin , Loeffler Johannes R. , Liedl Klaus R. , Tiwary Pratyush , Fernández-Quintero Monica L. 
Published: July 2023

ABSTRACTBiological events occurring on long timescales, such as protein folding, remain hard to capture with conventional molecular dynamics (MD) simulation. To overcome these limitations, enhanced sampling techniques can be used to sample regions of the free energy landscape separated by high energy barriers, thereby allowing to observe these rare events. However, many of these techniques require a priori knowledge of the appropriate reaction coordinates (RCs) that describe the process of interest. In recent years, Artificial Intelligence (AI) models have emerged as promising approaches to accelerate rare event sampling. However, integration of these AI methods with MD for automated learning of improved RCs is not trivial, particularly when working with undersampled trajectories and highly complex systems. In this study, we employed the State Predictive Information Bottleneck (SPIB) neural network, coupled with bias exchange metadynamics simulations (BE-metaD), to investigate the unfolding process of two proteins, chignolin and villin. By utilizing the high-dimensional RCs learned from SPIB even with poor training data, BE-metaD simulations dramatically accelerate the sampling of the unfolding process for both proteins. In addition, we compare different RCs and find that the careful selection of RCs is crucial to substantially speed up the sampling of rare events. Thus, this approach, leveraging the power of AI and enhanced sampling techniques, holds great promise for advancing our understanding of complex biological processes occurring on long timescales.Abstract FigureTABLE OF CONTENT GRAPHIC
Enhancer plasticity in endometrial tumorigenesis demarcates non-coding somatic mutations and 3D-genome alterations boosting the oncogenic driver ESR1
Authors: Gregoricchio Sebastian , Kojic Aleksandar , Hoogstraat Marlous , Schuurman Karianne , Stelloo Suzan , Severson Tesa M. , O’Mara Tracy A. , Droog Marjolein , Singh Abhishek A. , Glubb Dylan M. , Wessels Lodewyk F.A. , Vermeulen Michiel , van Leeuwen Flora E. , Zwart Wilbert 
Published: July 2023

ABSTRACTThe incidence and mortality of Endometrial Cancer (EC) is on the rise. 85% of ECs depend on Estrogen Receptor alpha (ERα) for proliferation, but little is known about its transcriptional regulation in these tumors.We generated epigenomics, transcriptomics and Hi-C datastreams in healthy and tumor endometrial tissues, identifying robust ERα reprogramming and profound alterations in 3D genome organization that lead to a gain of tumor-specific enhancer activity during EC development. Integration with endometrial cancer risk single-nucleotide polymorphisms, as well as WGS data from primary tumors and metastatic samples revealed a striking enrichment of risk variants and non-coding somatic mutations at tumor-enriched ERα sites. Through machine learning-based predictions and interaction proteomics analyses, we identified an enhancer mutation which alters 3D genome conformation, impairing recruitment of the transcriptional repressor EHMT2/G9a/KMT1C, thereby alleviating transcriptional repression ofESR1in EC.In summary, we identified a complex genomic-epigenomic interplay in EC development and progression, altering 3D genome organization to enhance expression of the critical driver ERα.
The role of greater competitive ability in countering age disadvantages in larval competition inDrosophila melanogaster
Authors: Venkitachalam Srikant , Deep Auroni , Das Srijan , Joshi Amitabh 
Published: July 2023

AbstractBackgroundPopulations ofDrosophila melanogasteradapted to high larval densities evolve increased larval competitive ability compared to low density controls. However, traits contributing to greater competitive ability can differ across such populations, depending on the exact details of high-density conditions imposed. In the current study, we consider three sets ofD. melanogasterpopulations adapted to three different kinds of high-density scenarios. These population sets have evolved different degrees of increases in egg size and decreases in egg hatching time as correlates of increased larval competitive ability.QuestionWe asked two related questions:Do populations adapted to larval crowding counter an imposed initial age disadvantage in larval competition, better than their controls?Do differences in egg size and egg hatching time among crowding-adapted populations matter in competitive performance when suffering age disadvantage?Study systemWe used three sets of outbred laboratoryDrosophila melanogasterpopulations selected for larval crowding with different egg number, food volume and vial type combinations (named MCU, CCU and LCU). We also used one set of low-density ancestral control populations (named MB).MethodsWe implemented high density cultures with half the eggs from one of the study (focal) populations, and the other half from a common marked competitor population (Orange Eye: OE). We provided head start durations of 0, 3, 5, or 7 hours to the eggs of the common competitor. This imposed the respective age disadvantage to the larvae of the focal population. Pre-adult development time of survivors was the indicator of competitive performance used.ResultsAll crowding-adapted populations countered an initial age disadvantage better than the control populations. We did not see any differences among crowding adapted populations regarding their performance in countering the age disadvantage. The common competitors showed the best competitive performance against the populations with the greatest egg size and shortest hatching time.ConclusionsAdaptation to crowding leads to significantly better chances against age disadvantages in larval competition. Temporal head starts need not be of overwhelming advantage in larval competition against superior competitors inDrosophila. Among crowding adapted populations, evolving greater egg size and shorter hatching time does not seem to better offset the effects of age disadvantage to larvae. Differences in larval effectiveness and tolerance of the populations are likely to explain these results.
Pathogenic CANVAS (AAGGG)nrepeats stall DNA replication due to the formation of alternative DNA structures
Authors: Hisey Julia A. , Radchenko Elina A. , Ceschi Silvia , Rastokina Anastasia , Mandel Nicholas H. , McGinty Ryan J. , Matos-Rodrigues Gabriel , Hernandez Alfredo , Nussenzweig André , Mirkin Sergei M. 
Published: July 2023

ABSTRACTCANVAS is a recently characterized repeat expansion disease, most commonly caused by homozygous expansions of an intronic (A2G3)nrepeat in theRFC1gene. There are a multitude of repeat motifs found in the human population at this locus, some of which are pathogenic and others benign. In this study, we conducted structure-functional analyses of the main pathogenic (A2G3)nand the main nonpathogenic (A4G)nrepeats. We found that the pathogenic, but not the nonpathogenic, repeat presents a potent, orientation-dependent impediment to DNA polymerizationin vitro. The pattern of the polymerization blockage is consistent with triplex or quadruplex formation in the presence of magnesium or potassium ions, respectively. Chemical probing of both repeats in supercoiled DNA reveals triplex H-DNA formation by the pathogenic repeat. Consistently, bioinformatic analysis of the S1-END-seq data from human cell lines shows preferential H-DNA formation genome-wide by (A2G3)nmotifs over (A4G)nmotifsin vivo. Finally, the pathogenic, but not the non-pathogenic, repeat stalls replication fork progression in yeast and human cells. We hypothesize that CANVAS-causing (A2G3)nrepeat represents a challenge to genome stability by folding into alternative DNA structures that stall DNA replication.
First report of geophagy by chimpanzees in Comoé National Park, Ivory Coast
Authors: Lapuente Juan , Linsenmair K. Eduard 
Published: July 2023

ABSTRACTWest African chimpanzees (Pan troglodytes verus) are critically endangered, therefore knowing their ecological needs is necessary to implement proper conservation measures, especially in the face of climatic change. We report here the consumption of soil by wild chimpanzees living in Comoé National Park, Ivory Coast. We confirmed through camera-trap recording that chimpanzees of all ages and both sexes consumed it for several years at least in one community and more occasionally in a second one, aided by leaf-sponge tools. Our results suggest that these chimpanzees living in a savanna-forest mosaic may need minerals supplement, including sodium or/and clay to aid digestion, mainly during the dry season.
Genes associated with fitness and disease severity in the pan-genome of mastitis-associatedEscherichia coli
Authors: Olson Michael A. , Cullimore Caz , Hutchison Weston D. , Grimsrud Aleksander , Nobrega Diego , Buck Jeroen De , Barkema Herman W. , Wilson Eric , Pickett Brett E. , Erickson David L. 
Published: July 2023

AbstractBovine mastitis caused byEscherichia colimay manifest as subclinical through severe acute disease and can be transient or persistent in nature. Little is known about bacterial factors that impact clinical outcomes or allow some strains to outcompete others in the mammary gland (MG) environment. Mastitis-associatedE. coli(MAEC) may have distinctive characteristics which may contribute to the varied nature of the disease. In this study, we sequenced the genomes of 96 MAEC strains isolated from cattle with clinical mastitis (CM). We utilized clinical severity data to perform genome-wide association studies to identify accessory genes associated with strains isolated from mild or severe CM, or with high or low competitive fitness duringin vivocompetition assays. Genes associated with pathogenic or commensal strains isolated from bovine and avian sources were also identified. A type-2 secretion system (T2SS) and a chitinase (ChiA) exported by this system were strongly associated with pathogenic isolates compared with commensal strains. Strains carrying these genes also had higher competitive fitness during experimental intramammary infections. Deletion ofchiAfrom MAEC isolates decreased their adherence to cultured bovine mammary epithelial cells, suggesting that the increased fitness associated with strains possessing this gene may be due to better attachment in the MG.ImportanceBovine mastitis caused by MAEC compromises animal health and inflicts substantial product losses in dairy farming. Given their high levels of intraspecies genetic variability, virulence factors of commonly used MAEC model strains may not be relevant to all members of this group. Here we analyzed clinical data as well as fitness (quantified in a mouse MG model) of diverse MAEC isolates to identify accessory genes that contribute to infection. We demonstrated a novel role for chitinase in promoting attachment to mammary epithelial cells. Reverse genetic approaches can be applied to the collection of strains and their complete genome sequences that we have presented here. Overall, these results provide a much richer understanding of MAEC and suggest bacterial processes that may underlie the clinical diversity associated with mastitis and their adaptation to this unique environment.
Genome assembly reconstruction of the Japanese honey bee,Apis cerana japonica(Hymenoptera: Apidae), using homology-based assembly and nanopore long-reads
Authors: Masuoka Yudai , Jouraku Akiya , Kuwazaki Seigo , Yoshiyama Mikio , Horigane-Ogihara Mari , Maeda Taro , Suzuki Yutaka , Bono Hidemasa , Kimura Kiyoshi , Yokoi Kakeru 
Published: July 2023

AbstractHoney bees are important for agriculture (e.g., pollination and honey production). Additionally, honey bees are an important insect model species, especially as model social insects. The Japanese honey bee,Apis cerana japonica(a subspecies of the Asian honey bee,Apis cerana), is a Japanese domestic honey bee, which has several subspecies-specific traits. We previously constructed the draft genome sequence data ofA. cerana japonica, but it needed to be improved considering the use of the genome sequence data for genome structural analysis and repetitive region analysis, as well as the availability of chromosome-level genome data ofA. melliferaandA. cerana. In this study, we constructed the improvedA. cerana japonicagenome data and new gene set data with functional annotations. The constructed genome data, including 16 pseudochromosomes, was found to be highly contiguous and complete, and the gene set data covered most of the core genes in the BUSCO database. Thus, the constructed genome and gene set data have become more suitable as the reference data ofA. cerana japonica.
The Feather Epithelium Contributes to the Dissemination and Ecology of clade 2.3.4.4b H5 High Pathogenicity Avian Influenza Virus in Ducks
Authors: Gaide Nicolas , Filaire Fabien , Bertran Kateri , Crispo Manuela , Dirat Malorie , Secula Aurélie , Foret-Lucas Charlotte , Payré Bruno , Perlas Albert , Cantero Guillermo , Majó Natàlia , Soubies Sébastien , Guérin Jean-Luc 
Published: July 2023

AbstractImmature feathers are known replication sites for high pathogenicity avian influenza viruses (HPAIVs) in poultry. However, it is unclear whether feathers play an active role in viral transmission. This study aims to investigate the contribution of the feather epithelium to the dissemination of clade 2.3.4.4b goose/Guangdong/1996 lineage H5 HPAIVs in the environment, based on natural and experimental infections of domestic ducks. During the 2016-22 outbreaks, H5 HPAIVs exhibited persistent and marked feather epitheliotropism in naturally infected commercial ducks. Infection of feathers resulted in epithelial necrosis, disruption, and the production and release of infectious virions. Viral and feather antigens colocalized in dust samples obtained from poultry barns housing naturally infected birds. In summary, the feather epithelium contributes to viral replication, and it is a likely source of environmental infectious material. This underestimated excretion route could greatly impact the ecology of HPAIVs, facilitating airborne and preening-related infections within a flock, and promoting prolonged viral infectivity and long-distance viral transmission between poultry farms.Abstract Figure
Bile-induced biofilm formation inBacteroides thetaiotaomicronrequires magnesium efflux by an RND pump
Authors: Lopes Anne-Aurélie , Deschamps Julien , Georgeault Sonia , Cokelaer Thomas , Briandet Romain , Ghigo Jean-Marc 
Published: July 2023

ABSTRACTBacteroides thetaiotaomicronis a prominent member of the human gut microbiota contributing to nutrient exchange, gut function, and maturation of the host’s immune system. This obligate anaerobe symbiont can adopt a biofilm lifestyle and it was recently shown thatB. thetaiotaomicronbiofilm formation is promoted by the presence of bile, a process also requiring aB. thetaiotaomicronextracellular DNase, which is not, however, regulated by bile. Here we showed that bile induces the expression of several Resistance-Nodulation-Division (RND) efflux pumps and that inhibiting their activity with a global competitive efflux inhibitor impaired bile-dependent biofilm formation. We then showed that, among the bile-induced RND-efflux pumps, only the tripartite BT3337-BT3338-BT3339 pump, re-named BipABC (for Bile Induced Pump A (BT3337), B (BT3338) and C (BT3339), is required for biofilm formation. We demonstrated that BipABC is involved in the efflux of magnesium to the biofilm extracellular matrix, which leads to a decrease of eDNA concentration. The release of magnesium in the biofilm matrix also impacts biofilm structure, potentially by modifying the electrostatic repulsion forces within the matrix, reducing interbacterial distance and allowing bacteria to interact more closely and form denser biofilms. Our study therefore identifies a new molecular determinant ofB. thetaiotaomicronbiofilm formation in response to bile salts and provides a better understanding on how an intestinal chemical cue regulates biofilm formation in a major gut symbiont.IMPORTANCEBacteroides thetaiotaomicronis a prominent member of the human gut microbiota able to degrade dietary and host polysaccharides, altogether contributing to nutrient exchange, gut function, and maturation of the host’s immune system. This obligate anaerobe symbiont can adopt a biofilm community lifestyle, providing protection against environmental factors that might, in turn, protect the host from dysbiosis and dysbiosis-related diseases. It was recently shown thatB. thetaiotaomicronexposure to intestinal bile promotes biofilm formation. Here we reveal that a specificB. thetaiotaomicronmembrane efflux pump is induced in response to bile, leading to the release of magnesium ions, potentially reducing electrostatic repulsion forces between components of the biofilm matrix. This leads to a reduction of interbacterial distance and strengthens the biofilm structure. Our study therefore provides a better understanding of how bile promotes biofilm formation in a major gut symbiont, potentially promoting microbiota resilience to stress and dysbiosis events.