bluuebunny/crossref_metadata_2025_split huggingface dataset:
HarbouringStarships: The accumulation of large Horizontal Gene Transfers in Domesticated and Pathogenic Fungi
Authors: O’Donnell Samuel , Rezende Gabriela , Vernadet Jean-Philippe , Snirc Alodie , Ropars Jeanne 
Published: July 2024

AbstractHuman-related environments, including food and clinical settings, present microorganisms with atypical and challenging conditions that necessitate adaptation. Several cases of novel horizontally acquired genetic material associated with adaptive traits have been recently described, contained within giant transposons namedStarships.While a handful ofStarshipshave been identified in domesticated species, their abundance has not yet been systematically explored in human-associated fungi. Here, we investigated whetherStarshipshave shaped the genomes of two major genera of fungi occurring in food and clinical environments,AspergillusandPenicillium.Using seven independent domestication events, we found in all cases that the domesticated strains or species exhibited significantly greaterStarshipcontent compared with close relatives from non-human-related environments. We found a similar pattern in clinical contexts. Our findings have clear implications for agriculture, human health and the food industry as we implicateStarshipsas a widely recurrent mechanism of gene transfer aiding the rapid adaptation of fungi to novel environments.
kcnb1loss-of-function in zebrafish causes neurodevelopmental and epileptic disorders associated with GABA dysregulation
Authors: Robichon Lauralee , Bar Claire , Marian Anca , Lehmann Lisa , Renault Solène , Kabashi Edor , Ciura Sorana , Nabbout Rima 
Published: July 2024

ABSTRACTKEY POINTSkcnb1 is expressed in distinct cell subtypes and various regions of the central nervous system in zebrafishBrain anatomy and neuronal circuits are not disrupted in thekcnb1loss-of-function zebrafish modelLoss ofkcnb1leads to altered behavior phenotype, light and sound-induced locomotor impairmentskcnb1knock-out zebrafish exhibit increased locomotor sensitivity to PTZ and elevated expression of epileptogenesis-related geneskcnb1-/-larvae show spontaneous and provoked epileptiform-like electrographic activity associated with disrupted GABA regulationObjectiveKCNB1encodes an α-subunit of the delayed-rectifier voltage-dependent potassium channel Kv2.1.De novopathogenic variants ofKCNB1have been linked to developmental and epileptic encephalopathies (DEE), diagnosed in early childhood and sharing limited treatment options. Loss-of-function (LOF) ofKCNB1with dominant negative effects has been proposed as the pathogenic mechanism in these disorders. Here, we aim to characterize a knock-out (KO) zebrafish line targetingkcnb1 (kcnb1+/-andkcnb1-/-) for investigating DEEs.MethodsThis study presents the phenotypic analysis of akcnb1knock-out zebrafish model, obtained by CRISPR/Cas9 mutagenesis. Through a combination of immunohistochemistry, behavioral assays, electrophysiological recordings, and neurotransmitter quantifications, we have characterized the expression, function, and impact of thiskcnb1LOF model at early stages of development.ResultsIn wild-type larval zebrafish, kcnb1 was found in various regions of the central nervous system and in diverse cell subtypes including neurons, oligodendrocytes and microglial cells. Bothkcnb1+/-andkcnb1-/-zebrafish displayed impaired swimming behavior and “epilepsy-like” features that persisted through embryonic and larval development, with variable severity. When exposed to the chemoconvulsant pentylenetetrazol (PTZ), both mutant models showed elevated locomotor activity. In addition, PTZ-exposedkcnb1-/-larvae exhibited higher bdnf mRNA expression and activated c-Fos positive neurons in the telencephalon. This same model presents spontaneous and provoked epileptiform-like electrographic activity associated with disrupted GABA regulation. In this KO model, neuronal circuit organization remained unaffected.SignificanceWe conclude thatkcnb1knock-out in zebrafish leads to early-onset phenotypic features reminiscent of DEEs, affecting neuronal functions and primarily inhibitory pathways in developing embryonic and larval brains. This study highlights the relevance of this model for investigating developmental neuronal signaling pathways inKCNB1-related DEEs.
Bacterial vaginosis-driven changes in cervicovaginal immunity that expand the immunological hypothesis for increased HIV susceptibility
Authors: MacLean Finn , Tsegaye Adino Tesfahun , Graham Jessica B. , Swarts Jessica L. , Vick Sarah C. , Potchen Nicole , Talavera Irene Cruz , Warrier Lakshmi , Dubrulle Julien , Schroeder Lena K. , Saito Ayumi , Thomas Katherine K. , Mack Matthias , Sabo Michelle C. , Chohan Bhavna H. , Ngure Kenneth , Mugo Nelly , Lingappa Jairam R. , Lund Jennifer M. ,   the Kinga Study Team
Published: July 2024

AbstractBacterial vaginosis (BV) is a dysbiosis of the vaginal microbiome that is prevalent among reproductive-age females worldwide. Adverse health outcomes associated with BV include an increased risk of sexually-acquired HIV, yet the immunological mechanisms underlying this association are not well understood. To investigate BV-driven changes to cervicovaginal tract (CVT) and circulating T cell phenotypes, participants with or without BV provided vaginal tract (VT) and ectocervical (CX) tissue biopsies and PBMC samples. High-parameter flow cytometry revealed an increased frequency of cervical conventional CD4+T cells (Tconv) expressing CCR5. However, we found no difference in number of CD3+CD4+CCR5+cells in the CX or VT of BV+ vs BV- individuals, suggesting that BV-driven increased HIV susceptibility may not be solely attributed to increased CVT HIV target cell abundance. Flow cytometry also revealed that individuals with BV have an increased frequency of dysfunctional CX and VT CD39+Tconv and CX tissue-resident CD69+CD103+Tconv, reported to be implicated in HIV acquisition risk and replication. Many soluble immune factor differences in the CVT further support that BV elicits diverse and complex CVT immune alterations. Our comprehensive analysis expands on potential immunological mechanisms that may underlie the adverse health outcomes associated with BV including increased HIV susceptibility.
Justify your disability! A simulated medical evaluation as a robust novel stress induction paradigm in chronic pain patients
Authors: Chiron Aimie , Fernandez Aurore , Schmidt Léa , Plaza-Wüthrich Sonia , Suter Marc R. , Leknes Siri , Berna Chantal 
Published: July 2024

AbstractMaladaptive stress responses may exacerbate chronic widespread pain (CWP) and deserve further investigations. Yet, existing stress induction paradigms lack relevance for individuals with this condition. Hence, we developed the Social Benefits Stress Test (SBST), adapted from the Trier Social Stress Test. Instead of a job interview, the main task consists in justifying the inability to work.Forty women with CWP in the context of hypermobile Ehlers-Danlos syndrome or hypermobility spectrum disorders were included. They underwent a 30-min baseline, the new stress task and a recovery period. The psychophysiological stress response was captured using self-reported stress ratings, salivary cortisol and α- amylase levels, as well as continuous physiological monitoring of heart rate variability (HRV) and electrodermal activity (EDA).Compared to baseline, the analysis revealed a significant and transient increase in stress ratings during the stress task, associated with a peak in salivary biomarkers concentrations. The HRV signal analysis showed a significant decrease in high frequency power (HF), and increases in heart rate, low frequency power (LF) and in LF/HF ratio. The EDA analysis revealed a significant increase in skin conductance level (SCL) tonic component and skin conductance response (SCR). Subjective stress ratings positively correlated with changes in salivary biomarkers, LF/HF ratio and EDA outcomes.The SBST induced a reproducible moderate stress response across subjective and physiological measures in a population of CWP patients, validating this task as a relevant experimental model of social stress in chronic pain. The SBST is a useful tool to study the relationship between stress and chronic pain.PerspectiveThis manuscript presents the Social Benefits Stress Test (SBST) as a novel paradigm to assess stress reactivity in chronic widespread pain patients. By simulating the challenge of justifying work incapacity, it elicits a reproducible stress response, supporting its use as a model to study stress-pain interactions and evaluate therapeutic interventions.
Phosphorylation-Dependent Activation of the bHLH Transcription Factor ICE1/SCRM Promotes Polarization of the Arabidopsis Zygote
Authors: Chen Houming , Xiong Feng , Bischoff Torren , Wang Kai , Miao Yingjing , Slane Daniel , Schwab Rebecca , Laux Thomas , Bayer Martin 
Published: July 2024

SummaryAsymmetric cell divisions are a key mechanism for breaking symmetry and orchestrating different cell identities in multicellular organisms. InArabidopsis thaliana, as in most flowering plants, the first zygotic cell division is asymmetric, giving rise to the embryo proper and an extraembryonic suspensor.Zygotic polarization and differential cell identities in the daughter cells are controlled by the ERECTA-YODA pathway, a prototype receptor kinase-MAP kinase signaling pathway. This pathway also controls asymmetric cell divisions in the epidermis during stomatal development. In this context, the bHLH transcription factor ICE1/SCRM is a direct target of MPK3/6, and phosphorylation negatively controls SCRM activity by targeting the protein for proteasomal degradation. This raises the question if this regulatory module is also involved in the asymmetric division of the zygote.Our results show that SCRM has a critical function in zygote polarization and acts in parallel with the known MPK3/6 target WRKY2 in activating the homeobox transcription factor geneWOX8. Our work further demonstrates that SCRM activity in the early embryo is positively controlled by MPK3/6-mediated phosphorylation. Therefore, the mode of MAP kinase regulation of the same target protein fundamentally differs between the embryo and the epidermis, shedding light on cell type-specific, differential gene regulation by common signaling pathways.
Dynamic Plk1 recruitment to the inner centromere
Authors: Norman Roshan X , Lera Robert F , Mattix Anuoluwapo A , Shen Zhouyuan , Carlsen Caleb L , Burkard Mark E 
Published: July 2024

AbstractMitosis is carefully orchestrated by reversible phosphorylation events. Polo-like kinase 1 (Plk1) regulates multiple functions across the kinetochore during mitotic progression. Recently, Bub1 (outer kinetochore) and CENP-U (inner kinetochore) were described as two major sites of Plk1 recruitment to the kinetochore. Here, we report an additional dynamic site of Plk1 recruitment to the inner centromere. Inner centromere docking occurs during late prometaphase and metaphase, exhibiting transient residency at multiple chromosomes. Chromosomes with inner centromere-localized Plk1 have end-on attached microtubules, diminished Spindle Assembly Checkpoint (SAC) components, and low Shugoshin 1 (Sgo1) levels at the inner centromere. Mechanistically, recruitment is driven by Cdk1 activity and requires Plk1’s Polo-Box Domain (PBD). Moreover, inhibition of Bub1 or Protein Phosphatase 2A (PP2A) increases Plk1 recruitment and residency at the inner centromere. Collectively, our data identify a novel pathway for Plk1 recruitment to the inner centromere that is dynamically regulated by counteracting activities of Cdk1 and Bub1/PP2A.
TheStaphylococcus aureussmall non-coding RNA IsrR regulates TCA cycle activity and virulence
Authors: Rios-Delgado Gustavo , McReynolds Aubrey K. G. , Pagella Emma A. , Norambuena Javiera , Briaud Paul , Zheng Vincent , Munneke Matthew J. , Kim Jisun , Racine Hugo , Carroll Ronan , Zelzion Ehud , Skaar Eric , Bose Jeffrey L. , Parker Dane , Lalaouna David , Boyd Jeffrey M. 
Published: July 2024

AbstractStaphylococcus aureushas evolved mechanisms to cope with low iron (Fe) availability in host tissues.S. aureususes the ferric uptake transcriptional regulator (Fur) to sense titers of cytosolic Fe. Upon Fe depletion, apo-Fur relieves transcriptional repression of genes utilized for Fe uptake. We demonstrate that anS. aureusΔfurmutant has decreased expression ofacnA, which codes for the Fe-dependent enzyme aconitase. DecreasedacnAexpression prevented the Δfurmutant from growing with amino acids as sole carbon and energy sources. Suppressor analysis determined that a mutation inisrR, which produces a regulatory RNA, permitted growth by decreasingisrRtranscription. The decreased AcnA activity of the Δfurmutant was partially relieved by an ΔisrRmutation. Directed mutation of bases predicted to facilitate the interaction between theacnAtranscript and IsrR, decreased the ability of IsrR to controlacnAexpressionin vivoand IsrR bound to theacnAtranscriptin vitro. IsrR also bound to the transcripts coding the alternate TCA cycle proteinssdhC,mqo,citZ, andcitM. Whole cell metal analyses suggest that IsrR promotes Fe uptake and increases intracellular Fe not ligated by macromolecules. Lastly, we determined that Fur and IsrR promote infection using murine skin and acute pneumonia models.Graphical Abstract
CPIExtract: A software package to collect and harmonize small molecule and protein interactions
Authors: Piras Andrea , Chenghao Shi , Sebek Michael , Ispirova Gordana , Menichetti Giulia 
Published: July 2024

AbstractSummaryThe binding interactions between small molecules and proteins are the basis of cellular functions. Yet, experimental data available regarding compound-protein interaction is not harmonized into a single entity but rather scattered across multiple institutions, each maintaining databases with different formats. Extracting information from these multiple sources remains challenging due to data heterogeneity. Here, we present CPIExtract (Compound-Protein Interaction Extract), a tool to interactively extract experimental binding interaction data from multiple databases, perform filtering, and harmonize the resulting information, thus providing a gain of compound-protein interaction data. When compared to a single source, DrugBank, we show that it can collect more than 10 times the amount of annotations. The end-user can apply custom filtering to the aggregated output data and save it in any generic tabular file suitable for further downstream tasks such as network medicine analyses for drug repurposing and cross-validation of deep learning models.AvailabilityCPIExtract is an open-source Python package under an MIT license. CPIExtract can be downloaded fromhttps://github.com/menicgiulia/CPIExtractandhttps://pypi.org/project/cpiextract. The package can run on any standard desktop computer or computing cluster.
Structure-based inference of eukaryotic complexity in Asgard archaea
Authors: Köstlbacher Stephan , van Hooff Jolien J. E. , Panagiotou Kassiani , Tamarit Daniel , De Anda Valerie , Appler Kathryn E. , Baker Brett J. , Ettema Thijs J. G. 
Published: July 2024

AbstractAsgard archaea played a key role in the origin of the eukaryotic cell. While previous studies found that Asgard genomes encode diverse eukaryotic signature proteins (ESPs), representing homologs of proteins that play important roles in the complex organization of eukaryotic cells, the cellular characteristics and complexity of the Asgard archaeal ancestor of eukaryotes remain unclear. Here, we usedde novoprotein structure modeling and sensitive sequence similarity detection algorithms within an expanded Asgard archaeal genomic dataset to build a structural catalogue of the Asgard archaeal pangenome and identify 908 new ‘isomorphic’ ESPs (iESPs), representing clusters of protein structures most similar to eukaryotic proteins and that likely underwent extensive sequence divergence. While most previously identified ESPs were involved in cellular processes and signaling, iESPs are enriched in information storage and processing functions, with several being potentially implicated in facilitating cellular complexity. By expanding the complement of eukaryotic proteins in Asgard archaea, this study indicates that the archaeal ancestor of eukaryotes was more complex than previously assumed.
Ketomimetic Nutrients Trigger a Dual Metabolic Defense in Breast Cancer Cells
Authors: Kamra Mohini , Chen Yuan-I , Delgado Paula C. , Seeley Erin , Seidlits Stephanie K. , Yeh Hsin-Chin , Brock Amy , Parekh Sapun H. 
Published: July 2024

ABSTRACTWhile the triggers for the metastatic transformation of breast cancer (BC) cells remain unknown, recent evidence suggests that intrinsic cellular metabolism could be a crucial driver of migratory disposition and chemoresistance. Aiming to decode the molecular mechanisms involved in BC cell metabolic maneuvering, we study how a ketomimetic (ketone body-rich, low glucose) medium affects Doxorubicin (DOX) susceptibility and invasive disposition of BC cells. We quantified glycocalyx sialylation and found an inverse correlation with DOX-induced cytotoxicity and DOX internalization. These measurements were coupled with single-cell metabolic imaging, bulk migration studies, along with transcriptomic and metabolomic analyses. Our findings revealed that a ketomimetic medium enhances chemoresistance and invasive disposition of BC cells via two main oncogenic pathways: hypersialylation and lipid synthesis. We propose that the crosstalk between these pathways, juxtaposed at the synthesis of the glycan precursor UDP-GlcNAc, furthers advancement of a metastatic phenotype in BC cells under ketomimetic conditions.
Tuning Ultrasensitivity in Genetic Logic Gates using Antisense RNA Feedback
Authors: Engelmann Nicolai , Molderings Maik , Koeppl Heinz 
Published: July 2024

AbstractThis work provides a study of a possible improvement of existing inverting genetic logic gates by introduction of a common sequestration reaction between their input and output chemical species. As a mechanism of study, we use antisense RNAs (asRNAs). The asRNAs are expressed with the existing messenger RNA (mRNA) of a logic gate in a single transcript and target mRNAs of adjacent gates, creating a feedback of the protein-mediated repression that implements the core function of the logic gates. The extended transcripts then share a common sequestration reaction mediated by the cellular host’s RNA metabolism. This sequestration consists of double-stranded RNA (dsRNA) formation by asRNA and adjacent mRNA and subsequent degradation by the host. Numerical and stochastic analysis suggests that the feedback increases the steepness of the gate’s transition region, reduces the leakage, and can potentially be used to adjust the transition location. To leverage these effects, we demonstrate how design parameters can be tuned to obtain desired dose-response curves and how arbitrary circuits can be assembled using the improved gates.
Natural field diagnosis and molecular confirmation of fungal and bacterial watermelon pathogens in Bangladesh: A case study from Natore and Sylhet district
Authors: Ferdous Raihan 
Published: July 2024

AbstractThe study investigated watermelon diseases in Sylhet and Natore Districts of Bangladesh, characterized by contrasting climatic conditions. Sylhet experiences lower temperatures and high rainfall, while Natore has higher temperatures and low rainfall. In these survey regions, 40 watermelon fields were selected, and 10 diseases were observed, including 4 fungal, 3 bacterial, 2 water mold, and 1 viral disease. The observed diseases were Anthracnose, Cercospora leaf spot, Fusarium wilt, Gummy stem blight, Downy mildew, Phytophthora fruit rot, Bacterial fruit blotch, Angular leaf spot, Yellow vine, and Watermelon mosaic disease. Molecular analysis was done in the Plant Pathology Lab at Sher-e-Bangla Agricultural University using the specific primers for fungal (ITS1/ITS4) and bacterial (27F/1492R) DNA regions and identified nine pathogen species, excluding the causal organism of the viral disease. The identified pathogens includedColletrotrichum orbiculare, Cercospora citrullina, Fusarium oxysporum, Stagonosporopsis cucurbitacearum, Pseudoperonospora cubensis, Phytophthora capsici, Acidovorax citrulli, Pseudomonas syringae,andSerratia marcescens. The sequencing of the identified pathogens revealed high homology (98.91-99.71%) with known sequences in the GenBank database. Phylogenetic analysis showed six clusters for fungal and water mold pathogen isolates and three for bacterial isolates where the percentages of replicate trees were 100% in all the cases. Among the identified diseases, the highest disease occurrence showed by Fusarium wilt (47.5%) following Gummy stem blight (41.5%) in the Sylhet region while Angular leaf spot (37.5%) followed Yellow vine (33%) in the Natore area. Fusarium wilt also showed high disease intensity showcasing its devastating impact on yield. The study highlights the influence of environmental conditions on disease prevalence and underscores the need for tailored management strategies. These findings provide a foundation for developing targeted disease management practices for sustainable watermelon cultivation in Bangladesh.
Knowledge, perception, and attitude toward premarital screening among university students in Kurdistan region- Iraq
Authors: Mahmood Kochr Ali , Sadraldeen Govand Saadadin , Othman Samir M. , Shabila Nazar P. , Saleh Abubakir M. , Ismail Kameran Hassan 
Published: July 2024

AbstractBackgroundPremarital screening programs are essential for identifying and providing counseling to couples at risk of transmitting genetic diseases or sexually transmitted infections. Despite their importance, university students’ awareness and knowledge of premarital screening programs remain inadequate. This study aimed to evaluate the knowledge, perceptions, and attitudes of university students in the Kurdistan Region of Iraq regarding premarital screening programs.MethodsA cross-sectional survey involving 960 students was conducted from December 2023 to February 2024. The survey assessed participants’ demographics, knowledge, perception, and attitudes toward PMSP using a structured questionnaire.ResultsFindings revealed that a significant portion of participants (39.4%) had poor knowledge of premarital screening programs, 35.9% had fair knowledge, and only 24.7% had good knowledge. Despite limited knowledge, there was strong support for premarital screening programs, with 83.1% agreeing on its importance and 78.8% recognizing the need for premarital awareness. Most participants (65.8%) believed premarital screening programs could reduce genetic diseases, and 65.6% thought it could lower sexually transmitted diseases’ prevalence. Cultural acceptance of marrying relatives was notable, with 59.7% disagreeing with the preference for not marrying relatives. Married participants showed significantly higher knowledge and attitude scores compared to single participants. Gender differences were observed, with males having higher knowledge scores. There were no significant differences in perception and attitude scores based on gender or residential area.ConclusionThe study underscores the need for enhanced educational campaigns to improve premarital screening programs awareness and positively influence attitudes, especially targeting cultural aspects like accepting relative marriages. Comprehensive education and fostering positive attitudes toward premarital screening programs are vital for their broader acceptance and implementation.