bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predictors of blood pressure control and antihypertensive drug adherence among hypertensive patients: Hospital-based cross-sectional study
Authors: Elias Tamrat P. , Minyilshewa Asteray T. , Tekle Mengesha A. , Gebreamlak Tsegaye W. , Adde Binyam L. 
Published: January 2024

AbstractBackgroundHypertension or elevated blood pressure is a serious medical condition that significantly increases the risk of diseases of the heart, brain, kidneys, and other organs. Antihypertensive drug adherence is a key to controlling blood pressure.ObjectiveTo assess factors associated with antihypertensive drug adherence and blood pressurecontrol among hypertensive patients in Selected Public Hospitals under Addis Ababa City Administration.MethodA hospital-based cross-sectional study was conducted among hypertensive patients on follow-up in randomly selected Public Hospitals under the Addis Ababa City Administration from May 1, 2022, to August 31, 2022. The study population was 393 and patients who fulfilled the eligibility criteria were selected by systematic random sampling and the first participant was selected randomly. Data collection was conducted by reviewing the patient’s electronic medical records and by interviewing patients with a structured questionnaire. Data was entered into Epi-Info 7.2.1 and exported to SPSS version 25 software for analysis. Logistic regression analysis was done to see the association between the dependent and independent variables.ResultThe rate of antihypertensive drug adherence and blood pressure control was 72.5 % and 23.4% respectively. Participants with uncontrolled blood pressure were found to be 41.7% less adherent than those with controlled blood pressure (AOR= 0.59; 95% CI, 0.36-0.97). Non-adherence to dietary restriction (AOR, 3.31; 95% CI, 1.84–5.96) and chronic kidney disease (AOR=3.85; 95% CI, 1.41-10.52) are associated with good adherence, whereas using single antihypertensive drug (AOR=0.53; 95% CI, 0.30-0.94), and non-adherence to moderate physical exercise (AOR=0.30; 95% CI, 0.20-0.65) were associated with poor adherence to antihypertensive medications. Male sex (AOR=1.95; 95% CI, 1.04–3.28) and blood pressure measurement at home (AOR=0.59; 95% CI,0.36– 0.99) were independent predictors of controlled blood pressure. Drinking alcohol (AOR=1.92; 95% CI, 1.05-3.49) is inversely associated with blood pressure control.ConclusionDespite good adherence to antihypertensive medications, blood pressure control was low. This signifies the importance of lifestyle measures beyond pharmacologic intervention.
Defining a small-molecule stimulator of the human Hsp70-disaggregase system with selectivity for DnaJB proteins
Authors: Chuang Edward , Cupo Ryan R. , Bevan Jeffrey R. , Rice Mikhaila L. , Mao Shuli , Gorenberg Erica L. , Mack Korrie L. , Huryn Donna M. , Wipf Peter , Brodsky Jeffrey L. , Shorter James 
Published: January 2024

AbstractHsp70, Hsp40, and Hsp110 form a human protein-disaggregase system that solubilizes and reactivates proteins trapped in aggregated states. However, this system fails to maintain proteostasis in fatal neurodegenerative diseases. Here, we potentiate the human Hsp70-disaggregase system pharmacologically. By scouring a collection of dihydropyrimidines, we disambiguate a small molecule that specifically stimulates the Hsp70-disaggregase system against disordered aggregates and α-synuclein fibrils. The newly identified lead compound stimulates the disaggregase activity of multiple active human Hsp70, Hsp40, Hsp110 chaperone sets, with selectivity for combinations that include DnaJB1 or DnaJB4 as the Hsp40. We find that the relative stoichiometry of Hsp70, Hsp40, and Hsp110 dictates disaggregase activity. Remarkably, our lead compound shifts the composition of active chaperone stoichiometries by preferentially activating combinations with lower DnaJB1 concentrations. Our findings unveil a small molecule that stimulates the Hsp70-disaggregase system, even at suboptimal chaperone stoichiometries, which could be developed for the treatment of neurodegenerative diseases.Graphical Abstract
RNA polymerase II-mediated rDNA transcription mediates rDNA copy number expansion in Drosophila
Authors: Watase George J. , Yamashita Yukiko M. 
Published: January 2024

AbstractRibosomal DNA (rDNA), which encodes ribosomal RNA, is an essential but unstable genomic element due to its tandemly repeated nature. rDNA’s repetitive nature causes spontaneous intrachromatid recombination, leading to copy number (CN) reduction, which must be counteracted by a mechanism that recovers CN to sustain cells’ viability. Akin to telomere maintenance, rDNA maintenance is particularly important in cell types that proliferate for an extended time period, most notably in the germline that passes the genome through generations. InDrosophila, the process of rDNA CN recovery, known as ‘rDNA magnification’, has been studied extensively. rDNA magnification is mediated by unequal sister chromatid exchange (USCE), which generates a sister chromatid that gains the rDNA CN by stealing copies from its sister. However, much remains elusive regarding how germ cells sense rDNA CN to decide when to initiate magnification, and how germ cells balance between the need to generate DNA double-strand breaks (DSBs) to trigger USCE vs. avoiding harmful DSBs. Recently, we identified an rDNA-binding Zinc-finger protein Indra as a factor required for rDNA magnification, however, the underlying mechanism of action remains unknown. Here we show that Indra is a negative regulator of rDNA magnification, balancing the need of rDNA magnification and repression of dangerous DSBs. Mechanistically, we show that Indra is a repressor of RNA polymerase II (Pol II)-dependent transcription of rDNA: Under low rDNA CN conditions, Indra protein amount is downregulated, leading to Pol II-mediated transcription of rDNA. This results in the expression of rDNA-specific retrotransposon, R2, which we have shown to facilitate rDNA magnification via generation of DBSs at rDNA. We propose that differential use of Pol I and Pol II plays a critical role in regulating rDNA CN expansion only when it is necessary.
Single-cell multiomics reveals the oscillatory dynamics of mRNA metabolism and chromatin accessibility during the cell cycle
Authors: Nariya Maulik K. , Santiago-Algarra David , Tassy Olivier , Cerciat Marie , Ye Tao , Riba Andrea , Molina Nacho 
Published: January 2024

AbstractThe cell cycle is a tightly regulated process that requires precise temporal expression of hundreds of cell cycledependent genes. However, the genome-wide dynamics of mRNA metabolism throughout the cell cycle remain uncharacterized. Here, we combined single-cell multiome sequencing, biophysical modeling, and deep learning to quantify rates of mRNA transcription, splicing, nuclear export, and degradation. Our approach revealed that both transcriptional and post-transcriptional processes exhibit distinct oscillatory waves at specific cell cycle phases, with post-transcriptional regulation playing a prominent role in shaping mRNA accumulation. We also observed dynamic changes in chromatin accessibility and transcription factor binding footprints, identifying key regulators underlying the oscillatory dynamics of mRNA. Taken together, our approach uncovered a high-resolution map of RNA metabolism dynamics and chromatin accessibility, offering new insights into the temporal control of gene expression in proliferating cells.HighlightsFourierCycle combines single-cell multiome sequencing, deep learning, and biophysical modeling to quantify gene-specific rates of mRNA metabolism during the cell cycleRates of mRNA transcription, nuclear export, and degradation show gene-specific oscillatory waves at distinct cell cycle phases.Post-transcriptional regulation, including mRNA degradation and nuclear export, plays a prominent role in shaping mRNA accumulation during the cell cycleDynamics of chromatin accessibility and transcription factor binding footprints uncover key regulators underlying the transcriptional control of gene expressionGraphical abstract
Structure of human DPPA3 bound to the UHRF1 PHD finger reveals its functional and structural differences from mouse DPPA3
Authors: Shiraishi Nao , Konuma Tsuyoshi , Chiba Yoshie , Hokazono Sayaka , Nakamura Nao , Islam Md Hadiul , Nakanishi Makoto , Nishiyama Atsuya , Arita Kyohei 
Published: January 2024

AbstractDNA methylation maintenance is essential for cell fate inheritance. In differentiated cells, this involves orchestrated actions of DNMT1 and UHRF1. In mice, the high-affinity binding of DPPA3 to the UHRF1 PHD finger regulates UHRF1 chromatin dissociation and cytosolic localization, which is required for oocyte maturation and early embryo development. However, the human DPPA3 ortholog functions during these stages remain unclear. Here, we report the structural basis for human DPPA3 binding to the UHRF1 PHD finger. The conserved human DPPA385VRT87motif binds to the acidic surface of UHRF1 PHD finger, whereas mouse DPPA3 binding additionally utilizes two unique α-helices. The binding affinity of human DPPA3 for the UHRF1 PHD finger was weaker than that of mouse DPPA3. Consequently, human DPPA3, unlike mouse DPPA3, failed to inhibit UHRF1 chromatin binding and DNA remethylation inXenopus eggextracts effectively. Our data provide novel insights into the distinct function and structure of human DPPA3.
Nucleocytoplasmic transport senses mechanics independently of cell density in cell monolayers
Authors: Granero-Moya Ignasi , Belthier Guillaume , Groenen Bart , Molina-Jordán Marc , González-Martín Miguel , Trepat Xavier , van Rheenen Jacco , Andreu Ion , Roca-Cusachs Pere 
Published: January 2024

AbstractCells sense and respond to mechanical forces through mechanotransduction, which regulates processes in health and disease. In single cells, mechanotransduction involves the transmission of force to the cell nucleus, where it affects nucleocytoplasmic transport (NCT) and the subsequent nuclear localization of transcriptional regulators such as YAP. However, if and how NCT is mechanosensitive in multicellular systems is unclear. Here, we characterize and use a fluorescent sensor of nucleocytoplasmic transport (Sencyt) and demonstrate that nucleocytoplasmic transport responds to mechanics but not cell density in cell monolayers. Using monolayers of both epithelial and mesenchymal phenotype, we show that NCT is altered in response both to osmotic shocks, and to the inhibition of cell contractility. Further, NCT correlates with the degree of nuclear deformation measured through nuclear solidity, a shape parameter related to nuclear envelope tension. In contrast and in opposition to YAP, NCT is not affected by cell density, showing that the response of YAP to both mechanics and cell-cell contacts operates through distinct mechanisms. Our results demonstrate the generality of the mechanical regulation of NCT.
Detection and Removal of Hyper-synchronous Artifacts in Massively Parallel Spike Recordings
Authors: Oberste-Frielinghaus Jonas , Morales-Gregorio Aitor , Essink Simon , Kleinjohann Alexander , Barthélemy Frederic , Musall Simon , Grün Sonja , Ito Junji 
Published: January 2024

AbstractCurrent electrophysiology experiments often involve massively parallel recordings of neuronal activity using multi-electrode arrays. While researchers have been aware of artifacts arising from electric cross-talk between channels in setups for such recordings, systematic and quantitative assessment of the effects of those artifacts on the data quality has never been reported. Here we present, based on examination of electrophysiology recordings from multiple laboratories, that multi-electrode recordings of spiking activity commonly contain extremely precise (at the data sampling resolution) spike coincidences far above the chance level. We derive, through modeling of the electric cross-talk, a systematic relation between the amount of such hyper-synchronous events (HSEs) in channel pairs and the correlation between the raw signals of those channels in the multi-unit activity frequency range (500-7500 Hz). We propose a method for cleaning the data to remove the artifact HSEs based on decorrelation of the band-pass filtered raw signals. We recommend to do that before spike sorting and any further analysis of the data, otherwise analysis results may be considerably affected. We demonstrate such effects of the cross-talk in estimation of firing rates and computation of cross-correlations between spike trains.
Stable isotopes and nanoSIMS single-cell imaging reveals soil plastisphere colonizers able to assimilate sulfamethoxazole
Authors: Xiang Qian , Stryhanyuk Hryhoriy , Schmidt Matthias , Richnow Hans H. , Zhu Yong-Guan , Cui Li , Musat Niculina 
Published: January 2024

AbstractThe presence and accumulation of both plastics and antibiotics in soils may lead to the colonization, selection and propagation of bacteria with certain metabolic traits e.g. antibiotic resistance, in plastisphere. However, the impact of plastic-antibiotic tandem on the soil ecosystem functioning, particularly on microbial function and metabolism remains currently unexplored. Herein, we investigated the competence of soil bacteria to colonize plastics and to mineralize/degrade13C-labelled sulfamethoxazole (SMX). Using single cell imaging, isotope tracers, soil respiration and SMX mineralization bulk measurements we show that microbial colonization of polystyrene (PE) and polyethylene (PS) surfaces takes place within the first 30 days of incubation. Morphologically diverse, microorganisms were colonizing both plastic types, with a preference for PE substrate. Nano-scale Secondary Ion Mass Spectrometry measurements show that13C enrichment was highest at 130 days with values up to 1.29 atom %, similar to those of the13CO2pool (up to 1.26 atom%, or 22.55 ‰). Our results provide direct evidence demonstrating, at single cell level, the capacity of bacterial colonizers of plastics to assimilate13C from13C-SMX. These findings expand our knowledge on the role of plastisphere microbiota in the ecological functioning of soils impacted by anthropogenic stressors.
Crystallographic fragment binding studies of theMycobacterium tuberculosistrifunctional enzyme suggest binding pockets for the tails of the acyl-CoA substrates at its active sites and a potential substrate channeling path between them
Authors: Dalwani Subhadra , Metz Alexander , Huschmann Franziska U. , Weiss Manfred S. , Wierenga Rik K. , Venkatesan Rajaram 
Published: January 2024

AbstractTheMycobacterium tuberculosistrifunctional enzyme (MtTFE) is an α2β2tetrameric enzyme in which the α-chain harbors the 2E-enoyl-CoA hydratase (ECH) and 3S-hydroxyacyl-CoA dehydrogenase (HAD) active sites, and the β-chain provides the 3-ketoacyl-CoA thiolase (KAT) active site. Linear, medium, and long chain 2E-enoyl-CoA molecules are the preferred substrates of MtTFE. Previous crystallographic binding and modelling studies have identified binding sites for the acyl-CoA substrates at the three active sites as well as the NAD+binding pocket at the HAD active site. These studies have also identified three additional CoA binding sites on the surface of MtTFE that are different from the active sites. It has been proposed that one of these additional sites could be of functional relevance for substrate channeling (by surface crawling) of reaction intermediates between the three active sites. Here, in a crystallographic fragment binding study with MtTFE crystals 226 fragments were screened, resulting in the structures of 17 MtTFE-fragment complexes. Analysis of the 143 fragment binding events shows that the ECH active site is the ‘binding hotspot’ for the tested fragments, with 50 binding events. The mode of binding of the fragments bound at the active sites provides additional insight on how the long chain acyl moiety of the substrates can be accommodated at their proposed binding pockets. In addition, the 24 fragment binding events between the active sites identify potential transient binding sites of reaction intermediates relevant for possible channeling of substrates between these active sites. These results provide a basis for further studies to understand the functional relevance of these binding sites and to identify substrates for which channeling is crucial.SynopsisCrystallographic fragment binding studies of theMycobacterium tuberculosistrifunctional enzyme (MtTFE) have resulted in 143 binding events of 17 fragments out of 226 investigated fragments, suggesting functional sites with respect to substrate binding and substrate channeling.
Temporal and Functional Relationship between Synaptonemal Complex Morphogenesis and Recombination during Meiosis
Authors: Ahuja Jasvinder S. , Sandhu Rima , Huang Lingzhi , Klein Franz , Börner G. Valentin 
Published: January 2024

AbstractDuring prophase of meiosis I, programmed double strand breaks (DSBs) are processed into crossovers, a critical requirement for segregation of homologous chromosomes (homologs) and genome haploidization in sexually reproducing organisms. Crossovers form via homologous recombination in close temporospatial association with morphogenesis of the synaptonemal complex (SC), a proteinaceous structure that connects paired homologs along their length during the pachytene stage. Synapsis and recombination are a paradigm for the interplay between higher order chromosome structure and DNA metabolism, yet their temporal and functional relationship remains poorly understood. Probing linkage between these processes in budding yeast, we show that SC assembly is associated with a distinct threshold number of unstable D-loops. The transition from bona fide paranemic D-loops to plectonemic DSB single end invasions (SEIs) is completed during midpachynema, when the SC is fully assembled. Double Holliday junctions (dHJs) form at the time of desynapsis and are resolved into crossovers during diplonema. The SC central element component Zip1 shepherds recombination through three transitions, including DSB first end strand exchange and second end capture, as well as dHJ resolution. Zip1 mediates SEI formation independent of its polymerization whereas precocious Zip1 assembly interferes with double Holliday junction resolution. Together, our findings indicate that the synaptonemal complex controls recombination while assembled but also beyond its disassembly, possibly by establishing spatial constraints at recombination sites.
Plant Cell Wall Enzymatic Deconstruction: Bridging the Gap Between Micro and Nano Scales
Authors: Refahi Yassin , Zoghlami Aya , Viné Thibaut , Terryn Christine , Paës Gabriel 
Published: January 2024

AbstractUnderstanding and overcoming the resistance of plant cell wall to enzymatic deconstruction is crucial to achieve a sustainable and economical conversion of plant biomass to bio-based products as alternatives to petroleum-based products. Despite the significant scientific advances over the past decades, the plant cell wall deconstruction at cell and tissue scales has remained under-investigated. In this study, to quantitatively characterize plant cell wall deconstruction, we set up an original imaging pipeline by combining time-lapse 4D (space + time) fluorescence confocal imaging, and a novel computational tool, to track and quantify cell wall deconstruction at cell and tissue scales offering a digital representation of cell wall deconstruction. Using this pipeline on poplar wood sections, we computed dynamics of several cellular parameters (e.g. cell wall volume, surface area, and number of cell neighbors) while measuring cellulose conversion. The results showed that the effect of enzymatic deconstruction at the cell scale is predominantly noticeable in terms of cell wall volume reduction rather than a significant decrease in surface area and accessible surface area. The results also revealed a negative correlation between pre-hydrolysis 3D cell wall compactness measures and volumetric cell wall deconstruction. The strength of this correlation was modulated by enzymatic activity. Combining cell wall compactness with the number of neighboring cells as a tissue-scale parameter yielded a stronger correlation. Our results also revealed a strong positive correlation between average volumetric cell wall deconstruction and cellulose conversion, thus establishing a link between key parameters and bridging the gap between nano and micro scales.
A dynamic subpopulation of CRISPR-Cas overexpressers allowsStreptococcus pyogenesto rapidly respond to phage
Authors: Stoltzfus Marie J. , Workman Rachael E. , Keith Nicholas C. , Modell Joshua W. 
Published: January 2024

ABSTRACTMany CRISPR-Cas systems, which provide bacteria with adaptive immunity against phages, are transcriptionally repressed in their native hosts. How CRISPR-Cas expression is induced as needed, for example during a bacteriophage infection, remains poorly understood. InStreptococcus pyogenes, a non-canonical guide RNAtracr-Ldirects Cas9 to autorepress its own promoter. Here, we describe a dynamic subpopulation of cells harboring single mutations that disrupt Cas9 binding and cause CRISPR-Cas overexpression. Cas9 actively expands this population by elevating mutation rates at thetracr-Ltarget site. Overexpressers exhibit higher rates of memory formation, stronger potency of old memories, and a larger memory storage capacity relative to wild-type cells, which are surprisingly vulnerable to phage infection. However, in the absence of phage, CRISPR-Cas overexpression reduces fitness. We propose that CRISPR-Cas overexpressers are critical players in phage defense, enabling bacterial populations to mount rapid transcriptional responses to phage without requiring transient changes in any one cell.
Origin and diversification of a globally distributed group of parasitic feather lice
Authors: Sweet Andrew D. , Doña Jorge , Johnson Kevin P. 
Published: January 2024

ABSTRACTDespite their extensive diversity and ecological importance, the history of diversification for most groups of parasitic organisms remains relatively understudied. Elucidating broad macroevolutionary patterns of parasites is challenging, often limited by the availability of samples, genetic resources, and knowledge about ecological relationships with their hosts. In this study, we explore the macroevolutionary history of parasites by focusing on parasitic body lice from doves. Building on extensive knowledge of ecological relationships and previous phylogenomic studies of their avian hosts, we tested specific questions about the evolutionary origins of the body lice of doves, leveraging whole genome data sets for phylogenomics. Specifically, we sequenced whole genomes from 68 samples of dove body lice, including representatives of all body louse genera from 51 host taxa. From these data, we assembled >2,300 nuclear genes to estimate dated phylogenetic relationships among body lice and several outgroup taxa. The resulting phylogeny of body lice was well supported, although some branches had conflicting signal across the genome. We then reconstructed ancestral biogeographic ranges of body lice and compared the body louse phylogeny to phylogeny of doves, and also to a previously published phylogeny of the wing lice of doves. Divergence estimates placed the origin of body lice in the late Oligocene. Body lice likely originated in Australasia and dispersed with their hosts during the early Miocene, with subsequent codivergence and host switching throughout the world. Notably, this evolutionary history is very similar to that of dove wing lice, despite the stronger dispersal capabilities of wing lice compared to body lice. Our results highlight the central role of hosts in driving macroevolutionary patterns of their parasites over long periods of time.