bluuebunny/crossref_metadata_2025 huggingface dataset:
Transient anti-interferon autoantibodies in the airways are associated with efficient recovery from COVID-19
Authors: Babcock Benjamin R. , Kosters Astrid , Eddins Devon J. , Donaire Maria Sophia Baluyot , Sarvadhavabhatla Sannidhi , Pae Vivian , Beltran Fiona , Murray Victoria W. , Gill Gurjot , Xie Guorui , Dobosh Brian S. , Giacalone Vincent D. , Tirouvanziam Rabindra M. , Ramonell Richard P. , Jenks Scott A. , Sanz Ignacio , Lee F. Eun-Hyung , Roan Nadia R. , Lee Sulggi A. , Ghosn Eliver E. B.
Published: January 2024

Pre-existing anti-interferon alpha (anti-IFN-α) autoantibodies in blood are associated with susceptibility to life-threatening COVID-19. However, it is unclear whether anti-IFN-α autoantibodies in the airways – the initial site of infection – can also determine disease outcomes. In this study, we developed a new multiparameter technology, flowBEAT, to quantify and profile the isotypes of anti-IFN-α and anti-SARS-CoV-2 antibodies in longitudinal samples collected over 20 months from the airway and matching blood of 129 donors with mild, moderate, and severe COVID-19. We found unexpectedly that nasal anti-IFN-α autoantibodies were induced post-infection onset in more than 70% of mild to moderate COVID-19 cases and associated with robust anti-SARS-CoV-2 immunity, fewer symptoms, and efficient recovery. Nasal anti-IFN-α autoantibodies followed the peak of host IFN-α production and waned with disease recovery, revealing a regulated balance between IFN-α and anti-IFN-α response. Notably, only a subset of mild to moderate patients progressed to develop systemic anti-IFN-α, which correlated with systemic inflammation and worsened symptoms. In contrast, patients with life-threatening COVID-19 sustained elevated anti-IFN-α in both airways and blood, coupled with uncontrolled viral load and IFN-α production. Our studies thereby reveal a novel protective role for nasal anti-IFN-α autoantibodies in the immunopathology of COVID-19 and, more broadly, suggest that anti-IFN-α may serve an important regulatory function to restore homeostasis following viral invasion of the respiratory mucosa.
Promoting healthy and sustainable diets through food service interventions in university settings: a scoping review
Authors: Kratzer Suzie , Theurich Melissa A. , Mareis Theresa , Pröbstl Simone , Holliday Nicole , Yan Sebrina , Leibinger Anna , Monsef Ina , Bach Leonie , Schwingshackl Lukas , Simonetti Aline , Hartmann Monika , Lemken Dominic , von Philipsborn Peter
Published: January 2024

Background

Food service operations in universities and colleges, such as cafeterias and canteens, may support healthy and sustainable diets among students and staff and contribute to a transformation of the wider food system. Multiple studies on interventions to promote health and sustainability in this setting have been conducted, but no up-to-date, comprehensive review exists. This study aims to fill this gap.

Methods

We used state-of-the-art scoping review methodology. We included any study examining interventions in university or college food service settings aimed at, or potentially suitable for: 1), supporting healthy and/or sustainable diets, 2) reducing food waste, or 3) otherwise increasing the sustainability of the food service operation (e.g. by improving energy efficiency). We considered studies using any study design published in any language without publication date restrictions. We comprehensively searched six academic databases and conducted forward and backward citation searches. We extracted and charted data on key study characteristics, including the reported direction of effects/associations.

Results

We identified 206 studies reporting on 273 interventions. Most studies (71%) used quasi- experimental study designs, were conducted in North America (53%) or Europe (34%), and were implemented in cafeterias or canteens (76%). The most common intervention types were labelling interventions (26%), improved or increased offerings of healthy and/or sustainable food and beverage options (24%), and information and awareness-raising interventions (18%). The most commonly assessed outcomes were implementation-related (e.g. costs, feasibility, acceptability), diet-related (e.g. sales or consumption of specific foods), and sustainability-related (e.g. carbon footprint). Most, but not all, studies reported mostly effects in the desired direction (e.g. increased vegetable consumption, or decreased food waste).

Discussion

Multiple approaches for promoting health and sustainability in university and college food service settings exist. The findings of this review suggest that such interventions can be effective, feasible, cost-effective, and aligned with customer and stakeholder expectations. We therefore suggest that they are considered for implementation more widely. Implementation should be accompanied by monitoring and methodologically robust evaluations to allow for evidence-informed tailoring and adjustments and to improve the existing evidence base.
Deep representation learning for clustering longitudinal survival data from electronic health records
Authors: Qiu Jiajun , Hu Yao , Li Li , Erzurumluoglu Abdullah Mesut , Braenne Ingrid , Whitehurst Charles , Schmitz Jochen , Arora Jatin , Bartholdy Boris Alexander , Gandhi Shrey , Khoueiry Pierre , Mueller Stefanie , Noyvert Boris , Ding Zhihao , Jensen Jan Nygaard , de Jong Johann
Published: January 2024

Precision medicine requires accurate identification of clinically relevant patient subgroups. Electronic health records provide major opportunities for leveraging machine learning approaches to uncover novel patient subgroups. However, many existing approaches fail to adequately capture complex interactions between diagnosis trajectories and disease-relevant risk events, leading to subgroups that can still display great heterogeneity in event risk and underlying molecular mechanisms. To address this challenge, we implemented VaDeSC-EHR, a transformer-based variational autoencoder for clustering longitudinal survival data as extracted from electronic health records. We show that VaDeSC-EHR outperforms baseline methods on both synthetic and real-world benchmark datasets with known ground-truth cluster labels. In an application to Crohn’s disease, VaDeSC-EHR successfully identifies four distinct subgroups with divergent diagnosis trajectories and risk profiles, revealing clinically and genetically relevant factors in Crohn’s disease. Our results show that VaDeSC-EHR can be a powerful tool for discovering novel patient subgroups in the development of precision medicine approaches.
Prolonged time to breast cancer surgery and the risk for metastasis
Authors: Hölzel Dieter , Schlesinger-Raab Anne , Schubert-Fritschle Gabriele , Halfter Kathrin
Published: January 2024

Background

A growing breast cancer (BC) is associated with an inherent risk of metastasis (MET). If surgical treatment of a BC is delayed, the prognosis worsens continuously with increasing tumor diameter (TD). This frequently overlooked topic in healthcare is currently the subject of debate.

Methods

Population-based data on BC incidence and surgery waiting period for the U.S. and Germany are used to examine the resulting risks. BC growth and initiation of MET are calculated in a simulation approach using hormone receptor status (HR), tumor volume doubling time (VDT), and TD- dependent survival.

Results

The U.S. and Germany report 287,850/71,375 BCs annually. Based on an initial mean TD of 19.8mm 15-year mortality in both countries is estimated using a Gompertz function at 19.6% without surgical delay. VDT of HR+ and HR- BCs differs by a factor of 2.4, leading to an estimated mortality increase of 1.34/3.26% (HR+/HR-) if all surgical procedures are pushed back by five weeks. The mean delay in the U.S. and Germany is 33.7/26.0 days respectively. Prolonged waiting periods lead to estimated 4,676/918 additional BC deaths or a 1.6/1.2% rise in BC mortality rate. Further increases are due to MET relapse up to 25 years after diagnosis.

Conclusions

A growing tumor can continuously initiate MET with every millimeter. The results of this study offer replicable and valid evidence, based on publicly available clinical and population-based data, that confirmed BCs should be treated according to HR status as soon as possible.
Impact of genome build on RNA-seq interpretation and diagnostics
Authors: Ungar Rachel A. , Goddard Pagé C. , Jensen Tanner D. , Degalez Fabien , Smith Kevin S. , Jin Christopher A. ,   Undiagnosed Diseases Network, Bonner Devon E. , Bernstein Jonathan A. , Wheeler Matthew T. , Montgomery Stephen B.
Published: January 2024

Transcriptomics is a powerful tool for unraveling the molecular effects of genetic variants and disease diagnosis. Prior studies have demonstrated that choice of genome build impacts variant interpretation and diagnostic yield for genomic analyses. To identify the extent genome build also impacts transcriptomics analyses, we studied the effect of the hg19, hg38, and CHM13 genome builds on expression quantification and outlier detection in 386 rare disease and familial control samples from both the Undiagnosed Diseases Network (UDN) and Genomics Research to Elucidate the Genetics of Rare Disease (GREGoR) Consortium. We identified 2,800 genes with build-dependent quantification across six routinely-collected biospecimens, including 1,391 protein-coding genes and 341 known rare disease genes. We further observed multiple genes that only have detectable expression in a subset of genome builds. Finally, we characterized how genome build impacts the detection of outlier transcriptomic events. Combined, we provide a database of genes impacted by build choice, and recommend that transcriptomics-guided analyses and diagnoses are cross-referenced with these data for robustness.
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

Background

Hypertension 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.

Objective

To assess factors associated with antihypertensive drug adherence and blood pressurecontrol among hypertensive patients in Selected Public Hospitals under Addis Ababa City Administration.

Method

A 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.

Result

The 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.

Conclusion

Despite 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

Hsp70, 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

Ribosomal 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

The 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.

Highlights

FourierCycle combines single-cell multiome sequencing, deep learning, and biophysical modeling to quantify gene-specific rates of mRNA metabolism during the cell cycle

Rates 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 cycle

Dynamics of chromatin accessibility and transcription factor binding footprints uncover key regulators underlying the transcriptional control of gene expression

Graphical 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

DNA 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

Cells 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

Current 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

The 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

TheMycobacterium 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.

Synopsis

Crystallographic 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

During 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

Understanding 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

Many 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

Despite 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.
Global Huntingtin Knockout in Adult Mice Leads to Fatal Neurodegeneration that Spares the Pancreas
Authors: Bragg Robert M. , Mathews Ella W. , Grindeland Andrea , Cantle Jeffrey P. , Howland David , Vogt Tom , Carroll Jeffrey B.
Published: January 2024

Huntington’s disease (HD) is a fatal neurogenerative disorder caused by an expanded glutamine-coding CAG tract in the Huntingtin (Htt) gene. HD is believed to primarily arise via a toxic gain of function, and as a result a wide range of Htt-lowering treatments are in clinical trials. The safety of these trials is contingent on the risks imposed by Htt lowering: Htt is widely conserved, ubiquitously expressed and its complete loss causes severe developmental symptoms in mice and humans. Recently, multiple labs have reported on the consequences of widespread inducible Htt loss in mice. One report describes that early induction of global Htt loss causes fatal pancreatitis, but that later onset lowering is benign. Another study did not report fatal pancreatitis but suggested that postnatal Htt loss was associated with widespread progressive phenotypes, including subcortical calcification and neurodegeneration. To better understand the risks posed by widespread inducible Htt loss we established the phenotypes of mice in which we knocked out Htt with two tamoxifen inducible Cre lines, which we have here extensively characterized. In short, we find that widespread loss of Htt at 2 months of age leads to a wide range of phenotypes, including subcortical calcification, but does not result in acute pancreatitis or histological changes in the pancreas. Additionally, we report here for the first time that Htt loss is followed by robust and sustained increases in the levels of neurofilament light chain (NfL), a peripherally accessible biomarker of neuroaxonal stress. These results confirm that complete loss of Htt in mice is associated with pronounced risks, including progressive subcortical calcification and neurodegeneration.
Dysregulated synaptic gene expression in oligodendrocytes of spinal and bulbar muscular atrophy
Authors: Iida Madoka , Sahashi Kentaro , Hirunagi Tomoki , Sakakibara Kenji , Maeda Kentaro , Ogura Yosuke , Iizuka Masaki , Akashi Tomohiro , Hinohara Kunihiko , Katsuno Masahisa
Published: January 2024

Spinal and bulbar muscular atrophy (SBMA) is a neuromuscular disease caused by an expanded CAG repeat in theandrogen receptor(AR) gene. To elucidate the cell type-specific temporal gene expression in SBMA, we performed single-nucleus RNA sequencing on the spinal cords of AR-97Q mice. Among all cell types, oligodendrocytes (OLs) had the highest number of differentially expressed genes before disease onset. Analysis of OL clusters suggested that pathways associated with cation channels and synaptic function were activated before disease onset, with increased output from OLs to neurons in AR-97Q mice compared to wild-type mice. These changes in the early stages were abrogated in the advanced stages. An OL cell model of SBMA showed phenotypes similar to those of AR-97Q mice at early stages, such as increased transcriptional changes in synapse organization. Our results indicate that the dysregulation of cell-to-cell communication has a major impact on the early pathology of SBMA and is a potential therapeutic target for SBMA.
Three-meson
τ
decays involving kaons and
η
mesons in the NJL model
Authors: Volkov M. K. , Pivovarov A. A. , Nurlan K.
Published: January 2024

Branching fractions of decays τ→K0π−ηντ, τ→K−π0ηντ, τ→K−K0ηντ, and τ→K−ηηντ are calculated in the U(3)×U(3) chiral Nambu–Jona-Lasinio quark model. The contact, vector, axial-vector, and pseudoscalar channels are considered. It is shown that the axial vector channel is dominant. The obtained results are in satisfactory agreement with experiment.

Published by the American Physical Society
2024
Dynamics of heavy quarks in the Fock space
Authors: Serafin Kamil , Gómez-Rocha María , More Jai , Głazek S. D.
Published: January 2024

This paper concerns a method of describing hadrons that starts with the canonical front form Hamiltonian of QCD. The method is developed in the relatively simple context of QCD with only heavy quarks. We regulate its canonical Hamiltonian by introducing a vanishingly small gluon mass mg. For positive mg, the small-x gluon divergences become ultraviolet and hence they are renormalized in the same way the ultraviolet transverse divergences are. This is done using the renormalization group procedure for effective particles. Up to the second order of expansion of the renormalized Hamiltonian in powers of the quark-gluon coupling constant g, only the quark mass-squared and gluon-exchange divergences require counterterms. In these circumstances, we calculate an effective potential between quarks in heavy quarkonia in an elementary way, replacing all the quarkonium-state components with gluons of mass mg by only one component with just one gluon that is assigned a mass mG, comparable to or exceeding the scale of typical relative momenta of bound quarks. In the limit of mg→0 and large

m

G

two results are obtained. (1) While the color-singlet quarkonium mass eigenvalue stays finite and physically reasonable in that limit, the eigenvalues for single quarks and octet quarkonia are infinite. (2) Besides the coulomb terms, the effective quark-antiquark potential is quadratic as a function of the distance and spherically symmetric for typical separations between quarks but becomes logarithmic and no longer spherically symmetric for large separations. Our conclusion indicates how to systematically improve upon the approximations made in this paper.

Published by the American Physical Society
2024
Crystal structure of poly[hexa-μ-bromido-bis{2-[1-(pyridin-2-yl)ethylideneamino]ethanolato}tetracopper(II)]
Authors: Traoré Bocar , Diouf Ngoné , Kébé Momath , Guéye-Sylla Rokhaya , Thiam Ibrahima Elhadji , Diouf Ousmane , Retailleau Pascal , Gaye Mohamed
Published: January 2024

The reaction of the Schiff base 2-[1-(pyridin-2-yl)ethylideneamino]ethanol (HL), which is formed by reaction of 2-aminoethanol and 2-acetylpyridine with CuBr2 in ethanol results in the isolation of the new polymeric complex poly[hexa-μ-bromido-bis{2-[1-(pyridin-2-yl)ethylideneamino]ethanolato}tetracopper(II)], [Cu4Br6(C9H11N2O)2]
n
or [Cu4Br6
L
2]
n
. The asymmetric unit of the crystal structure of the polymeric [Cu4Br6
L
2]
n
complex is composed by four copper (II) cations, two monodeprotonated molecules of the ligand, and six bromide anions, which act as bridges. The ligand molecules act in a tridentate fashion through their azomethine nitrogen atoms, their pyridine nitrogen atoms, and their alcoholate O atoms. The crystal structure shows two types of geometries in the coordination polyhedrons around Cu2+ ions. Two copper cations are situated in a square-based pyramidal environment, while the two other copper cations adopt a tetrahedral geometry. Bromides anions acting as bridges between two metal ions connect the units, resulting in a tetranuclear polymer compound.
Synthesis and crystal structure of N
1,N
2-dimethylethanedihydrazide
Authors: Bibik Yurii S. , Khomenko Dmytro M. , Doroshchuk Roman O. , Raspertova Ilona V. , Bargan Alexandra , Lampeka Rostyslav D.
Published: January 2024

The title compound, N
1,N
2-dimethylethanedihydrazide, C4H10N4O2, was obtained by the methylation of oxalyl dihydrazide protected with phthalimide. The molecule is essentially non-planar with a dihedral angle between the two planar hydrazide fragments of 86.5 (2)°. This geometry contributes to the formation of a multi-contact three-dimensional supramolecular network via C—H...O, N—H...O and N—H...N hydrogen bonds.
Industry 4.0 and supply chain sustainability: benchmarking enablers to build reliable supply chain
Authors: Pandey Ajay Kumar , Pratap Saurabh , Dwivedi Ashish , Khan Sharfuddin Ahmed
Published: January 2024

Purpose

The existing literature reflects that the connection between enablers of Industry 4.0 (I4.0), Supply Chain (SC) sustainability and reliability is understudied. To cover this gap, the purpose of this study is to identify and benchmark the enablers of I4.0 for SC sustainability to build a Reliable Supply Chain (RSC).

Design/methodology/approach

This study benchmarks the I4.0 enablers for SC sustainability for building a RSC and analyses them with a multi-method approach. The identified potential enablers are validated empirically. A multi-method approach of Analytical Hierarchy Process (AHP), Decision Making Trial and Evaluation Laboratory (DEMATEL) and Preference Ranking for Organization Method for Enrichment Evaluation (PROMETHEE-II) was used to investigate the influence of the identified benchmarking enablers and develop an interrelationship diagram among the identified enablers.

Findings

This study benchmarks the potential enablers of I4.0 to achieve high ecological-economic-social gains in SCs considering the Indian scenario. Digitalization of the supply chain, decentralization, smart factory technologies and data security and handling are the most prominent enablers of I4.0 for SC sustainability to build a RSC.

Originality/value

The findings from the study may benefit managers, practitioners, specialists, researchers and policymakers interested in I4.0 sustainability applications.
Apocalypse unleashed: a critical perspective on complexity science, catastrophes, and black swan events in international business
Authors: Gonzales Martinez Rolando
Published: January 2024

Purpose

The purpose of this study is to propose a methodological approach for modeling catastrophic consequences caused by black swan events, based on complexity science, and framed on Feyerabend’s anarchistic theory of knowledge. An empirical application is presented to illustrate the proposed approach.

Design/methodology/approach

Thom’s nonlinear differential equations of morphogenesis are used to develop a theoretical model of the impact of catastrophes on international business (IB). The model is then estimated using real-world data on the performance of multinational airlines during the SARS-CoV-2 (COVID-19) pandemic.

Findings

The catastrophe model exhibits a remarkable capability to simultaneously capture complex linear and nonlinear relationships. Through empirical estimations and simulations, this approach enables the analysis of IB phenomena under normal conditions, as well as during black swan events.

Originality/value

To the best of the author’s knowledge, this study is the first attempt to estimate the impact of black swan events in IB using a catastrophe model grounded in complexity theory. The proposed model successfully integrates the abrupt and profound effects of catastrophes on multinational corporations, offering a critical perspective on the theoretical and practical use of complexity science in IB.
Students' industrial work experience scheme (SIWES): exploring higher institution student’s participation and sense of belonging
Authors: Umar Musa Abba , Medan Penuel , Atiku Zainab Aliyu
Published: January 2024

Purpose

The purpose of this study was to determine the extent to which students' industrial work experience scheme (SIWES) students in higher education institutions experienced a high level of engagement in workplace activities and a strong sense of affiliation with their workplace environment. The additional purpose encompassed the identification of factors that both facilitated and hindered their engagement and self-efficacy.

Design/methodology/approach

The data for this study were collected via a cross-sectional survey of 243 students who were undertaking the SIWES as a mandatory component of their graduation requirements. The survey was conducted at selected tertiary institutions in Nigeria.

Findings

The qualitative replies yielded valuable insights on the factors that motivated and supported participation, with self-efficacy emerging as a significant facilitator as well as a potential barrier. There is a positive association between more interactions, a professional atmosphere and self-efficacy.

Research limitations/implications

The study may not comprehensively include all contextual variables that might potentially impact students' perception of belongingness and self-efficacy during the SIWES program, including the distinct industry or workplace setting.

Practical implications

This exploratory study analyzes SIWES students' cultural and personal affiliation. The study suggests these changes improve student performance. Engagement and belonging techniques for students, supervisors, coworkers and professionals are classified by the study. The study found that supervisors and coworkers help students at work. It underlines academics' responsibility in creating SIWES curricula that increase student confidence and active learning. According to this study, students should receive self-confidence therapy before SIWES. Self-confidence and student success and well-being need additional investigation, the report says.

Originality/value

This study takes a unique approach by examining belongingness and self-efficacy in the SIWES course. It examines the interdependence of these notions and the curriculum's various challenges and opportunities. By addressing these important issues, study adds to existing knowledge and lays the groundwork for future research.