bluuebunny/crossref_metadata_2025_split huggingface dataset:
A natural bacterial pathogen ofC. elegansuses a small RNA to induce transgenerational inheritance of learned avoidance
Authors: Sengupta Titas , Ange Jonathan St. , Moore Rebecca , Kaletsky Rachel , Marogi Jacob , Myhrvold Cameron , Gitai Zemer , Murphy Coleen T. 
Published: July 2023

SummaryPreviously, we discovered that a small RNA from a clinical isolate ofPseudomonas aeruginosa, PA14, induces learned avoidance and its transgenerational inheritance inC. elegans. Pseudomonas aeruginosais an important human pathogen, and there are otherPseudomonadsinC. elegans’natural habitat, but it is unclear whetherC. elegansever encounters PA14-like bacteria in the wild. Thus, it is not known if small RNAs from bacteria found inC. elegans’natural habitat can also regulate host behavior and produce heritable behavioral effects. Here we found that a pathogenicPseudomonas vranovensisstrain isolated from theC. elegansmicrobiota, GRb0427, like PA14, regulates worm behavior: worms learn to avoid this pathogenic bacterium following exposure to GRb0427, and this learned avoidance is inherited for four generations. The learned response is entirely mediated by bacterially-produced small RNAs, which induce avoidance and transgenerational inheritance, providing further support that such mechanisms of learning and inheritance exist in the wild. Using bacterial small RNA sequencing, we identified Pv1, a small RNA from GRb0427, that matches the sequence ofC. elegans maco-1. We find that Pv1 is both necessary and sufficient to induce learned avoidance of Grb0427. However, Pv1 also results in avoidance of a beneficial microbiome strain,P. mendocina; this potentially maladaptive response may favor reversal of the transgenerational memory after a few generations. Our findings suggest that bacterial small RNA-mediated regulation of host behavior and its transgenerational inheritance are functional inC. elegans’natural environment, and that different bacterial small RNA-mediated regulation systems evolved independently but define shared molecular features of bacterial small RNAs that produce transgenerationally-inherited effects.
High performance enrichment-based genome sequencing to support the investigation of hepatitis A virus outbreaks
Authors: Zufan Sara E. , Mercoulia Karolina , Kwong Jason , Judd Louise M. , Howden Benjamin P. , Seemann Torsten , Stinear Timothy P. 
Published: July 2023

AbstractHepatitis A virus (HAV) infections are an increasing public health concern in low-endemicity regions due to outbreaks from foodborne infections and sustained transmission among vulnerable groups, including persons experiencing homelessness, those who inject drugs, and men who have sex with men (MSM), which is further compounded by aging, unvaccinated populations. DNA sequence characterisation of HAV for source tracking is performed by comparing small subgenomic regions of the virus. While this approach has been successful when robust epidemiological data are available, poor genetic resolution can lead to conflation of outbreaks with sporadic cases. HAV outbreak investigations would greatly benefit from the additional phylogenetic resolution obtained by whole virus genome sequence comparisons. However, HAV genomic approaches can be difficult because of challenges in isolating the virus, low sensitivity of direct metagenomic sequencing in complex sample matrices like various foods such as fruits, vegetables and molluscs, and difficulty designing highly multiplexed PCR primers across diverse HAV genotypes. Here, we introduce a proof-of-concept pan-HAV oligonucleotide hybrid capture enrichment assay from serum and frozen berry specimens that yields complete and near-complete HAV genomes from as few as four input HAV genome copies. We used this method to recover HAV genomes from human serum specimens with high Cτ values (34·7—42·7), with high assay performance for all six human HAV sub-genotypes, both contemporary and historical. Our approach provides a highly sensitive and streamlined workflow for HAV WGS from diverse sample types, that can be the basis for harmonised and high-resolution molecular epidemiology during HAV outbreak surveillance.ImportanceThis proof-of-concept study introduces a hybrid capture oligo panel for whole genome sequencing (WGS) of all six human pathogenic hepatitis A virus (HAV) subgenotypes, exhibiting a higher sensitivity than some conventional genotyping assays. The ability of hybrid capture to enrich multiple targets allows for a single, streamlined workflow, thus facilitating the potential harmonization of molecular surveillance of HAV with other enteric viruses. Even challenging sample matrices can be accommodated, making it suitable for broad implementation in clinical and public health laboratories. The ability to capture small amounts of virus from complex samples is promising for passive surveillance application to environmental substrates, such as wastewater. This innovative approach has significant implications for enhancing multijurisdictional outbreak investigations, as well as our understanding of the global diversity and transmission dynamics of HAV.
Large-scale deep tissue voltage imaging with targeted illumination confocal microscopy
Authors: Xiao Sheng , Cunningham William J. , Kondabolu Krishnakanth , Lowet Eric , Moya Maria V. , Mount Rebecca , Ravasio Cara , Economo Michael N. , Han Xue , Mertz Jerome 
Published: July 2023

ABSTRACTVoltage imaging with cellular specificity has been made possible by the tremendous advances in genetically encoded voltage indicators (GEVIs). However, the kilohertz rates required for voltage imaging lead to weak signals. Moreover, out-of-focus fluorescence and tissue scattering produce background that both undermines signal-to-noise ratio (SNR) and induces crosstalk between cells, making reliablein vivoimaging in densely labeled tissue highly challenging. We describe a microscope that combines the distinct advantages of targeted illumination and confocal gating, while also maximizing signal detection efficiency. The resulting benefits in SNR and crosstalk reduction are quantified experimentally and theoretically. Our microscope provides a versatile solution for enabling high-fidelityin vivovoltage imaging at large scales and penetration depths, which we demonstrate across a wide range of imaging conditions and different GEVI classes.
Visible light-induced specific protein reaction delineates early stages of cell adhesion
Authors: Rahikainen Rolle , Vester Susan K. , Turkki Paula , Janosko Chasity P. , Deiters Alexander , Hytönen Vesa P. , Howarth Mark 
Published: July 2023

AbstractLight is well established for control of bond breakage, but not for control of specific bond formation in complex environments. We previously engineered diffusion-limited reactivity of SpyTag003 peptide with its protein partner SpyCatcher003 through spontaneous transamidation. This system enables precise and irreversible assembly of biological building blocks, with applications from biomaterials to vaccines. Here, we establish a system for rapid control of this amide bond formation with visible light. We have generated a caged SpyCatcher003, which allows light triggering of covalent bond formation to SpyTag003 in mammalian cells. Photocaging is achieved through site-specific incorporation of an unnatural coumarin-lysine at the reactive site of SpyCatcher003. We showed uniform specific reaction in cell lysate upon light activation. We then used the spatiotemporal precision of a 405 nm confocal laser for uncaging in seconds, probing the earliest events in mechanotransduction by talin, the key force sensor between the cytoskeleton and extracellular matrix. Reconstituting talin induced rapid biphasic extension of lamellipodia, revealing the kinetics of talin-regulated cell spreading and polarization. Thereafter we determined the hierarchy of recruitment of key components for cell adhesion. Precise control over site-specific protein reaction with visible light creates diverse opportunities for cell biology and nanoassembly.
An oxadiazole-based compound potentiates anti-tuberculosis treatment by increasing host resistance via zinc poisoning
Authors: Maure Alexandra , Lawarée Emeline , Fiorentino Francesco , Pawlik Alexandre , Gona Saideep , Giraud-Gatineau Alexandre , Eldridge Matthew J.G. , Danckaert Anne , Hardy David , Frigui Wafa , Keck Camille , Aulner Nathalie , Mai Antonello , Hamon Mélanie , Barreiro Luis , Brodin Priscille , Brosch Roland , Rotili Dante , Tailleux Ludovic 
Published: July 2023

AbstractAnti-tuberculosis drugs, mostly developed over 60 years ago, combined with a poorly effective vaccine, have failed to eradicate tuberculosis. More worryingly, multi-resistant strains ofMycobacterium tuberculosisare constantly emerging. Innovative strategies are thus urgently needed to improve tuberculosis treatment. Recently, host-directed therapy has emerged as a promising strategy to be used in adjunct with existing or future antibiotics, by improving innate immunity or limiting immunopathology. Here, using high content imaging, we identified novel 1,2,4-oxadiazole-based compounds, that allow human macrophages to control MTB replication. Genome-wide gene expression analysis revealed that these molecules induced zinc remobilization inside cells, resulting in bacterial zinc intoxication. More importantly, we also demonstrated that, upon treatment with these novel compounds,M. tuberculosisbecame even more sensitive to anti-tuberculosis drugs,in vitroandin vivo, in a mouse model of tuberculosis. Manipulation of heavy metal homeostasis holds thus great promise to be exploited to develop host-directed therapeutic interventions.
Enucleation of theC. elegansembryo revealed the mechanism of dynein-dependent spacing between microtubule asters
Authors: Fujii Ken , Kondo Tomo , Kimura Akatsuki 
Published: July 2023

ABSTRACTThe centrosome is a major microtubule-organizing center in animal cells. The intracellular positioning of the centrosomes is important for proper cellular function. One of the features of centrosome positioning is the spacing between centrosomes. The spacing activity is mediated by microtubules extending from the centrosomes; however, the underlying mechanisms are not fully understood. To characterize the spacing activity in theCaenorhabditis elegansembryo, a genetic setup was developed to produce enucleated embryos. The centrosome duplicated multiple times in the enucleated embryo, which enabled us to characterize the chromosome-independent spacing activity between sister and non-sister centrosome pairs. We knocked down genes in the enucleated embryo and found that the timely spacing was dependent on cytoplasmic dynein. Based on these results, we propose a stoichiometric model of cortical and cytoplasmic pulling forces for the spacing between centrosomes. We also found a dynein-independent but non-muscle myosin II-dependent movement of the centrosomes in a later cell cycle phase. The dynein-dependent spacing mechanisms for positioning the centrosomes revealed in this study is likely functioning in the cell with nucleus and chromosomes, including the processes of centrosome separation and spindle elongation.
Integrative determination of the atomic structure of mutant huntingtin exon 1 fibrils implicated in Huntington’s disease
Authors: Bagherpoor Helabad Mahdi , Matlahov Irina , Kumar Raj , Daldrop Jan O. , Jain Greeshma , Weingarth Markus , van der Wel Patrick C.A. , Miettinen Markus S. 
Published: July 2023

AbstractNeurodegeneration in Huntington’s disease (HD) is accompanied by the aggregation of fragments of the mutant huntingtin protein, a biomarker of disease progression. A particular pathogenic role has been attributed to the aggregation-prone huntingtin exon 1 (HTTex1), generated by aberrant splicing or proteolysis, and containing the expanded polyglutamine (polyQ) segment. Unlike amyloid fibrils from Parkinson’s and Alzheimer’s diseases, the atomic-level structure of HTTex1 fibrils has remained unknown, limiting diagnostic and treatment efforts. We present and analyze the structure of fibrils formed by polyQ peptides and polyQ-expanded HTTex1 in vitro. Atomic-resolution perspectives are enabled by an integrative analysis and unrestrained all-atom molecular dynamics (MD) simulations incorporating experimental data from electron microscopy (EM), solid-state NMR, and other techniques. Alongside the use of prior data, we report new magic angle spinning NMR studies of glutamine residues of the polyQ fibril core and surface, distinguished via hydrogen-deuterium exchange (HDX). Our study provides a new understanding of the structure of the core as well as surface of aggregated HTTex1, including the fuzzy coat and polyQ–water interface. The obtained data are discussed in context of their implications for understanding the detection of such aggregates (diagnostics) as well as known biological properties of the fibrils.
Identification and Characterization of Calcium Binding Protein, Spermatid Associated 1 (CABS1) in Selected Human Tissues and Fluids
Authors: Reyes-Serratos E. , Santos J. Ramielle L. , Puttagunta L. , Lewis S. , Watanabe M. , Gonshor A. , Buck R , Befus A.D. , Marcet-Palacios M. 
Published: July 2023

AbstractCalcium binding protein, spermatid associated 1 (CABS1) is a protein most widely studied in spermatogenesis. However, mRNA for CABS1 has been found in numerous tissues, albeit with little information about the protein. Previously, we identified CABS1 mRNA and protein in human salivary glands and provided evidence that in humans CABS1 contains a heptapeptide near its carboxyl terminus that has anti-inflammatory activities. Moreover, levels of an immunoreactive form of CABS1 were elevated in psychological stress. To more fully characterize human CABS1 we developed additional polyclonal and monoclonal antibodies to different sections of the protein and used these antibodies to characterize CABS1 in an overexpression cell lysate, human salivary glands, saliva, serum and testes using western blot, immunohistochemistry and bioinformatics approaches exploiting the Gene Expression Omnibus (GEO) database. CABS1 appears to have multiple molecular weight forms, consistent with its recognition as a structurally disordered protein, a protein with structural plasticity. Interestingly, in human testes, its cellular distribution differs from that in rodents and pigs, and includes Leydig cells, primary spermatogonia, Sertoli cells and developing spermatocytes and spermatids, Geodata suggests that CABS1 is much more widely distributed than previously recognized, including in the urogenital, gastrointestinal and respiratory tracts, as well as in the nervous system, immune system and other tissues. Much remains to be learned about this intriguing protein.
Unravelling the novel genetic diversity and marker-trait associations of corn leaf aphid resistance in wheat using microsatellite markers
Authors: Yadav Jayant , Jasrotia Poonam , Jaglan Maha Singh , Sareen Sindhu , Kashyap Prem Lal , Kumar Sudheer , Yadav Surender Singh , Singh Gyanendra , Singh Gyanendra Pratap 
Published: July 2023

ABSTRACTThe study was conducted to identify novel simple sequence repeat (SSR) markers associated with resistance to corn aphid (CLA),Rhopalosiphum maidisL. in 48 selected bread wheat (Triticum aestivumL.) and wild wheat (Aegilopsspp. &T. dicoccoides) genotypes during two consecutive cropping seasons (2018-19 and 2019-20). A total of 51 polymorphic markers containing 143 alleles were used for the analysis. The frequency of the major allele ranged from 0.552 (Xgwm113) to 0.938 (Xcfd45, Xgwm194andXgwm526), with a mean of 0.731. Gene diversity ranged from 0.116 (Xgwm526) to 0.489 (Xgwm113), with a mean of 0.354. The polymorphic information content (PIC) value for the SSR markers ranged from 0.107 (Xgwm526) to 0.370 (Xgwm113) with a mean of 0.282. The results of the STRUCTURE analysis revealed the presence of four main subgroups in the populations. Analysis of molecular variance (AMOVA) showed that the between-group difference was around 37% of the total variation contributed to the diversity by the whole germplasm, while 63% of the variation was attributed between individuals within the group. A general linear model (GLM) was used to identify marker-trait associations, which detected a total of 23 and 27 significant new marker-trait associations (MTAs) at the p < 0.01 significance level during the 2018-19 and 2019-20 crop seasons, respectively. The findings of this study have important implications for the identification of molecular markers associated with CLA resistance. These markers can increase the accuracy and efficiency of aphid-resistant germplasm selection, ultimately facilitating the transfer of resistance traits to desirable wheat genotypes.
Identification of Periostin as a critical niche for myofibroblast dynamics and fibrosis during tendon healing
Authors: Ackerman Jessica E. , Adjei-Sowah Emmanuela , Korcari Antonion , Muscat Samantha N. , Nichols Anne E.C. , Buckley Mark R. , Loiselle Alayna E. 
Published: July 2023

AbstractTendon injuries are a major clinical problem, with poor patient outcomes caused by abundant scar tissue deposition during healing. Myofibroblasts play a critical role in the initial restoration of structural integrity after injury. However, persistent myofibroblast activity drives the transition to fibrotic scar tissue formation. As such, disrupting myofibroblast persistence is a key therapeutic target. While myofibroblasts are typically defined by the presence of αSMA+ stress fibers, αSMA is expressed in other cell types including the vasculature. As such, modulation of myofibroblast dynamics via disruption of αSMA expression is not a translationally tenable approach. Recent work has demonstrated that Periostin-lineage (PostnLin) cells are a precursor for cardiac fibrosis-associated myofibroblasts. In contrast to this, here we show that PostnLincells contribute to a transient αSMA+ myofibroblast population that is required for functional tendon healing, and that Periostin forms a supportive matrix niche that facilitates myofibroblast differentiation and persistence. Collectively, these data identify the Periostin matrix niche as a critical regulator of myofibroblast fate and persistence that could be targeted for therapeutic manipulation to facilitate regenerative tendon healing.
An mTOR/RNA pol I axis shapes chromatin architecture in response to fasting
Authors: Al-Refaie Nada , Padovani Francesco , Binando Francesca , Hornung Johanna , Zhao Qiuxia , Towbin Benjamin D. , Cenik Elif Sarinay , Stroustrup Nicholas , Schmoller Kurt M. , Cabianca Daphne S. 
Published: July 2023

AbstractChromatin architecture is a fundamental mediator of genome function. Fasting is a major environmental cue across the animal kingdom. Yet, how it impacts on 3D genome organization is unknown. Here, we show that fasting induces a reversible and large-scale spatial reorganization of chromatin inC. elegans. This fasting-induced 3D genome reorganization requires inhibition of the nutrient-sensing mTOR pathway, a major regulator of ribosome biogenesis. Remarkably, loss of transcription by RNA Pol I, but not RNA Pol II nor Pol III, induces a similar 3D genome reorganization in fed animals, and prevents the restoration of the fed-state architecture upon restoring nutrients to fasted animals.Our work documents the first large-scale chromatin reorganization triggered by fasting and reveals that mTOR and RNA Pol I shape genome architecture in response to nutrients.
Extracting herbicide and antibiotic natural products from a plant-microbe interaction system
Authors: Pan Shiyu , Li Xiaojie , Pan Chao , Li Jixiao , Fan Siting , Zhang Liner , Du Kehan , Du Zhiying , Zhang Jiayu , Huang Han , Li Jie , Zhang Heqian , Huang Jiaquan , Qin Zhiwei 
Published: July 2023

AbstractPlants and their associated microbes live in complicated, changeable, and unpredictable environments. They usually interact with each other in many ways by proceeding in multi-dimensional, multi-scale and multi-level coupling manners, leading to challenges of the co-existence of randomness and determinism, or continuity and discreteness. Gaining a deeper understanding of these diverse interaction mechanisms can facilitate the development of new data mining theories and methods for complex systems, new coupled modelling for the system with different spatiotemporal scales and functional properties, or even universal theory of information and information interactions. In this study, we use a “close-loop” model to present a plant-microbe interaction system and describe the probable functions from the microbial natural products. Specifically, we report a rhizosphere species,Streptomyces ginsengnesisG7, which produces polyketide lydicamycins and other active metabolites. Interestingly, these distinct molecules have the potential to function both as antibiotics and herbicides for crop protection. Detailed laboratory experiments combined with comprehensive bioinformatics analysis allow us to rationalise a model for this specific plant-microbe interaction process. Our work reveals the benefits of exploring otherwise neglectable resources for the identification of novel functional molecules and provides a good reference to better understand the system biology in the complex ecosystems.
Post-occupancy assessment of student housing facilities in an educational campus: case study of Visvesvaraya National Institute of Technology Nagpur, India
Authors: Kumar Meenal , Khan Smita 
Published: July 2023

PurposeThis study attempts to conduct a post-occupancy assessment of the primary technical, functional and behavioral features in a student housing facility at the Visvesvaraya National Institute of Technology campus in Nagpur, India to see if the students are satisfied with the residential hostel's environs and facilities.Design/methodology/approachThe study reviews knowledge areas pertinent to the technical, functional and behavioral performance of student housing facilities by looking at the body of accessible literature. Even though the literature review gave a thorough overview of the broad issues, it was essential to learn about the situation as it is and addresses the specific issues brought up to undertake a thorough evaluation, just as every in-depth study depends on a reliable methodology. Therefore, a methodology appropriate for the research was developed, which helped in identifying relevant attributes for the questionnaire to be used for the survey. This aided in analyzing the building's performance evaluation through the sole users of the hostel which are the students. The survey data is analyzed by statical methods using SPSS software to identify the key determinants of satisfaction in students' residential hostels and if these are affected by the gender of the students.FindingsThe survey results were examined to determine the level of satisfaction with the selected performance aspects, and the major determinants governing it. The findings concluded that most of the technical and functional determinants of satisfaction in hostels are identified the same by both genders, except for some of the attributes in behavioral elements. The research looked at how well key success elements in the student housing facility had been implemented.Research limitations/implicationsResearch is carried out in CFTI only wherein architecture is one of the branches.Originality/valuePlanning professionals, architects, housing managers and facility managers involved in the design, construction and management of student housing facilities might benefit from feedback from a post-occupancy evaluation. The post-occupancy study can therefore aid in continually enhancing the standard and effectiveness of the facilities for planning, constructing, managing and maintaining student residential housing.