bluuebunny/crossref_metadata_2025_split huggingface dataset:
Outer Membrane Vesicle Mediated Multidrug Resistance Gene Transfer in Avibacterium Paragallinarum
Authors: Xu Jie , Mei Chen , Zhi Yan , Liang Zhi-xuan , Zhang Xue , Wang Hong-jun 
Published: April 2022

ABSTRACTInfectious coryza is an acute upper respiratory tract infectious disease caused by Avibacterium paragallinarum, which can cause growth retardation and egg production decline of bred chickens, and bring great economic losses to poultry industry. A. Paragallinarum is a Gram-negative bacterium and can release outer membrane vesicles (OMVs). In this study, a comparative genomic analysis of A. Paragallinarum isolate P4chr1 and its OMVs were carried out, and the ability to transfer antibiotic resistance genes via the OMVs was studied. The sequencing and data analysis showed that genome size of A. paragallinarum P4chr1 is about 2.77 Mb and it has a 25 kb tolerance island covering 6 types of antibiotics and 11 resistance genes. The genome size of its OMVs is about 2.69 Mb, covering 97% genome length and almost all gene sequences of P4chr1. When purified and DNase treated A. paragallinarum P4chr1 OMVs were co-cultured with antibiotic sensitive A. paragallinarum Modesto strain on an antibiotic containing plate, the colonies grown on the plate were detected corresponding antibiotic resistance gene (ARG). However, antimicrobial susceptibility test exposed that drug resistance genes delivered by OMVs were not persistent, they only existed temporarily on the antibiotic plates. The antibiotic resistance and ARGs disappeared at second bacterial passage. Overall, this study is the first report to compare genomic characteristics of OMVs with its parent A. paragallinarum strain, and to study A. paragallinarum ARG transfer via OMVs. This work has provided useful data for further study on the issue of non-plasmid ARG transfer mediated by A. paragallinarum OMVs.
p66Shc is an apoptotic rheostat whose targeted ROS inhibition improves MI outcomes
Authors: Haslem Landon , Hays Jennifer M. , Schmitz Hannah , Matsuzaki Satoshi , Sjoelund Virginie , Byrum Stephanie D. , Humphries Kenneth M. , Frazer J. Kimble , Demeler Borries , Benbrook Doris M. , Tierney Ryan M. , Duggan Kelli D. , Hays Franklin A. 
Published: April 2022

SUMMARYp66Shc is an oxidoreductase that responds to cell stress by translocating to mitochondria, where p66Shc produces pro-apoptotic reactive oxygen species (ROS). This study identifies ROS-active p66Shc as a monomer that produces superoxide anion independent of metal ions, inhibits cytochrome c peroxidase, and is regulated by environmental condition-induced structural changes. p66Shc anti-apoptotic functions, including: cytochrome c reduction, increased electron transport chain activity, and caspase cascade inhibition were also discovered. This study also demonstrates that p66Shc is a stress-dependent rheostat of apoptosis, regulated by p66Shc-mortalin complexes. These complexes decrease pro-apoptotic ROS production, without blocking p66Shc-mediated cytochrome c reduction. However, stress disrupts p66Shc-mortalin interactions, promoting apoptosis. Tipping p66Shc’s apoptotic balance toward anti-apoptotic functions by genetic knockdown or p66Shc-selective ROS inhibition decreased pro-apoptotic effects and improved outcomes in zebrafish myocardial infarction models, representing a potential new myocardial infarction treatment with promising results.
Single Nucleus Sequencing of Human Colon Visceral Smooth Muscle Cells, PDGFRα Cells, and Interstitial Cells of Cajal
Authors: Schneider Sabine , Hashmi Sohaib K. , Thrasher A. Josephine , Kothakapa Deepika R. , Wright Christina M. , Heuckeroth Robert O. 
Published: April 2022

AbstractBackground and AimsSmooth muscle cells (SMCs), Interstitial cells of Cajal (ICCs), and PDGFRα+ cells (PαCs) form a functional syncytium in the bowel known as the ‘SIP syncytium’. The SIP syncytium works in concert with the enteric nervous system (ENS) to coordinate bowel motility. However, our understanding of individual cell types that form this syncytium and how they interact with each other remains limited, with no prior single cell RNAseq analyses focused on human SIP syncytium cells.MethodsWe analyzed single-nucleus RNA sequencing data from 10,749 human colon SIP syncytium cells (5572 SMC, 372 ICC, and 4805 PαC nuclei) derived from 15 individuals.ResultsConsistent with critical contractile and pacemaker functions and with known ENS interactions, SIP syncytium cell types express many ion channels including mechanosensitive channels in ICCs and PαCs. PαCs also prominently express ECM-associated genes and the inhibitory neurotransmitter receptor for vasoactive intestinal peptide (VIPR2), a novel finding. We identified two PαC clusters that differ in expression of many ion channels and transcriptional regulators. Interestingly, SIP syncytium cells co-express 6 transcription factors (FOS, MEIS1, MEIS2, PBX1, SCMH1, and ZBTB16) that may be part of a combinatorial signature that specifies these cells. Bowel region-specific differences in SIP syncytium gene expression may correlate with regional differences in function, with right (ascending) colon SMCs and PαCs expressing more transcriptional regulators and ion channels than SMCs and PαCs in left (sigmoid) colon.ConclusionThese studies provide new insights into SIP syncytium biology that may be valuable for understanding bowel motility disorders and lead to future investigation of highlighted genes and pathways.SynopsisIn this first single nucleus RNASeq analysis of human SIP syncytium, we identify novel features of SIP syncytium cells, including two types of PDGFRα+ cells, a SIP-specific combinatorial transcription factor signature, and colon region differences in gene expression.
Combined nanometric and phylogenetic analysis of unique endocytic compartments in Giardia lamblia sheds light on the evolution of endocytosis in Fornicata
Authors: Santos Rui , Ástvaldsson Ásgeir , Pipaliya Shweta V. , Zumthor Jon Paulin , Dacks Joel B. , Svärd Staffan , Hehl Adrian B. , Faso Carmen 
Published: April 2022

ABSTRACTGiardia lamblia, a parasitic protist of the metamonada supergroup, has evolved one of the most diverged endocytic compartment systems investigated so far. Peripheral endocytic compartments, currently known as peripheral vesicles or vacuoles (PVs), perform bulk uptake of fluid phase material which is then digested and sorted either to the cell cytosol or back to the extracellular space. Here, we present a quantitative morphological characterization of these organelles using volumetric electron microscopy and super-resolution microscopy (SRM). We defined a morphological classification for the heterogenous population of PVs and performed a comparative analysis of PVs and endosome-like organelles in representatives of phylogenetically-related taxa,Spironucleus spp.andTritrichomonas foetus. To investigate the as-yet insufficiently understood connection between PVs and clathrin assemblies inG. lamblia, we further performed an in-depth search for two key elements of the endocytic machinery, clathrin heavy chain (CHC) and clathrin light chain (CLC) across different lineages in Metamonada. Our data point to the loss of abona fideCLC in the last Fornicata common ancestor (LFCA) with the emergence of a protein analogous to CLC (GlACLC) in theGiardiagenus. Taken together, this provides the first comprehensive nanometric view ofGiardia’s endocytic system architecture and sheds light on the evolution of GLACLC analogues in the Fornicata supergroup and, specific to Giardia, as a possible adaptation to the formation and maintenance of stable clathrin assemblies at PVs.
Targeted Sequencing of Alzheimer’s Disease Genes in Gujarat Cohort
Authors: Budhbhatti Urvi , Joshi Chaitanya , Chauhan Ajay , Bhatt Deeptiben , Parmar Chirag , Damani Vishalbhai , Patel Amrutlal 
Published: April 2022

AbstractAlzheimer’s Disease (AD) is the most common type of dementia affecting cognitive and behavioural functions. It’s a complex disease that results from the modest effect of gene interaction and environmental factors, as a result of which its exact pathogenesis is still unknown. In the present study, we have performed an association study of exonic regions of 94 genes with AD using the Haloplex target enrichment method and genotyping of 4 genes NOTCH4(rs367398), NEP(rs61760379), APOE (rs121918398), and ATP7B(rs1801243) using PCR RFLP technique. In this study, we screened 32 AD cases and 11 control samples. We have identified 19 variants assigned to 16 genes that were significantly associated with AD with a p-value < 0.05. However, no variants have passed multiple test corrections except NOTCH4/rs367398 genotyped using the PCR-RFLP approach. The functional enrichment analysis of the significant genes for the disease indicates that the genes are significantly involved in AD. Also, functional enrichment analysis for biological processes using ClueGo and network analysis using the STRING database indicated that the genes are directly and indirectly playing a role in AD pathogenesis. The eQTL analysis of the variants with GTEx dataset indicate that out of 19 variants ACHE/rs1799806 and NOTCH4/rs367398 variants is showing significant eQTL for the neighbouring genes for different brain regions and whole blood. Regardless, additional studies with a large cohort are required to establish the role and prevalence of these variants in the local population of Gujarat.
Asymmetric survival in single-cell lineages of cyanobacteria in response to photodamage
Authors: Tay Jian Wei , Cameron Jeffrey C. 
Published: April 2022

Summary paragraphOxygenic photosynthesis is driven by the coupled action of the light-dependent pigment protein complexes, photosystem I and II, located within the internal thylakoid membrane system. However, photosystem II is known to be prone to photooxidative damage. Thus, photosynthetic organisms have evolved a repair cycle to continuously replace the damaged proteins in photosystem II. However, it has remained difficult to deconvolute the damage and repair processes using traditional ensemble approaches. Here we demonstrate an automated approach using time-lapse fluorescence microscopy and computational image analysis to study the dynamics and effects of photodamage in single cells at sub-cellular resolution in cyanobacteria. By growing cells in a two-dimensional layer, we avoid shading effects, thereby generating uniform and reproducible growth conditions. Using this platform, we analyzed the growth and physiology of multiple strains simultaneously under defined photoinhibitory conditions stimulated by UV-A light. Our results reveal an asymmetric cellular response to photodamage between sibling cells and the generation of an elusive subcellular structure, here named a ‘photoendosome’, derived from the thylakoid which could indicate the presence of a previously unknown photoprotective mechanism. We anticipate these results to be a starting point for further studies to better understand photodamage and repair at the single-cell level.
Specific targeting of plasmids with Argonaute enables genome editing
Authors: Esyunina Daria , Okhtienko Anastasiia , Olina Anna , Prostova Maria , Aravin Alexei A. , Kulbachinskiy Andrey 
Published: April 2022

AbstractProkaryotic Argonautes (pAgos) are programmable nucleases involved in cell defense against invading DNA. Recent studies showed that pAgos can bind small single-stranded guide DNAs (gDNAs) to recognize and cleave complementary DNA in vitro. In vivo pAgos preferentially target plasmids, phages and multicopy genetic elements. Here, we reveal that CbAgo nuclease from Clostridium butyricum can be used for genomic DNA cleavage and engineering in bacteria. CbAgo-dependent targeting of genomic loci with plasmid-derived gDNAs promotes recombination between plasmid and chromosomal DNA. Efficient genome cleavage and recombineering depends on the catalytic activity of CbAgo, its interactions with gDNAs, and the extent of homology between plasmid and chromosomal sequences. Specific targeting of plasmids with Argonautes can be used to integrate plasmid-encoded sequences into the chromosome thus enabling genome editing.One-Sentence SummaryProkaryotic Argonaute nuclease induces DNA interference between plasmid and chromosomal DNA to promote genome recombineering.
RNA localization mechanisms transcend cell morphology
Authors: Goering Raeann , Arora Ankita , Taliaferro J. Matthew 
Published: April 2022

ABSTRACTRNA molecules are localized to specific subcellular regions through interactions between RNA regulatory elements and RNA binding proteins (RBPs). Generally, our knowledge of the mechanistic details behind the localization of a given RNA is restricted to a particular cell type. Here, we show that RNA/RBP interactions that regulate RNA localization in one cell type predictably regulate localization in other cell types with vastly different morphologies. To determine transcriptome-wide RNA spatial distributions across the apicobasal axis of human intestinal epithelial cells, we used our recently developed RNA proximity labeling technique, Halo-seq. We found that mRNAs encoding ribosomal proteins (RP mRNAs) were strongly localized to the basal pole of these cells. Using reporter transcripts and single molecule RNA FISH, we found that pyrimidine-rich TOP motifs in the 5′ UTRs of RP mRNAs were suﬃcient to drive basal RNA localization. Interestingly, the same TOP motifs were also suﬃcient to drive RNA localization to the neurites of mouse neuronal cells. In both cell types, the regulatory activity of the TOP motif was dependent on it being at the extreme 5′ end of the transcript, was abolished upon perturbation of the TOP-binding protein LARP1, and was reduced upon inhibition of kinesins. To extend these findings, we compared subcellular RNAseq data from neuronal and epithelial cells. We found that the basal compartment of epithelial cells and the projections of neuronal cells were enriched for highly similar sets of RNAs, indicating that broadly similar mechanisms may be transporting RNAs in both cell types. These findings identify the first RNA element known to regulate RNA localization across the apicobasal axis of epithelial cells, establish LARP1 as an RNA localization regulator, and demonstrate that RNA localization mechanisms cut across cell morphologies.
Beta infection combined with Pfizer BNT162b2 vaccination leads to broadened neutralizing immunity against Omicron
Authors: Cele Sandile , Bernstein Mallory , Karim Farina , Khan Khadija , Ganga Yashica , Jule Zesuliwe , Reedoy Kajal , Lustig Gila , Samsunder Natasha , Mazibuko Matilda , Hwa Shi-Hsia , Manickchund Nithendra , Gottberg Anne von , Magula Nombulelo , Lessells Richard J. , de Oliveira Tulio , Abdool Karim Salim S. , Hanekom Willem ,   COMMIT-KZN Team, Gosnell Bernadett I. , Moosa Mahomed-Yunus S. , Sigal Alex 
Published: April 2022

AbstractOmicron (B.1.1.529) shows extensive escape from vaccine immunity, although vaccination reduces severe disease and death1. Boosting with vaccines incorporating variant spike sequences could possibly broaden immunity2. One approach to choose the variant may be to measure immunity elicited by vaccination combined with variant infection. Here we investigated Omicron neutralization in people infected with the Beta (B.1.351) variant and subsequently vaccinated with Pfizer BNT162b2. We observed that Beta infection alone elicited poor Omicron cross-neutralization, similar to what we previously found3 with BNT162b2 vaccination alone or in combination with ancestral or Delta virus infection. In contrast, Beta infection combined with BNT162b2 vaccination elicited neutralization with substantially lower Omicron escape.
Integrating sustainability practices into the Irish construction supply chain: main contractors' perspective
Authors: Ewuga Duga , Adesi Michael 
Published: April 2022

PurposeThe low level of sustainable practices in the architectural, engineering and construction (AEC) sector continues to increase. In driving sustainability practice adoption and implementation, construction-contracting firms have introduced sustainability practices to their supply chain network. This study examines the strategies adopted by large construction-contracting firms in Ireland to integrate sustainability practices into their supply chain.Design/methodology/approachThe study adopts the mixed-method approach using questionnaires and interviews to collect data. The relative importance index (RII) was used to analyse the data collected through the questionnaire survey. In terms of theoretical underpinning, the study was positioned in the resourced-based view (RBV) theory, which focusses on the link between a firm's internal characteristics and performance.FindingsThe results revealed that, in building a long-term relationship, trust, knowledge of the construction process, commitment, a common goal and mutual support were the key factors considered. While in developing their supply chain, suppliers' assessment and promoting competition in the supply chain were ranked high amongst the mechanisms utilised. Additional findings revealed that long-term relationships with a supply chain organisation have little impact on the project sustainability performance; instead, close collaboration and trust amongst the project team influenced the project sustainability performance.Research limitations/implicationsThe study focusses only on the main contractor's organisation. Further study will require exploring the supply chain organisations to provide a deeper understanding.Practical implicationsThe research demonstrates that for construction-contracting firms to contribute positively to sustainability objectives, they will have to collaborate closely with their supply chain.Originality/valueThe study provided practical and empirical evidence to guide construction-contracting firms to develop strategies to drive and implement sustainable construction practices.
Communication in service ecosystems through value propositions: dilemmas and future research avenues
Authors: Verleye Katrien , Reber Bryan 
Published: April 2022

PurposeThis paper aims to provide insight into communication strategies that may enable service ecosystem actors to co-create economic, social and/or environmental value.Design/methodology/approachTo achieve this end, the authors rely upon the literature on value propositions, which represent strategic tools for communicating about the value package (i.e. the benefits that actors can offer to one another along with its costs). This literature stream – in combination with the communication literature – allows the authors to unravel five dilemmas that service ecosystem actors face when communicating about the value package with one another.FindingsTo co-create value in service ecosystems with the help of value propositions, actors need to reflect upon (1) whether to involve third parties when sending messages about their value package (cf. sender), (2) what information to share about their value package (cf. message), (3) whether to invest resources in face-to-face communication when conveying messages about the value package (cf. channel), (4) whether to reach out to a broad audience with value package messages (cf. receiver) and (5) whether to engage in institutional work through communication in response to various interpretations of messages about the value package (cf. effect).Originality/valueThis research advances the literature on value co-creation in service ecosystems by relying upon communication theory to unravel the dilemmas that come along with using and/or creating value propositions as strategic tools for communication.
Applying the national mental health policy in conflict-affected regions: towards better social inclusion (Ukrainian case)
Authors: Quirke Eleanor , Klymchuk Vitalii , Gusak Nataliia , Gorbunova Viktoriia , Sukhovii Oleksii 
Published: April 2022

Purpose
The ongoing armed conflict in Ukraine has had wide-ranging health, social and economic consequences for the civilian population. It has emphasised the need for comprehensive and sustainable reform of the Ukrainian mental health system. The Ukrainian Government has approved a vision for national mental health reform. This study aims to draw on the lessons of mental health reform in other conflict-affected settings to identify areas of priority for applying the national mental health policy in conflict-affected regions in the direction of better social inclusion of people with mental health conditions (Donetsk and Luhansk regions, directly affected by the conflict).

Design/methodology/approach
A literature review was conducted to identify lessons from implementing mental health reform in other conflict-affected settings. Findings were summarized, and best practices were applied to the national and regional policy context.

Findings
The literature described emergencies as an opportunity to build sustainable mental health systems. A systematic and long-term view for reform is required to capitalise on this opportunity. For better social inclusion, implementation of the concept for mental health and mental health action plans in Donetsk and Luhansk regions should prioritise raising mental health awareness and reducing stigma; developing the capacity of local authorities in the development and coordination of services; tailoring mental health service provision according to the availability of services and population need; targeting the needs of particularly vulnerable groups and embedding the activities of humanitarian actors in local care pathways.

Research limitations/implications
This study summarises the literature on mental health reform in conflict-affected settings and applies key findings to Eastern Ukraine. This study has drawn on various sources, including peer-reviewed journals and grey literature and made several practical recommendations. Nevertheless, potentially relevant information could have been contained in sources that were excluded based on their publication in another language (i.e. not in English). Indeed, while the included studies provided rich examples of mental health reform implemented in conflict-affected settings, further research is required to better understand the mechanisms for effecting sustainable mental health reform in conflict-affected settings

Originality/value
The paper describes opportunities for developing a local community-based mental health-care system in Ukraine, despite the devastating effects of the ongoing war.