bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome-Wide Exploration of the OpportunisticProvidencia stuartiiUnveils the Novel Genetic Interactions with the Virulence Gene of Diarrheal Pathogens
Authors: Hossain Mohammad Uzzal , Hossain Md. Shahadat , Rahman A.B.Z Naimur , Dey Shajib , Chowdhury Zeshan Mahmud , Bhattacharjee Arittra , Ahammad Ishtiaque , Aziz Md. Abdul , Hashem Abu , Das Keshob Chandra , Keya Chaman Ara , Salimullah Md. 
Published: November 2023

AbstractDiarrhea typically indicates an intestinal disorder, which can occur from viruses, parasites or bacterial infection. Along with the common diarrhea-causing pathogens, opportunistic bacteria may also play a role in the etiology of diarrheal disease. One of the opportunist’s bacteria that can cause diarrhea in both children and adults isProvidencia stuartii. Therefore, the goal of this study is to explore the genetic mechanism of the opportunisticP. stuartiiin microbial interactions with common diarrheal pathogens. Hence,P. stuartiiwas identified by utilizing the morphological observation and molecular techniques. Afterwards, the entire genome ofP. stuartiiwas sequenced, assembled and annotated to explore the genomic insights. In addition, the virulence genes of 100 whole genome sequences from ten prevalent diarrhea-causing bacteria were identified and prioritized. Finally, the system biology approach was used to predict the protein-protein interaction network betweenP. stuartiiand the virulence genes. The results of the present study suggests that complete genome sequencing of this bacteria contains 4011 proteins, which are crucial for this bacterium to survive. Additionally, 16 gene clusters provide 207 interacting genes that could interact with biological and molecular function, subcellular localization and pathway. The microbial interaction accompanying the virulence gene was found in all 10 diarrhea-causing bacteria exceptClostridium difficile. These findings of this study could aid in the exploration ofProvidencia stuartiias the major causative agent of diarrhea. Additionally, the pathophysiology of diarrhea can be investigated using the microbial interactions betweenP. stuartiiand the typical diarrheal bacteria. The results of this study may therefore be used to determine the most effective therapeutic targets for the development of medications to treat diarrhea.
In the murine and bovine maternal mammary gland signal transducer and activator of transcription 3 is activated in clusters of epithelial cells around the day of birth
Authors: Hardwick Laura J. A. , Davies Benjamin P. , Pensa Sara , Burge-Rogers Maedee , Davies Claire , Baptista André Figueiredo , Knott Robert , McCrone Ian , Po Eleonora , Strugnell Benjamin W. , Waine Katie , Wood Paul , Khaled Walid T. , Summers Huw D. , Rees Paul , Wills John W. , Hughes Katherine 
Published: November 2023

AbstractSignal Transducers and Activators of Transcription (STATs) regulate mammary gland development. Here we investigate the expression of pSTAT3 in the murine and bovine mammary gland around the day of birth. We identify polarisation of mammary alveoli towards either a low- or high-proportion of pSTAT3 positive alveolar epithelial cells. We present localised colocation analysis applicable to other mammary studies where identification, quantification and interrogation of significant, spatially congregated events is required. We demonstrate that pSTAT3-positive events are multifocally clustered in a non-random and statistically significant fashion. This finding represents a new facet of mammary STAT3 biology meriting further functional investigation.
An Environmental Restriction impairs HIV-1 virion fusion and triggers innate immune recognition
Authors: Ahmed Samy Sid , Zimmerman Liv , Imle Andrea , Wuebben Katrin , Tibroni Nadine , Rauch-Wirth Lena , Münch Jan , Chlanda Petr , Graw Frederik , Fackler Oliver T. 
Published: November 2023

AbstractIn vivo, HIV-1 replicates within 3D tissues, yet the impact of tissue-like environments on viral spread is largely unknown. Our previous research identified that synthetic 3D environments impose anEnvironmental Restriction to cell-free Virus Infectivity(ERVI) that diminishes HIV-1 particle infectivity. Here, mechanistic studies reveal that ERVI is implemented within minutes, saturable and induced by different adhesive tissue-like 3D matrices. ERVI reduces infectivity across a wide range of primary HIV-1 strains and virions bearing distinct viral glycoproteins but does not damage virion morphology or affect their binding to target cells. Rather, ERVI impairs virion fusion with target cells and infectivity enhancing peptide nanofibrils can restore efficient infection. In addition, ERVI sensitizes HIV-1 particles for recognition by monocyte-derived macrophages via toll-like receptors 4 and 8, triggering pronounced pro-inflammatory cytokine secretion. These results suggest that ERVI represents a broadly acting, tissue-intrinsic barrier to virus spread that reduces the fusogenicity of cell-free virions and sensitizes them for innate immune recognition.
A genome-wide segmentation approach for the detection of selection footprints
Authors: Mary-Huard Tristan , Rigaill Guillem 
Published: November 2023

AbstractMotivationIn population genetics, the detection of genomic regions under positive selection is essential to understand the genetic basis of locally adaptive trait variation. We propose a principled approach to detect those regions that combines a robust moment basedFSTestimator with a segmentation algorithm.ResultsOur approach allows for pairwise comparisons of populations and does not require any prior knowledge about the size of the regions to be detected. The procedure runs within seconds even for large genome datasets with millions of SNPs, and provides a complete landscape of theFSTdistribution over the chromosome. The procedure comes with a grounded estimator of the baselineFSTlevel, allowing the detection of regions exhibiting high departures from this reference value. The potential of our procedure is illustrated in two applications in animal and human population genetics. We were able to recover in a matter of seconds regions known to be under selection, often with greater precision than what was reported in previous studies.AvailabilityOur approach is implemented in thefst4pgR package available from the CRAN repository. The Sheep dataset is downloadable from the Zenodo repositoryhttps://doi.org/10.5281/zenodo.237116. The 1000 Genome dataset is downloadable fromftp.1000genomes.ebi.ac.uk/vol1/ftp/release/20130502
MitoTracer facilitates the identification of informative mitochondrial mutations for precise lineage reconstruction
Authors: Yu Xuexin , Hu Jing , Tan Yuhao , Pan Mingyao , Zhang Hongyi , Li Bo 
Published: November 2023

AbstractMitochondrial (MT) mutations serve as natural genetic markers for inferring clonal relationships using single cell sequencing data. However, the fundamental challenge of MT mutation-based lineage tracing is automated identification of informative MT mutations. Here, we introduced an open-source computational algorithm called “MitoTracer”, which accurately identified clonally informative MT mutations and inferred evolutionary lineage from scRNA-seq or scATAC-seq samples. We benchmarked MitoTracer using the ground-truth experimental lineage sequencing data and demonstrated its superior performance over the existing methods measured by high sensitivity and specificity. MitoTracer is compatible with multiple single cell sequencing platforms. Its application to a cancer evolution dataset revealed the genes related to primary BRAF-inhibitor resistance from scRNA-seq data of BRAF-mutated cancer cells. Overall, our work provided a valuable tool for capturing real informative MT mutations and tracing the lineages among cells.TeaserMitoTracer enables automatically and accurately discover informative mitochondrial mutations for lineage tracing.
Selective activation of intracellular β1AR using a spatially restricted antagonist
Authors: Liccardo Federica , Morstein Johannes , Lin Ting-Yu , Pampel Julius , Shokat Kevan M. , Irannejad Roshanak 
Published: November 2023

ABSTRACTG-protein-coupled receptors (GPCRs) regulate several physiological and pathological processes and represent the target of approximately 30% of FDA-approved drugs. GPCR-mediated signaling was thought to occur exclusively at the plasma membrane. However, recent studies have unveiled their presence and function at subcellular membrane compartments. There is a growing interest in studying compartmentalized signaling of GPCRs. This requires development of novel tools to separate GPCRs signaling at the plasma membrane from the ones initiated at intracellular compartments. We took advantage of the structural and pharmacological information available for β1-adrenergic receptor (β1AR), an exemplary GPCR that functions at subcellular compartments, and rationally designed spatially restricted antagonists. We generated a cell impermeable β1AR antagonist by conjugating a suitable pharmacophore to a sulfonate-containing fluorophore. This cell-impermeable antagonist only inhibited β1AR on the plasma membrane. In contrast, a cell permeable β1AR agonist containing a non-sulfonated fluorophore, efficiently inhibited both the plasma membrane and Golgi pools of β1ARs. Furthermore, the cell impermeable antagonist selectively inhibited the phosphorylation of downstream effectors of PKA proximal to the plasma membrane in adult cardiomyocytes while β1AR intracellular pool remained active. Our tools offer promising avenues for investigating compartmentalized β1AR signaling in various context, potentially advancing our understanding of β1AR-mediated cellular responses in health and disease. They also offer a general strategy to study compartmentalized signaling for other GPCRs in various biological systems.
An EPHB4-RASA1 signaling complex inhibits shear stress-induced Ras-MAPK activation in lymphatic endothelial cells to promote the development of lymphatic vessel valves
Authors: Chen Di , Wiggins David , Sevick Eva M. , Davis Michael J. , King Philip D. 
Published: November 2023

SUMMARYEPHB4 is a receptor protein tyrosine kinase that is required for the development of lymphatic vessel (LV) valves. We show here that EPHB4 is necessary for the specification of LV valves, their continued development after specification, and the maintenance of LV valves in adult mice. EPHB4 promotes LV valve development by inhibiting the activation of the Ras-MAPK pathway in LV endothelial cells (LEC). For LV specification, this role for EPHB4 depends on its ability to interact physically with the p120 Ras-GTPase-activating protein (RASA1) that acts as a negative regulator of Ras. Through physical interaction, EPHB4 and RASA1 dampen oscillatory shear stress (OSS)-induced Ras-MAPK activation in LEC, which is required for LV specification. We identify the Piezo1 OSS sensor as a focus of EPHB4-RASA1 regulation of OSS-induced Ras-MAPK signaling mediated through physical interaction. These findings contribute to an understanding of the mechanism by which EPHB4, RASA1 and Ras regulate lymphatic valvulogenesis.
Proteomic mapping of macrophages in response to the clearance of apoptotic cells reveals a unique reprogramming profile
Authors: Raymond Benjamin Bernard Armando , Frey Andrew Michael , Trost Matthias 
Published: November 2023

AbstractDuring the daily process of healthy cellular turnover, billions of cells undergo apoptosis in the human body. These cells are removed by phagocytic cells, namely macrophages through a process known as efferocytosis, which triggers a cascade of reprogramming events in the cell, with a shift towards a pro-resolving or ‘wound healing’ phenotype. To date, no study has attempted to investigate these phenotypic changes from a proteomic perspective. Here, we present a novel and robust workflow for the investigation of proteome and secretome changes in bone marrow-derived macrophages (BMDMs) following efferocytosis using stable isotope labelling by amino acids in cell culture (SILAC) combined with data-independent acquisition (DIA) mass spectrometry. We show that using this workflow we can dissect the mixed proteomes of BMDMs and apoptotic cells to specifically map the reprogramming events occurring in macrophages in the later stages of efferocytosis. Specifically, we find that efferocytic macrophages adopt an alternatively activated phenotype underpinned by an increase in efferocytic and anti-inflammatory markers. We also show that the secretome contains factors that can reprogram naïve BMDMs towards an efferocytosis-like, pro-resolving, phenotype. Our results provide an unprecedented view of the efferocytic landscape of macrophages and will aid in further understanding this important immunological process in the larger context of immune homeostasis and inflammatory disorders.
The Sec61/TRAP Translocon Scrambles Lipids
Authors: Javanainen Matti , Karki Sudeep , Tranter Dale , Biriukov Denys , Paavilainen Ville O. 
Published: November 2023

AbstractCell growth relies on the rapid flip–flop of newly synthesized lipids across the ER membrane. This process is facilitated without the need for ATP by specific membrane proteins—scramblases—a few of which have been very recently identified in the ER. We have previously resolved the structure of the translocon-associated protein (TRAP) bound to the Sec61 translocon in the ER membrane, and found this complex to render the membrane locally thinner. Moreover, Sec61 and TRAP each contain a crevice rich in polar residues that can shield a lipid head group as it traverses the hydrophobic membrane environment. We thus hypothesized that both Sec61 and TRAP act as ER scramblases. Here, we characterized the scrambling activity of Sec61 and TRAP using extensive molecular dynamics simulations. We observed that both Sec61 and TRAP efficiently scramble lipidsviaa credit card mechanism. We analyzed the kinetics and thermodynamics of lipid scrambling and demonstrated that local membrane thinning provides a key contribution to scrambling efficiency. Both proteins appear seemingly selective towards phosphatidylcholine lipids over phosphatidylethanolamine and phosphatidylserine, yet this behavior rather reflects the trends observed for these lipids in a protein-free membrane. The identified scrambling pathway in Sec61 structure is physiologically rarely unoccupied due to its role in protein translocation. Furthermore, we found that the scrambling activity of this pathway might be impeded by the presence of ions at a physiological concentration. However, the trimeric bundle of TRAPβ, TRAPγ, and TRAPδmight provide scrambling activity insensitive to the functional state of the translocon and the solvent conditions.
Tagging of water masses with covariance of trace metals and prokaryotic taxa in the Southern Ocean
Authors: Zhang Rui , Blain Stéphane , Baudet Corentin , Planquette Hélène , Vivier Frédéric , Catala Philippe , Crispi Olivier , Guéneuguès Audrey , Marie Barbara , Debeljak Pavla , Obernosterer Ingrid 
Published: November 2023

AbstractMarine microbes are strongly interrelated to trace metals in the ocean. How the availability of trace metals selects for prokaryotic taxa and the potential feedbacks of microbial processes on the trace metal distribution in the ocean remains poorly understood. We investigate here the potential reciprocal links between diverse prokaryotic taxa and iron (Fe), manganese (Mn), copper (Cu), Nickel (Ni) as well as apparent oxygen utilization (AOU) across 12 well-defined water masses in the Southern Indian Ocean (SWINGS-South West Indian Ocean GEOTRACES GS02 Section cruise). Applying Partial Least Square Regression (PLSR) analysis we show that the water masses are associated with particular latent vectors that are a combination of the spatial distribution of prokaryotic taxa, trace elements and AOU. This approach provides novel insights on the potential interactions between prokaryotic taxa and trace metals in relation to organic matter remineralization in distinct water masses of the ocean.
Neuronal dynamics of cerebellum and medial prefrontal cortex in adaptive motor timing
Authors: Ren Zhong , Wang Xiaolu , Angelov Milen , De Zeeuw Chris I. , Gao Zhenyu 
Published: November 2023

AbstractPrecise temporal control of sensorimotor coordination and adaptation is a fundamental basis of animal behavior. How different brain regions are involved in regulating the flexible temporal adaptation remains elusive. Here we investigated the neuronal dynamics of cerebellar interposed nucleus (IpN) and medial prefrontal cortex (mPFC) neurons during temporal adaptation between delay eyeblink conditioning (DEC) and trace eyeblink conditioning (TEC). When mice trained for either DEC or TEC and subsequently subjected to a new paradigm, their conditioned responses (CRs) adapted virtually instantaneously. Changes in the activity of the IpN neurons to CR timing were prominent during DEC-to-TEC adaptation, but less so during TEC-to-DEC adaptation. In contrast, mPFC neurons could rapidly alter their modulation patterns during both adaptation paradigms. Accordingly, silencing of mPFC blocked the adaptation of CR timing. These results illuminate how cerebral and cerebellar mechanisms may play differential roles during adaptive control of associative motor timing.
SmERF6 promotes the expression of terpenoid pathway in Salvia officinalis and improves the production of high value abietane diterpenes, carnosol and carnosic acid
Authors: Bharadwaj Revuru , Thashanamoorthi Gayathri , Demiwal Pratibha , Sircar Debabrata , Ramalingam Sathishkumar 
Published: November 2023

SummaryCarnosol (CO) and carnosic acid (CA) are pharmaceutically important diterpenes predominantly produced in members of Lamiaceae,Salvia officinalis,Salvia fruticosaandRosmarinus officinalis. Nevertheless, availability of these compounds in plant system is very low.With an effort to improve thein plantacontent of these diterpenes,SmERF6(Salvia miltiorrhiza Ethylene Responsive Factor 6) transcription factor was expressed inS. officinalisheterologously. SmERF6 is known to bind at the promoter regions ofCopalyl diphosphate synthase(CPS) andKaurene synthase like(KSL) genes and improve ferruginol content, a common precursor for abietane diterpenes inSalviagenus.Transient expression ofSmERF6exhibited the inter-specific activity in promoting differential accumulation of diterpenes inS. officinalis. Overexpression studies showed elevation in the levels of CO (10-folds) and CA (8-folds). Further, in infiltrated leaves levels of ferruginol (50%) and CA derivatives (rosmanol, epirosmanal, methyl carnosic acid) were significantly upregulated along with the other signature terpenes. While, knockdown of homologousERF6resulted in drastic reduction of the metabolite content.Finally, stable transgenic lines ofS. officinalisdeveloped throughin planta Agrobacteriummediated genetic transformation method accumulated higher levels of CO (4-folds) and CA (3-folds) as compared to wild plants.Overall, the present study is the first report on improving the content of pharmaceutically important diterpenes inS. officinalisby overexpressing pathway specific transcription factor. The current results showed convincing evidence for the concept of improving the content of specialized metabolite(s) in medicinal plants by manipulating the expression of key transcription factors.
A survey study of Iraqi auditors' adoption of blockchain technology
Authors: Majeed Rasha H. , Taha Alaa A.D. 
Published: November 2023

PurposeThis paper seeks to investigate the factors influencing auditors' behavioural intentions towards blockchain technology (BT) adoption in Iraqi government banks. It also highlights the relationships between these factors to determine if the proposed model can provide a more comprehensive means of comprehending how auditors in government banks have adopted BT.Design/methodology/approachThe study uses the unified theory of acceptance and use of technology and expands it by incorporating five external constructs: “system trust”, “cost”, “transparency”, “security” and “auditor's skill.” This study employed a quantitative and exploratory methodology through the gathering and examination of data from 300 auditors. For the evaluation of the measurement and structural models, the authors adopted the partial least squares structural equation modelling approach with SmartPLS v4.FindingsThe findings demonstrate that “auditor's skill and four government features of BT adoption” are major factors in government bank auditors' adoption of BT. Additionally, the findings indicate that social influence is a potent indicator of one's intention to adopt BT in the banking industry.Research limitations/implicationsOne limit of this study is the selection of governmental perspective. This study is limited to auditors' opinions, who work at the government banks. Further studies may consider other perspectives in order to provide an in-depth analysis of blockchain.Practical implicationsThis paper offers valuable insights into the factors influencing the adoption of blockchain technology in Iraqi governmental banks. It provides empirical evidence supporting auditing units and internal auditors in enhancing their job performance through the adoption of such technology.Originality/valueThis study contributes to the existing literature on technology adoption within the audit profession, specifically examining the use of blockchain technology. By exploring the features of technology adoption within government institutions in the auditing field, it introduces a new perspective, emphasizing the importance of auditor skills.
Does social proof and herd behaviour drive food choices of consumers?
Authors: Begho Toritseju , Liu Shuainan 
Published: November 2023

PurposePeople often look to the opinions and actions of others to guide their food choices, especially when they are uncertain or unfamiliar with a particular food. This influence can be positive or negative depending on the context and can have an impact on food consumption and health outcomes.Design/methodology/approachThe paper analysed data from 500 young adult consumers in China and employed a multi-study design to examine various aspects of social proof and herd behaviour in food choices. Experiment 1 examined the influence of testimonials from an influential person on buying decisions and eating behaviour. Experiment 2 explored whether herd behaviour drives food options. Experiment 3 assessed the influence of social proof on food choices. Chi-square tests of independence were conducted to examine the relationship between social proof and food choice, as well as herd behaviour and food decision-making. Several logit regression analyses were performed to identify the factors that drive consumers' susceptibility to social proof and herding.FindingsThe results indicated that the source of feedback, whether from an influential person or a family member, did not have a statistically significant effect on the likelihood of following the food guide recommendations. The preference for a healthier food option was stronger than following the herd. In contrast, social proof in the form of reviews and ratings influenced participants' choices. The paper highlights the usefulness for stakeholders and policymakers seeking to promote healthier eating habits.Originality/valueThe originality lies in its comprehensive approach, combining multiple experiments and analytical methods.