bluuebunny/crossref_metadata_2025_split huggingface dataset:
ER Stress Impedes Regulated Secretion by Governing Key Exocytotic and Granulogenic Molecular Switches
Authors: Mukherjee Mohima , Mukherjee Chandramouli , Ghosh Vinayak , Jain Aamna , Sadhukhan Souren , Dagar Sushma , Sahu Bhavani Shankar 
Published: April 2023

AbstractDense core vesicles (DCVs) and synaptic vesicles (SVs) are specialised secretory vesicles (SSVs) in neurons/neuroendocrine cells harbouring cargo whose abnormal release is associated with pathophysiology. Endoplasmic Reticulum (ER) stress and inter-organellar communication are also associated with disease biology. In pursuit of investigating the cell physiological consequences arising from the crosstalk of a stressed ER and DCVs, ER stress was modelled in PC12 neuroendocrine cells using Thapsigargin (Tg). DCV exocytosis was severely compromised in ER-stressed PC12 cells, reversed by Docosahexaenoic acid (DHA). Experiments with Tunicamycin(Tm), an independent ER stressor, yielded similar results. Concurrently, ER stress caused impaired DCV exocytosis also in INS-1 cells. Molecular analysis revealed blunted SNAP25 expression, potentially attributed to augmented levels of ATF4 (a well-known CREB inhibitor) and its transcriptional regulator CREB (also known to regulate key granulogenic players Chromogranin A, Secretogranin II). Our studies revealed severe defects in DCV exocytosis in ER-stressed cells for the first time, mediated by reduced levels of key ‘exocytotic’ and ‘granulogenic’ switches regulated via the CREB/ATF4/eIF2α axis.
The distribution, phenology, host range and pathogen prevalence ofIxodes ricinusin France: a systematic map and narrative review
Authors: Perez Grégoire , Bournez Laure , Boulanger Nathalie , Fite Johanna , Livoreil Barbara , McCoy Karen D. , Quillery Elsa , René-Martellet Magalie , Bonnet Sarah I. 
Published: April 2023

AbstractThe tickIxodes ricinusis the most important vector species of infectious diseases in European France. Understanding its distribution, phenology, and host species use, along with the distribution and prevalence of associated pathogens at national scales is essential for developing prevention strategies. The aim of this paper is to provide a systematic map and narrative review of the existing knowledge on the eco-epidemiology ofI.ricinusin France. Using literature published up to 2020, the present paper provides a distribution map for the species and a summary of environmental factors explaining observed geographical differences in phenology and temporal differences in abundance. The diversity of vertebrate host species used by this tick, along with their degree of infestation when available, are presented and discussed with respect to their potential contribution to the population dynamics ofI.ricinusand the circulation of tick-borne zoonotic pathogens. Prevalence data of detected pathogens are summarised in different maps. Results from 187 identified references show that the species is present in most departments, but scarce under Mediterranean climate and in coastal habitats. Its phenology is generally bimodal with variations depending on climate. Abundance seems positively influenced by forest cover and host abundance. Rodents and ruminants are the most studied species groups, but the diversity of sampling protocols (e.g., location, season, exhaustivity of inspection) precluded direct comparisons between species groups. Data on pathogens are patchy, with most studies conducted near research units. Among pathogens,Borrelia burgdorferisensu lato is the most searched for in ticks and seems more prevalent in north-eastern and central France. The review carried out here has made it possible to highlight the gaps in our knowledge of tick-host-pathogen interactions, their ecology and their distribution, and the need to address these gaps in order to optimize tick and tick-borne diseases prevention and control strategies.
The Sterile Insect Technique can efficiently reduce the reproduction of the spotted wing drosophila (Drosophila suzukii) in strawberry
Authors: Gard B. , Panel A. , Labbetoul A. , Bosshard N. , Xuereb A. , Cariou B. , Debelle A. , Oliva C. , Fellous S. 
Published: April 2023

AbstractThe spotted wing drosophila (SWD)Drosophila suzukii(Diptera: Drosophilidae) is a pest of soft fruit. Since its introduction in Europe in 2008 farmers struggle to protect their crops. The sterile insect technique (SIT) has proven efficient at controlling numerous fruit fly species and could be deployed to controlD. suzukii. In recent years, key elements of SIT applied toD. suzukiihave become available. However, field- and field-like experiments are scarce. In this experiment, we assayed the efficacy of a high-performance strain at reducing the reproduction ofD. suzukiiin complex, yet replicated and controlled conditions. Two ratios of sterile to fertile insects (5:1 and 1:1) using bisexual releases were compared to a control treatment with fertile, wild flies only. The presence of sterile individuals at a 5:1 ratio significantly reduced fly reproduction, measured after 5 days, by an approximate threefold factor. However, the proportion of infested fruits in the treated plots remained unaffected. The number of available berries in the cage appeared an unexpected determinant of fly infestation, suggesting undocumented density-dependent processes. The success of this assay opens the door to larger scales experiments, over several generations, and, in the near future, the field-evaluation of the efficacy of the SIT to controlD. suzukii.
GABA, glucose and insulin orchestrate CD4+T cells effector functions
Authors: Jin Z , Hammoud H , Bhandage AK , Korol SV , Trujeque-Ramos O , Koreli S. , Chowdhury AI , Sandbaumhüter FA , Jansson ET , Andrén PE , Bergsten P , Kamali-Moghaddam M , Birnir B 
Published: April 2023

AbstractMetabolic programs of immune cells are closely linked to their effector functions. Physiological molecules including glucose, insulin and γ-aminobutyric acid (GABA) provide environmental cues and guidance, although how they coordinate to regulate the cells is still being unraveled. Here, we demonstrate that GABA-mediated reduction of metabolic activity and release of inflammatory molecules, including IFNγ and IL-10, was abolished in human CD4+T cells when the glucose concentration was elevated above normal levels. Insulin enhanced the GABAAreceptors-mediated currents and Ca2+influx. GABA decreased, whereas insulin sustained glycolysis but in a SGLT (Na+-glucose transporter)-dependent manner. In high glucose (16.7 mM), the SGLTs antagonist phlorizin alone or together with GABA restored the inhibition of IFNγ and IL-10 release. This study exposes concerted effects of GABA, glucose and insulin on CD4+T cells metabolic activity and release of inflammatory molecules, and identifies a role for SGLTs in CD4+T cells function.
WITHDRAWN: Purifying Selection and Persistent Polymorphism among Nuclei in the Multinucleate Arbuscular Mycorrhizal (AM) Fungi
Authors: Manyara David , Sánchez-García Marisol , Thorén Markus Hiltunen , Montoliu-Nerin Merce , Cheng George , Bever James D. , Johannesson Hanna , Rosling Anna 
Published: April 2023

Withdrawal StatementThe authors have withdrawn this manuscript and do not wish it to be cited. As we have reviewed the quality of our datasets, we have discovered that our initial analyses do not confidently support our biological inferences well. We are recalibrating and intend to submit a new manuscript in the future. If you have any questions, please get in touch with the corresponding author.
A statistical learning method for simultaneous copy number estimation and subclone clustering with single cell sequencing data
Authors: Qin Fei , Cai Guoshuai , Xiao Feifei 
Published: April 2023

ABSTRACTThe availability of single cell sequencing (SCS) enables us to assess intra-tumor heterogeneity and identify cellular subclones without the confounding effect of mixed cells. Copy number aberrations (CNAs) have been commonly used to identify subclones in SCS data using various clustering methods, since cells comprising a subpopulation are found to share genetic profile. However, currently available methods may generate spurious results (e.g., falsely identified CNAs) in the procedure of CNA detection, hence diminishing the accuracy of subclone identification from a large complex cell population. In this study, we developed a CNA detection method based on a fused lasso model, referred to as FLCNA, which can simultaneously identify subclones in single cell DNA sequencing (scDNA-seq) data. Spike-in simulations were conducted to evaluate the clustering and CNA detection performance of FLCNA benchmarking to existing copy number estimation methods (SCOPE, HMMcopy) in combination with the existing and commonly used clustering methods. Interestingly, application of FLCNA to a real scDNA-seq dataset of breast cancer revealed remarkably different genomic variation patterns in neoadjuvant chemotherapy treated samples and pre-treated samples. We show that FLCNA is a practical and powerful method in subclone identification and CNA detection with scDNA-seq data.
In vivometabolomics identifies CD38 as an emergent vulnerability inLKB1-mutant lung cancer
Authors: Deng Jiehui , Peng David H. , Fenyo David , Yuan Hao , Lopez Alfonso , Levin Daniel S. , Meynardie Mary , Quinteros Mari , Ranieri Michela , Sahu Soumyadip , Lau Sally C. M. , Shum Elaine , Velcheti Vamsidhar , Punekar Salman R. , Rekhtman Natasha , Dowling Catríona M. , Weerasekara Vajira , Xue Yun , Ji Hongbin , Siu Yik , Jones Drew , Hata Aaron N. , Shimamura Takeshi , Poirier John T. , Rudin Charles M , Hattori Takamitsu , Koide Shohei , Papagiannakopoulos Thales , Neel Benjamin G. , Bardeesy Nabeel , Wong Kwok-kin 
Published: April 2023

ABSTRACTLKB1/STK11 is a serine/threonine kinase that plays a major role in controlling cell metabolism, resulting in potential therapeutic vulnerabilities in LKB1-mutant cancers. Here, we identify the NAD+degrading ectoenzyme, CD38, as a new target in LKB1-mutant NSCLC. Metabolic profiling of genetically engineered mouse models (GEMMs) revealed that LKB1 mutant lung cancers have a striking increase in ADP-ribose, a breakdown product of the critical redox co-factor, NAD+. Surprisingly, compared with other genetic subsets, murine and human LKB1-mutant NSCLC show marked overexpression of the NAD+-catabolizing ectoenzyme, CD38 on the surface of tumor cells. Loss of LKB1 or inactivation of Salt-Inducible Kinases (SIKs)—key downstream effectors of LKB1— induces CD38 transcription induction via a CREB binding site in the CD38 promoter. Treatment with the FDA-approved anti-CD38 antibody, daratumumab, inhibited growth of LKB1-mutant NSCLC xenografts. Together, these results reveal CD38 as a promising therapeutic target in patients with LKB1 mutant lung cancer.SIGNIFICANCELoss-of-function mutations in theLKB1tumor suppressor of lung adenocarcinoma patients and are associated with resistance to current treatments. Our study identified CD38 as a potential therapeutic target that is highly overexpressed in this specific subtype of cancer, associated with a shift in NAD homeostasis.
The covariance environment defines cellular niches for spatial inference
Authors: Haviv Doron , Gatie Mohamed , Hadjantonakis Anna-Katerina , Nawy Tal , Pe’er Dana 
Published: April 2023

AbstractThe tsunami of new multiplexed spatial profiling technologies has opened a range of computational challenges focused on leveraging these powerful data for biological discovery. A key challenge underlying computation is a suitable representation for features of cellular niches. Here, we develop the covariance environment (COVET), a representation that can capture the rich, continuous multivariate nature of cellular niches by capturing the gene-gene covariate structure across cells in the niche, which can reflect the cell-cell communication between them. We define a principled optimal transport-based distance metric between COVET niches and develop a computationally efficient approximation to this metric that can scale to millions of cells. Using COVET to encode spatial context, we develop environmental variational inference (ENVI), a conditional variational autoencoder that jointly embeds spatial and single-cell RNA-seq data into a latent space. Two distinct decoders either impute gene expression across spatial modality, or project spatial information onto dissociated single-cell data. We show that ENVI is not only superior in the imputation of gene expression but is also able to infer spatial context to disassociated single-cell genomics data.
Targeting Sex Determination to Suppress Mosquito Populations
Authors: Li Ming , Kandul Nikolay P. , Sun Ruichen , Yang Ting , Benetta Elena D. , Brogan Daniel J. , Antoshechkin Igor , Sánchez C. Héctor M. , Zhan Yinpeng , DeBeaubien Nicolas A. , Loh YuMin M. , Su Matthew P. , Montell Craig , Marshall John M. , Akbari Omar S. 
Published: April 2023

AbstractEach year, hundreds of millions of people are infected with arboviruses such as dengue, yellow fever, chikungunya, and Zika, which are all primarily spread by the notorious mosquitoAedes aegypti. Traditional control measures have proven insufficient, necessitating innovations. In response, here we generate a next generation CRISPR-based precision-guided sterile insect technique (pgSIT) forAedes aegyptithat disrupts genes essential for sex determination and fertility, producing predominantly sterile males that can be deployed at any life stage. Using mathematical models and empirical testing, we demonstrate that released pgSIT males can effectively compete with, suppress, and eliminate caged mosquito populations. This versatile species-specific platform has the potential for field deployment to effectively control wild populations of disease vectors.
Barriers and facilitators to sexual and reproductive health rights for Persons with Disability in Nepal: a scoping review
Authors: Bhattarai Sanju , Saugat Pratap KC , Kakchapati Sampurna , Poudel Shraddha , Baral Sushil Chandra , Marston Cicely 
Published: April 2023

AbstractPersons with disability have the same sexual and reproductive health needs as people without disability but their rights have consistently been overlooked. They face numerous challenges to access sexual and reproductive health services in Nepal, however coherent evidence on nature, size, and extent of these challenges are not available. We carried out a literature review to explore barriers and facilitators encountered by persons with disability while accessing sexual and reproductive health services in Nepal. We reviewed published government policies on reproductive health and disability, searched PubMed database and used google scholar search engine to find literature published between 2011 to 2021 that reported on barriers and facilitators to sexual and reproductive health rights for person with disability in Nepal. Out of 2145 identified literature only 21 literatures meeting the eligibility criteria were included in the analysis. We found inadequate inclusion of PWDs in health sector policies, lack of knowledge about SRH needs, misconception and poor attitude and lack of social support in accessing SRH rights and services. In Nepal, people with disabilities face multitude of barriers in accessing sexual and reproductive healthcare. Multilevel measures informed by further studies on vulnerabilities and experience of different subgroups of PWDs.
Adherence to the TRIPOD statement of clinical prediction models for spinal pain or osteoarthritis: a protocol for a meta-research study
Authors: Feller Daniel , Wingbermuhle Roel , Innocenti Tiziano , Ostelo Raymond , Chiarotto Alessandro 
Published: April 2023

ABSTRACTBackgroundStudies that develop and/or validate a clinical (diagnostic or prognostic) prediction model should be reported with sufficient details to enable the clinician to use the model in clinical practice. Also, an adequate reporting enables researchers to externally validate the model and assess its validity and reliability. To improve the reporting of multivariable prediction models, the TRIPOD checklist was released in 2015.ObjectiveEvaluate the quality of reporting of prediction model studies conducted in patients with back pain, neck pain or osteoarthritis.MethodsWe will perform a systematic review of the literature, searching MEDLINE (via Ovid), Embase, Web of Science, and CINHAL (via EBSCO) for studies that describe a model development, external validation, update, or a combination of these in patients with back pain, neck pain or osteoarthritis. The completeness of the reporting will be evaluated using a specific adherence assessment form of the TRIPOD. Two authors will independently perform the study selection and data extraction processes. A descriptive analysis of the total score and the individual items of the TRIPOD will be produced.Ethics and disseminationUpon the completion of the study, a manuscript with the results will be submitted for publication in a peer-reviewed journal.
A novel Energy Landscape method incorporating the Latent Dirichlet Allocation topic model and the pairwise Maximum Entropy model, revealing the significant contribution of Bactericides to the development of Inflammatory Bowel Disease
Authors: Zhang Kaiyang , Nakaoka Shinji 
Published: April 2023

1AbstractThe dysbiosis of microbiota has been reported to be associated with numerous human pathophysiological processes, including Inflammatory Bowel Disease (IBD). With advancements in highthroughput sequencing, various methods have been developed to study the alteration of microbiota in the development and progression of diseases. However, a suitable approach to assess the global stability of the microbiota in disease states through time-series microbiome data is yet to be established. In this study, we introduce a novel Energy Landscape construction method, which incorporates the Latent Dirichlet Allocation (LDA) model and the pairwise Maximum Entropy (MaxEnt) model, and demonstrate its utility by applying it to an IBD time-series dataset. Through this method, we obtained the “energy” profile for the potential patterns of microbiota to occur under disease, indicating their stability and prevalence. The results suggest the potential contribution of several microbial genera, includingBacteroides, Alistipes, andFaecalibacterium, as well as their interactions, to the development of IBD. Our proposed method provides a novel and insightful tool for understanding the alteration and stability of the microbiota under disease states and offers a more holistic view of its complex dynamics at play in microbiota-mediated disease.
Unravelling genome organization of neopolyploid flatwormMacrostomum lignano
Authors: Zadesenets Kira S. , Ershov Nikita I. , Bondar Natalya P. , Rubtsov Nikolai B. 
Published: April 2023

AbstractWhole genome duplication (WGD) is an evolutionary event resulting in a redundancy of genetic material. Different mechanisms of genome doubling through allo- or autopolyploidization could lead to distinct evolutionary trajectories of newly formed polyploids. Genome studies on such species are undoubtedly important for understanding one of the crucial stages of genome evolution. However, assembling neopolyploid appears to be a challenging task because its genome consists of two homologous (or homeologous) chromosome sets and therefore contains the extended paralogous regions with a high homology level. Post-WGD evolution of polyploids includes rediploidization, first part of which is cytogenetic diploidization led to the formation of species, whose polyploid origin might be hidden by disomic inheritance and diploid-like meiosis. Earlier we uncovered the hidden polyploid origin of free-living flatworms of the genusMacrostomum(Macrostomum lignano, M. janickei, andM. mirumnovem). Despite the different mechanisms for their genome doubling, cytogenetic diploidization in these species accompanied by intensive chromosomal rearrangements including chromosomes fusions. In this study, we reported unusual subgenomic organization ofM. lignanothrough generation and sequencing of two new laboratory sublines of DV1 that differ only by a copy number of the large chromosome MLI1. Using non-trivial assembly-free comparative analysis of their genomes, including adapted multivariate k-mer analysis, and self-homology within the published genome assembly ofM. lignano, we deciphered DNA sequences belonging to MLI1 and validated them by sequencing the pool of microdissected MLI1. Here we presented the uncommon mechanism of genome rediplodization ofM. lignano, which consists in (1) presence of three subgenomes, emerged via formation of large fused chromosome and its variants, and (2) sustaining their heterozygosity through inter- and intrachromosomal rearrangements.
ER-to-lysosome Ca2+refilling followed by K+efflux-coupled store-operated Ca2+entry in inflammasome activation and metabolic inflammation
Authors: Kang Hyereen , Choi Seong Woo , Kim Joo Young , Oh Soo-Jin , Kim Sung Joon , Lee Myung-Shik 
Published: April 2023

AbstractWe studied lysosomal Ca2+in inflammasome. LPS+palmitic acid (PA) decreased lysosomal Ca2+([Ca2+]Lys) and increased [Ca2+]ithrough mitochondrial ROS, which was suppressed inTrpm2-KO macrophages. Inflammasome activation and metabolic inflammation in adipose tissue of high-fat diet (HFD)-fed mice were ameliorated byTrpm2KO. ER→lysosome Ca2+refilling occurred after lysosomal Ca2+release whose blockade attenuated LPS+PA-induced inflammasome. Subsequently, store-operated Ca2+entry (SOCE) was activated whose inhibition suppressed inflammasome. SOCE was coupled with K+efflux whose inhibition reduced ER Ca2+content ([Ca2+]ER) and impaired [Ca2+]Lysrecovery. LPS+PA activated KCa3.1 channel, a Ca2+-activated K+channel. Inhibitors of KCa3.1 channel orKcnn4KO reduced [Ca2+]ER, attenuated increase of [Ca2+]ior inflammasome activation by LPS+PA, and ameliorated HFD-induced inflammasome or metabolic inflammation. Lysosomal Ca2+release induced delayed JNK and ASC phosphorylation through CAMKII-ASK1. These results suggest a novel role of lysosomal Ca2+release sustained by ER→lysosome Ca2+refilling and K+efflux through KCa3.1 channel in inflammasome activation and metabolic inflammation.