bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bio-guided isolation of a new sesquiterpene fromArtemisia cinawith anthelmintic activity againstHaemonchus contortusL3infective larvae
Authors: Arango-De-la Pava Luis David , González-Cortázar Manasés , Zamilpa Alejandro , Cuéllar-Ordaz Jorge Alfredo , de la Cruz-Cruz Héctor Alejandro , Higuera-Piedrahita Rosa Isabel , López-Arellano Raquel 
Published: March 2024

AbstractHaemonchus contortusis a blood-feeding gastrointestinal parasite that impacts grazing sheep, causing economic losses in animal production and presenting anthelmintic resistance, requiring alternative antiparasitic treatments, including the exploration of plant-based anthelmintics.Artemisia cina(Asteraceae) is a plant whosen-hexane (n-HE) and ethyl acetate extract (EAE) exhibits anthelmintic activity againstH. contortus, being then-HE more active. With the aim of discovering additional bioactive metabolites, a chemical analysis was performed on EAE, which presented a LC90of 3.30 mg/mL and allowed the isolation of 11-[(1R,5S,7R,8R,10S,)-1,8-dihydroxy-5,10-dimethyl-4-oxodecahydroazulen-7-yl] acrylic acid, a new sesquiterpene that was identified through one and two-dimensional NMR. The compound was named cinic acid and displayed a CL50of 0.13 (0.11 -0.14) mg/mL and CL90of 0.40 (0.37 - 0.44) mg/mL, which, compared with EAE larvicidal activity, was 256-fold more active at LC50and 15.71-fold at LC90. In this study, a new sesquiterpene with anthelmintic effects againstH. contortusL3infective larvae was isolated from the EAE ofArtemisia cina.Author summaryHaemonchus contortusis a hematophagous gastrointestinal parasite that affects grazing sheep. Due to its feeding habits, it induces anemia, poor digestion, diarrhea, and weight loss in animals, potentially leading to death in young individuals and causing economic losses in animal production. Moreover, it demonstrates resistance to drugs, making it imperative to explore alternative antiparasitic treatments againstH. contortus, such as the discovery and development of plant-based anthelmintics. In this work, we explore the ethyl acetate extract (EAE) ofArtemisia cinain the search of bioactive compounds. A new sesquiterpene was separated through a bio-guided isolation monitoring the larvicidal effect againstH. ContortusL3infective larvae and was named cinic acid. These findings suggest that the EAE could be promising candidate for the development of a plant-based pharmaceutical preparation with notable anthelmintic activity againstH. contortus.
Investigation of the Association of Acute Pancreatitis Outcomes with Social Vulnerability Indicators
Authors: Chhoda Ankit , Liyen-Cartelle Anabel , Noriega Marco , Anderson Kelsey , Zuberi Shaharyar A. , Sur Alana , Olivares Miriam , Kelly Jill , Freedman Steven D. , Rabinowitz Loren G. , Sheth Sunil G. 
Published: February 2024

ABSTRACTBACKGROUND AND AIMGeospatial analyses integrate location-based sociodemographic data, offering a promising approach to investigate the impact of social determinants on acute pancreatitis (AP) outcomes. This study aimed to examine the association of social vulnerability index (SVI) and its constituent 16 attributes in 4 domains (socioeconomic status, household composition and disability, minority status and language, and housing type and transportation), with outcomes of patients with AP.METHODSThis study included AP patients hospitalized between 1/1/2008 and 12/31/2018 and recorded their demographics and clinical outcomes. Physical addresses were geocoded to determine SVI, a composite variable which was ranked and divided into quartiles (I to IV: IV representing the highest vulnerability).RESULTIn 824 patients [age of 53.0±10 years and 48.2% females], with 993 AP-related hospitalizations, we noted significantly higher prevalence of no/federal/state insurance(P<0.001)and racial minorities(P<0.001)in patients residing in communities with higher SVI. A non-significant trend of higher 30-day admission rate amongst patients from higher SVI regions (III/IV: 27(18.0%)/31(18.9%)vs.I/II: 40(13.8%)/36(16.3%);p=0.49) was noted. We observed a significant association of alcohol withdrawal with residence in areas with higher SVI despite adjustment for age, body mass index, and comorbidities (OR:1.62[95%CI:1.19-2.22];p=0.003). However, we observed no association of SVI with severity of AP, inpatient opioid use, length of stay, and mortality.CONCLUSIONWe noted significantly higher alcohol withdrawal in patients residing in areas with higher SVI ranks although AP severity and other outcomes lacked significant association with SVI. Given our findings further investigation of various social determinants of health in AP is warranted in large sized prospective studies.
A SNP-based honey bee paternity assignment test for evaluating the effectiveness of mating stations and its application to the Ataun valley, Basque Country, Spain
Authors: Parejo Melanie , Galartza Egoitz , Momeni Jamal , Gorrochategui-Ortega June , Farajzadeh Leila , Wegener Jakob , Bienefeld Kaspar , Zarraonaindia Iratxe , Estonba Andone 
Published: March 2024

AbstractGeographically isolated mating stations are deployed across Europe to facilitate controlled mating with selected drone-producing colonies. To assess the reliability of these stations, we developed a paternity assignment test using a custom Illumina genotyping chip with 6457 SNPs based on two metrics (number of mismatch alleles and kinship). The method demonstrated remarkable accuracy during validation with an independent dataset of known parent-offspring pairs, with an accuracy rate of 97.7%. We then applied the developed paternity assignment test to theApis mellifera iberiensismating station in the Ataun valley, Basque Country, Spain, in 2021. Drone-producing colonies in the valley were sampled and genotyped, as well as 156 worker offspring of queens mated at the station, and 56 drones collected in the drone congregation area. Out of the 156 worker samples, we could assign paternity of 120 (76.9%) to one of the drone-producing colonies in the valley, while 23.1% were of unknown patriline. Out of the 56 drones collected in the air, 52 (92.9%) were assigned to drone-producing colonies. We were also able to determine the colonies and apiaries that made the most significant contributions to the matings. This information aids in effective apiary management, including the selection of suitable mating station locations and the positioning of drone-producing colonies therein. Overall, our SNP-based paternity assignment test offers a valuable tool for evaluating mating station effectiveness across Europe, crucial for advancing breeding objectives in honey bee populations.
Endometriotic lesions exhibit distinct metabolic signature compared to paired eutopic endometrium at the single-cell level
Authors: Sarsenova Meruert , Lawarde Ankita , Pathare Amruta D. S. , Saare Merli , Modhukur Vijayachitra , Soplepmann Pille , Terasmaa Anton , Käämbre Tuuli , Gemzell-Danielsson Kristina , Lalitkumar Parameswaran Grace Luther , Salumets Andres , Peters Maire 
Published: March 2024

AbstractCurrent therapeutics of endometriosis are limited to hormonal action on endometriotic lesions to disrupt their growth. Based on the recent findings of the high utilization of glycolysis over oxidative metabolism (Warburg-like effect) in endometriotic lesions, a new strategy of nonhormonal management by addressing cellular metabolism has been proposed. However, it remains unclear which cell types are metabolically altered and contribute to endometriotic lesion growth for targeting them with metabolic drugs. Using single-cell RNA-sequencing, we investigated the activity of twelve metabolic pathways and genes involved in steroidogenesis in paired samples of eutopic endometrium (EuE) and peritoneal lesions (ectopic endometrium, EcE) from women with confirmed endometriosis. We detected nine major cell clusters in both EuE and EcE. The metabolic pathways were differentially regulated in perivascular, stromal and to a lesser extent in endothelial cell clusters, with the highest changes in AMP-activated protein kinase signaling, Hypoxia-Inducible Factor-1 signaling, glutathione metabolism, oxidative phosphorylation, and glycolysis/gluconeogenesis. We identified a transcriptomic co-activation of glycolysis and oxidative metabolism in perivascular and stromal cells of EcE compared with EuE, suggesting that metabolic reprogramming may play a critical role in maintaining cell growth and survival of endometriotic lesions. Additionally, progesterone receptor was significantly downregulated in perivascular and endothelial cells of EcE. The expression of estrogen receptor 1 was significantly reduced in perivascular, stromal and endothelial cells of EcE. In parallel, perivascular cells exhibited a high expression of estrogen receptor 2 andHSD17B8gene that encodes for protein converting estrone (E1) to estradiol (E2), while in endothelial cellsHSD17B2gene coding for enzyme converting E2 to E1 was downregulated. Overall, our results identified different expression patterns of energy metabolic pathways and steroidogenesis-related genes in perivascular, stromal, and endothelial cells in EcE compared with EuE. Perivascular cells, known to contribute to the restoration of endometrial stroma and angiogenesis, can be a potential target for non-hormonal treatment of endometriosis.
Exploring a large cancer cell line RNA-sequencing dataset with k-mers
Authors: Bessière Chloé , Xue Haoliang , Guibert Benoit , Boureux Anthony , Rufflé Florence , Viot Julien , Chikhi Rayan , Salson Mikaël , Marchet Camille , Commes Thérèse , Gautheret Daniel 
Published: March 2024

AbstractAnalyzing the immense diversity of RNA isoforms in large RNA-seq repositories requires laborious data processing using specialized tools. Indexing techniques based on k-mers have previously been effective at searching for RNA sequences across thousands of RNA-seq libraries but falling short of enabling direct RNA quantification. We show here that RNAs queried in the form of k-mer sets can be quantified in seconds, with a precision akin to that of conventional RNA quantification methods. We showcase several applications by exploring an index of the Cancer Cell Line Encyclopedia (CCLE) collection consisting of 1019 RNA-seq samples. Non-reference RNA sequences such as RNAs harboring driver mutations and fusions, splicing isoforms or RNAs derived from repetitive elements, can be retrieved with high accuracy. Moreover, we show that k-mer indexing offers a powerful means to reveal variant RNAs induced by specific gene alterations, for instance in splicing factors. A web server allows public queries in CCLE and other indexes:https://transipedia.fr. Code is provided to allow users to set up their own server from any RNA-seq dataset.
Cognate Antigen Engagement Induces HIV-1 Expression In CD4+T Cells From People On Long-Term ART
Authors: Moskovljevic Milica , Dragoni Filippo , Board Nathan L. , Wu Fengting , Lai Jun , Zhang Hao , White James R. , Hoh Rebecca , Lynn Kenneth , Tebas Pablo , Mounzer Karam , Deeks Steven G. , Montaner Luis J. , Siliciano Janet D. , Simonetti Francesco R. , Siliciano Robert F. 
Published: March 2024

SummaryDespite antiretroviral therapy (ART), HIV-1 persists in latently-infected CD4+T cells, preventing cure. Antigens drive the proliferation of infected cells, precluding latent reservoir decay. However, the relationship between antigen recognition and HIV-1 gene expression is poorly understood since most studies of latency reversal use agents that induce non-specific global T cell activation. Here, we isolated rare CD4+T cells responding to cytomegalovirus (CMV) or HIV-1 Gag antigens from participants on long-term ART and assessed T cell activation and HIV-1 RNA expression upon co-culture with autologous dendritic cells (DCs) presenting cognate antigens. Physiological presentation of cognate antigens induced broad T cell activation (median 42-fold increase in CD154+CD69+cells) and significantly increased HIV-1 transcription (median 4-fold), mostly through the induction of rare cells with higher viral expression. Thus, despite low proviral inducibility, physiologic antigen recognition can promote HIV-1 expression, potentially contributing to spontaneous reservoir activity on ART and viral rebound upon ART interruption.
Spatial control of sensory adaptation modulates mechanosensing inPseudomonas aeruginosa
Authors: Patino Ramiro , Kühn Marco J. , Macmillan Henriette , Inclan Yuki F. , Chavez Ivan , Von Dollen John , Johnson Jeffrey R. , Swaney Danielle L. , Krogan Nevan J. , Persat Alexandre , Engel Joanne N. 
Published: February 2024

SummarySensory signaling pathways use adaptation to dynamically respond to changes in their environment. Here, we report the mechanism of sensory adaptation in the Pil-Chp mechanosensory system, which the important human pathogenPseudomonas aeruginosauses to sense mechanical stimuli during surface exploration. Using biochemistry, genetics, and cell biology, we discovered that the enzymes responsible for adaptation, a methyltransferase and a methylesterase, are segregated to opposing cell poles asP. aeruginosaexplore surfaces. By coordinating the localization of both enzymes, we found that the Pil-Chp response regulators influence local receptor methylation, the molecular basis of bacterial sensory adaptation. We propose a model in which adaptation during mechanosensing spatially resets local receptor methylation, and thus Pil-Chp signaling, to modulate the pathway outputs, which are involved inP. aeruginosavirulence. Despite decades of bacterial sensory adaptation studies, our work has uncovered an unrecognized mechanism that bacteria use to achieve adaptation to sensory stimuli.
Spatial transcriptomics profiling of gallbladder adenocarcinoma: a detailed two-case study of progression from precursor lesions to cancer
Authors: Pirenne Sophie , Manzano-Núñez Fátima , Loriot Axelle , Cordi Sabine , Desmet Lieven , Aydin Selda , Hubert Catherine , Toffoli Sébastien , Limaye Nisha , Sempoux Christine , Komuta Mina , Gatto Laurent , Lemaigre Frédéric P. 
Published: March 2024

AbstractBackgroundMost studies on tumour progression from precursor lesion toward gallbladder adenocarcinoma investigate lesions sampled from distinct patients, providing an overarching view of pathogenic cascades. Whether this reflects the tumourigenic process in individual patients remains insufficiently explored. Genomic and epigenomic studies suggest that a subset of gallbladder cancers originate from biliary intraepithelial neoplasia (BilIN) precursor lesions, whereas others form independently from BilINs. Spatial transcriptomic data supporting these conclusions are missing. Moreover, multiple areas with precursor or adenocarcinoma lesions can be detected within the same pathological sample. Yet, knowledge about intra-patient variability of such lesions is lacking.MethodsTo characterise the spatial transcriptomics of gallbladder cancer tumourigenesis in individual patients, we selected two patients with distinct cancer aetiology and whose samples simultaneously displayed multiple areas of normal epithelium, BilINs and adenocarcinoma. Using GeoMx digital spatial profiling, we characterised the whole transcriptome of a high number of regions of interest (ROIs) per sample in the two patients (24 and 32 ROIs respectively), with each ROI covering approximately 200 cells of normal epithelium, low-grade BilIN, high-grade BilIN or adenocarcinoma. Human gallbladder organoids and cell-ine derived tumours were used to investigate the tumour-promoting role of genes.ResultsSpatial transcriptomics revealed that each type of lesion displayed limited intra-patient transcriptomic variability. Our data further suggest that adenocarcinoma derived from high-grade BilIN in one patient and from low-grade BilIN in the other patient, with co-existing high-grade BilIN evolving via a distinct process in the latter case. The two patients displayed distinct sequences of signalling pathway activation during tumour progression, but Semaphorin 4A (SEMA4A) expression was repressed in both patients. Using human gallbladder-derived organoids and cell line-derived tumours, we provide evidence that repression ofSEMA4Apromotes pseudostratification of the epithelium and enhances cell migration and survival.ConclusionGallbladder adenocarcinoma can develop according to patient-specific processes, and limited intra-patient variability of precursor and cancer lesions was noticed. Our data suggest that repression ofSEMA4Acan promote tumour progression. They also highlight the need to gain gene expression data in addition to histological information to avoid understimating the risk of low-grade preneoplastic lesions.
Methods for imaging intracellular calcium signals in the mouse mammary epithelium in 2- and 3-dimensions
Authors: Folacci Mathilde , Chalmers Silke B. , Davis Felicity M. 
Published: March 2024

SummaryThe mammary gland has a central role in optimal mammalian development and survival. Contractions of smooth muscle-like basal (or myoepithelial) cells in the functionally mature mammary gland in response to oxytocin are essential for milk ejection and are tightly regulated by intracellular calcium (Ca2+). Using mice expressing a genetically encoded Ca2+indicator (GCaMP6f), we present in this chapter a method to visualise at high spatiotemporal resolution changes in intracellular Ca2+in mammary epithelial cells, bothin vitro(2D) andex vivo(3D). The procedure to optimally prepare mammary tissue and primary cells is presented in detail.
Benchmarking transcriptional deconvolution methods for estimating tissue- and cell type-specific extracellular vesicle abundances
Authors: Larsen Jannik Hjortshøj , Jensen Iben Skov , Svenningsen Per 
Published: March 2024

AbstractExtracellular vesicles (EVs) contain cell-derived lipids, proteins, and RNAs; however, the challenge to determine the tissue- and cell type-specific EV abundances in body fluids remains a significant hurdle for our understanding of EV biology. While tissue- and cell type-specific EV abundances can be estimated by matching the EV’s transcriptome to a tissue’s/cell type’s expression signature using deconvolutional methods, a comparative assessment of deconvolution methods’ performance on EV transcriptome data is currently lacking. We benchmarked 11 deconvolution methods using data from 4 cell lines and their EVs,in silicomixtures, 118 human plasma, and 88 urine EVs. We identified deconvolution methods that estimated cell type-specific abundances of pure andin silicomixed cell line-derived EV samples with high accuracy. Using data from two urine EV cohorts with different EV isolation procedures, four deconvolution methods produced highly similar results. The four methods were also highly concordant in their tissue-specific plasma EV abundance estimates. We identified driving factors for deconvolution accuracy and highlight the importance of implementing biological knowledge in creating the tissue/cell type signature. Overall, our analyses demonstrate that the deconvolution algorithms DWLS and CIBERSORTx produce highly similar and accurate estimates of tissue- and cell type-specific EV abundances in biological fluids.
The NLRP3 inflammasome is essential for IL-18 production in a murine model of macrophage activation syndrome
Authors: Gleeson Tara A. , Kaiser Christina , Lawrence Catherine B. , Brough David , Allan Stuart M. , Green Jack P. 
Published: March 2024

AbstractHyperinflammatory disease is associated with an aberrant immune response resulting in cytokine storm. One such instance of hyperinflammatory disease is known as macrophage activation syndrome (MAS). The pathology of MAS can be characterised by significantly elevated serum levels of interleukin (IL)-18 and interferon (IFN)-γ. Given the role for IL-18 in MAS, we sought to establish the role of inflammasomes in the disease process. Using a murine model of CpG-DNA induced MAS, we discovered that the expression of the NLRP3 inflammasome was increased and correlated with IL-18 production. Inhibition of the NLRP3 inflammasome, or downstream caspase-1, prevented MAS-mediated upregulation of plasma IL-18 but interestingly did not alleviate key features of hyperinflammatory disease including hyperferritinaemia and splenomegaly. Furthermore IL-1 receptor blockade with IL-1Ra did not prevent the development of CpG-induced MAS, despite being clinically effective in the treatment of MAS. These data demonstrate that in the development of MAS, the NLRP3 inflammasome was essential for the elevation in plasma IL-18, a key cytokine in clinical cases of MAS, but was not a driving factor in the pathogenesis of CpG-induced MAS.
Measuring the orientation of segmented Deep Brain Stimulation leads using electroencephalography
Authors: Jacob Alan Bince , Krueger Marie T. , Akram Harith , Aristovich Kirill , Litvak Vladimir 
Published: March 2024

AbstractSegmented Deep Brain Stimulation (DBS) leads enable current steering in specific directions, but this comes with an increased level of programming complexity. Precise measurement of lead orientation is crucial for facilitating stimulation programming. Presently employed methods involve radiation technology posing inherent risks and limitations. Additionally, the potential rotation of leads post-implantation may require repeated measurements. To address these challenges, we propose an outpatient-friendly, radiation-free method using post-operative imaging-informed electroencephalography (EEG). The method was tested in an EEG phantom yielding maximal errors of under 10 ° with under 30s of data. It works with as few as 4 EEG electrodes with only a small error increase. Measurement variance was of the order of a few degrees, indicating that the method could reach this precision if all the sources of bias are removed. Thus, with optimised hardware, software and measurement protocol, the method is feasible for routine use in a clinical setting.
SIRT2-Mediated ACSS2 K271 Deacetylation Suppresses Lipogenesis Under Nutrient Stress
Authors: Karim Rezwana , Teng Wendi , Behram Cameron , Lin Hening 
Published: March 2024

AbstractDe novo lipogenesis is associated with the development of human diseases such as cancer, diabetes, and obesity. At the core of lipogenesis lies acetyl coenzyme A (CoA), a metabolite that plays a crucial role in fatty acid synthesis. One of the pathways contributing to the production of cytosolic acetyl-CoA is mediated by acetyl-CoA synthetase 2 (ACSS2). Here, we reveal that when cells encounter nutrient stress, particularly a deficiency in amino acids, Sirtuin 2 (SIRT2) catalyzes the deacetylation of ACSS2 at the lysine residue K271. This results in K271 ubiquitination and subsequently proteasomal degradation of ACSS2. Substitution of K271 leads to decreased ubiquitination of ACSS2, increased ACSS2 protein level, and thus increased lipogenesis. Our study uncovers a mechanism that cells employ to efficiently manage lipogenesis during periods of nutrient stress.