bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spatiotemporal dynamic models ofAmblyomma americanumquesting activity in the Central Great Plains
Authors: Cobos Marlon E. , Winters Taylor , Martinez Ismari , Yao Yuan , Xiao Xiangming , Ghosh Anuradha , Sundstrom Kellee , Duncan Kathryn , Brennan Robert E. , Little Susan E. , Peterson A. Townsend 
Published: May 2024

AbstractTicks represent important vectors of a number of bacterial and viral disease agents, owing to their hematophagous nature and their questing behavior (the process in which they seek new hosts). Questing activity is notably seasonal with spatiotemporal dynamics that needs to be understood in detail as part of mediating and mitigating tick-borne disease risk. Models of the geography of tick questing activity developed to date, however, have ignored the temporal dimensions of that behavior; more fundamentally, they have often not considered the sampling underlying available occurrence data. Here, we have addressed these shortfalls forAmblyomma americanum, the most commonly encountered tick in the central Great Plains, via (1) detailed, longitudinal sampling to characterize the spatiotemporal dimensions of tick questing activity; (2) randomization tests to establish in which environmental dimensions a species is manifesting selective use; and (3) modeling methods that include both presence data and absence data, taking fullest advantage of the information available in the data resource. The outcome was a detailed picture of geographic and temporal variation in suitability for the species through the two-year course of this study. Such models that take full advantage of available information will be crucial in understanding the risk of tick-borne disease into the future.
Pilot study of a ketogenic diet in bipolar disorder: a process evaluation
Authors: Rigby Benjamin P. , Needham Nicole , Grossi Helen , Kamenska Ivana , Campbell Iain H. , Meadowcroft Ben , Creasy Frances , Fisher Cheryl , Bahuguna Pankaj , Norrie John , Thompson Gerard , Gibbs Melissa C. , Mitchell-Grigorjeva Maja , McLellan Ailsa , Moses Tessa , Burgess Karl , Brown Rachel , Thrippleton Michael J. , Campbell Harry , Smith Daniel J. , Simpson Sharon A. 
Published: May 2024

AbstractBackgroundBipolar disorder is a serious mental illness, which requires new strategies for prevention and management. Recent evidence suggests that a ketogenic diet may be an effective intervention. This research aimed to explore the feasibility and acceptability of a ketogenic diet intervention for bipolar disorder, fidelity to its behavioural components and the experiences of the participants and research clinicians involved.MethodsA mixed-methods process evaluation was conducted. Semi-structured telephone interviews were carried out with 15 participants 1-2 months after completing a 6-8 week modified ketogenic diet intervention, and 4 research clinicians from the study team following the completion of data collection. Data were thematically analysed. Fidelity checklists completed by research dietitians were analysed using descriptive count and percentage statistics. Findings are reported post-hoc, following the analysis and publication of the main pilot study findings.ResultsQualitative data indicated that participants had various motives for taking part in the study, including weight loss. It was important to support people’s motives while facilitating clear and realistic expectations. Despite the challenges of initiating and maintaining a ketogenic diet, including for some its disruptive effects on daily living, many participants perceived physical and psychological benefits (e.g. significant weight loss, mood stability and an enhanced ability to focus). A range of behavioural (e.g.goal setting), social (e.g.family and dietitians) and technological (e.g.apps for monitoring) support mechanisms were generally considered key facilitating factors. Meanwhile, dietary preferences, concerns about the diet and its impact, the testing burden and capacity of the delivery team were perceived as barriers for some. The importance of wider contextual influences (e.g.the cost of living and sociocultural expectations) were highlighted. Overall, descriptive analyses indicated moderate-to-good fidelity to the behaviour change components of the study.ConclusionWe provide novel insight into the experiences of people living with bipolar disorder initiating and following a ketogenic diet, as well as those of research clinicians who support the intervention. Future trials may benefit from increased clinical research capacity, better-defined entry and exit routes, additional interpersonal support, and greater understanding of how social and societal factors impact participation.Trial registrationStudy registration number:ISRCTN6163198(02 March 2022)
The mutagenic forces shaping the genomic landscape of lung cancer in never smokers
Authors: Díaz-Gay Marcos , Zhang Tongwu , Hoang Phuc H. , Khandekar Azhar , Zhao Wei , Steele Christopher D. , Otlu Burçak , Nandi Shuvro P. , Vangara Raviteja , Bergstrom Erik N. , Kazachkova Mariya , Pich Oriol , Swanton Charles , Hsiung Chao Agnes , Chang I-Shou , Wong Maria Pik , Leung Kin Chung , Sang Jian , McElderry John , Yang Lixing , Nowak Martin A , Shi Jianxin , Rothman Nathaniel , Wedge David C. , Homer Robert , Yang Soo-Ryum , Lan Qing , Zhu Bin , Chanock Stephen J. , Alexandrov Ludmil B. , Landi Maria Teresa 
Published: May 2024

ABSTRACTLung cancer in never smokers (LCINS) accounts for up to 25% of all lung cancers and has been associated with exposure to secondhand tobacco smoke and air pollution in observational studies. Here, we evaluate the mutagenic exposures in LCINS by examining deep whole-genome sequencing data from a large international cohort of 871 treatment-naïve LCINS recruited from 28 geographical locations within the Sherlock-Lungstudy.KRASmutations were 3.8-fold more common in adenocarcinomas of never smokers from North America and Europe, while a 1.6-fold higher prevalence ofEGFRandTP53mutations was observed in adenocarcinomas from East Asia. Signature SBS40a, with unknown cause, was found in most samples and accounted for the largest proportion of single base substitutions in adenocarcinomas, being enriched inEGFR-mutated cases. Conversely, the aristolochic acid signature SBS22a was almost exclusively observed in patients from Taipei. Even though LCINS exposed to secondhand smoke had an 8.3% higher mutational burden and 5.4% shorter telomeres, passive smoking was not associated with driver mutations in cancer driver genes or the activities of individual mutational signatures. In contrast, patients from regions with high levels of air pollution were more likely to haveTP53mutations while exhibiting shorter telomeres and an increase in most types of somatic mutations, including a 3.9-fold elevation of signature SBS4 (q-value=3.1 × 10−5), previously linked mainly to tobacco smoking, and a 76% increase of clock-like signature SBS5 (q-value=5.0 × 10−5). A positive dose-response effect was observed with air pollution levels, which correlated with both a decrease in telomere length and an elevation in somatic mutations, notably attributed to signatures SBS4 and SBS5. Our results elucidate the diversity of mutational processes shaping the genomic landscape of lung cancer in never smokers.
Time-Lapse Quantitative Analysis of Drying Patterns and Machine Learning for Classifying Abnormalities in Sessile Blood Droplets
Authors: Pal Anusuya , Yanagisawa Miho , Gope Amalesh 
Published: May 2024

AbstractWhen a colloidal droplet dries on a substrate, a unique pattern results from multi-facet phenomena such as Marangoni convection, capillary flow, mass transport, mechanical stress, colloid-colloid, and colloid-substrate interactions. Even under uniform conditions (surface wettability, humidity, and temperature), slight differences in the initial colloidal composition alter the drying pattern. This paper shows how the evolving patterns during drying in the sessile droplets depend on the initial composition and are crucial for assessing any abnormalities in the blood. To do so, texture statistics are derived from time-lapse images acquired during drying, and different traditional machine learning are applied. In addition, a neural network analysis is performed on both images and their texture statistics. As the drying phenomena are correlated with the varying composition, these methods exhibit excellent performance in distinguishing blood abnormalities with an Fl score of over 97%. This indicates that analysis of time-lapse images during drying and their texture statistics, rather than conventional analysis using images at the final dry state, are crucial for classification. Our results highlight the potential of droplet drying as a low-volume, accurate, and simple screening tool for detecting the type and stage of any disease in bio-fluid samples, such as blood, urine, and saliva.
Cell-of-origin epigenome underlies SS18::SSX-mediated transformation
Authors: Hill Lesley A. , Scott R. Wilder , Martin Lauren , Arostegui Martin , Davenport George , Vemon Marcos , Hofvander Jakob , Wang Xue Qi , Li Jinxiu , Nielsen Torsten O. , Jones Kevin B. , Hirst Martin , Underhill T. Michael 
Published: May 2024

SummarySynovial sarcoma is an aggressive soft-tissue malignancy that is characterized by a pathognomonic t(X;18)(p11.2;q11.2) translocation, which produces the fusion oncogene namedSS18::SSX. Despite recent advancements in our understanding of synovial sarcoma biology, the cell-of-origin remains undefined. A mesenchymal stromal cell (MSC) specific CreERT2 line was employed to expressSS18::SSXin fibroblasts and related cell types, resulting in 100% penetrant synovial sarcoma development in mice, with a median latency period of 16.2 ± 2.5 weeks. Murine tumours exhibited high concordance with human synovial sarcoma sub-types at the histological and molecular levels1. Genetic refinement of the cell-of-origin revealed that synovial sarcomas derive from a rareHic1+Pdgfra+Lgr5+fibroblastic population. Furthermore, longitudinal multi-omic profiling along the transformation continuum revealed the step-wise acquisition of a transformed phenotype initiated by the loss of a mature fibroblastic profile and subsequently, the gradual unmasking of an epigenetically embedded embryonic MSC program. Adult and embryonic MSCs exhibited overlapping H2AK119ub and H3K4me3/H3K27me3 (bivalent) histone marks, while SS18::SSX-mediated transformation culminated in the widespread loss of H3K27me3 at these genes and their consequent transcription. Collectively, these studies define a rare MSC context, conducive for SS18::SSX-mediated transformation, and demonstrate that SS tumorigenesis involves the induction and maintenance of an embryonic-like MSC phenotype.
The role of vocalizations in agonistic interactions during competition for roosts in a solitary bat
Authors: Castillo-Salazar Cristian , Schöner Michael G. , Schöner Caroline R. , Chaverri Gloriana 
Published: May 2024

AbstractInter- and intraspecific competition for resources is common among individuals which share ecological niches. To avoid physical confrontations, individuals can use various types of signals to demonstrate their dominance, including vocalizations.Kerivoula hardwickiiis a solitary bat species that lives in highly ephemeral plant structures, which are therefore a limited resource. So far, it is unknown if individuals ofK. hardwickiiuse vocalizations during competitive encounters for roosts, and if the intention of these vocalizations can be deduced by potential rivals. We hypothesized that the calls emitted during roost competition contain information that influences the ability of an individual to defend its roost. We conducted roost competition experiments in a flight cage, where there was an individual roost owner and an intruder who would attempt to evict the owner from the roost. All the vocalizations emitted during these encounters were recorded and analyzed to determine which acoustic parameters, if any, had an influence on the successful defense of the roost. We found that the calls emitted by males can influence their ability to defend the roost, and that entropy is the parameter that most strongly explains a successful defense. High entropy suggests that encounters between individuals ofK. hardwickiiescalate to high levels of aggressiveness and explain whether calls influence an individual’s capacity to defend a roost. We suggest that bat vocalizations contain important information about individual characteristics, which in turn help bats make decisions during resource competition.
SNX10 functions as a modulator of piecemeal mitophagy and mitochondrial bioenergetics
Authors: Trachsel-Moncho Laura , Veroni Chiara , Mathai Benan John , Lapao Ana , Singh Sakshi , Asp Nagham Theres , Schultz Sebastian W. , Pankiv Serhiy , Simonsen Anne 
Published: May 2024

ABSTRACTWe here identify the endosomal protein SNX10 as a negative regulator of piecemeal mitophagy of OXPHOS machinery components. In control conditions, SNX10 localizes to early endocytic compartments in a PtdIns3P-dependent manner and modulates endosomal trafficking but also shows dynamic connections with mitochondria. Upon hypoxia-mimicking conditions, SNX10 localizes to late endosomal structures containing selected mitochondrial proteins, including COX- IV and SAMM50, and the autophagy proteins SQSTM1/p62 and LC3B. The turnover of COX-IV and the ATP synthase subunit pSu9 was enhanced in SNX10-depleted cells, with a corresponding reduced mitochondrial respiration and citrate synthase activity. Importantly, zebrafish larvae lacking Snx10 show reduced levels of COX-IV, as well as elevated ROS levels and ROS-mediated cell death in the brain, demonstrating the in vivo relevance of SNX10-mediated modulation of mitochondrial bioenergetics.eTOC summaryTrachsel-Moncho et al. identify the endosomal protein SNX10 as a modulator of piecemeal mitophagy of OXPHOS machinery components and mitochondrial homeostasis. They show that loss of SNX10 enhances mitochondrial protein degradation, reduces respiration, and increases ROS levels leading to elevated cell death in vivo.
Diverse plant RNAs coat Arabidopsis leaves and are distinct from apoplastic RNAs
Authors: Borniego Lucía , Singla-Rastogi Meenu , Baldrich Patricia , Sampangi-Ramaiah Megha Hastantram , Zand Karimi Hana , McGregor Madison , Meyers Blake C. , Innes Roger W. 
Published: May 2024

AbstractTransgenic expression of a double-stranded RNA in plants can induce silencing of homologous mRNAs in fungal pathogens. Although such host-induced gene silencing is well-documented, the molecular mechanisms by which RNAs can move from the cytoplasm of plant cells across the plasma membrane of both the host cell and fungal cell are poorly understood. Indirect evidence suggests that this RNA transfer may occur at a very early stage of the infection process, prior to breach of the host cell wall, suggesting that silencing RNAs might be secreted onto leaf surfaces. To assess whether Arabidopsis plants possess a mechanism for secreting RNA onto leaf surfaces, we developed a protocol for isolating leaf surface RNA separately from intercellular (apoplastic) RNA. This protocol yielded abundant leaf surface RNA that displayed an RNA banding pattern distinct from apoplastic RNA, suggesting that it may be secreted directly from the leaf surface rather than exuded through stomata or hydathodes. Notably, this RNA was not associated with either extracellular vesicles or protein complexes; however, RNA species longer than 100 nucleotides could be pelleted by ultracentrifugation. Pelleting was inhibited by the divalent cation chelator EGTA, suggesting that these RNAs may form condensates on the leaf surface. These leaf surface RNAs are derived almost exclusively from Arabidopsis, but come from diverse genomic sources, including rRNA, tRNA, mRNA, intergenic RNA, microRNAs, and small interfering RNAs, with tRNAs especially enriched. We speculate that endogenous leaf surface RNA plays an important role in the assembly of distinct microbial communities on leaf surfaces.Significance StatementPlant leaves are colonized by a complex community of microbes that is shaped by host genetics. Although secreted metabolites are thought to mediate this effect, we investigated whether plants might also secrete RNA that could potentially structure microbial communities via cross-kingdom RNA interference. Here we report that Arabidopsis leaves are covered with diverse RNAs of plant origin, including abundant tRNAs and tRNA fragments. This leaf surface RNA is not associated with extracellular vesicles or protein complexes; however, it is less degraded than RNA found inside the extracellular spaces of leaves, suggesting that leaf surface RNA is secreted directly rather than exuded through stomata or hydathodes. We propose that this RNA plays a direct role in shaping the leaf microbiome.
Netrin G1 Ligand is a new stromal immunomodulator that promotes pancreatic cancer
Authors: Vendramini-Costa Débora B. , Francescone Ralph , Franco-Barraza Janusz , Luong Tiffany , Graves Myree , de Aquino Ariana Musa , Steele Nina , Gardiner Jaye C. , dos Santos Sérgio Alexandre Alcantara , Ogier Charline , Malloy Emily , Borghaei Leila , Martinez Esteban , Zhigarev Dmitry I. , Tan Yinfei , Lee Hayan , Zhou Yan , Cai Kathy Q. , Klein-Szanto Andres J. , Wang Huamin , Andrake Mark , Dunbrack Roland L. , Campbell Kerry , Cukierman Edna 
Published: May 2024

AbstractUnderstanding pancreatic cancer biology is fundamental for identifying new targets and for developing more effective therapies. In particular, the contribution of the stromal microenvironment to pancreatic cancer tumorigenesis requires further exploration. Here, we report the stromal roles of the synaptic protein Netrin G1 Ligand (NGL-1) in pancreatic cancer, uncovering its pro-tumor functions in cancer-associated fibroblasts and in immune cells. We observed that the stromal expression of NGL-1 inversely correlated with patients’ overall survival. Moreover, germline knockout (KO) mice for NGL-1 presented decreased tumor burden, with a microenvironment that is less supportive of tumor growth. Of note, tumors from NGL-1 KO mice produced less immunosuppressive cytokines and displayed an increased percentage of CD8+T cells than those from control mice, while preserving the physical structure of the tumor microenvironment. These effects were shown to be mediated by NGL-1 in both immune cells and in the local stroma, in a TGF-β-dependent manner. While myeloid cells lacking NGL-1 decreased the production of immunosuppressive cytokines, NGL-1 KO T cells showed increased proliferation rates and overall polyfunctionality compared to control T cells. CAFs lacking NGL-1 were less immunosuppressive than controls, with overall decreased production of pro-tumor cytokines and compromised ability to inhibit CD8+T cells activation. Mechanistically, these CAFs downregulated components of the TGF-β pathway, AP-1 and NFAT transcription factor families, resulting in a less tumor-supportive phenotype. Finally, targeting NGL-1 genetically or using a functionally antagonistic small peptide phenocopied the effects of chemotherapy, while modulating the immunosuppressive tumor microenvironment (TME), rather than eliminating it. We propose NGL-1 as a new local stroma and immunomodulatory molecule, with pro-tumor roles in pancreatic cancer.Statement of SignificanceHere we uncovered the pro-tumor roles of the synaptic protein NGL-1 in the tumor microenvironment of pancreatic cancer, defining a new target that simultaneously modulates tumor cell, fibroblast, and immune cell functions. This study reports a new pathway where NGL-1 controls TGF-β, AP-1 transcription factor members and NFAT1, modulating the immunosuppressive microenvironment in pancreatic cancer. Our findings highlight NGL-1 as a new stromal immunomodulator in pancreatic cancer.
Ecotin protectsSalmonellaTyphimurium against the microbicidal activity of host proteases
Authors: Saposnik L. , Coria L.M. , Bruno L. , Guaimas F.F. , Pandolfi J. , Pol M. , Urga M.E. , Sabbione F. , McClelland M. , Trevani A. , Pasquevich K.A. , Cassataro J. 
Published: May 2024

ABSTRACTSalmonella entericaserovar Typhimurium causes acute diarrhea upon oral infection in humans. The harsh and proteolytic environment found in the gastrointestinal tract is the first obstacle that these bacteria face after infection. However, the mechanisms that allowSalmonellato survive the hostile conditions of the gut are poorly understood. Theecotingene is found in an extensive range of known phyla of bacteria and it encodes a protein that has been shown to inhibit serine proteases. Thus, in the present work we studied the role ofecotinofSalmonellaTyphimurium in host-pathogen interactions. We found thatSalmonellaTyphimurium Δecotinstrain exhibited lower inflammation in a murine model ofSalmonellainduced colitis. The Δecotinmutant was more susceptible to the action of pancreatin and purified pancreatic elastase. In addition, the lack ofecotinled to impaired adhesion to Caco-2 and HT-29 cell lines, related to the proteolytic activity of brush border enzymes. Besides, Δecotinshowed higher susceptibility to lysosomal proteolytic content and intracellular replication defects in macrophages. In addition, we found Ecotin to have a crucial role inSalmonellaagainst the microbicide action of granules released and neutrophil extracellular traps from human polymorphonuclear leukocytes. Thus, the work presented here highlights the importance ofecotininSalmonellaas countermeasures against the host proteolytic defense system.IMPORTANCEThe gastrointestinal tract is a very complex and harsh environment.Salmonellais a successful food borne pathogen, but little is known about its capacity to survive against the proteolysis of the gut lumen and intracellular proteases. Here, we show that Ecotin, a serine protease inhibitor, plays an important role in protectingSalmonellaagainst proteases present at different sites encountered during oral infection. Our results indicate that Ecotin is an important virulence factor inSalmonella, adding another tool to the wide range of features this pathogen uses during oral infection.
Controlling lipid droplet dynamics via tether condensates
Authors: Amari Chems , Simon Damien , Bellon Theodore , Plamont Marie-Aude , Thiam Abdou Rachid , Gueroui Zoher 
Published: May 2024

AbstractLipid droplets (LDs) exhibit remarkable diversity and functionality within cells, depending on the metabolic needs of cells and the maintenance of lipid homeostasis. Such versatility is acquired through dynamic spatial and temporal positioning, enabling tight communication with other organelles. However, this complexity poses challenges in understanding LD biology. Controlled sequestration and release of LDs within their intracellular environment could offer a method to synchronize their behavior and better understand their function. Here, to advance in this direction, we developed ControLD (Controlled Trapping of Lipid Droplets), a novel approach designed to manipulate LDs and influence their dynamics and life cycle. By orchestrating the assembly/disassembly of engineered condensates, ControLD allows precise sequestration and release of LDs in cells. This technique effectively isolates LDs from the intracellular environment, drastically reducing interactions with other organelles. Notably, our experiments demonstrate that physically isolating LDs impairs their dynamics and remobilization during metabolic needs. ControLD represents a versatile tool for reversible LD trapping, with potential applications in controlling various cellular organelles.