bluuebunny/crossref_metadata_2025_split huggingface dataset:
Semi-supervised Bayesian integration of multiple spatial proteomics datasets
Authors: Coleman Stephen D. , Breckels Lisa , Waller Ross F. , Lilley Kathryn S. , Wallace Chris , Crook Oliver M. , Kirk Paul D.W. 
Published: February 2024

AbstractThe subcellular localisation of proteins is a key determinant of their function. High-throughput analyses of these localisations can be performed using mass spectrometry-based spatial proteomics, which enables us to examine the localisation and relocalisation of proteins. Furthermore, complementary data sources can provide additional sources of functional or localisation information. Examples include protein annotations and other high-throughput ‘omic assays. Integrating these modalities can provide new insights as well as additional confidence in results, but existing approaches for integrative analyses of spatial proteomics datasets are limited in the types of data they can integrate and do not quantify uncertainty. Here we propose a semi-supervised Bayesian approach to integrate spatial proteomics datasets with other data sources, to improve the inference of protein sub-cellular localisation. We demonstrate our approach outperforms other transfer-learning methods and has greater flexibility in the data it can model. To demonstrate the flexibility of our approach, we apply our method to integrate spatial proteomics data generated for the parasiteToxoplasma gondiiwith time-course gene expression data generated over its cell cycle. Our findings suggest that proteins linked to invasion organelles are associated with expression programs that peak at the end of the first cell-cycle. Furthermore, this integrative analysis divides the dense granule proteins into heterogeneous populations suggestive of potentially different functions. Our method is disseminated via the mdir R package available on the lead author’s Github.Author summaryProteins are located in subcellular environments to ensure that they are near their interaction partners and occur in the correct biochemical environment to function. Where a protein is located can be determined from a number of data sources. To integrate diverse datasets together we develop an integrative Bayesian model to combine the information from several datasets in a principled manner. We learn how similar the dataset are as part of the modelling process and demonstrate the benefits of integrating mass-spectrometry based spatial proteomics data with timecourse gene-expression datasets.
Hamster (Cricetus cricetus) and ground squirrel (Spermophilus citellus) in the metropolitan area of Vienna, Austria: Urban development vs. species protection
Authors: Rubel Franz 
Published: February 2024

AbstractAlthough European hamsters and European ground squirrels are listed as critically endangered on theIUCN Red List of Threatened Species, their habitats are becoming increasingly smaller due to the rapid expansion of the city of Vienna. The distribution of both species over the period 2000–2023 was documented by compiling a map based on georeferenced data from scientific monitoring and citizen science collections. Based on this, the population sizes in the metropolitan area of Vienna were estimated at 4000 hamsters and 16000 ground squirrels. An overview map was also created for each of the two species, which contains the names of the most important local occurrences. Satellite images were used to document populations that became extinct during the study period or in which animals lost large parts of their traditional habitat due to new urban development. This is considered particularly important in terms of conservation, as future generations would otherwise see the absence of wildlife in cities as normal, an effect known as shifting baseline syndrome. The Court of Justice of the European Union clarified key concepts for strict species protection. These also include eco-offsetting, i.e. creating habitats to replace ones lost to development, which was already applied before a recent construction project was implemented. On the occasion of this project, the application of eco-offsetting to protect the local ground squirrel population was documented and critically discussed.
Impaired transitioning of the FXR ligand binding domain to an active state underlies a PFIC5 phenotype
Authors: Behrendt Annika , Stindt Jan , Pfister Eva-Doreen , Grau Kathrin , Brands Stefanie , Bastianelli Alex , Dröge Carola , Stalke Amelie , Bonus Michele , Sgodda Malte , Cantz Tobias , Franke Sabine , Baumann Ulrich , Keitel Verena , Gohlke Holger 
Published: February 2024

AbstractNuclear receptor farnesoid X receptor (FXR) acts as a key regulator of bile acid pool homeostasis and metabolism. Within the enterohepatic circulation, reabsorbed bile acids act as agonists on FXR, which transcriptionally controls the synthesis and transport of bile acids. Binding occurs in the ligand binding domain (LBD), favoring a conformational change to the active state in which helix 12 interacts with the LBD to form an interaction surface for nuclear co-activators. The homozygous missense variant T296I, identified in a PFIC5 patient, is located close to the critical helix 12 interaction. Here, we identified reduced transcriptional activity of the variant protein on the downstream targets BSEP and SHPin vitroand within the patient’s liver. Analysis of the structural dynamics of the conformational change from an inactive to an active state of the FXR LBD with molecular dynamics simulations revealed that while the wildtype protein frequently transitions into the active state, this movement and the necessary perfect placement of helix 12 was significantly impeded in the T296I mutated protein. To our knowledge, this is the first study to describe the conformational change from an inactive to an active state of the FXR LBD. This might be useful for new therapeutic approaches targeting the activation of FXR. Overall, combiningin vivodata within vitroandin silicoexperiments, we suggest a molecular mechanism underlying the PFIC phenotype of a patient with an FXR missense variant.
The Fossilised Birth-Death Model is Identifiable
Authors: Truman Kate , Vaughan Timothy G , Gavryushkin Alex , Gavryushkina Alexandra “Sasha” 
Published: February 2024

AbstractTime-dependent birth-death sampling models have been used in numerous studies for inferring past evolutionary dynamics in different areas, e.g. speciation and extinction rates in macroevolutionary studies, or effective reproductive number in epidemiological studies. These models are branching processes where lineages can bifurcate, die, or be sampled with time-dependent birth, death, and sampling rates, generating phylogenetic trees. It has been shown that in some subclasses of such models, different sets of rates can result in the same distributions of reconstructed phylogenetic trees, and therefore the rates become unidentifiable from the trees regardless of their size. Here we show that widely used time-dependent fossilised birth-death (FBD) models are identifiable. This subclass of models makes more realistic assumptions about the fossilisation process and certain infectious disease transmission processes than the unidentifiable birth-death sampling models. Namely, FBD models assume that sampled lineages stay in the process rather than being immediately removed upon sampling. Identifiability of the time-dependent FBD model justifies using statistical methods that implement this model to infer the underlying temporal diversification or epidemiological dynamics from phylogenetic trees or directly from molecular or other comparative data. We further show that the time-dependent fossilised-birth-death model with an extra parameter, the removal after sampling probability, is unidentifiable. This implies that in scenarios where we do not know how sampling affects lineages we are unable to infer this extra parameter together with birth, death, and sampling rates solely from trees.
Helicobacter pyloriseropositivity associates with hyperglycemia, but not obesity in Danish children and adolescents
Authors: Kløve Sigri , Stinson Sara E. , Romme Fie O. , Butt Julia , Graversen Katrine B. , Lund Morten A. V. , Fonvig Cilius E. , Waterboer Tim , Perez-Perez Guillermo I. , Hansen Torben , Holm Jens-Christian , Andersen Sandra B. 
Published: February 2024

AbstractHelicobacter pyloricolonizes the human stomach and may affect the inflammatory response, hormone production related to energy regulation, and gut microbiota composition. Previous studies have demonstrated an inverse correlation betweenH. pyloriseropositivity and pediatric obesity. We hypothesized that we would find a similar relationship among Danish children and adolescents. We assessedH. pyloriseroprevalence in 713 subjects from an obesity clinic cohort and 990 subjects from a population-based cohort, and its association with obesity and other cardiometabolic risk factors. No association was found betweenH. pyloriand body mass index (BMI) standard deviation score (SDS).H. pyloriseropositivity was, however, associated with higher fasting blood glucose levels and the prevalence of hyperglycemia, suggesting thatH. pylorimay contribute to impaired glucose regulation in Danish children and adolescents.Graphical abstract
Clostridium tetanibacteraemia in the plague area in France: two cases
Authors: Boualam M.A. , Bouri A. , Signoli M. , Drancourt M. , Caputo A. , Terrerzz E. , Aboudharam G. 
Published: February 2024

ABSTRACTBackgroundPaleoculturomics aims to culture ancient pathogens from human remains such as dental pulp, which traps a drop of blood at the time of the death, to diagnose bacteraemia.Clostridium tetani(C. tetani) bacteraemia is a rare situation, with only four case reports in the literature.MethodsFourteen teeth collected from 14 individuals buried at the site of the 1590 plague in Fedons, France, were surface decontaminated before the pulp was cultured under strict anaerobiosis with negative controls. Colonies were identified by mass spectrometry and whole genome sequencing, andC. tetani-specific PCR was performed using DNA extracted from dental pulps, calculus and sediments.ResultsC. tetanicultured in two dental pulp specimens from two individuals was firmly identified by MALDI-TOF mass spectrometry, and whole genome sequencing confirmed toxigenicC. tetani. In the remaining twelve individuals, no suchC. tetaniwas recovered and further detection by PCR and palaeoculturomics of dental calculus and sediments surrounding the teeth in these two individuals remained negative.ConclusionToxigenicC. tetaniwhich did not result from mere environmental contamination, caused bacteraemia in two individuals from a modern time plague site in France.
Frequency of lipoprotein(a) testing and its levels in Pakistani population
Authors: Batool Hijab , Khan Madeeha , Ain Quratul , Chughtai Omar R. , Khan Muhammad D. , Khan Mohammad I. , Sadiq Fouzia 
Published: February 2024

AbstractBackgroundLipoprotein(a) [Lp(a)] is a highly atherogenic particle identified as an independent risk factor for the development of atherosclerotic cardiovascular disease (ASCVD). This study aimed to investigate the frequency of Lp(a) testing and incidence of elevated Lp(a) in the Pakistani population.MethodsFor this observational study, Lp(a) and lipid profile data from five years (June 2015 to October 2020) were acquired from the electronic patient records of a diagnostic laboratory (Chughtai Laboratories, Lahore). The association of age, total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein cholesterol (LDL-C), non-HDL, and triglyceride (TG) levels with two thresholds for Lp(a), that is, <30 mg/dL and ≥30 mg/dL, was calculated using the Kruskal Wallis test, while the association between Lp(a) levels and lipid variables was calculated using Spearman correlation.ResultsFor five years, 1060 tests were conducted, averaging 212 tests per year. Of these tests, 37.2% showed Lp(a) levels above 30 mg/dL. There were no significant differences observed in the results between males and females. However, younger individuals displayed significantly higher Lp(a) levels. Additionally, there was only a weak correlation between Lp(a) levels and other lipid variables.ConclusionDespite being recognized as a risk factor for ASCVD in the Pakistani population, only a small proportion of the large population had their Lp(a) tested. Moreover, a significant proportion of the population lies above the threshold.
Use of a Continuous Single Lead Electrocardiogram Analytic to Predict Patient Deterioration Requiring Rapid Response Team Activation
Authors: Lee Sooin , Benson Bryce , Belle Ashwin , Medlin Richard P. , Jerkins David , Goss Foster , Khanna Ashish K. , DeVita Michael A. , Ward Kevin R. 
Published: February 2024

AbstractIdentifying the onset of patient deterioration is challenging despite the potential to respond to patients earlier with better vital sign monitoring and rapid response team (RRT) activation. In this study an ECG based software as a medical device, the Analytic for Hemodynamic Instability Predictive Index (AHI-PI), was compared to the vital signs of heart rate, blood pressure, and respiratory rate, evaluating how early it indicated risk before an RRT activation. A higher proportion of the events had risk indication by AHI-PI (92.71%) than by vital signs (41.67%). AHI-PI indicated risk early, with an average of over a day before RRT events. In events whose risks were indicated by both AHI-PI and vital signs, AHI-PI demonstrated earlier recognition of deterioration compared to vital signs. A case-control study showed that situations requiring RRTs were more likely to have AHI-PI risk indication than those that did not. The study derived several insights in support of AHI-PI’s efficacy as a clinical decision support system. The findings demonstrated AHI-PI’s potential to serve as a reliable predictor of future RRT events. It could potentially help clinicians recognize early clinical deterioration and respond to those unnoticed by vital signs, thereby helping clinicians improve clinical outcomes.Author SummaryRecognizing patient deterioration remains challenging even for experienced clinicians and nurses. RRTs can help mobilize resources to respond to patients earlier. However, determining when to activate RRTs is difficult. We retrospectively evaluated a software as a medical device, AHI-PI, compared the vital signs of heart rate, blood pressure, and respiratory rate to understand if AHI-PI could provide an earlier indicator of patient deterioration than vital signs. Our findings demonstrated AHI-PI’s potential to serve as a reliable predictor of future RRT events, before vital sign changes occur. This could potentially help clinicians recognize patients at risk for clinical deterioration and improve clinical outcomes through early targeted therapy or interventions.
Myocardial-derived small extracellular vesicles spontaneously released from living myocardial slices under biomimetic culture conditions regulate contractility and cardiac remodelling
Authors: Nicastro L. , Lal A. , Kyriakou A. , Kholia S. , Toldra R. Nunez , Downing B. , Kermani F. , Anwar M. , Martino F. , Chokron D. , Sarathchandra P. , Sarkar M. , Emanueli C. , Terracciano C.M. 
Published: February 2024

AbstractBACKGROUNDSmall extracellular vesicles (sEVs) released in the cardiac microenvironment are reported to regulate cardiac remodelling, partially via microRNA transfer. Harvesting sEVs produced exclusively from the myocardium remains challenging and a solid research platform for sEV cardiovascular testing needs to be established. Organotypic living myocardial slices (LMS) allow to mimic cardiac disease and to record electrophysiological responses to biological and pharmacological stimuli. This study aims at understanding how cardiac sEVs obtained from donor and failing human LMS and rat LMS under physiological or heart failure-mimicking conditions impact myocardial function and remodelling.METHODS & RESULTSHuman LMS were obtained from the left ventricle (LV) of human donor non-failing and end-stage failing hearts and cultured at 2.2 µm sarcomere length (SL). Rat LV LMS from healthy Sprague-Dawley rats were cultured at a preload of 2.2 or 2.4 µm SL, to recapitulate physiological load and overload, respectively. Following 48-hours biomimetic culture, sEVs were isolated from the culture media by size exclusion chromatography and characterized for their size, concentration, and expression of exosome markers. LMS from human failing hearts presented impaired contractility (P<0.05 vs donor-LMS), which was improved by application of donor heart-derived sEVs at 15 and 20% stretch. Whilst rat overloaded sEVs did not alter the force production of physiological LMS, physiological sEVs significantly increased the active force and decreased their passive force. In rat LMS, 1×108physiological EVs/slice restored the contractility of overloaded slices, reduced apoptosis, fibrosis-related gene expression and promoted angiogenesis. microRNAs analysis showed significant upregulation of miR-23a-3p and miR-378a-3p in rat physiological sEVs. Finally, to test whether sEVs have a direct effect on cardiomyocytes, we applied sEVs on cultured induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs). sEVs did not affect the contractility of iPSC-CM monoculture but increased the contractility of iPSC-CM co-cultured with human microvasculature endothelial cells (MVECs).CONCLUSIONSCardiac sEVs isolated from healthy hearts increase the contractility of failing LMS. This effect is associated with, and possibly brought about by, a combination of inhibition of apoptosis, reduction of fibrosis and increased microvascular density, and could involve the transfer of sEV-microRNA into myocardial cells. Our data support the hypothesis that the sEV inotropic action is mediated by endothelial cells.
Real-time Imaging of Decompression Gas Bubble Growth in the Spinal Cord of Live Rats
Authors: Alvarado Roman , Scheven Ulrich M. , Meiners J.-C. 
Published: February 2024

1)Structured AbstractPurposeTo observe the growth and resolution of decompression gas bubbles in the spinal cord of live rats in real time using magnetic resonance imaging (MRI).MethodsWe constructed an MRI-compatible pressure chamber system to visualize gas bubble dynamics in deep tissues in real time. The system pressurizes and depressurizes rodents inside an MRI scanner and monitors their respiratory rate, heart rate, and body temperature while providing gaseous anesthesia under pressure during the experiments.ResultsWe observed the formation of decompression gas bubbles in the spinal cord of rats after compression to 7.1 bar absolute and rapid decompression inside the MRI scanner while maintaining continuous gaseous anesthesia and vital monitoring.ConclusionWe have shown the direct observation of decompression gas bubble formation in real time by MRI in live, anesthetized rats.
Ubiquity of inverted ’gelatinous’ ecosystem pyramids in the global ocean
Authors: Fabien Lombard , Lionel Guidi , Brandão Manoela C. , Pedro Coelho Luis , Sébastien Colin , Richard Dolan John , Amanda Elineau , Gasol Josep M , Luc Grondin Pierre , Nicolas Henry , Ibarbalz Federico M , Laëtitia Jalabert , Michel Loreau , Séverinne Martini , Zoé Mériguet , Marc Picheral , Pierella Karlusich Juan José , Pepperkok Rainer , Jean-Baptiste Romagnan , Lucie Zinger ,   Tara Oceans Coordinators, Lars Stemmann , Acinas Silvia G , Lee Karp-Boss , Emmanuel Boss , Sullivan Matthew B. , de Vargas Colomban , Chris Bowler , Eric Karsenti , Gabriel Gorsky 
Published: February 2024

Summary paragraphPlankton are essential in marine ecosystems. However, our knowledge of overall community structure is sparse due to inconsistent sampling across their very large organismal size range. Here we use diverse imaging methods to establish complete plankton inventories of organisms spanning five orders of magnitude in size. Plankton community size and trophic structure variation validate a long-held theoretical link between organism size-spectra and ecosystem trophic structures. We found that predator/grazer biomass and biovolume unexpectedly exceed that of primary producers at most (55%) locations, likely due to our better quantification of gelatinous organisms. Bottom- heavy ecosystems (the norm on land) appear to be rare in the ocean. Collectively, gelatinous organisms represent 30% of the total biovolume (8-9% of carbon) of marine plankton communities from tropical to polar ecosystems. Communities can be split into three extreme typologies: diatom/copepod-dominated in eutrophic blooms, rhizarian/chaetognath-dominated in oligotrophic tropical oceans, and gelatinous-dominated elsewhere. While plankton taxonomic composition changes with latitude, functional and trophic structures mostly depend on the amount of prey available for each trophic level. Given future projections of oligotrophication of marine ecosystems, our findings suggest that rhizarian and gelatinous organisms will increasingly dominate the apex position of planktonic ecosystems, leading to significant changes in the ocean’s carbon cycle.
Olive mill solid waste induces beneficial mushroom-specialized metabolite diversity revealed by computational metabolomics strategies
Authors: Khatib Soliman , Pereman Idan , Kostanda Elizabeth , Zdouc Mitja M. , Ezov Nirit , Schweitzer Ron , van der Hooft Justin J. J. 
Published: February 2024

AbstractIntroductionMushrooms contain besides proteins a diverse pallet of specialized metabolites bioactive in either beneficial or harmful manner. Therefore, mushrooms have been exploited by humans for centuries for dietary or medical purposes. For example, the edible and medicinal mushroomsHericium erinaceusandPleurotus eryngiiare grown commercially around the world. In nature,H. erinaceusgrows on old or dead tree trunks, andP. eryngiigrows on Apiaceae plant roots, whereas in cultivation, they grow on substrates mainly consisting of dry wood chips, straw, and cereals. To make their farming more sustainable, supplements such as olive mill solid waste (OMSW) have been added to support mushroom development. However, so far, the impact of substrate additives on the edible mushroom metabolic content has not been assessed.MethodsHere, we examined the effect of different proportions of OMSW added to the substrate on the metabolic profiles of the fruiting body (FB) and mycelium ofH. erinaceusandP. eryngiimushrooms. We used computational metabolomics strategies including GNPS molecular networking, MS2Query, and the FERMO dashboard, to organize, annotate, and prioritize metabolite features from the untargeted Q-Exactive Plus HR-LC-MS/MS metabolomics data. Following chromatography-based fractionation, the metabolite annotation of four metabolite features was further validated or fine-tuned using1H-NMR, to resolve structural isomers.Results & DiscussionOur computational metabolomics strategies showed several annotated metabolite features to be affected by OSMW concentration. In general, the methanolic extracts ofH. erinaceusFB and mycelium were more highly enriched with specialized metabolites than those ofP. eryngii. Interestingly, OMSW increased several hericenone analogues in theH. erinaceusFB, to which beneficial properties, such as anti-inflammatory, anticancer and neuroprotective properties are assigned, as well as several erinacerin metabolites from the mycelium. In addition, high concentrations of OMSW decreased the toxic enniatin metabolite abundance. In conclusion, we demonstrate how a change in substrate composition affects the mushroom’s specialized metabolome and can induce beneficial mushroom metabolite diversity. These results highlight the importance of including computational metabolomic strategies to investigate new sustainable growth options for edible mushrooms and other natural foods.