bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrative analysis of blood cells DNA methylation, transcriptomics and genomics identifies novel epigenetic regulatory mechanisms of insulin resistance during puberty in children with obesity
Authors: Anguita-Ruiz A , Torres-Martos A , Ruiz-Ojeda FJ , Alcalá-Fdez J , Bueno G , Gil-Campos M , Roa-Rivas J , Moreno LA , Gil A , Leis R , Aguilera CM 
Published: December 2022

AbstractBackgroundPuberty is a time of considerable metabolic and hormonal changes associated with a physiological increase in peripheral tissue insulin resistance (IR). There is evidence that physiological IR does not resolve in youth who are obese, which may result in increased cardio-metabolic risk. Understanding the molecular and biological processes underlying the development of IR in puberty and the additional impact of obesity on these processes is crucial to prevent type 2 diabetes.MethodsThis is a longitudinal study based on the follow-up until puberty of a cohort of prepubertal Spanish boys and girls. The study population was composed of 139 children organized in a longitudinal approach of 90 subjects (47 females) and two cross-sectional approaches of 99 (52 females) and 130 (71 females) subjects for prepubertal and pubertal stages, respectively. Children were allocated into experimental groups according to their obesity and IR status before and after the onset of puberty. All participants presented blood DNA samples for GWAS and EWAS analyses. In 44 children of the pubertal stage, we counted on blood RNA samples for RNA-seq analysis.ResultsOur large-scale integrative molecular analysis identified novel blood multi-omics signatures (mapping the lociABCG1, ESR1andVASN, among others) significantly associated with IR longitudinal trajectories in children with obesity during pubertal maturation. Functional enrichment analysis revealed that identified loci participate in systemic metabolic pathways and sexual maturation processes relevant to the pathogenesis of IR in the context of puberty. Additional analyses on cardiometabolic and inflammatory phenotypes showed that blood DNAm patterns of some of the identified loci are further associated, beyond IR, with an overall risky-cardiometabolic profile in children. Serum protein levels of vasorin (VASN), one of the most promising novel biomarkers identified in this study, were further associated with IR in the pubertal stage.ConclusionsTo our knowledge, this is the first longitudinal multi-omics approach characterizing molecular blood alterations for IR and obesity during the metabolically critical period of puberty. Our results shed light on the molecular mechanisms underlying epigenetic alterations in obesity and propose novel and promising biomarkers for IR and metabolic alterations in children.
Unbiased serology reveals autoimmunity and HIV antibody signatures in HIV CNS Escape
Authors: Hawes I.A. , Alvarenga B.D. , Browne W. , Wapniarski A. , Dandekar R. , Bartley C.M. , Sowa G.M. , DeRisi J.L. , Cinque P. , Dravid A.N. , Pleasure S.J. , Gisslen M. , Price R.W. , Wilson M.R. 
Published: December 2022

AbstractBackgroundAntiretroviral therapy (ART) suppresses plasma and cerebrospinal fluid (CSF) HIV replication with occasional asymptomatic episodes of detectable HIV RNA known as asymptomatic (AS) escape. Neurosymptomatic (NS) CSF escape is a rare exception in which CNS HIV replication occurs in the setting of neurologic impairment. The origins of NS escape are not fully understood.MethodsUsing a large cohort of PLWH (n=111), including elite controllers (n=4), viral controllers (n=4), ART untreated subjects (n=18), HIV-associated dementia (n=4), ART suppressed (n=16), AS escape (n=19), NS escape (n=35), secondary escape (n=5) subjects, and HIV-negative controls (n=6), we investigated immunoreactivity to self-antigens in the CSF of NS escape by employing neuroanatomic CSF immunostaining and massively multiplexed self-antigen serology (PhIP-Seq). Additionally, we utilized pan-viral serology (VirScan) to deeply profile the CSF anti-viral antibody response and metagenomic next-generation sequencing (mNGS) for pathogen detection.ResultsWe detected Epstein-Barr virus (EBV) DNA more frequently in the CSF of NS escape subjects than in AS escape controls. Based on immunostaining and PhIP-Seq, there was evidence for increased immunoreactivity against self-antigens in NS escape CSF. Finally, VirScan revealed several immunodominant epitopes that map to the HIV env and gag proteins in the CSF of PLWH.DiscussionWe deployed agnostic tools to study whether there was evidence for a neuroinvasive co-infection and/or autoimmunity in HIV escape syndromes. We more frequently detected EBV DNA and immunoreactivity to self-antigens in NS escape. Whether these additional inflammatory markers are byproducts of an HIV-driven inflammatory process or whether they independently contribute to the neuropathogenesis of NS escape will require further study.
Multifunctional properties of mycorrhizal helper bacteria: improve mycorrhizal colonization and increase phosphate uptake in Banana
Authors: Shah Chandni , Mali Himanshu , Kamble Vijay , Mandavgane Shachi , Subramanian R B 
Published: December 2022

AbstractUsing mycorrhizal fungi with their helper bacteria (MHB) to alleviate phosphate deficiency improve plant growth and rejuvenate the soil is the newer safer and most promising environment-friendly approach to limiting synthetic agrochemicals. Here 65 MHBs were isolated from the mycorrhizosphere of the Banana plant and 12 were screened based on their biofilm formation protease and N-acyl homoserine lactones production. A newly reported MHBEnterobactersp. was identified through the 16S ribotyping method and posed plant growth-promoting properties i.e solubilized phosphate produced indole acetic acid ammonia and hydrogen sulfide. The biocompatibility experiment showed a 4-fold increased mycorrhizal proliferation in MHB added plate compared to the control. Further field experiments suggested the banana plants 10-4-fold increment in plant height (216.54 cm) and stem diameter (10.66 cm). At the same time10-fold significant improvements were noted in leaf carbohydrate (639.9 mg g-1) protein (432.76 mg g-1) chlorophyll (268.66 mg g-1) phenol (1.9 mg g-1) and proline (uMole g-1) content of experimental plant compared to control. The study also showed a 5-fold increase in phosphate content (12.84 mg g-1) than the control (2.4 mg g-1). The isolates increased the mycorrhizal colonization and spore number by 79.33 % and 14.31 g-1in the rhizospheric soil. Total organic carbon and nitrogen (0.68 %) total phosphorus (55 kg ha-1) and potassium (499.66 kg ha-1) content of soil were positively affected by MHB and AMF. Further-more principal component analysis (PCA) and Pearsons correlation analysis of all the obtained results clearly showed the positive insights of inoculated MHB and AMF on the growth of the banana plant and soil restoration.
Offspring overcome poor parenting by being better parents
Authors: Potticary Ahva L. , Cunningham Christopher B. , Moore Allen J. 
Published: December 2022

AbstractThe evolutionary repercussions of parental effects are often discussed as static effects that can have negative influences on offspring fitness that may even persist across generations. However, individuals are not passive recipients and may mitigate the persistence of parental effects through their behaviour. Here, we tested how the burying beetleNicrophorus orbicollis, a species with complex parental care, responded to poor parenting. We manipulated the duration of parental care received and measured the impact on traits of both F1 and F2 offspring. As expected, reducing parental care negatively affected traits that are ecologically important for burying beetles, including F1 offspring development time and body size. However, F1 parents that received reduced care as larvae spent more time feeding F2 offspring than parents that received full care as larvae. As a result, both the number and mass of F2 offspring were unaffected by the developmental experience of their parents. Our results show that flexible parental care may be able to overcome poor developmental environments and limit negative parental effects to a single generation.
Merging short and stranded long reads improves transcript assembly
Authors: Kainth Amoldeep S. , Haddad Gabriela A. , Hall Johnathon M. , Ruthenburg Alexander J. 
Published: December 2022

AbstractLong-read RNA sequencing has arisen as a counterpart to short-read sequencing, with the potential to capture full-length isoforms, albeit at the cost of lower depth. Yet this potential is not fully realized due to inherent limitations of current long-read assembly methods and underdeveloped approaches to integrate short-read data. Here, we critically compare the existing methods and develop a new integrative approach to characterize a particularly challenging pool of low-abundance long noncoding RNA (lncRNA) transcripts from short- and long-read sequencing in two distinct cell lines. Our analysis reveals severe limitations in each of the sequencing platforms. For short-read assemblies, coverage declines at transcript termini resulting in ambiguous ends, and uneven low-coverage results in segmentation of a single transcript into multiple transcripts. Conversely, long-read transcript assembly lacks strand-of-origin information and depth, culminating in erroneous assembly and quantitation of transcripts. We also discover a cDNA synthesis artifact in long-read datasets that markedly impacts the identity and quantitation of assembled transcripts. Towards remediating these problems, we develop a computational pipeline to “strand” long-read cDNA libraries that rectifies inaccurate mapping and assembly of long-read transcripts. Leveraging the strengths of each platform and our computational stranding, we present and benchmark a hybrid assembly approach that drastically increases the sensitivity and accuracy of full-length transcript assembly on the correct strand and improves detection of biological features of the transcriptome. When applied to a challenging set of under-annotated and cell-type variable lncRNA, our method resolves the segmentation problem of short-read sequencing and the depth problem of long-read sequencing, resulting in the assembly of coherent transcripts with precise 5’ and 3’ ends. Our workflow can be applied to existing datasets for superior demarcation of transcript ends and refined isoform structure, which can enable better differential gene expression analyses and molecular manipulations of transcripts.
Free and interfacial boundaries in individual-based models of multicellular biological systems
Authors: Germano Domenic P. J. , Zanca Adriana , Johnston Stuart T. , Flegg Jennifer A. , Osborne James M. 
Published: December 2022

AbstractCoordination of cell behaviour is key to a myriad of biological processes including tissue morphogenesis, wound healing, and tumour growth. As such, individual-based computational models, which explicitly describe inter-cellular interactions, are commonly used to model collective cell dynamics. However, when using individual-based models, it is unclear how descriptions of cell boundaries affect overall population dynamics. In order to investigate this we define three cell boundary descriptions of varying complexities for each of three widely used off-lattice individual-based models: overlapping spheres, Voronoi tessellation, and vertex models. We apply our models to multiple biological scenarios to investigate how cell boundary description can influence tissue-scale behaviour. We find that the Voronoi tessellation model is most sensitive to changes in the cell boundary description with basic models being inappropriate in many cases. The timescale of tissue evolution when using an overlapping spheres model is coupled to the boundary description. The vertex model is demonstrated to be the most stable to changes in boundary description, though still exhibits timescale sensitivity. When using individual-based computational models one should carefully consider how cell boundaries are defined. To inform future work, we provide an exploration of common individual-based models and cell boundary descriptions in frequently studied biological scenarios and discuss their benefits and disadvantages.
Highly defended nudibranchs ‘escape’ to visually distinct background habitats
Authors: van den Berg Cedric P. , Santon Matteo , Endler John A. , Cheney Karen L. 
Published: December 2022

AbstractThe ‘escape and radiate’ hypothesis predicts that once species have evolved aposematism, defended species can utilise more visually diverse visual backgrounds as they ‘escape’ the need to be well camouflaged. This enables species to explore new ecological niches, resulting in increased diversification rates. To test this hypothesis’ ‘escape’ component, we examined whether the background habitats of 12 nudibranch mollusc species differed among species depending on the presence and strength of chemical defences. We obtained a rich array of colour pattern statistics using Quantitative Colour Pattern Analysis (QCPA) to analyse backgrounds viewed through the eyes of a potential predator (triggerfish,Rhinecanthus aculeatus). Colour pattern analysis was done at viewing distances simulating an escalating predation sequence. We identified four latent factors comprising 17 non-correlated colour pattern parameters, which captured the among-species variability associated with differences in chemical defences. We found that chemically defended species, indeed, were found on visually distinct backgrounds with increased colour and luminance contrast, independent of viewing distance. However, we found no evidence for increased among-species background diversity coinciding with the presence and strength of chemical defences. Our results agree with the ‘escape and radiate’ hypothesis, suggesting that potent chemical defences in Dorid nudibranchs coincide with spatiochromatic differences of visual background habitats perceived by potential predators.Lay SummaryAccording to the ‘escape and radiate’ hypothesis, the ability to store potent chemical defences as protection from predators enables animals to be minimally dependent on matching visual backgrounds for camouflage. We found evidence supporting this hypothesis in 12 species of nudibranch molluscs. Aposematic species were found on visual backgrounds that differed consistently in appearance from the visual background of undefended cryptic species. However, we found no difference in the variability of visual backgrounds between species with or without chemical defences. This suggests that warning colouration in eastern Australian Dorid nudibranchs coincides with broadly generalisable spatiochromatic properties of visual backgrounds.
Multi-Response Phylogenetic Mixed Models: Concepts and Application
Authors: Halliwell Ben , Holland Barbara R. , Yates Luke A. 
Published: December 2022

AbstractThe scale and resolution of trait databases and molecular phylogenies is increasing rapidly. These resources permit many open questions in comparative biology to be addressed with the right statistical tools. Multi-response (MR) phylogenetic mixed models (PMM) offer great potential for multivariate analyses of trait evolution. While flexible and powerful, these methods are not often employed by researchers in ecology and evolution, reflecting a specialised and technical literature that creates barriers to usage for many biologists. Here we present a practical and accessible guide to MR-PMM. We begin with a review of single-response (SR) PMM to introduce key concepts and outline the limitations of this approach for characterizing patterns of trait co-evolution. We emphasise MR-PMM as a preferable approach to analyses involving multiple species traits, due to the explicit decomposition of trait covariance across levels in the model hierarchy. We discuss multilevel distributional models, meta-analyses, multivariate models of evolution, and extensions to non-Gaussian response traits. We highlight techniques for causal inference using precision matrices, as well as advanced topics including prior specification and latent factor models. Using simulated data and visual examples, we discuss interpretation, prediction, and model validation. We implement many of the techniques discussed in example analyses of plant functional traits to demonstrate the general utility of MR-PMM in handling complex real world datasets. Finally, we discuss the emerging synthesis of comparative techniques made possible by MR-PMM, highlight strengths and weaknesses, and offer practical recommendations to analysts. To complement this material, we provide extensive online tutorials including side-by-side model implementations in two popular R packages,MCMCglmmandbrms.
Apoplast-localized β-Glucosidase Elevates Isoflavone Accumulation in the Soybean Rhizosphere
Authors: Matsuda Hinako , Yamazaki Yumi , Moriyoshi Eiko , Nakayasu Masaru , Yamazaki Shinichi , Aoki Yuichi , Takase Hisabumi , Okazaki Shin , Nagano Atsushi J. , Kaga Akito , Yazaki Kazufumi , Sugiyama Akifumi 
Published: December 2022

AbstractPlant specialized metabolites (PSMs) are often stored as glycosides within cells and released from the roots with some chemical modifications. While isoflavones are known to function as symbiotic signals with rhizobia and to modulate the soybean rhizosphere microbiome, the underlying mechanisms of root-to-soil delivery are poorly understood. In addition to transporter-mediated secretion, the hydrolysis of isoflavone glycosides in the apoplast by an isoflavone conjugate-hydrolyzing β-glucosidase (ICHG) has been proposed but not yet verified. To clarify the role of ICHG in isoflavone supply to the rhizosphere, we have isolated two independent mutants defective in ICHG activity from a soybean high-density mutant library. In theichgmutants, the isoflavone contents and composition in the root apoplast and root exudate significantly changed. When grown in a field, the lack of ICHG activity considerably reduced isoflavone aglycone contents in roots and the rhizosphere soil, although the transcriptomes showed no distinct differences between theichgmutants and WTs. Despite the change in isoflavone contents and composition of the root and rhizosphere of the mutants, root and rhizosphere bacterial communities were not distinctive from those of the WTs. Root bacterial communities and nodulation capacities of theichgmutants did not differ from the WTs under nitrogen-deficient conditions, either. Taken together, these results indicate that ICHG elevates the accumulation of isoflavones in the soybean rhizosphere but is not essential in isoflavone-mediated plant-microbe interactions.
Disentangling shared and group-specific variations in single-cell transcriptomics data with multiGroupVI
Authors: Weinberger Ethan , Lopez Romain , Hütter Jan-Christian , Regev Aviv 
Published: December 2022

AbstractSingle-cell RNA sequencing (scRNA-seq) technologies have enabled a greater understanding of previously unexplored biological diversity. Based on the design of such experiments, individual cells from scRNA-seq datasets can often be attributed to non-overlapping “groups”. For example, these group labels may denote the cell’s tissue or cell line of origin. In this setting, one important problem consists in discerning patterns in the data that are shared across groups versus those that are group-specific. However, existing methods for this type of analysis are mainly limited to (generalized) linear latent variable models. Here we introduce multiGroupVI, a deep generative model for analyzing grouped scRNA-seq datasets that decomposes the data into shared and group-specific factors of variation. We first validate our approach on a simulated dataset, on which we significantly outperform state-of-the-art methods. We then apply it to explore regional differences in an scRNA-seq dataset sampled from multiple regions of the mouse small intestine. We implemented multiGroupVI using the scvi-tools library [1], and released it as open-source software athttps://github.com/Genentech/multiGroupVI.
Host-derived protease promotes aggregation ofStaphylococcus aureusby cleaving the surface protein SasG
Authors: Crosby Heidi A. , Keim Klara , Kwiecinski Jakub M. , Langouët-Astrié Christophe J. , Oshima Kaori , LaRivière Wells B. , Schmidt Eric P. , Horswill Alexander R. 
Published: December 2022

AbstractStaphylococcus aureusis one of the leading causes of hospital acquired infections, many of which begin following attachment and accumulation on indwelling medical devices or diseased tissue. These infections are often linked to establishment of biofilms, but another often overlooked key characteristic allowingS. aureusto establish persistent infection is formation of planktonic aggregates. Such aggregates are physiologically similar to biofilms and protect pathogen from innate immune clearance and increase its antibiotic tolerance. The cell wall-associated protein SasG has been implicated in biofilm formation via mechanisms of intercellular aggregation, but the mechanism in the context of disease is largely unknown. We have previously shown that expression of cell wall-anchored proteins involved in biofilm formation is controlled by the ArlRS-MgrA regulatory cascade. In this work, we demonstrate that the ArlRS two-component system controls aggregation, by repressing expression ofsasGby activation of the global regulator MgrA. We also demonstrate that SasG must be proteolytically processed by a non-native protease to induce aggregation, and that strains expressing functional full-lengthsasGaggregate significantly upon proteolysis by a mucosal-derived host protease found in human saliva. We used fractionation and N-terminal sequencing to demonstrate that human trypsin within saliva cleaves within the A domain of SasG to expose the B domain and induce aggregation. Finally, we demonstrated that SasG is involved in virulence during mouse lung infection. Together, our data point to SasG, its processing by host proteases, and SasG-driven aggregation as important elements ofS. aureusadaptation to host environment.
Impact of exposure to per- and polyfluoroalkyl substances on fecal microbiota composition in mother-infant dyads
Authors: Lamichhane Santosh , Härkönen Taina , Vatanen Tommi , Hyötyläinen Tuulia , Knip Mikael , Orešič Matej 
Published: December 2022

AbstractCurrent evidence suggests that chemical exposure alters gut microbiota composition, with higher exposure to environmental chemicals being associated with reduced microbiome diversity. However, not much is known about the impact of per- and polyfluoroalkyl substances (PFAS) on gut bacteria. Here we set out to identify the gut bacterial species that associate with chemical exposure before (maternal) and after (maternal, infant) birth in a mother-infant series. Paired blood and stool samples were collected from mother-infant dyads (n = 30) in a longitudinal setting. PFAS were quantified in maternal blood to examine their associations with the microbial compositions (determined by shotgun metagenomic sequencing) in mothers and infants. High maternal exposure to PFAS was persistently associated with increased abundance ofMethanobrevibacter smithiiin maternal stool. Among individual PFAS compounds, PFOS and PFHpS showed the strongest connection withM. smithii. However, maternal PFAS exposure associated only weakly with the infant microbiome. Our findings suggest that PFAS exposure contributes to the modulation of the adult gut microbiome composition.