bluuebunny/crossref_metadata_2025_split huggingface dataset:
Down regulation of the liver lipid metabolism induced by hypothyroidism in mice: metabolic flexibility favors compensatory mechanisms in white adipose tissue
Authors: Chamas Lamis , Seugnet Isabelle , Tanvé Odessa , Enderlin Valérie , Clerget-Froidevaux Marie-Stéphanie 
Published: December 2022

AbstractIn mammals, the maintenance of energy homeostasis relies on complex mechanisms requiring tight synchronization between peripheral organs and the brain. Thyroid hormones (TH), among their pleiotropic actions, play a central role in these regulations. Hypothyroidism, which is characterized by low circulating TH levels, slows down the metabolism, leading to a reduction in energy expenditure, as well as in lipid and glucose metabolism, and to insulin resistance. Our objective was to evaluate whether metabolic deregulations induced by hypothyroidism could be avoid by regulatory mechanisms involved in metabolic flexibility. To this aim, we compared the response to hypothyroidism in two mouse strains, the wild-derived WSB/EiJ mouse strain characterized by a diet-induced obesity (DIO) resistance due to its high metabolic flexibility phenotype and the C57BL/6J mice, prone to DIO. Adult mice were fed with a low-iodine diet supplemented with 6-n-propyl-2-thiouracyl (PTU) for 7 weeks to induce hypothyroidism. Our results show that hypothyroidism, characterized by a decrease in serum T4 levels, led to metabolic deregulations, as an alteration of lipid metabolism in the liver of both strains. However, the decrease in hepatic lipid synthesis was compensated in WSB/EiJ mice by a mobilization of lipid reserves from white adipose tissue, but not in the C57BL/6J mice. No peripheral or hypothalamic inflammatory response to hypothyroidism was observed in both strains. Moreover, gene expression analysis showed that hypothyroidism stimulates the hypothalamic orexigenic circuit in both strains, but unchanged Mc4r and LepR expression in hypothyroid WSB/EiJ mice strain, which reflect their adaptability to maintain their body weight, contrary to C57BL/6J mice. Our results show that WSB/EiJ mice displayed a phenotype of resistance to metabolic dysregulations induced by hypothyroidism, by compensatory mechanisms. This response as well as their resistance to HFD-induced obesity highlights their adaptive capacities to maintain metabolic homeostasis, namely, their high metabolic flexibility, despite serum hypothyroidism. This model sheds light on the importance of local thyroid homeostasis to maintain lipid metabolism and metabolic homeostasis.
Vessel Metrics: A python based software tool for automated analysis of vascular structure in confocal imaging
Authors: McGarry Sean D. , Adjekukor Cynthia , Ahuja Suchit , Greysson-Wong Jasper , Vien Idy , Rinker Kristina D. , Childs Sarah.J. 
Published: December 2022

AbstractImages contain a wealth of information that is often under analyzed in biological studies. Developmental models of vascular disease are a powerful way to quantify developmentally regulated vessel phenotypes to identify the roots of the disease process. We present vessel Metrics, a software tool specifically designed to analyze developmental vascular microscopy images that will expedite the analysis of vascular images and provide consistency between research groups.We developed a segmentation algorithm that robustly quantifies different image types, developmental stages, organisms, and disease models at a similar accuracy level to a human observer. We validate the algorithm on confocal, lightsheet, and two photon microscopy data in zebrafish. The tool accurately segments data taken by multiple scientists on varying microscopes. We validate vascular parameters such as vessel density, network length, and diameter, across developmental stages, genetic mutations, and drug treatments, and show a favorable comparison to other freely available software tools. Vessel Metrics reduces the time to analyze experimental results, improves repeatability within and between institutions, and expands the percentage of a given vascular network analyzable in experiments.Summary statementVessel Metrics is an automated software tool designed to standardize and streamline the analysis of vascular microscopy images.
Development and characterization of a recombinant silk network for 3D culture of immortalized and fresh tumor-derived breast cancer cells
Authors: Collodet Caterina , Blust Kelly , Gkouma Savvini , Ståhl Emmy , Chen Xinsong , Hartman Johan , Hedhammar My 
Published: December 2022

AbstractTraditional cancer models rely on 2D cell cultures or 3D spheroids, which fail to recapitulate cell-extracellular matrix (ECM) interactions, a key element of tumor development. Existing hydrogel-based 3D alternatives lack mechanical support for cell growth and often suffer from low reproducibility. Here we report a novel strategy to make 3D models of breast cancer using a tissue-like, well-defined network environment based on recombinant spider silk, functionalized with a cell adhesion motif from fibronectin (FN-silk). With this approach, the canonical cancer cells SK-BR-3, MCF-7, and MDA-MB-231, maintain their characteristic expression of markers (i.e., ERα, HER2, and PGR) while developing distinct morphology. Transcriptomic analyses demonstrate how culture in the FN-silk networks modulates the biological processes of cell adhesion and migration while affecting physiological events involved in malignancy, such as inflammation, remodeling of the ECM, and resistance to anticancer drugs. Finally, we show that integration in FN-silk networks promotes the viability of cells obtained from the superficial scraping of patients’ breast tumors.
An annotated chromosome-scale reference genome for Eastern Black-eared Wheatear (Oenanthe melanoleuca)
Authors: Peona Valentina , Palacios-Gimenez Octavio Manuel , Lutgen Dave , Olsen Remi André , Kakhki Niloofar Alaei , Andriopoulos Pavlos , Bontzorlos Vasileios , Schweizer Manuel , Suh Alexander , Burri Reto 
Published: December 2022

AbstractPervasive convergent evolution and in part high incidences of hybridization distinguish wheatears (songbirds of the genusOenanthe) as a versatile system to address questions at the forefront of research on the molecular bases of phenotypic and species diversification. To prepare the genomic resources for this venture, we here generated and annotated a chromosome-scale assembly of the Eastern Black-eared Wheatear (O. melanoleuca). This species is part of theO. hispanica-complex that is characterized by convergent evolution of plumage coloration and high rates of hybridization. The long-read-based male nuclear genome assembly comprises 1.04 Gb in 32 autosomes, the Z chromosome, and the mitogenome. The assembly is highly contiguous (contig N50: 12.6 Mb; scaffold N50: 70 Mb), with 96% of the genome assembled at chromosome level and 96% BUSCO completeness. The nuclear genome was annotated with 18’160 protein-coding genes and 30’730 mRNAs, and about 10% of the genome consists of repetitive DNA. The annotated chromosome-scale reference genome of Eastern Black-eared Wheatear provides a crucial resource for research into the genomics of adaptation and speciation in an intriguing group of passerines.
Evidence for intraflagellar transport in butterfly spermatocyte cilia
Authors: Gottardo Marco , Riparbelli Maria Giovanna , Callaini Giuliano , Megraw Timothy L. 
Published: December 2022

AbstractIn the model organism insectDrosophila melanogastershort cilia assemble on spermatocytes that elaborate into 1.8 mm long flagella during spermatid differentiation. A unique feature of these cilia/flagella is their lack of dependence on intraflagellar transport (IFT) for their assembly. Here we show that in the common butterflyPieris brassicaethe spermatocyte cilia are exceptionally long: about 40 µm compared to less than 1 µm in Drosophila. By transmission electron microscopy we show thatP. brassicaespermatocytes display several features not found in melanogaster, including compelling evidence of IFT structures and features of motile cilia.Summary statementThis work shows ultrastructural definition of the exceptionally long cilia that persist on butterfly (P. brassicae) spermatocytes, including evidence of intraflagellar transport, during meiotic division.
Recursive splicing discovery using lariats in total RNA sequencing
Authors: Hoppe Emma R. , Udy Dylan B. , Bradley Robert K. 
Published: December 2022

ABSTRACTRecursive splicing is a noncanonical splicing mechanism in which an intron is removed in segments via multiple splicing reactions. Relatively few recursive splice sites have been identified with high confidence in human introns, and more comprehensive analyses are needed to better characterize where recursive splicing happens and whether or not it has a regulatory function. In this study, we use an unbiased approach utilizing intron lariats to search for recursive splice sites in constitutive introns and alternative exons in the human transcriptome. We find evidence for recursive splicing in a broader range of intron sizes than previously reported and detail a new location for recursive splicing at the distal ends of cassette exons. Additionally, we identify evidence for the conservation of these recursive splice sites among higher vertebrates and the use of these sites to influence alternative exon exclusion. Together, our data demonstrate the prevalence of recursive splicing and its potential influence on gene expression through alternatively spliced isoforms.
High Estradiol reduces adult neurogenesis but strengthens functional connectivity within the hippocampus during spatial pattern separation in adult female rats
Authors: Yagi Shunya , Lieblich Stephanie E. , Galea Liisa A.M. 
Published: December 2022

AbstractAdult neurogenesis in the dentate gyrus plays an important role for pattern separation, the process of separating similar inputs and forming distinct neural representations. Estradiol modulates neurogenesis and hippocampus function, but to date no examination of estradiol’s effects on pattern separation have been conducted. Here, we examined estrogenic regulation of adult neurogenesis and functional connectivity in the hippocampus after the spatial pattern separation task in female rats. Ovariectomized Sprague-Dawley rats received daily injections of vehicle, 0.32µg (Low) or 5 µg (High) of estradiol benzoate until the end of experiment. A single bromodeoxyuridine (BrdU) was injected one day after initiation of hormone or vehicle treatment and rats were tested in the delayed nonmatching to position spatial pattern separation task in the 8-arm radial maze for 14 days beginning two weeks after BrdU injection. Rats were perfused 90 minutes after the final trial and brain sections were immunohistochemically stained for BrdU/neuronal nuclei (NeuN) (new neurons), Ki67 (cell proliferation), and the immediate early gene, zif268 (activation). Results showed that only high estradiol reduced the density of BrdU/NeuN-ir cells and had significant inter-regional correlations of zif268-ir cell density in the hippocampus following pattern separation. Estradiol treatment did not influence pattern separation performance or strategy use. These results show that higher doses of estradiol can reduce neurogenesis but at the same time increases correlations of activity of neurons within the hippocampus during spatial pattern separation.
Biogenesis of specialized lysosomes in differentiated keratinocytes relies on close apposition with the Golgi apparatus
Authors: Mahanty Sarmistha , Bergam Ptissam , Belapurkar Vivek , Eluvathingal Litralson , Gupta Nikita , Goud Bruno , Nair Deepak , Raposo Graca , Gangi Setty Subba Rao 
Published: December 2022

AbstractIntracellular organelles support cellular physiology in diverse conditions. In the skin, epidermal keratinocytes undergo differentiation with gradual changes in cellular physiology, accompanying remodeling in lysosomes and the Golgi apparatus. However, the functional significance and the molecular link between lysosome and Golgi remodeling were unknown. Here, we show that in differentiated keratinocytes, the Golgi apparatus redistributes as ministacks leading to a significant increase in total protein secretion. The Golgi ministacks establish contact with lysosomes facilitated by Golgi tethering protein GRASP65, the depletion of which is associated with the loss of Golgi-lysosome contact and malformation of lysosomes defined by their aberrant morphology, size, and function. Strikingly, these lysosomes receive secretory Golgi cargoes, contribute to the protein secretion from the Golgi, and are critically maintained by the secretory function of the Golgi apparatus. We uncovered a novel mechanism of lysosome specialization through unique Golgi-lysosome contact that likely supports high secretion from differentiated keratinocytes.Key pointsCalcium induced differentiation of human keratinocytes accompanies the dispersal of functional Golgi stacks and lysosomes.Dispersed Golgi stacks establish contact/physical apposition with the lysosomes.Golgi tether GRASP65 surrounds keratinocyte lysosomes and facilitates Golgi-lysosome apposition.GRASP65 depletion abolishes Golgi-lysosome apposition and accumulates morphologically altered non-degradative lysosomes.Lysosomes of differentiated keratinocytes receive secretory Golgi cargo and contribute to the protein secretion from the Golgi.Specialized lysosomes are maintained by the secretory function of the Golgi apparatus.
Yeasts have evolved divergent enzyme strategies to deconstruct and metabolize xylan
Authors: Ravn Jonas L. , Ristinmaa Amanda Sörensen , Coleman Tom , Larsbrink Johan , Geijer Cecilia 
Published: December 2022

SummaryTogether with bacteria and fungi, yeasts actively take part in the global carbon cycle. Over a hundred yeast species have been shown to grow on the major plant polysaccharide xylan, which requires an arsenal of carbohydrate active enzymes. However, which enzymatic strategies yeasts use to deconstruct xylan and what specific biological roles they play in its conversion remain unclear. In fact, genome analyses reveal that many xylan-metabolizing yeasts lack expected xylanolytic enzymes. Guided by bioinformatics, we have here selected three xylan-metabolizing ascomycetous yeasts for in-depth characterization of growth behavior and xylanolytic enzymes. The savanna soil yeastBlastobotrys mokoenaiidisplays superior growth on xylan thanks to an efficient secreted glycoside hydrolase family 11 (GH11) xylanase; solving its crystal structure revealed a high similarity to xylanases from filamentous fungi. The termite gut-associatedScheffersomyces lignosusin contrast grows more slowly and its xylanase activity was found to be mainly cell surface-associated. The wood-isolatedWickerhamomyces canadensissurprisingly could not utilize xylan as the sole carbon source without adding xylooligosaccharides, exogenous xylanases or even by co-culturing withB. mokoenaii, suggesting thatW. canadensisrelies on initial xylan hydrolysis by neighboring cells. Furthermore, our characterization of a novelW. canadensisGH5 subfamily 49 (GH5_49) xylanase represents the first demonstrated activity in this subfamily. Our collective results provide new information on the variable xylanolytic systems evolved by yeasts and their potential roles in natural carbohydrate conversion.ImportanceMicrobes that take part in the degradation of the polysaccharide xylan, the major hemicellulose component in plant biomass, are equipped with specialized enzyme machineries to hydrolyze the polymer into monosaccharides for further metabolism. However, despite being found in virtually every habitat, little is known of how yeasts break down and metabolize xylan and what biological role they may play in its turnover in nature. Here, we have explored the enzymatic xylan deconstruction strategies of three underexplored yeasts from diverse environments:Blastobotrys mokoenaiifrom soil,Scheffersomyces lignosusfrom insect guts andWickerhamomyces canadensisfrom trees, and show that each species has a distinct behavior regarding xylan conversion. These findings may be of high relevance for future design and development of microbial cell factories and biorefineries utilizing renewable plant biomass.
plastiC: A pipeline for recovery and characterization of plastid genomes from metagenomic datasets
Authors: Cameron Ellen S. , Blaxter Mark L. , Finn Robert D. 
Published: December 2022

AbstractThe use of culture independent molecular methods, often referred to as metagenomics, have revolutionized the ability to explore and characterize microbial communities from diverse environmental sources. Most metagenomic workflows have been developed for identification of prokaryotic and eukaryotic community constituents, but tools for identification of plastid genomes are lacking. The endosymbiotic origin of plastids also poses challenges where plastid metagenomic assembled genomes (MAGs) may be misidentified as low-quality bacterial MAGs. Current tools are limited to classification of contigs as plastid and do not provide further assessment or characterization of plastid MAGs.plastiCis a workflow that allows users to identify plastid genomes in metagenome assemblies, assess completeness, and predict taxonomic association from diverse environmental sources.plastiCis a Snakemake workflow available athttps://github.com/Finn-Lab/plastiC. We demonstrate the utility of this workflow with the successful recover of algal plastid MAGs from publicly available lichen metagenomes.
New mitochondrial genomes of leptosporangiate ferns allow modeling the mitogenomic inflation syndrome across all land plant lineages
Authors: Feng Yanlei , Wicke Susann 
Published: December 2022

AbstractPlants’ mitochondrial genomes (mitogenome) evolve in a hard-to-predict fashion. To reconstruct the evolutionary trajectories of land plant mitogenomes, we, here, filled the last major mitogenomic gap within land plants by assembling the mitogenomes of the leptosporangiate fernsAzolla filiculoidesandPteridium revolutumand, secondly, analyzed the mitogenomic evolutionary regime shifts across land plants. By testing various Ornstein-Uhlenbeck stabilizing selection models in an a priori-free analysis of five selected mitogenomic traits, we observed 71 evolutionary regime shifts across 218 land plant species. These shifts can lead to genomic convergence, in which certain traits such as size, GC content, and the proportion of non-coding DNA converge, or non-converging regimes, which are characterized by exceptional paths of genomic evolution such as extreme GC content or size. We also found that non-seed plants have a slightly, but significantly, higher rate of synonymous substitutions across all gene classes than seed plants, and that ferns differ significantly in the number of nonsynonymous and synonymous changes compared with other non-seed and seed plants. This pattern matches an outstandingly high rate of RNA editing in the small but repeat-rich mitogenomes of leptosporangiate ferns. In sum, our study highlights the considerable changes in mito-chromosomal architecture that occur during land plant evolution and suggests that these changes may be related to increases in error-prone repair mechanisms. Further study of underrepresented plant groups such as ferns and lycophytes is needed to understand the mechanisms and dominating forces behind the evolutionary dynamics and the mitogenomic inflation syndrome.Significance StatementOur study provides new insights into the complexity and diversity of land plant mitogenome evolution and reveals that they take many turns of molecular evolutionary directions across 218 land plant species. Our results have the potential to inform future research in this area and to advance our understanding of the mitogenomic inflation syndrome during plant evolution.
Genetic architecture of inter-specific and -generic grass hybrids by network analysis on multi-omics data
Authors: Bornhofen Elesandro , Fè Dario , Nagy Istvan , Lenk Ingo , Greve Morten , Didion Thomas , Jensen Christian Sig , Asp Torben , Janss Luc 
Published: December 2022

AbstractUnderstanding the mechanisms underlining forage production and its biomass nutritive quality at the omics level is crucial for boosting the output of high-quality dry matter per unit of land. Despite the advent of multiple omics integration for the study of biological systems in major crops, investigations on forage species are still scarce. Therefore, this study aimed to combine multi-omics from grass hybrids by prioritizing omic features based on the reconstruction of interacting networks and assessing their relevance in explaining economically important phenotypes. Transcriptomic and NMR-based metabolomic data were used for sparse estimation via the fused graphical lasso, followed by modularity-based gene expression and metabolite-metabolite network reconstruction, node hub identification, omic-phenotype association via pairwise fitting of a multivariate genomic model, and machine learning-based prediction study. Analyses were jointly performed across two data sets composed of family pools of hybrid ryegrass (Lolium perenne×L. multiflorum) andFestulolium loliaceum(L. perenne×Festuca pratensis), whose phenotypes were recorded for eight traits in field trials across two European countries in 2020/21. Our results suggest substantial changes in gene co-expression and metabolite-metabolite network topologies as a result of genetic perturbation by hybridizingL. perennewith another species within the genus relative to across genera. However, conserved hub genes and hub metabolomic features were detected between pedigree classes, some of which were highly heritable and displayed one or more significant edges with agronomic traits in a weighted omics-phenotype network. In spite of tagging relevant biological molecules as, for example, the light-induced rice 1 (LIR1), hub features were not necessarily better explanatory variables for omics-assisted prediction than features stochastically sampled. The use of the graphical lasso method for network reconstruction and identification of biological targets is discussed with an emphasis on forage grass breeding.
Cycad phylogeny predicts host plant use ofEumaeusbutterflies
Authors: Sierra-Botero Laura , Calonje Michael , Robbins Robert K. , Rosser Neil , Pierce Naomi E. , López-Gallego Cristina , Valencia-Montoya Wendy A. 
Published: December 2022

AbstractEumaeusbutterflies are obligate herbivores ofZamia, the most diverse neotropical genus of cycads.Eumaeus-Zamiainteractions have been mainly characterized for species distributed in North and Central America. However, host plant use by the southernEumaeusclade remains largely unknown, precluding a comprehensive study of co-evolution between the genera. Here, we combine fieldwork with museum and literature surveys to expand herbivory records forEumaeusfrom 21 to 38Zamiaspecies. We inferred a time-calibrated phylogeny ofEumaeusto test for distinct macroevolutionary scenarios of host plant conservatism and co-evolution. We found remarkable coincidence betweenEumaeusandZamiadiversification, with the butterfly stem group diverging at the same time as the most recent radiation ofZamiain the Miocene. Cophylogenetic reconciliation analyses show a strong cophylogenetic signal between cycads and their butterfly herbivores. Bipartite model-based approaches indicate that this is because closely relatedZamiaspecies are used by the sameEumaeusspecies, suggesting host plant resource tracking by the butterfly herbivores. Our results highlight a case of tight evolution betweenEumaeusbutterflies and cycads, pointing to the generality of correlated evolution and phylogenetic tracking in plant-herbivore interactions across seed plants.