bluuebunny/crossref_metadata_2025_split huggingface dataset:
A method for morphological feature extraction based on variational auto-encoder : an application to mandible shape
Authors: Tsutsumi Masato , Saito Nen , Koyabu Daisuke , Furusawa Chikara 
Published: May 2022

ABSTRACTShape analysis of biological data is crucial for investigating the morphological variations during development or evolution. However, conventional approaches for quantifying shapes are difficult as exemplified by the ambiguity in the landmark-based method in which anatomically prominent “landmarks” are manually annotated. In this study, a morphological regulated variational autoencoder (Morpho-VAE) is proposed that conducts image-based shape analysis using imaging processing through a deep-learning framework, thereby removing the need for defining landmarks. The proposed architecture comprises a VAE combined with a classifier module. This integration of unsupervised and supervised learning models (i.e., VAE and classifier modules) is designed to reduce dimensionality by focusing on the morphological features in which the differences between data with different labels are best distinguished. The proposed method is applied to the image dataset of the primate mandible to extract morphological features, which allow us to distinguish different families in a low dimensional latent space. Furthermore, the visualization analysis of decision-making of Morpho-VAE clarifies the area of the mandibular joint that is important for family-level classification. The generative nature of the proposed model is also demonstrated to complement a missing image segment based on the remaining structure. Therefore, the proposed method, which flexibly performs landmark-free feature extraction from complete and incomplete image data is a promising tool for analyzing morphological datasets in biology.AUTHOR SUMMARYShape is the most intuitive visual characteristic; however, shape is generally difficult to measure using a small number of variables. Specifically, for biological data, shape is sometimes highly diverse as it has been acquired through a long evolutionary process, adaptation to environmental factors, etc., which limits the straightforward approach to shape measurement. Therefore, a systematic method for quantifying such a variety of shapes using a low-dimensional quantity is needed. To this end, we propose a novel method that extracts low-dimensional features to describe shapes from image data using machine learning. The proposed method is applied to the primate mandible image data to extract morphological features that reflect the characteristics of the groups to which the organisms belong and then those features are visualized. This method also reconstructs a missing image segment from an incomplete image based on the remaining structure. To summarize, this method is applicable to the shape analysis of various organisms and is a useful tool for analyzing a wide variety of image data, even those with a missing segment.
Extremely low level of genetic diversity in Gentiana yakushimensis, an endangered species in Yakushima Island, Japan
Authors: Ishii Naohiro I. , Hirota Shun K. , Tsunamoto Yoshihiro , Matsuo Ayumi , Abe Harue , Suyama Yoshihisa 
Published: May 2022

AbstractRare or endangered species largely contributing to global biodiversity are essential components of ecosystems. Because genetic diversity depends not only on apparent population size but also demographic processes, the conservation priority of endangered species based on population genetics needs to be assessed by comparison with common congeners and demographic events. In this study, we performed population genetic analysis for Gentiana yakushimensis Makino, a rare and endangered plant species with an isolated distribution on Yakushima Island, Japan. We performed comparison of genetic diversity with the congener (Gentiana triflora Pall. var. japonica (Kusn.) H.Hara), demographic inference, and bottleneck test based on genome-wide single nucleotide polymorphisms. The result was that G. yakushimensis had an extremely low genetic diversity level and a high inbreeding coefficient level compared to those of the congener. The population of G. yakushimensis was estimated to experience an expansion during the Last Glacial Maximum and a recent bottleneck by the demographic inference and the bottleneck test. Therefore, the low level of genetic diversity of this species might have resulted from the impact of the recent bottleneck and the long-term maintenance of a small population size. Due to the long lifespan of the genus Gentiana, the current level of genetic diversity probably does not reflect a large part of recent demographic events, which requires long-term monitoring of changes in genetic diversity to identify the time lag between the reduction in apparent population size and genetic diversity as a future outlook.
Gut microbiota of homing pigeons shows summer-winter variation under constant diet indicating a substantial effect of temperature
Authors: Dietz Maurine W. , Matson Kevin D. , Versteegh Maaike A. , van der Velde Marco , Parmentier Henk K. , Arts Joop. A.J. , Salles Joana F. , Tieleman B. Irene 
Published: May 2022

AbstractBackgroundGut microbiotas play a pivotal role in host physiology and behaviour, and may affect host life-history traits such as seasonal variation in host phenotypic state. Generally, seasonal gut microbiota variation is attributed to seasonal diet variation. However, seasonal temperature and day length variation may also drive gut microbiota variation. We investigated summer-winter differences in gut microbiota in 14 homing pigeons living outdoors under a constant diet by collecting cloacal swabs in both seasons during two years. Because temperature effects may be mediated by host metabolism, we determined basal metabolic rate (BMR) and body mass. Immune competence is influenced by day length and has a close relationship with gut microbiota, and it may thus be a link between day length and gut microbiota. Therefore, we measured seven innate immune indices. We expected gut microbiota to show summer-winter differences and gut microbiota to correlate with metabolism and immune indices.ResultsBMR, body mass, and two immune indices varied seasonally, other host factors did not. Gut microbiota showed differences between seasons and sexes, and correlated with metabolism and immune indices. The most abundant genus (Lachnoclostridium 12, 12%) and associated higher taxa, were more abundant in winter, though not significantly at the phylum level, Firmicutes. Bacteroidetes were more abundant in summer. The Firmicutes:Bacteroidetes ratio tended to be higher in winter. The KEGG ortholog functions for fatty acid biosynthesis and linoleic acid metabolism (PICRUSt2) had increased abundances in winter.ConclusionsThe gut microbiota of homing pigeons varied seasonally, even under a constant diet. The correlations between immune indices and gut microbiota did not involve consistently specific immune indices and included only one of the two immune indices that showed seasonal differences, suggesting that immune competence may be an unlikely link between day length and gut microbiota. The correlations between gut microbiota and metabolism indices, the higher Firmicutes:Bacteroidetes ratio in winter, and the resemblance of the summer-winter differences in gut microbiota with the general temperature effects on gut microbiota in the literature, suggest that temperature partly drove the summer-winter differences in gut microbiota in homing pigeons.
Increasing protein stability by inferring substitution effects from high-throughput experiments
Authors: Norrild Rasmus Krogh , Johansson Kristoffer Enøe , O’Shea Charlotte , Morth Jens Preben , Lindorff-Larsen Kresten , Winther Jakob Rahr 
Published: May 2022

AbstractProtein stability is an important parameter in almost all protein-engineering efforts. Evaluating the effects of the many possible amino acid changes to guide such projects is a significant task, even with recent advances in experimental and computational approaches. Here, we apply a computational model, GMMA, to extract substitution effects from a cost-effective genetic screen of a randomly mutated protein library. Using a high mutation frequency, the method can map stability effects of even very stable proteins for which conventional selection systems have reached their limit. Thus, we screened a mutant library of a highly stable and optimised model protein using an in vivo genetic sensor for folding and assigned a stability effect to 374 of 912 possible single amino acid substitutions. Combining the top 9 substitutions increased the thermodynamic stability by almost 50% in a single engineering step. This illustrates the capability of the method, which is applicable to any screen for protein function.
A deeply conserved protease, acylamino acid-releasing enzyme (AARE), acts in ageing in Physcomitrella and Arabidopsis
Authors: Hoernstein Sebastian N.W. , Özdemir Buğra , van Gessel Nico , Miniera Alessandra A. , von Bieberstein Bruno Rogalla , Nilges Lars , Farinha Joana Schweikert , Komoll Ramona , Glauz Stella , Weckerle Tim , Scherzinger Friedrich , Rodriguez-Franco Marta , Müller-Schüssele Stefanie J. , Reski Ralf 
Published: May 2022

AbstractReactive oxygen species (ROS) are constant by-products of aerobic life. In excess, ROS lead to cytotoxic protein aggregates, which are a hallmark of ageing in animals and linked to age-related pathologies in humans. Acylamino acid-releasing enzymes (AARE) are bifunctional serine proteases, acting on oxidized proteins. AARE are found in all domains of life, albeit under different names, such as acylpeptide hydrolase (APEH/ACPH), acylaminoacyl peptidase (AAP), or oxidized protein hydrolase (OPH). In humans, AARE malfunction is associated with age-related pathologies, while their function in plants is less clear. Here, we provide a detailed analysis ofAAREgenes in the plant lineage and an in-depth analysis of AARE localization and function in the moss Physcomitrella and the angiosperm Arabidopsis.AAREloss-of-function mutants have not been described for any organism so far. We generated and analysed such mutants and describe a connection between AARE function, aggregation of oxidized proteins and plant ageing, including accelerated developmental progression and reduced life span. Our findings complement similar findings in animals and humans, and suggest a unified concept of ageing may exist in different life forms.
Western diet-induced shifts in the maternal microbiome are associated with altered microRNA expression in baboon placenta and fetal liver
Authors: Sugino Kameron Y. , Mandala Ashok , Janssen Rachel C. , Gurung Sunam , Trammell MaJoi , Day Michael W. , Brush Richard S. , Papin James F. , Dyer David W. , Agbaga Martin-Paul , Friedman Jacob E. , Castillo-Castrejon Marisol , Jonscher Karen R. , Myers Dean A. 
Published: May 2022

AbstractMaternal consumption of a high-fat, Western-style diet (WD) disrupts the maternal/infant microbiome and contributes to developmental programming of the immune system and nonalcoholic fatty liver disease (NAFLD) in the offspring. Epigenetic changes, including non-coding miRNAs in the fetus and/or placenta may also underlie this risk. We previously showed that obese nonhuman primates (NHP) fed a WD during pregnancy results in the loss of beneficial maternal gut microbes and dysregulation of cellular metabolism and mitochondrial dysfunction in the fetal liver, leading to a perturbed postnatal immune response with accelerated NAFLD in juvenile offspring. Here, we investigated associations between WD-induced maternal metabolic and microbiome changes, in the absence of obesity, and miRNA and gene expression changes in the placenta and fetal liver. After ∼8-11 months of maternal WD feeding (mWD), dams were similar in body weight but exhibited mild, systemic inflammation (elevated CRP and neutrophil count) and dyslipidemia (increased triglycerides and cholesterol) compared with dams fed a control diet. The maternal gut microbiome was mainly comprised ofLactobacillalesandClostridiales, with significantly decreased alpha diversity (P= 0.0163) in WD-fed dams but no community-wide differences (P= 0.26). At 0.9 gestation, mRNA expression ofIL6andTNFin mWD-exposed placentas trended higher, while increased triglycerides, expression of pro-inflammatoryCCR2, and histological evidence for fibrosis were found in mWD-exposed fetal livers. In the mWD-exposed fetus, hepatic expression levels of miR-204-5p and miR-145-3p were significantly downregulated, whereas in mWD-exposed placentas, miR-182-5p and miR-183-5p were significantly decreased. Notably, miR-1285-3p expression in the liver and miR-183-5p in the placenta were significantly associated with inflammation and lipid synthesis pathway genes, respectively.BlautiaandRuminococcuswere significantly associated with miR-122-5p in liver, whileCoriobacteriaceaandPrevotellaceawere strongly associated with miR-1285-3p in the placenta; both miRNAs are implicated in pathways mediating postnatal growth and obesity. Our findings demonstrate that mWD shifts the maternal microbiome, lipid metabolism, and inflammation prior to obesity and are associated with epigenetic changes in the placenta and fetal liver. These changes may underlie inflammation, oxidative stress, and fibrosis patterns that drive NAFLD and metabolic disease risk in the next generation.
Non-aging despite high mutation rate – genomic insights into the evolution ofHydra
Authors: Sahm Arne , Riege Konstantin , Groth Marco , Bens Martin , Kraus Johann , Fischer Martin , Kestler Hans , Englert Christoph , Schaible Ralf , Platzer Matthias , Hoffmann Steve 
Published: May 2022

AbstractHydrais a genus of freshwater polyps with remarkable regeneration abilities and a non-senescent phenotype under laboratory conditions. Thus, this animal is particularly interesting for aging research. Here, we gained insights intoHydra’srecent genetic evolution by genome sequencing of single cells and whole individuals. Despite its extreme longevity,Hydradoes not show a lower somatic mutation rate than humans or mice. While we identify biological processes that have evolved under positive selection in animals kept in optimal laboratory conditions for decades, we found no signs of strong negative selection during this tiny evolutionary window. Interestingly, we observe the opposite pattern for the preceding evolution in the wild over a longer time period. Moreover, we found evidence thatHydraevolution in captivity was accompanied and potentially accelerated by loss of heterozygosity. Processes under positive selection in captive animals include pathways associated withHydra’s simple nervous system, its nucleic acid metabolic process, cell migration, and hydrolase activity. Genes associated with organ regeneration, regulation of mRNA splicing, histone ubiquitination, and mitochondrial fusion were identified as highly conserved in the wild. Remarkably, several of the processes under strongest selection are closely related to those considered essential for the exapted, i. e. not brought about by natural selection, feature:Hydra’snon-aging.
Rap1 uses Canoe-dependent and Canoe-independent mechanisms to regulate apical contractility and allow embryonic morphogenesis without tissue disruption
Authors: Perez-Vale Kia Z. , Yow Kristi D. , Greene Melissa , Gurley Noah J. , Peifer Mark 
Published: May 2022

AbstractEmbryonic morphogenesis is powered by dramatic changes in cell shape and arrangement, driven by the cytoskeleton and its connections to adherens junctions. This requires robust linkage, allowing morphogenesis without disrupting tissue integrity. The small GTPase Rap1 is a key regulator of cell adhesion, controlling both cadherin-mediated and integrin-mediated processes. We have defined multiple roles in morphogenesis for one Rap1 effector, Canoe/Afadin, which ensures robust junction-cytoskeletal linkage. We now ask what mechanisms regulate Canoe and other junction-cytoskeletal linkers during Drosophila morphogenesis, defining roles for Rap1 and one of its guanine nucleotide exchange factor (GEF) regulators, Dizzy. Rap1 uses Canoe as one effector, regulating junctional planar polarity. However, Rap1 has additional roles in junctional protein localization and balanced apical constriction—in its absence, Bazooka/Par3 localization is fragmented, and cells next to mitotic cells apically constrict and invaginate, disrupting epidermal integrity. In contrast, the GEF Dizzy has phenotypes similar to but slightly less severe than Canoe loss, suggesting this GEF regulates Rap1 action via Canoe. Taken together, these data reveal that Rap1 is a crucial regulator of morphogenesis, likely acting in parallel via Canoe and other effectors, and that different Rap1 GEFs regulate distinct functions of Rap1.
Enhancer plasticity sustains oncogenic transformation and progression of B-Cell Acute Lymphoblastic leukemia
Authors: Corleone G , Sorino C , Caforio M , Di Giovenale S , De Nicola F , Bertaina V , Pitisci A , Cortile C , Locatelli F , Folgiero V , Fanciulli M 
Published: May 2022

ABSTRACTGrowing evidence report that non-genetic-driven events such as enhancer reprogramming promote neoplastic transformation and strongly contribute to the phenotypical heterogeneity of cancers as much as genetic variation. In this context, we investigated the role of enhancers in sustaining oncogenic transformation in B-Cell Acute Lymphoblastic leukemia in children (BCP-ALL), a type of cancer caused by the accumulation of lymphoid progenitor cells in the bone marrow and a leading cause of cancer-related mortality in children. Using next-generation sequencing (ATAC-seq), we built the most up-to-date map of chromatin accessibility in pediatric BCP-ALL. We observed that enhancer activity dynamically changes during cancer progression and represents principal phenomena underlying phenotypic–functional characteristics of BCP-ALL progression. BCP-ALL patients are dominated by a regulatory repertoire (N=∼11k) originally represented at diagnosis that shrinks under treatments and subsequently re-expands, driving the relapse. We then deployed a wide range of in-vivo, in-vitro assays, and in-silico analyses to demonstrate the impact of enhancer activity in determining the phenotypical complexity. CRISPR-Cas-9-mediated validation of selected productive enhancers demonstrated a high capability of these regions to control MYB and DCTD oncogenic activities. Taken together, these findings provide direct support to the notion that enhancer plasticity is a crucial determinant of the BCP-ALL phenotype.
The epigenomic landscape of single vascular cells reflects developmental origin and identifies disease risk loci
Authors: Weldy Chad S. , Cheng Paul P. , Guo Wenduo , Pedroza Albert J. , Dalal Alex R. , Worssam Matthew D. , Sharma Disha , Nguyen Trieu , Kundu Ramendra , Fischbein Michael P. , Quertermous Thomas 
Published: May 2022

AbstractRationaleVascular beds have distinct susceptibility to atherosclerosis and aneurysm, yet the biological underpinnings of vascular bed specific disease risk are largely unknown. Vascular tissues have different developmental origins which may influence global chromatin accessibility. Understanding chromatin accessibility and gene expression profiles on single cell resolution is crucial to gain insight into vascular bed specific disease risk.ObjectiveWe aim to understand, at single cell resolution, the global chromatin accessibility and gene expression profiles across distinct vascular beds in the healthy adult mouse to provide insight into the potential mechanisms of vascular bed specific disease risk.Methods and ResultsWe performed single cell chromatin accessibility (scATACseq) and gene expression profiling (scRNAseq) of healthy adult mouse vascular tissue from three vascular beds, 1) aortic root and ascending aorta, 2) brachiocephalic and carotid artery, and 3) descending thoracic aorta. By integrating datasets and comparing vascular beds within cell type, we identified thousands of differentially accessible chromatin peaks within smooth muscle cells, fibroblasts, and endothelial cells, demonstrating numerous enhancers to be vascular bed specific. We revealed an epigenetic ‘memory’ of embryonic origin with differential chromatin accessibility of key developmental transcription factors such asTbx20,Hand2,Gata4, andHoxbfamily members. Increased transcription factor motif accessibility in ascending fibroblasts compared to descending further highlights SMAD2/3 functions and suggests a differential susceptibility to TGFβ. By isolating primary adventitial fibroblasts from ascending and descending thoracic aorta from adult mice, we demonstrate ascending fibroblasts to have a distinctly higher transcriptional response to TGFβ compared to descending fibroblasts, highlighting that distinct chromatin accessibility between vascular beds is retained following primaryin vitroculture and influences responsiveness to disease relevant signaling.ConclusionsThis work supports a paradigm that the epigenomic and transcriptional landscapes of vascular cells are cell type and vascular bed specific and that differentially accessible regions are enriched for disease risk genes.
Serverless Prediction of Peptide Properties with Recurrent Neural Networks
Authors: Ansari Mehrad , White Andrew D. 
Published: May 2022

AbstractWe present three deep learning sequence prediction models for hemolysis, solubility, and resistance to non-specific interactions of peptides that achieve comparable results to the state-of-the-art models. Our sequence-based solubility predictor, MahLooL, outperforms the current state-of-art methods for short peptides. These models are implemented as a static website without the use of a dedicated server or cloud computing. Web-based models like this allow for accessible and effective reproducibility. Most existing approaches rely on third-party servers typically that require upkeep and maintenance. That trend leads to a relatively longer lifetime of web-based models. These predictive models do not require servers, require no installation of dependencies, and work on across a range of devices. The models are bidirectional recurrent neural networks. Thisserverlessprediction model is a demonstration of edge machine learning that removes the dependence on cloud providers. The code and models are accessible athttps://github.com/ur-whitelab/peptide-dashboard.
AI-guided screen identifies probucol-mediated mitophagy enhancement through modulation of lipid droplets
Authors: Moskal Natalia , Visanji Naomi P. , Gorbenko Olena , Narasimhan Vijay , Tyrrell Hannah , Nash Jess , Lewis Peter N. , McQuibban G. Angus 
Published: May 2022

AbstractFailures in mitophagy, a process by which damaged mitochondria are cleared, results in neurodegeneration, while enhancing mitophagy promotes the survival of dopaminergic neurons. Using an artificial intelligence platform, we employed a natural language processing approach to evaluate the semantic similarity of candidate molecules to a set of well-established mitophagy enhancers. Top candidates were screened in a cell-based mitochondrial clearance assay. Probucol, a lipid-lowering drug, was validated across several orthogonal mitophagy assays. In vivo, probucol improved survival, locomotor function and dopaminergic neuron loss in zebrafish and fly models of mitochondrial damage. Probucol functioned independently of PINK1/Parkin but its effects on mitophagy and in vivo depended on ABCA1, which negatively regulated mitophagy following mitochondrial damage. Autophagosome and lysosomal markers were elevated by probucol treatment in addition to increased contact between lipid droplets and mitochondria. Conversely, lipid droplet expansion, which occurs following mitochondrial damage was suppressed by probucol and probucol-mediated mitophagy enhancement required lipid droplets. Probucol-mediated lipid droplet dynamics changes may prime the cell for a more efficient mitophagic response to mitochondrial damage.