Miracle-dz/UniFAR-FTUs huggingface dataset:
Evolutionary history of an Alpine Archaeognath (Machilis pallida): Insights from different variant

Abstract Reconstruction of species histories is a central aspect of evolutionary biology. Patterns of genetic variation within and among populations can be leveraged to elucidate evolutionary processes and demographic histories. However, interpreting genetic signatures and unraveling the contributing processes can be challenging, in particular for non‐model organisms with complex reproductive modes and genome organization. One way forward is the combined consideration of patterns revealed by different molecular markers (nuclear vs. mitochondrial) and types of variants (common vs. rare) that differ in their age, mode, and rate of evolution. Here, we applied this approach to RNAseq data generated for Machilis pallida (Archaeognatha), an Alpine jumping bristletail considered parthenogenetic and triploid. We generated de novo transcriptome and mitochondrial assemblies to obtain high‐density data to investigate patterns of mitochondrial and common and rare nuclear variation in 17 M. pallida individuals sampled from all known populations. We find that the different variant types capture distinct aspects of the evolutionary history and discuss the observed patterns in the context of parthenogenesis, polyploidy, and survival during glaciation. This study highlights the potential of different variant types to gain insights into evolutionary scenarios even from challenging but often available data and the suitability of M. pallida and the genus Machilis as a study system for the evolution of sexual strategies and polyploidization during environmental change. We also emphasize the need for further research which will be stimulated and facilitated by these newly generated resources and insights.
Directing Multicellular Organization by Varying the Aspect Ratio of Soft Hydrogel Microwells

Multicellular organization with precise spatial definition is an essential step in a wide range of biological processes, including morphogenesis, development, and healing. Gradients and patterns of chemoattractants are well-described guides of multicellular organization, but the influences of three-dimensional geometry of soft hydrogels on multicellular organization are less well defined. Here, we report the discovery of a new mode of self-organization of endothelial cells in ring-like patterns on the perimeters of hydrogel microwells that is independent of protein or chemical patterning and is driven only by geometry and substrate stiffness. We observe quantitatively striking influences of both the microwell aspect ratio (ε = perimeter/depth) and the hydrogel modulus. We systematically investigate the physical factors of cells and substrates that drive this multicellular behavior and present a mathematical model that explains the multicellular organization based upon balancing extracellular and cytoskeletal forces. These forces are determined in part by substrate stiffness, geometry, and cell density. The force balance model predicts the direction and distance of translational cell migration based on the dynamic interaction between tangential cytoskeletal tension and cell-cell and cell-substrate adhesion. We further show that the experimental observations can be leveraged to drive customized multicellular self-organization. Our observation of this multicellular behavior demonstrates the importance of the combinatorial effects of geometry and stiffness in complex biological processes. It also provides a new methodology for direction of cell organization that may facilitate the engineering of bionics and integrated model organoid systems.
Identification and classification of cis-regulatory elements in the amphipod crustacean Parhyale hawaiensis

Emerging research organisms enable the study of biology that cannot be addressed using classical “model” organisms. The development of novel data resources can accelerate research in such animals. Here, we present new functional genomic resources for the amphipod crustacean Parhyale hawaiensis, facilitating the exploration of gene regulatory evolution using this emerging research organism. We use Omni-ATAC-Seq, an improved form of the Assay for Transposase-Accessible Chromatin coupled with next-generation sequencing (ATAC-Seq), to identify accessible chromatin genome-wide across a broad time course of Parhyale embryonic development. This time course encompasses many major morphological events, including segmentation, body regionalization, gut morphogenesis, and limb development. In addition, we use short- and long-read RNA-Seq to generate an improved Parhyale genome annotation, enabling deeper classification of identified regulatory elements. We leverage a variety of bioinformatic tools to discover differential accessibility, predict nucleosome positioning, infer transcription factor binding, cluster peaks based on accessibility dynamics, classify biological functions, and correlate gene expression with accessibility. Using a Minos transposase reporter system, we demonstrate the potential to identify novel regulatory elements using this approach, including distal regulatory elements. This work provides a platform for the identification of novel developmental regulatory elements in Parhyale, and offers a framework for performing such experiments in other emerging research organisms. Primary Findings - Omni-ATAC-Seq identifies cis-regulatory elements genome-wide during crustacean embryogenesis - Combined short- and long-read RNA-Seq improves the Parhyale genome annotation - ImpulseDE2 analysis identifies dynamically regulated candidate regulatory elements - NucleoATAC and HINT-ATAC enable inference of nucleosome occupancy and transcription factor binding - Fuzzy clustering reveals peaks with distinct accessibility and chromatin dynamics - Integration of accessibility and gene expression reveals possible enhancers and repressors - Omni-ATAC can identify known and novel regulatory elements
Programmed Cell Death Recruits Macrophages Into the Developing Mouse Cochlea

Programmed cell death (PCD) plays a critical role in the development and maturation of the cochlea. Significant remodeling occurs among cells of the greater epithelial ridge (GER) of Kölliker’s organ, leading to tissue regression and formation of the inner sulcus. In mice, this event normally occurs between postnatal days 5-15 (P5-15) and is regulated by thyroid hormone (T3). During this developmental time period, the cochlea also contains a large population of macrophages. Macrophages are frequently involved in the phagocytic clearance of dead cells, both during development and after injury, but the role of macrophages in the developing cochlea is unknown. This study examined the link between developmental cell death in the GER and the recruitment of macrophages into this region. Cell death in the basal GER begins at P5 and enhanced numbers of macrophages were observed at P7. This pattern of macrophage recruitment was unchanged in mice that were genetically deficient for CX3CR1, the receptor for fractalkine (a known macrophage chemoattractant). We found that injection of T3 at P0 and P1 caused GER cell death to begin at P3, and this premature PCD was accompanied by earlier recruitment of macrophages. We further found that depletion of macrophages from the developing cochlea (using CX3CR1DTR/+ mice and treatment with the CSF1R antagonist BLZ945) had no effects on the pattern of GER regression. Together, these findings suggest that macrophages are recruited into the GER region after initiation of developmental PCD, but that they are not essential for GER regression during cochlear remodeling.
A B73 x Palomero Toluqueño mapping population reveals local adaptation in Mexican highland maize

Generations of farmer selection have produced a unique collection of traditional maize varieties adapted to the environmental challenges of the central Mexican highlands. In addition to agronomic and cultural value, Mexican highland maize represents a good system for the study of local adaptation and acquisition of adaptive phenotypes under cultivation. In this study, we characterized a recombinant inbred line population derived from the cross of the B73 reference line and the Mexican highland maize variety Palomero Toluqueño. Evaluation over multiple years in lowland and highland field sites in Mexico identified genomic regions linked to yield components and putatively adaptive morphological traits. A region on chromosome 7 associated with ear weight showed antagonistic allelic effects in lowland and highland fields, suggesting a trade-off consistent with local adaptation. We identified several alleles of highland origin associated with characteristic highland traits, including reduced tassel branching, increased stem pigmentation and the presence of stem macrohairs. The oligogenic architecture of characteristic morphological traits supports their role in adaptation, suggesting they have arisen from consistent directional selection acting at distinct points across the genome. We discuss these results in the context of the origin of phenotypic novelty during selection, commenting on the role of de novo mutation and the acquisition of adaptive variation by gene flow from endemic wild relatives.
Androglobin, a chimeric mammalian globin, is required for male fertility

Spermatogenesis is a highly specialised process, involving multiple dedicated pathways and regulatory check-points. Defects ultimately lead to male sub-fertility or sterility, and numerous aspects of mammalian sperm formation remain unknown. The predominant expression of the latest globin family member, androglobin (Adgb) in mammalian testis tissue prompted us to assess its physiological function in spermatogenesis. Adgb knockout mice display male infertility, reduced testis weight, impaired maturation of elongating spermatids, abnormal sperm shape and ultrastructural defects in microtubule and mitochondrial organisation. Epididymal sperm from Adgb knockout animals display multiple flagellar malformations including coiled, bifide or shortened flagella, and erratic acrosomal development. Following immunoprecipitation and mass spectrometry, we could identify septin 10 (Sept10) as interactor of Adgb. The Sept10-Adgb interaction was confirmed both in vivo using testis lysates, and in vitro by reciprocal co-immunoprecipitation experiments. Furthermore, absence of Adgb leads to mislocalisation of Sept10 in sperm, indicating defective manchette and sperm annulus formation. Finally, in vitro data suggest that Adgb contributes to Sept10 proteolysis in a calmodulin (CaM)-dependent manner. Collectively, our results provide evidence that Adgb is essential for murine spermatogenesis and further suggest that interdependence between Adgb and Sept10 is required for sperm head shaping via the manchette and proper flagellum formation.
AF-vapeR: A multivariate genome scan for detecting parallel evolution using allele frequency change vectors

The repeatability of evolution at the genetic level has been demonstrated to vary along a continuum from complete parallelism to divergence. In order to better understand why this continuum exists within and among systems, hypotheses must be tested using high confidence sets of candidate loci for repeatability. Despite this, few methods have been developed to scan SNP data for signatures specifically associated with repeatability, as opposed to local adaptation. Here we present AF-vapeR (Allele Frequency Vector Analysis of Parallel Evolutionary Responses), an approach designed to identify genome regions exhibiting highly correlated allele frequency changes within haplotypes and among replicated allele frequency change vectors. The method divides the genome into windows of an equivalent number of SNPs, and within each window performs eigen decomposition over normalised allele frequency change vectors (AFV), each derived from a replicated pair of populations/species. Properties of the resulting eigenvalue distribution can be used to compare regions of the genome for those exhibiting strong parallelism, and can also be compared against a null distribution derived from randomly permuted AFV. Further, the shape of the eigenvalue distribution can reveal multiple axes of parallelism within datasets. We demonstrate the utility of this approach to detect different modes of parallel evolution using simulations, and also demonstrate a reduction in error rate compared with intersecting FST outliers. Lastly, we apply AF-vapeR to three previously published datasets (stickleback, guppies, and Galapagos finches) which comprise a range of sampling and sequencing strategies, and lineage ages. We detect known parallel regions whilst also identifying novel candidates. The main benefits of this approach include a reduced false-negative rate under many conditions, an emphasis on signals associated specifically with repeatable evolution as opposed to local adaptation, and an opportunity to identify different modes of parallel evolution at the first instance.
Taxonomy Analysis in Bacteria Kingdom based on Protein Domain: A Comparison Study

It is important to conduct taxonomy research on the bacteria kingdom for deeper understanding, which can utilize the conserved genes, 16s rRNA, protein domain, and so on. Among them, the methods based on the protein domain has a direct relationship with phenotype. However, these methods still lack analysis of their biological significance, models evaluation and the comparison of taxonomy results. To this end, we propose a complete framework to standardize the process for taxonomy problem based on the protein functional domain. By applying it to bacteria kingdom and comparing the results with the NCBI taxonomy, we point out the most appropriate method in each step of the framework and evaluate models according to the biological significance. Finally, taxonomy suggestions and recommendations are proposed based on the phylogenetic tree generated by the framework with the most appropriate combination. Significance Statement We standardize a framework to confirmed the feasibility of utilizing protein domain to carry out bacterial taxonomy research. Furthermore, we filter out the best solution that generates the most appropriate classification result and drill down to the biological significant of the algorithms it depends on. Finally, we put forward suggestions on bacteria taxonomy modification based on our classification results.
Transcriptional and translational regulation of pathogenesis in Alzheimer’s disease model mice

Background Defining the cellular mechanisms that drive Alzheimer’s disease (AD) pathogenesis and progression will be aided by studies defining how gene expression patterns change during pre-symptomatic AD and the ensuing periods of steadily declining cognition. Previous studies have emphasized changes in transcriptional regulation, but not translational regulation, leaving the ultimate results of gene expression alterations relatively unexplored in the context of AD. Objective To identify genes whose expression might be regulated at the transcriptional, and especially at the translational levels in AD, we analyzed gene expression in cerebral cortex of two AD model mouse strains, CVN (APPSwDI;NOS2-/-) and Tg2576 (APPSw), and their companion wild type (WT) strains at 6 months of age by tandem RNA-Seq and Ribo-Seq (ribosome profiling). Methods Identical starting pools of bulk RNA were used for RNA-Seq and Ribo-Seq. Differential gene expression analysis was performed at the transcriptional and translational levels separately, and also at the translational efficiency level. Regulated genes were functionally evaluated by gene ontology tools. Results Compared to WT mice, AD model mice had similar levels of transcriptional regulation, but displayed differences in translational regulation. A specific microglial signature associated with early stages of Aβ accumulation was up-regulated at both transcriptome and translatome levels in CVN mice. Although the two mice strains did not share many regulated genes, they showed common regulated pathways related to APP metabolism associated with neurotoxicity and neuroprotection. Conclusion This work represents the first genome-wide study of brain translational regulation in animal models of AD, and provides evidence of a tight and early translational regulation of gene expression controlling the balance between neuroprotective and neurodegenerative processes in brain.
Diet-derived metabolites and mucus link the gut microbiome to fever after cytotoxic cancer treatment

Not all cancer patients with severe neutropenia develop fever, and the fecal microbiome may play a role. In neutropenic hematopoietic cell transplant patients (n=119), 63 (53%) developed a subsequent fever and had increased fecal Akkermansia muciniphila, a mucus-degrading bacteria (p=0.006, corrected for multiple comparisons). In mouse models, two therapies, irradiation and melphalan, similarly expanded A. muciniphila. Dietary restriction of unirradiated mice also expanded A. muciniphila and thinned the colonic mucus layer. Azithromycin treatment depleted A. muciniphila and preserved colonic mucus. Dietary restriction raised colonic luminal pH and reduced acetate, propionate, and butyrate. Culturing A. muciniphila with lower pH and increased propionate prevented utilization of mucin. Treating irradiated mice with azithromycin or propionate preserved the mucus layer, lessened hypothermia, and reduced inflammatory cytokines in the colon. These results suggest that diet, metabolites and colonic mucus link the microbiome to neutropenic fever, and could guide future microbiome-based preventive strategies.
Integrated Cobaloxime and Mesoporous Silica-Supported Ruthenium/Diamine Co-Catalysis for One-Pot Hydration/Reduction Enantioselective Sequential Reaction of Alkynes

This study developed a cost-efficient hydration/asymmetric transfer hydrogenation (ATH) process for the one-pot synthesis of valuable chiral alcohols from alkynes. During this process, the initial homogeneous cobaloxime-catalyzed hydration of alkynes was followed by heterogeneous Ru/diamine-catalyzed ATH transformation of the in-situ generated ketones, which provided varieties of chiral alcohols in good yields with up to 99% ee values. The immobilized Ru/diamine catalyst could be recycled at least three times before its deactivation in the sequential reaction system. This work shows a general method for developing one-pot asymmetric sequential catalysis towards sustainable organic synthesis.
Effect of Training and Detraining in the Components of Physical Fitness in People Living With HIV/AIDS

The aim of the study was to evaluate the effect of training and detraining on the physical fitness components of people living with HIV/AIDS (PLHA). The study was characterized as experimental with a sample composed of 21 people divided into two groups: 11 volunteers (PLHA, 46.9 ± 8.0 years, 63.8 ± 12.7 kg, 161.7 ± 8.7 cm, 7 men, and 4 women), using antiretroviral therapy (ART) and 10 people without HIV/AIDS in the control group (CG, 43.8 ± 13.8 years, 75.2 ± 11.2 kg, 163.3 ± 7.8 cm, 3 men, and 7 women), with the same average age and level of physical activity. The intervention, applied to both groups, consisted of combined training for 15 weeks, followed by detraining for 5 weeks. Before and after the training and detraining period the following parameters were evaluated: body composition by dual energy radiological absorptiometry (DXA), cardiorespiratory fitness by ergospirometer, and strength of upper and lower limbs by isometric dynamometer. The results show the effect of the intervention moments on the strength and oxygen consumption variables (time factor), considering the two study groups. Regarding the analysis of the interaction (group vs. time), there was a significant effect on the isometric extension strength of the left (p = 0.019) and right (p = 0.030) knees, with training (left: 10.4%; right: 12.4%) and detraining (left: −10.8%; right: −12.1%) effect in PLHA, when compared with the control group (left: 8.1 and 3.9%, respectively; right: 11.5 and −0.2%, respectively). In addition, there was a significant interaction on ventilatory threshold 1 (p = 0.002), indicating a significantly greater increase with training (27.3%) and decrease with detraining (−22.7%) in the PLHA group compared with the Control group (19.9 and −6.7%, respectively). In conclusion, combined training and the subsequent period of detraining caused similar responses in body composition, isometric strength, and cardiorespiratory fitness of PLHA and CG, except for the extensor strength of the lower limbs and ventilatory threshold 1, which presented positive effects on training and negative effects on detraining for PLHA. Clinical Trial Registration: www.ClinicalTrials. gov, identifier NCT03075332.
Non-stenotic Carotid Plaques in Embolic Stroke of Unknown Source

Embolic stroke of unknown source (ESUS) represents one in five ischemic strokes. Ipsilateral non-stenotic carotid plaques are identified in 40% of all ESUS. In this narrative review, we summarize the evidence supporting the potential causal relationship between ESUS and non-stenotic carotid plaques; discuss the remaining challenges in establishing the causal link between non-stenotic plaques and ESUS and describe biomarkers of potential interest for future research. In support of the causal relationship between ESUS and non-stenotic carotid plaques, studies have shown that plaques with high-risk features are five times more prevalent in the ipsilateral vs. the contralateral carotid and there is a lower incidence of atrial fibrillation during follow-up in patients with ipsilateral non-stenotic carotid plaques. However, non-stenotic carotid plaques with or without high-risk features often coexist with other potential etiologies of stroke, notably atrial fibrillation (8.5%), intracranial atherosclerosis (8.4%), patent foramen ovale (5–9%), and atrial cardiopathy (2.4%). Such puzzling clinical associations make it challenging to confirm the causal link between non-stenotic plaques and ESUS. There are several ongoing studies exploring whether select protein and RNA biomarkers of plaque progression or vulnerability could facilitate the reclassification of some ESUS as large vessel strokes or help to optimize secondary prevention strategies.
Humanizing Stakeholders by Rethinking Business

Can business humanize its stakeholders? And if so, how does this relate to moral consideration for stakeholders? In this paper we compare two business orientations that are relevant for current business theory and practice: a stakeholder orientation and a profit orientation. We empirically investigate the causal relationships between business orientation, humanization, and moral consideration. We report the results of six experiments, making use of different operationalizations of a stakeholder and profit orientation, different stakeholders (employees, suppliers, labor unions), and different participant samples. Our findings support the prediction that individual stakeholders observing a stakeholder-oriented firm see the firm’s other stakeholders as more human than individual stakeholders observing a profit-oriented firm. This humanization, in turn, increases individual stakeholders’ moral consideration for the firm’s other stakeholders. Our findings underscore the importance of humanization for stakeholders’ moral consideration for each other. This paper contributes to a deeper understanding of the firm as a moral community of stakeholders. Specifically, we move away from a focus on managers, and how they can make business more moral. Instead we direct attention to (other) stakeholders, and how business can make these stakeholders more moral.