Miracle-dz/UniFAR-FTUs huggingface dataset:
Genomic Signature of Shifts in Selection and Alkaline Adaptation in Highland Fish

Understanding how organisms adapt to aquatic life at high altitude is fundamental in evolutionary biology. This objective has been addressed primarily related to hypoxia adaptation by recent comparative studies, whereas highland fish has also long suffered extreme alkaline environment, insight into the genomic basis of alkaline adaptation has rarely been provided. Here, we compared the genomes or transcriptomes of 15 fish species, including two alkaline tolerant highland fish species and their six alkaline intolerant relatives, three alkaline tolerant lowland fish species and four alkaline intolerant species. We found putatively consistent patterns of molecular evolution in alkaline tolerant species in a large number of shared orthologs within highland and lowland fish taxa. Remarkably, we identified consistent signatures of accelerated evolution and positive selection in a set of shared genes associated with ion transport, apoptosis, immune response and energy metabolisms in alkaline tolerant species within both highland and lowland fish taxa. This is one of the first comparative studies that began to elucidate the consistent genomic signature of alkaline adaptation shared by highland and lowland fish. This finding also highlights the adaptive molecular evolution changes that support fish adapting to extreme environments at high altitude. Significance Statement Little is known about how wild fish responds to extreme alkaline stress besides hypoxia at high altitude. Comparative genomics has begun to elucidate the genomic basis of alkaline adaptation in lowland fish, such as killifish, but insight from highland fish has lagged behind. The common role of adaptive molecular evolution during alkaline adaptation in highland and lowland fish has rarely been discussed. We address this question by comparing 15 fish omics data. We find numbers of shared orthologs exhibited consistent patterns of molecular evolution in alkaline tolerant species relative to intolerant species. We further identify remarkably consistent signatures of rapidly evolving and positive selection in a substantial shared core of genes in both highland and lowland alkaline tolerant species.
Examining the genetic influences of migratory status on island colonisation by naturally and recently established populations of a bird species

Seasonal migration influences long-distance dispersal and population establishment, which are the two important steps for successful island colonisation. Migratory behaviour facilitates the long-distance dispersal of individuals through frequent appearance outside a species’ normal range, while sedentary behaviour may lead to dispersal by post-fledgling flocks whose accidental immigration provide sufficient propagules for population establishment. We assessed the relative contributions of migratory and sedentary populations to island colonisation, by performing population genetics analyses on four recently and naturally established island populations of the Bull-headed Shrike (Lanius bucephlaus). Analyses using 15 microsatellite loci inferred colonisation by flocks of immigrants from possibly sedentary populations for all the islands studied. On one island, we found a correlation between wing length and the genetic probability of assignment to a migratory population, indicating a genetic contribution by migratory immigrants. Yet migratory immigrants to this island were inferred to be only two over eight years of sampling. We imply that sedentary populations were successful island colonists because more immigrants can be provided through their post-fledgling dispersal than through solitary migration. This is the first attempt to examine, using population genetics, influence of migratory behaviour on island colonisation thereby, bridging the gap between population ecology and island biogeography.
Marine Community Metabolomes Carry Fingerprints of Phytoplankton Community Composition

Microscopic phytoplankton transform 100 million tons of inorganic carbon into thousands of different organic compounds each day. The structure of each chemical is critical to its biological and ecosystem function, yet the diversity of biomolecules produced by marine microbial communities remained mainly unexplored, especially small polar molecules which are often considered the currency of the microbial loop. ABSTRACT Phytoplankton transform inorganic carbon into thousands of biomolecules that represent an important pool of fixed carbon, nitrogen, and sulfur in the surface ocean. Metabolite production differs between phytoplankton, and the flux of these molecules through the microbial food web depends on compound-specific bioavailability to members of a wider microbial community. Yet relatively little is known about the diversity or concentration of metabolites within marine plankton. Here, we compare 313 polar metabolites in 21 cultured phytoplankton species and in natural planktonic communities across environmental gradients to show that bulk community metabolomes reflect the chemical composition of the phytoplankton community. We also show that groups of compounds have similar patterns across space and taxonomy, suggesting that the concentrations of these compounds in the environment are controlled by similar sources and sinks. We quantify several compounds in the surface ocean that represent substantial understudied pools of labile carbon. For example, the N-containing metabolite homarine was up to 3% of particulate carbon and is produced in high concentrations by cultured Synechococcus, and S-containing gonyol accumulated up to 2.5 nM in surface particles and likely originates from dinoflagellates or haptophytes. Our results show that phytoplankton composition directly shapes the carbon composition of the surface ocean. Our findings suggest that in order to access these pools of bioavailable carbon, the wider microbial community must be adapted to phytoplankton community composition. IMPORTANCE Microscopic phytoplankton transform 100 million tons of inorganic carbon into thousands of different organic compounds each day. The structure of each chemical is critical to its biological and ecosystem function, yet the diversity of biomolecules produced by marine microbial communities remained mainly unexplored, especially small polar molecules which are often considered the currency of the microbial loop. Here, we explore the abundance and diversity of small biomolecules in planktonic communities across ecological gradients in the North Pacific and within 21 cultured phytoplankton species. Our work demonstrates that phytoplankton diversity is an important determinant of the chemical composition of the highly bioavailable pool of organic carbon in the ocean, and we highlight understudied yet abundant compounds in both the environment and cultured organisms. These findings add to understanding of how the chemical makeup of phytoplankton shapes marine microbial communities where the ability to sense and use biomolecules depends on the chemical structure.
RNA polymerase II condensate formation and association with Cajal and histone locus bodies in living human cells

In eukaryotic nuclei, a number of phase-separated nuclear bodies (NBs) are present. RNA polymerase II (Pol II) is the main player in transcription and forms large condensates in addition to localizing at numerous transcription foci. Cajal bodies (CBs) and histone locus bodies (HLBs) are NBs that are involved in transcriptional and post-transcriptional regulation of small nuclear RNA and histone genes. By live-cell imaging using human HCT116 cells, we here show that Pol II condensates (PCs) nucleated near CBs and HLBs, and the number of PCs increased during S phase concomitantly with the activation period of histone genes. Ternary PC–CB– HLB associates were formed via three pathways: nucleation of PCs and HLBs near CBs, interaction between preformed PC–HLBs with CBs, and nucleation of PCs near preformed CB– HLBs. Coilin knockout increased the co-localization rate between PCs and HLBs, whereas the number, nucleation timing, and phosphorylation status of PCs remained unchanged. Depletion of PCs did not affect CBs and HLBs. Treatment with 1,6-hexanediol revealed that PCs were more liquid-like than CBs and HLBs. Thus, PCs are dynamic structures often nucleated following the activation of gene clusters associated with other NBs. (187 words)
Development of novel in vitro human alveolar epithelial cell models to study distal lung biology and disease

Many acute and chronic lung diseases affect the distal lung alveoli. Although airway-derived human cell lines exist, alveolar epithelial cell (AEC)-derived lines are needed to better model these diseases. We have generated and characterized novel immortalized cell lines derived from human AECs. They grow as epithelial monolayers expressing lung progenitor markers SOX9 and SOX2, with little to no expression of mature AEC markers. Co-cultured in 3-dimensions (3D) with lung fibroblasts, the cells form NKX2-1+ organoids expressing mature AEC markers AQP5 and GPRC5A. Single-cell RNA sequencing of an AEC line in 2D versus 3D revealed increased cellular heterogeneity and induction of cytokine and lipoprotein signaling, consistent with organoid formation. Activating WNT and FGF pathways resulted in larger organoids. Our approach appears to yield lung progenitor lines that retain a genetic and structural memory of their alveolar cell lineage despite long-term expansion and whose differentiation may be modulated under various 3D conditions. These cell lines provide a valuable new system to model the distal lung in vitro.
The comprehensive roadmaps of reprogramming and transformation unveiled antagonistic roles for bHLH transcription factors in the control of cellular plasticity

Coordinated changes of cellular identity and plasticity are critical for pluripotent reprogramming (PR) and malignant transformation (MT). However, the molecular circuitries orchestrating these modifications, as well as their degree of analogy during reprogramming and transformation, remain unknown. To address this question, we generated “repro-transformable” mice models and dissected comparatively the early events underpinning PR - mediated by Oct4, Sox2, Klf4, c-Myc - and MT - triggered by oncogenic Ras and c-Myc. Transcriptomic analyses allowed the identification of a unique set of markers - the cell surface glycoprotein Thy1 and the transcription factor (TF) Bcl11b - that are commonly downregulated during PR and MT and delineate cellular intermediates (CI) highly amenable to generate pluripotent or malignant derivatives. Comprehensive transcriptomic, epigenomic and functional analyses of different CI, prone or refractory to PR/MT, unveiled that cellular plasticity acquisition precedes the broad extinction of cellular identity. It also demonstrated the existence of specific and shared molecular features of PR and MT while ensuring the identification of broad-range regulators of cellular plasticity. As a proof-of-concept, we revealed that the basic helix-loop-helix (bHLH) class A TF Atoh8 constrains rodent and human iPS cells generation as well as MT and direct neuron conversion. Mechanistically, this TF hampers the reactivation of the pluripotent network during PR and limits the acquisition of phenotypic plasticity during MT. Furthermore, an integrated analysis of Atoh8 genome-wide binding, alongside the other bHLH TFs c-Myc, Ascl1 and MyoD promoting reprogramming/transdifferentiation, unveiled how Atoh8 constrains cellular plasticity by occupying a specific subset of MEF enhancers and by finetuning WNT signalling activity. Collectively, by deconvoluting the early steps of the reprogramming and transformation roadmaps, this integrated study uncoupled changes of cellular plasticity and identity to shed light on novel insights into reprogramming and cancer biology. Graphical abstract One-sentence summary Comparative roadmaps of cellular plasticity acquisition during pluripotent reprogramming and malignant transformation.
Docosahexaenoic fatty acid-containing phospholipids affect plasma membrane susceptibility to disruption by bacterial toxin-induced macroapertures

Metabolic studies and animal knockout models point to the critical role of polyunsaturated docosahexaenoic acid (22:6, DHA)-containing phospholipids (PLs) in physiology. Here, we study the impact of DHA-PLs on the dynamics of transendothelial cell macroapertures (TEMs) tunnels triggered by the RhoA GTPase inhibitory exotoxin C3 from Clostridium botulinum. Through lipidomic analyses, we show that primary human umbilical vein endothelial cells (HUVECs) subjected to DHA-diet undergo a 6-fold DHA-PLs enrichment in plasma membrane at the expense of monounsaturated OA-PLs. In contrast, OA-diet had almost no effect on PLs composition. Consequently, DHA treatment increases the nucleation rate of TEMs by 2-fold that we ascribe to a reduction of cell thickness. We reveal that the global transcellular area of cells remains conserved through a reduction of the width and lifetime of TEMs. Altogether, we reveal a homeostasis between plasma membrane DHA-PLs content and large-scale membrane dynamics.
Fragment analysis in forensic anthropology

Abstract Anthropological analysis of fragmentary evidence can be challenging but diverse methods allow substantial information to be gleaned. Scanning electron microscopy/energy dispersive X-ray spectroscopy enables determination if bone and/or tooth tissue is present. Protein radioimmunoassay or DNA analysis can establish the species present. Histological analysis can assist in species determination and reveal information about thermal changes. Radiocarbon analysis with special reference to the modern bomb-curve can clarify the postmortem interval. Anthropologists should also be aware that DNA analysis not only can enable positive identification but assist in the evaluation of sex and age at death.
One Sentence Summary : Lactate-dependent axons rely on Warburg effect in Schwann cells

Affiliations: 1 INM, INSERM, Université de Montpellier, 80 Rue A. Fliche, 34090 Montpellier, France. 2 Aix-Marseille University, INSERM, MMG, 13385 Marseille, France 15 3 Departments of Clinical Neuroscience and Neuroscience, Karolinska Intitutet, Stockholm, Sweden. 4 Département de Biochimie et Génétique, Centre Hospitalier Universitaire, Angers, France. 5 Equipe Mitolab, MITOVASC, CNRS 6015, INSERM U1083, Université d'Angers, Angers, France. 20
Hyperbolic matrix factorization reaffirms the negative curvature of the native biological space

Past research in systems biology has taken for granted the Euclidean geometry of biological space. This has not only drawn parallels to other fields but has also been convenient due to the ample statistical and numerical optimization tools available to address the core task and downstream machine learning problems. However, emerging theoretical studies now demonstrate that biological databases exhibit hierarchical topology, characterized by heterogeneous degree distribution and a high degree of clustering, thus contradicting the flat geometry assumption. Namely, since the number of nodes in hierarchical structures grows exponentially with node depth, the biological networks naturally reside in a hyperbolic space where the circle circumference and disk area are the exponential functions of the radius. To test these claims and assess potential benefits of the applications grounded in the above hypothesis, we have developed a mathematical framework and an accompanying computational procedure for matrix factorization and implied biological relationship inference in hyperbolic space. Not only does our study demonstrate a significant increase in the accuracy of hyperbolic embedding compared to Euclidean embedding, but it also shows that the latent dimension of an optimal hyperbolic embedding is by more than an order of magnitude smaller than the latent dimension of an optimal Euclidean embedding. We see this as additional evidence that hyperbolic geometry, rather than Euclidean, underlines the biological system.
Signaling interaction link prediction using deep graph neural networks integrating protein-protein interactions and omics data

Uncovering signaling links or cascades among proteins that potentially regulate tumor development and drug response is one of the most critical and challenging tasks in cancer molecular biology. Inhibition of the targets on the core signaling cascades can be effective as novel cancer treatment regimens. However, signaling cascades inference remains an open problem, and there is a lack of effective computational models. The widely used gene co-expression network (no-direct signaling cascades) and shortest-path based protein-protein interaction (PPI) network analysis (with too many interactions, and did not consider the sparsity of signaling cascades) were not specifically designed to predict the direct and sparse signaling cascades. To resolve the challenges, we proposed a novel deep learning model, deepSignalingLinkNet, to predict signaling cascades by integrating transcriptomics data and copy number data of a large set of cancer samples with the protein-protein interactions (PPIs) via a novel deep graph neural network model. Different from the existing models, the proposed deep learning model was trained using the curated KEGG signaling pathways to identify the informative omics and PPI topology features in the data-driven manner to predict the potential signaling cascades. The validation results indicated the feasibility of signaling cascade prediction using the proposed deep learning models. Moreover, the trained model can potentially predict the signaling cascades among the new proteins by transferring the learned patterns on the curated signaling pathways. The code was available at: https://github.com/fuhaililab/deepSignalingPathwayPrediction.
Prenatal THC Does Not Affect Female Mesolimbic Dopaminergic System in Preadolescent Rats

Cannabis use among pregnant women is increasing worldwide along with permissive sociocultural attitudes towards it. Prenatal cannabis exposure (PCE), however, is associated with adverse outcome among offspring ranging from reduced birth weight to child psychopathology. We have previously shown that male rat offspring prenatally exposed to Δ9-tetrahydrocannabinol (THC), a rat model of PCE, exhibit extensive molecular, cellular and synaptic changes in dopamine neurons of the ventral tegmental area (VTA), resulting in a susceptible mesolimbic dopamine system associated with a psychotic-like endophenotype. This phenotype only reveals itself upon a single exposure to THC in males but not females. Here, we characterized the impact of PCE on female behaviors and mesolimbic dopamine system function by combining in vivo single-unit extracellular recordings in anesthetized animals and ex vivo patch clamp recordings, along with neurochemical and behavioral analyses. We find that PCE female offspring do not show any spontaneous or THC-induced behavioral disease-relevant phenotypes. The THC-induced increase of dopamine levels in nucleus accumbens was reduced in PCE female offspring, even when VTA dopamine activity in vivo and ex vivo did not differ compared to control. These findings indicate that PCE impacts mesolimbic dopamine function and its related-behavioral domains in a sex-dependent manner and warrant further investigations to decipher the mechanisms determining this sex-related protective effect from intrauterine THC exposure. Highlights PCE female offspring do not manifest a disease-relevant phenotype Prenatal THC does not affect female dopaminergic neurons PCE female mesolimbic dopamine function is less responsive to acute THC
Reflections from the ‘Strava-sphere’: Kudos, community, and (self-)surveillance on a social network for athletes

ABSTRACT In recent years, there has been a growing interest in the practice of digital self-tracking. Researchers have drawn attention to who self-tracks, why people self-track, and what it feels like to self-track in the context of sport and physical activity. To date, limited research has focused on self-tracking as a social practice and there has been minimal engagement with the specific online platforms that individuals use to share their self-tracking data online. In this paper I engage with findings from an ethnographic study of Strava, a popular social fitness platform. I propose that while Strava can be a source of motivation and entertainment for its users, and even help to establish or strengthen social networks, the platform invites users to adopt and adapt to technologically-mediated surveillance strategies that encourage and reward displays of bodily self-discipline.
Feeding F1 Holstein x Zebu cows with different roughages and pseudostem hay of banana trees does not influence milk yield and chemical composition of milk and cheese

Abstract The aim of the study was to determine the effect of different roughage associated with pseudostem hay of banana trees on nutrients intake, chemical composition of milk and cheese and the fatty acid profile of F1 Holstein x Zebu cows. Eight cows F1 Holstein x Zebu were used in a replicated 4 × 4 Latin square design, each composed of four animals, four treatments and four experimental periods. Four experimental diets were used: diet 1 – sorghum silage as exclusive dietary roughage; diet 2 – sorghum silage (70%) associated with 30% pseudostem hay of banana trees (dry matter basis; SS); diet 3 – 70% elephant grass (Pennisetum purpureum cv. Roxo) with 30% pseudostem hay of banana trees (dry matter basis; EGPS); and diet 4 – 70% sugar cane with 30% pseudostem hay of banana trees (dry matter basis; SCPS). The roughage: concentrate ratio in the four experimental diets was 75:25 in dry matter basis. For the chemical composition of milk and cheese, there was no difference between diets except for milk urea nitrogen which was higher with the EGPS diet. However, in the lipid fraction of milk, the EGPS diet favoured the increase of total monounsaturated fatty acids, besides increasing the concentration of conjugated linoleic acid, contributing to the improvement of some nutritional evaluation indexes of the milk lipid fraction. The pseudostem hay of banana trees associated with different roughages did not influence the chemical composition of milk and cheese of F1 Holstein x Zebu cows. Highlights The inclusion of pseudostem hay of banana trees in the diet of F1 Holstein x Zebu cows does not change the milk yield corrected for 3.5% fat. Pseudostem hay of banana trees diet of lactating cows increased the concentration of omega 6 in milk. Pseudostem hay in the diet of lactating crossbred cows did not change the yield, flavour and appearance of the cheese.
How critical are Germans of democracy? The pattern and origins of constitutional support in Germany

ABSTRACT Academic studies have consistently demonstrated that citizens have lost trust in democratic institutions, grown sceptical of elected leaders, and become dissatisfied with how democracy works. These studies, however, neglect the analysis of some of the most important objects of the democracies they analyse. A case in point is the German constitution (Basic Law), which prescribes the values of German democracy and the institutions through which they are realized. By analysing 28 years of individual-level data from the German General Social Survey (ALLBUS), this article makes two important discoveries about attitudes towards the constitution. First, support for it is widespread, enduring and increasing amongst citizens in the east and west of the country. Second, generalized linear models demonstrate that this form of support is grounded in phenomena which provide it with durability. Postmaterialist values, centrist ideology, and age all nurture attachments to the constitution. These effects are confirmed by post-estimation analyses of average marginal effects. By demonstrating that German democracy is underpinned by a fund of enduring support, the research challenges suggestions of a crisis of democracy and concludes that Germans are not cynically rejecting of democracy, but critically democratic: they desire a fuller expression of the constitutional ideals.