Miracle-dz/UniFAR-FTUs huggingface dataset:
Physiology of Energy Expenditure in the Weight‐Reduced State

Although many individuals achieve weight loss of 10% or more, the ability to maintain a reduced body mass over months and years is much rarer. Unfortunately, our understanding of the adverse consequences of having overweight and obesity argues that long‐term maintenance of a reduced weight provides the greatest health benefit. However, to achieve long‐term weight reduction requires overcoming neuroendocrine systems that favor restoration of one’s initial weight. Identifying and characterizing the components of these systems will be important if we are to develop therapies and strategies to reduce the rates of obesity and its complications in our modern society. During this session, Eric Ravussin and Steven R. Smith, respectively, discussed the physiology of the weight‐reduced state that favors weight regain and a molecular component that contributes to this response.
Nitrate fluxes in squash seedlings measured with 13N

Abstract Influx of 13N"‐labelled NO3” was studied in roots of intact squash seedlings (Cucurbita max. Duch.) previously grown in nutrient solution without (uninduced) or with NO3” (induced). At the uninduced constitutive level NO3” influx was saturable (Vmax=6.2 μmol (g FW)‐1‐h"1; Km=37.0 μM), but it increased again, probably passively, at high external NO3” concentrations. Initial NO3” efflux started during induction of the transport system when the influx rate increased and conceivably the NO3” concentration in the cytoplasm was raised. Likewise, this tendency was observed after a period of NO3” starvation. The kinetic parameters of NO3” influx of the substrate‐induced high capacity transport system accounted for a Vmax of 14.0 μmol (gFW)‐1 h‐1 and a Km of 15 μM. Both the uninduced and the induced uptake reacted in a similar pattern to the treatment of inhibitors affecting the protein synthesis (cycloheximide, fluorophenylalanine or puromycin) suggesting a single membrane protein population carrying NO3.
Comparison of Fermentation Kinetics (in vitro) of Napier Grass and Fruit Peels for Ruminants: The Pattern of Organic Matter Degradability, Volatile Fatty Acids Concentration, Estimated Methane and Microbial Biomass Production

The study was conducted to determine the pattern of organic matter degradability, volatile fatty acid concentration, estimated methane and microbial protein products of napier grass and fruit peels when fermented in the rumen. In vitro method was used to determine the pattern of these end-products. Five experimental samples were randomly assigned to five treatments with one sample per treatment in a completely randomized design. The compared experimental samples were napier grass (NG), orange peel (OP), pawpaw peel (PPL), mango peel (MP) and plantain peel (PP). Results obtained showed that parameters observed under in vitro gas production characteristics, organic matter degradation, volatile fatty acids concentration, estimated methane and microbial protein products were significantly (P<0.05) affected with the exception of intercept (a) and gas production rate constant for the insoluble fraction (b) (P<0.05). The incubation time (t 1 /2) (18.00hr), acetate (74.42%) and methane (38.00mmol) were significantly (P<0.05) highest for NG. Gas production from the insoluble but degradable fraction (58.98ml), potential gas production (62.00ml) and propionate (13.42%) were significantly (P<0.05) higher for PPL whereas organic matter degraded (42.01mg), volatile fatty acid concentration (72.75 mmol/litre), butyrate (10.20%) and microbial protein (2393g) were better for MP. It was concluded that MP and PP have the potentials to improve rumen fermentation efficiency and reduce methane gas.
MLL3/MLL4 Histone Methyltranferase Activity Dependent Chromatin Organization at Enhancers during Embryonic Stem Cell Differentiation

MLL3 (KMT2C) and MLL4 (KMT2D), the major mono-methyltransferases of histone H3 lysine 4 (H3K4), are required for cellular differentiation and embryonic development in mammals. We previously observed that MLL3/4 promote long-range chromatin interactions at enhancers, however, it is still unclear how their catalytic activities contribute to enhancer-dependent gene activation in mammalian cell differentiation. To address this question, we mapped histone modifications, long-range chromatin contacts as well as gene expression in MLL3/4 catalytically deficient mouse embryonic stem (ES) cells undergoing differentiation toward neural precursor cells. We showed that MLL3/4 activities are responsible for deposition of H3K4me1 modification and formation of long-range enhancer-promoter contacts at a majority of putative enhancers gained during cell differentiation, but are dispensable for most candidate enhancers found in undifferentiated ES cells that persist through differentiation. While transcriptional induction at most genes is unaltered in the MLL3/4 catalytically deficient cells, genes making more contacts with MLL3/4-dependent putative enhancers are disproportionately affected. These results support that MLL3/4 contributes to cellular differentiation through histone-methyltransferase-activity dependent induction of enhancer-promoter contacts and transcriptional activation at a subset of lineage-specific genes.
Bridging cell-scale simulations and radiologic images to explain short-time intratumoral oxygen fluctuations

Radiologic images provide a way to monitor tumor development and its response to therapies in a longitudinal and minimally invasive fashion. However, they operate on a macroscopic scale (average value per voxel) and are not able to capture microscopic scale (cell level) phenomena. Nevertheless, to examine the causes of frequent fast fluctuations in tissue oxygenation, the models simulating individual cells’ behavior are needed. Here, we provided a link between the average data value recorded for radiologic image voxels and the cellular and vascular architecture of the tissue that fills these voxels. Using hybrid agent-based modeling, we generated a set of tissue morphologies capable of reproducing tissue oxygenation levels observed in radiologic images. We applied this approach to investigate whether oxygen fluctuations can be explained by changes in vascular oxygen supply or by modulations in cellular oxygen absorption. Our studies showed that intravascular changes in oxygen supply can reproduce the observed fluctuations in tissue oxygenation in all considered regions of interest. However, large magnitude fluctuations cannot be recreated by modifications in cellular absorption of oxygen in biologically feasible manner. Additionally, we developed a procedure to identify plausible tissue morphologies for a given temporal series of average data from radiology images. In future applications this approach can be used to generate a set of tissues representative for radiology images and to simulate tumor response to various anti-cancer treatments on the tissue-scale level. Authors Summary Low levels of oxygen, called hypoxia, are observable in many solid tumors. They are associated with more aggressive malignant cells which are resistant to chemo-, radio- and immunotherapies. Recently developed imaging techniques provide a way to measure the magnitude of frequent short-term oxygen fluctuation, however they operate on a macro-scale voxel level. To examine the causes of rapid oxygen fluctuations on the cell level, we developed a hybrid agent-based mathematical model. We tested two different mechanisms that could be responsible for these cyclic effects in tissue oxygenation: variations in vascular influx of oxygen and modulations in cellular oxygen absorption. Additionally, we developed a procedure to identify plausible tissue morphologies from data collected from radiological images. This will also provide a bridge between the micro-scale simulations with individual cells and the longitudinal medical images containing average voxel values. In the future applications, this approach can be used to generate a set of tissues representative of radiology images and to simulate tumor response to various anticancer treatments on the cell-scale level.
Differential responses of amphibians and reptiles to land-use change in the biodiversity hotspot of north-eastern Madagascar

Large expanses of tropical rainforest have been converted into agricultural landscapes cultivated by smallholder farmers. This is also the case in north-eastern Madagascar; a region that retains significant proportions of forest cover despite slash-and-burn hill rice cultivation and vanilla agroforestry expansion. The region is also a global hotspot for herpetofauna diversity, but how amphibians and reptiles are affected by land-use change remains largely unknown. Using a space-for-time study design, we compared species diversity and community composition across seven prevalent land uses: unburned (old-growth forest, forest fragment, and forest-derived vanilla agroforest) and burned (fallow-derived vanilla agroforest, woody fallow, and herbaceous fallow) land-use types, and rice paddy. We conducted six comprehensive, time-standardized searches across at least ten replicates of each land-use type and applied genetic barcoding to confirm species identification. We documented an exceptional diversity of herpetofauna (119 species; 91% endemic). Plot-level amphibian species richness was significantly higher in old-growth forest than in all other land-use types. Plot-level reptile species richness was significantly higher in unburned land-use types compared to burned land-use types. For both amphibians and reptiles, the less-disturbed land-use types showed more uneven communities and the species composition in old-growth forest differed significantly from all other land-use types. Amphibians had higher forest dependency (38% of species occurred exclusively in old-growth forest) than reptiles (26%). Our analyses thus revealed that the two groups respond differently to land-use change: we found less pronounced losses of reptile species richness especially in unburned agricultural habitats, suggesting that reptiles are less susceptible to land-use change than amphibians, possibly due to their ability to cope with hotter and drier microclimates. Overall, old-growth forest harboured a unique diversity, but some species also thrived in vanilla agroforestry systems, especially if these were forest-derived. This highlights the importance of conserving old-growth forests and non-burned land-use types within agricultural landscapes.
Transcriptomic analysis reveals that severity of infectious bursal disease in White Leghorn inbred chicken lines is associated with greater bursal inflammation in vivo and more rapid induction of pro-inflammatory responses in primary bursal cells stimulated ex vivo

In order to better understand differences in the outcome of infectious bursal disease virus (IBDV) infection, we inoculated a very virulent (vv) strain into White Leghorn chickens of inbred line W that was previously reported to experience over 24% flock mortality, and three inbred lines (15I, C.B4 and 0) that were previously reported to display no mortality. Within each experimental group, some individuals experienced more severe disease than others but line 15I birds experienced milder disease based on average clinical scores, percentage of birds with gross pathology, average bursal lesion scores and average peak bursal virus titre. RNA-Seq analysis revealed that more severe disease in line W was associated with significant up-regulation of pathways involved in inflammation, cytoskeletal regulation by Rho GTPases, nicotinic acetylcholine receptor signaling, and Wnt signaling in the bursa compared to line 15I. Primary bursal cell populations isolated from uninfected line W birds contained a significantly greater percentage of KUL01+ macrophages than cells isolated from line 15I birds (p<0.01) and, when stimulated ex vivo with LPS, showed more rapid up-regulation of pro-inflammatory gene expression than those from line 15I birds. We hypothesize that a more rapid induction of pro-inflammatory cytokine responses in bursal cells following IBDV infection leads to more severe disease in line W birds than in line 15I.
Diet-induced changes in titer support a threshold effect of Wolbachia-associated plastic recombination in Drosophila melanogaster

Plastic recombination in Drosophila melanogaster has been associated with a variety of extrinsic and intrinsic factors such as temperature, starvation, and parasite infection. The bacterial endosymbiont Wolbachia pipientis has also been associated with plastic recombination in D. melanogaster. Wolbachia infection is pervasive in arthropods and this infection induces a variety of phenotypes in its hosts, the strength of which can depend on bacterial concentration, or titer. Here we test the hypothesis that the magnitude of Wolbachia-associated plastic recombination in D. melanogaster depends on titer. To manipulate titer, we raised Wolbachia-infected and uninfected flies on diets that have previously been shown to increase or decrease Wolbachia titer relative to controls. We measured recombination in treated and control individuals using a standard backcrossing scheme with two X-linked visible markers. Our results recapitulate previous findings that Wolbachia infection is associated with increased recombination rate across the yellow-vermillion interval of the X chromosome. Our data show no significant effect of diet or diet by Wolbachia interactions on recombination, suggesting that diet-induced changes in Wolbachia titer have no effect on the magnitude of plastic recombination. These findings represent the first step toward investigating the mechanisms behind Wolbachia-associated plastic recombination and demonstrate that the effect may be threshold-based as opposed to dose-dependent.
Structural intermediates observed only in intact Escherichia coli indicate a mechanism for TonB-dependent transport

Outer membrane TonB-dependent transporters facilitate the uptake of trace nutrients and carbohydrates in Gram negative bacteria and are essential for pathogenic bacteria and the health of the microbiome. Despite this, their mechanism of transport is still unknown. Here, pulse EPR measurements were made in intact cells on the Escherichia coli vitamin B12 transporter, BtuB. Substrate binding was found to alter the C-terminal region of the core and shift an extracellular substrate binding loop 2 nm towards the periplasm; moreover, this structural transition is regulated by an ionic lock that is broken upon binding of the inner membrane protein TonB. Significantly, this structural transition is not observed when BtuB is reconstituted into phospholipid bilayers. These measurements suggest an alternative to existing models of transport, where TonB binding alone is sufficient to produce allosteric rearrangements in the transporter. They also demonstrate the importance of studying outer membrane proteins in their native environment.
Representation learning of RNA velocity reveals robust cell transitions

Significance The recently introduced RNA velocity methods, by leveraging the intrinsic RNA splicing process, have shown their unique capability of identifying the directionality of the cell differentiation trajectory. However, due to the minimal amount of unspliced RNA contents, the estimation of RNA velocity suffers from high noise and may result in less reliable trajectories. Here, we present Velocity Autoencoder (VeloAE), a tailored autoencoder to denoise RNA velocity for more accurate quantification of cell transitions. Through various biological systems, we demonstrate its effectiveness for correcting the inferred trajectory and its interpretability for linking the learned dimensions to underlying biological processes. RNA velocity is a promising technique for quantifying cellular transitions from single-cell transcriptome experiments and revealing transient cellular dynamics among a heterogeneous cell population. However, the cell transitions estimated from high-dimensional RNA velocity are often unstable or inaccurate, partly due to the high technical noise and less informative projection. Here, we present Velocity Autoencoder (VeloAE), a tailored representation learning method, to learn a low-dimensional representation of RNA velocity on which cellular transitions can be robustly estimated. On various experimental datasets, we show that VeloAE can both accurately identify stimulation dynamics in time-series designs and effectively capture expected cellular differentiation in different biological systems. VeloAE, therefore, enhances the usefulness of RNA velocity for studying a wide range of biological processes.
Drosophila Male Accessory Gland Displays Developmental Ground Plan of a Primitive Prostate

Conservation of developmental genetic toolkits of functionally comparable organs from disparate phyla reveals their deep homology, which may help overcome the challenges of their confounding categorization as either homologous or analogous organs. A male accessory sexual organ in mammals, prostate, for instance, is anatomically disparate from its phylogenetically distant counterpart—the male accessory gland (MAG)—in insects like Drosophila. By examining a select set of toolkit gene expression patterns, here we show that Drosophila MAG displays deep homology with the mammalian prostate. Like mammalian prostate, MAG morphogenesis is marked by recruitment of fibroblast growth factor receptor, FGFR, a tubulogenesis toolkit signaling pathway, starting early during its adepithelial genesis. Specialization of the individual domains of the developing MAG tube on the other hand is marked by expression of a posterior Hox gene transcription factor, Abd-B, while Hh-Dpp signaling marks its growth. Drosophila MAG thus reveals developmental design of unitary bud-derived tube—a ground plan that appears to have been reiteratively co-opted during evolutionary diversification of male accessory sexual organs across distant phylogeny.
Odor identity can be extracted from the reciprocal connectivity between olfactory bulb and piriform cortex in humans

Neuronal oscillations route external and internal information across brain regions. In the olfactory system, the two central nodes—the olfactory bulb (OB) and the piriform cortex (PC)—communicate with each other via neural oscillations to shape the olfactory percept. Communication between these nodes have been well characterized in non-human animals but less is known about their role in the human olfactory system. Using a recently developed and validated EEG-based method to extract signals from the OB and PC sources, we show in healthy human participants that there is a bottom-up information flow from the OB to the PC in the beta and gamma frequency bands, while top-down information from the PC to the OB is facilitated by delta and theta oscillations. Importantly, we demonstrate that there was enough information to decipher odor identity above chance from the low gamma in the OB-PC oscillatory circuit as early as 100ms after odor onset. These data further our understanding of the critical role of bidirectional information flow in human sensory systems to produce perception. However, future studies are needed to determine what specific odor information is extracted and communicated in the information exchange.
The Vaginal Microbiome in Women of Reproductive Age with Healthy Weight versus Overweight/Obesity

Objective Evaluate differences between the vaginal microbiome of reproductive-aged women with overweight and obesity (Ow/Ob) compared with healthy weight (HW). Methods A cohort of 367 non-pregnant women (18-40 years) with Ow/Ob (body mass index [BMI] ≥25 kg/m2) was case-matched with 367 women with HW (BMI 18.0-24.9 kg/m2). The study was a secondary analysis of 16S rRNA vaginal microbiome surveys through the Vaginal Human Microbiome Study (VaHMP). Groups were matched on age, race/ethnicity, income, and nulliparity status. Results Mean age and BMI of Ow/Ob and HW groups were 26.8 versus 26.7 years and 37.0 versus 22.1 kg/m2, respectively. The overall vaginal microbiome composition differed between groups (PERMANOVA, p=0.035). Women with Ow/Ob had higher alpha-diversity compared with women with HW (Wilcoxon test, Shannon index p=0.025; Inverse Simpson index p=0.026). Lactobacillus dominance (≥30% proportional abundance) was observed in a greater proportion of women with HW (48.7%) compared with Ow/Ob (40.1%; p=0.026). Conclusions The vaginal microbiome differs in reproductive-aged women with Ow/Ob compared with women with HW, with increased alpha-diversity and decreased predominance of Lactobacillus. Observed differences in vaginal microbiome may partially explain differences in preterm birth and bacterial vaginosis risk between these populations.
Deep learning-based pan-cancer classification model reveals cancer-specific gene expression signatures

The identification of cancer-specific biomarkers and therapeutic targets is one of the primary goals of cancer genomics. Thousands of cancer genomes, exomes, and transcriptomes have been sequenced to date. In this study, we conducted a pan-cancer analysis of transcriptome datasets from 37 cancer types provided by The Cancer Genome Atlas (TCGA) in an effort to identify cancer-specific gene expression signatures. We employed deep neural networks to train a model on the transcriptome profile datasets for all cancer types. The model was validated, and its predictive accuracy was determined using an independent dataset, achieving > 97% prediction accuracy across cancer types. This strongly suggests that there are distinct gene expression signatures associated with various cancer types. We interpreted the model using SHapley Additive exPlanations (SHAP) to identify specific gene signatures that significantly contributed to the classification of cancer types. In addition to known biomarkers, we identified several novel biomarkers in different cancer types. These cancer-specific gene signatures are valuable candidates for future studies of their potential utility as cancer biomarkers and putative therapeutic targets.
Gene network simulations provide testable predictions for the molecular domestication syndrome

The domestication of plant species lead to repeatable morphological evolution, often referred to as the phenotypic domestication syndrome. Domestication is also associated with important genomic changes, such as the loss of genetic diversity compared to adequately large wild populations, and modifications of gene expression patterns. Here, we explored theoretically the effect of a domestication-like scenario on the evolution of gene regulatory networks. We ran population genetics simulations in which individuals were featured by their genotype (an interaction matrix encoding a gene regulatory network) and their gene expressions, representing the phenotypic level. Our domestication scenario included a population bottleneck and a selection switch mimicking human-mediated directional and canalizing selection, i.e., change in the optimal gene expression level and selection towards more stable expression across environments. We showed that domestication profoundly alters genetic architectures. Based on four examples of plant domestication scenarios, our simulations predict (i) a drop in neutral allelic diversity, (ii) a change in gene expression variance that depends upon the domestication scenario, (iii) transient maladaptive plasticity, (iv) a deep rewiring of the gene regulatory networks, with a trend towards gain of regulatory interactions, and (v) a global increase in the genetic correlations among gene expressions, with a loss of modularity in the resulting coexpression patterns and in the underlying networks. We provide empirically testable predictions on the differences of genetic architectures between wild and domesticated forms. The characterization of such systematic evolutionary changes in the genetic architecture of traits contributes to define a molecular domestication syndrome.