Miracle-dz/UniFAR-FTUs huggingface dataset:
Application of computational data modeling to a large-scale population cohort assists the discovery of specific nutrients that influence beneficial human gut bacteria Faecalibacterium prausnitzii

Faecalibacterium prausnitzii (F. prausnitzii) is a bacterial taxon of the human gut with anti-inflammatory properties and negative associations with chronic inflammatory conditions. F. prausnitzii may be one of key species contributing to the effects of healthy eating habits, and yet little is known about the nutrients that enhance the growth of F. prausnitzii other than simple sugars and fibers. Here we combined dietary and microbiome data from the American Gut Project (AGP) to identify nutrients that may be linked to the relative abundance of F. prausnitzii. Using a machine learning approach in combination with univariate analyses, we identified that sugar alcohols, carbocyclic sugar and vitamins may contribute to F. prausnitzii growth. We next explored the effects of these nutrients on the growth of two F. prausnitzii strains in vitro and observed strain dependent growth patterns on the nutrient tested. In the context of a complex community using in vitro fermentation, none of the tested nutrients and nutrient combinations exerted a significant growth-promoting effect on F. prausnitzii due to high variability in batch responses. A positive association between F. prausnitzii and butyrate concentrations was observed. Future nutritional studies aiming to increase relative abundance of F. prausnitzii should explore a personalized approach accounting for strain-level genetic variations and community-level microbiome composition.
Pre-Injury Mechanoreceptor Ablation Reduces Nociceptor-Driven Spinal Cord Injury-Induced Neuropathic Pain

Evidence from previous studies supports the concept that spinal cord injury (SCI) induced neuropathic pain (NP) has its neural roots in the peripheral nervous system. There is uncertainty about how and to which degree nociceptors and mechanoreceptors contribute. Sensorimotor activation-based interventions (e.g. treadmill training) have been shown to reduce NP following experimental SCI, suggesting transmission of pain-alleviating signals through mechanoreceptors. At the same time, nociceptors have been shown to become hyperexcitable early after SCI and peptidergic axons sprout into deeper laminae of the below injury level dorsal horn. The aim of the present study is to comprehensively understand the relative contribution of each pathway in respect to NP presentation in a moderate mouse contusion SCI model. After genetic ablation of tropomyosin receptor kinase B (TrkB) expressing mechanoreceptors before SCI mechanical allodynia was reduced. The identical genetic ablation after SCI did not yield any change in pain behavior. CGRP sprouting into lamina III/IV below injury level as a consequence of SCI was not altered by either mechanoreceptor ablation. Moreover, detection of hyperexcitability in nociceptors, not in mechanoreceptors, in skin-nerve preparations of contusion SCI mice 7 days after injury makes a substantial direct contribution of mechanoreceptors to NP maintenance unlikely. SNS reporter mice allowing specific visualization of the entire nociceptor population confirmed significant sprouting of respective neurons into laminae III/IV as early as 5 days post-injury. Genetic ablation of SNS-Cre mice severely affected their overall health condition, which precluded them to undergo experimental SCI and subsequent further analysis. Complementing animal data, quantitative sensory testing in human SCI subjects indicated reduced mechanical pain thresholds, whereas the mechanical detection threshold was not altered. Taken together, early mechanoreceptor ablation modulates pain behavior, most likely through indirect mechanisms. Hyperexcitable nociceptors with consecutive peptidergic fiber sprouting in the dorsal horn are confirmed as the likely main driver of SCI-induced NP. Future studies need to focus on injury-derived factors triggering early onset nociceptor hyperexcitability, which could serve as targets for more effective therapeutic interventions.
Cytokine signaling converging on IL11 in ILD fibroblasts provokes aberrant epithelial differentiation signatures

Interstitial lung disease (ILD) is a heterogenous group of lung disorders where destruction and incomplete regeneration of the lung parenchyma often results in persistent architectural distortion of the pulmonary scaffold. Continuous mesenchyme-centered, disease-relevant signaling likely initiates and perpetuates the fibrotic remodeling process, specifically targeting the epithelial cell compartment, thereby destroying the gas exchange area. With the aim of identifying functionally relevant mediators of the lung mesenchymal-epithelial crosstalk that hold potential as new targets for therapeutic strategies, we developed a 3D organoid co-culture model based on human induced pluripotent stem cell-derived alveolar epithelial type 2 cells that form alveolar organoids in presence of lung fibroblasts from ILD patients as well as a control cell line (IMR-90). While organoid formation capacity and size was comparable in the presence of ILD or control lung fibroblasts, metabolic activity was significantly increased in ILD co-cultures. Alveolar organoids cultured with ILD fibroblasts further demonstrated reduced stem cell function as reflected by reduced Surfactant Protein C gene expression together with an aberrant basaloid-prone differentiation program indicated by elevated Cadherin 2, Bone Morphogenic Protein 4 and Vimentin transcription. In order to screen for key mediators of the misguided mesenchymal-to-epithelial crosstalk with a focus on disease-relevant inflammatory processes, we used mass spectrometry and characterized the secretome of end stage ILD lung fibroblasts in comparison to non-chronic lung disease (CLD) patient fibroblasts. Out of the over 2000 proteins detected by this experimental approach, 47 proteins were differentially abundant comparing ILD and non-CLD fibroblast secretome. The ILD secretome profile was dominated by chemokines, including CXCL1, CXCL3, and CXCL8, interfering with growth factor signaling orchestrated by Interleukin 11 (IL11), steering fibrogenic cell-cell communication, and proteins regulating extracellular matrix remodeling including epithelial-to-mesenchymal transition. When in turn treating alveolar organoids with IL11, we recapitulated the co-culture results obtained with primary ILD fibroblasts including changes in metabolic activity. In summary, we identified mediators likely contributing to the disease-perpetuating mesenchymal-to-epithelial crosstalk in ILD. In our alveolar organoid co-cultures, we were able to highlight the importance of fibroblast-initiated aberrant epithelial differentiation and confirmed IL11 as a key player in ILD pathogenesis by unbiased ILD fibroblast secretome analysis.
1-nm-capacitance-equivalent-thickness HfO2/Al2O3/InGaAs metal-oxide-semiconductor structure with low interface trap density and low gate leakage current density

We have studied the impact of the Al2O3 inter-layer on interface properties of HfO2/InGaAs metal-oxide-semiconductor (MOS) interfaces. We have found that the insertion of the ultrathin Al2O3 inter-layer (2 cycle: 0.2 nm) can effectively improve the HfO2/InGaAs interface properties. The frequency dispersion and the stretch-out of C-V characteristics are improved, and the interface trap density (Dit) value is significantly decreased by the 2 cycle Al2O3 inter-layer. Finally, we have demonstrated the 1-nm-thick capacitance equivalent thickness in the HfO2/Al2O3/InGaAs MOS capacitors with good interface properties and low gate leakage of 2.4 × 10−2 A/cm2.
MTL neurons phase-lock to human hippocampal theta

Memory formation depends on neural activity across a network of regions, including the hippocampus and broader medial temporal lobe (MTL). Interactions between these regions have been studied indirectly using functional MRI, but the bases for inter-regional communication at a cellular level remain poorly understood. Here we evaluate the hypothesis that oscillatory currents in the hippocampus synchronize the firing of neurons both within and outside the hippocampus. We recorded extracellular spikes from 1,854 single- and multi-units simultaneously with hippocampal local field potentials (LFPs) in 28 neurosurgical patients who completed virtual navigation experiments. A majority of hippocampal neurons phase-locked to oscillations in the slow (2-4Hz) or fast (6-10Hz) theta bands, with a significant subset exhibiting nested slow theta × beta frequency (13-20Hz) phase-locking. Outside of the hippocampus, phase-locking to hippocampal oscillations occurred only at theta frequencies and primarily among neurons in the entorhinal cortex and amygdala. Extrahippocampal neurons phase-locked to hippocampal theta even when theta did not appear locally. These results indicate that spike-time synchronization with hippocampal theta is a defining feature of neuronal activity in the hippocampus and structurally-connected MTL regions. Theta phase-locking could mediate flexible communication with the hippocampus to influence the content and quality of memories.
Analysing the role of SERPINE1 network in the pathogenesis of human glioblastoma

Background Glioblastoma multiforme (GBM) is one of the most aggressive and difficult to treat brain tumour in humans with a 5 year survival rate of less than 6%. SERPINE1 is a novel tumour receptor found on GBM that modulates the progression of this cancer through growth signals and remodelling of the extracellular matrix. Hence, we investigated the role of SERPINE1 and its network proteins in pathogenesis of GBM and assessed its targetability. Material and methods Network proteins of SERPINE1 in homo sapiens was identified using the String database, and the affinity of the protein-protein interaction of this network was analysed using Chimera software. The expression profile of SERPINE1 in the different brain regions was evaluated to correlate its relevance to GBM pathology. Selected small molecules from Calotropis gigantea were screened using AutoDock vina to assess targetability of human SERPINE1. Results VTN, PLG, TGFB1, VWF, FGF2 and CXCR1 were identified as the major network proteins of SERPINE1. The strongest interaction was observed between SERPINE1 and FGF2 (42884 H-bonds) followed by CXCR1 (20279 H-bonds). Our results suggest that SERPINE1 and its network proteins identified here play a vital role in GBM development and progression through brain parenchyma by creating the prime microenvironment for carcinogenesis, tumour invasion and migration. The highest expression of SERPINE1 was observed in the pons, medulla, midbrain, corpus callosum and spinal cord. Expression of SERPINE1 was consistent with high grade lesions of GBM, suggesting association of SERPINE1 with advanced stages of GBM. The selected small molecules from Calotropis gigantea were observed to have therapeutically feasible binding affinity (140 - 550 μM) and predicted efficacy (290 - 1115 μM) against human SERPINE1. Conclusion SERPINE1 plays a vital role in the progression of GBM through its critical network proteins identified in this study. The expression of SERPINE1 aligns with the advanced stages of GBM. Small molecules from Calotropis gigantea tested in this study can serve as lead compounds for developing novel anti-SERPINE1 therapeutics for advanced stages of GBM.
Loss of species richness with land use intensity is explained by a reduction in niche differences

Increases in land use intensity (LUI) reduce species richness. However, we have a poor understanding of how underlying coexistence mechanisms are altered by land use and whether diversity loss occurs due to changes in plant-plant interactions (competition and facilitation) or in species intrinsic growth rates. We expect that LUI could reduce stabilizing niche differences and the indirect interactions that promote coexistence (e.g., intransitivity), while increasing competitive inequalities between species. To test the importance of these different processes, we use 8-yr time series from 150 grasslands differing in LUI to evaluate the role of direct and indirect interactions in promoting coexistence between 50 plant species. We show that LUI reduces the number of coexisting species mostly by causing a non-linear reduction in niche differences, rather than by enhancing competitive inequalities. However, surprisingly, niche differences remained important in stabilizing coexistence between those species remaining at high LUI. Indirect interactions were generally less important than direct ones, and played a moderate role in promoting coexistence in smaller assemblages of species at intermediate LUI. Our models could accurately reproduce the decline in diversity seen with LUI, indicating that our time series approach captures the important interactions between species. By analyzing land use effects through recent advances in structural stability applied to community ecology we provide a more mechanistic understanding of its effects. Our results highlight the importance of identifying the niche differences that are lost with increasing LUI, to better predict and manage effects of land use on biodiversity. Significant statement Human land use is a major threat to grassland biodiversity. Grasslands with high rates of fertilization, grazing and mowing, contain many fewer plant species. Knowing the underlying causes is necessary for a better management of biodiversity. Here we apply ecological theory to spatiotemporal data on changes in plant abundance in managed grasslands in central Europe. We show that the observed decline in diversity can be explained by how interactions among plant species change with increases in land use intensity. In particular, intensive land use removes the stabilizing effect of self-limiting processes that buffer species against extinction as well as limit competitive dominance. Therefore, actions to promote these stabilizing dynamics among interacting species seem key to restore plant diversity.
Skin microbiota dynamics of dairy cows affected by digital dermatitis

Bovine digital dermatitis (DD), is a highly prevalent disease among dairy cattle characterized by ulcerative and painful lesions. While multiple management factors are involved in the disease, its precise etiology remains uncertain and the effectiveness of current control strategies remains highly variable. The major role of Treponema spp. in the development of the disease is consistently recognized. Nevertheless, it remains unclear how other bacterial communities are relevant to the onset and progression of the disease, and how the skin microbiota is affected by the environment during the course of the disease. The objective of this study was to describe the dynamics of microbiota recovered from DD affected feet under field conditions. This study described the diversity, structure, and composition of DD lesion microbiota over 45 days according to different clinical and management factors. The results of this investigation confirmed the existence of a specific skin microbiota associated with DD lesions, dominated by Treponema spp. and very different from the microbiota of healthy skin. Interestingly, the diversity and structure of the microbiota in DD lesions did not vary with the footbath disinfectant or the individual topical antibiotic treatments used. In addition, microbiotas from proliferative lesions evidenced a different structure and diversity in comparison to non-proliferative lesions. Our results confirm the major role of Treponema spp. And highlight the potential role of Mycoplasmopsis spp. in the DD lesion onset. Further studies are needed to confirm whether the clinical course of DD lesions is driven by a particular microbiota and how that microbiota may induce disease. Highlights Multiple bacteria have been identified in DD lesions. However, many of these microorganisms are inhabitants of the foot skin and the farm environment. For the first time, the microbiota of DD lesions was monitored for 45 days under field conditions to describe its evolution over time. The results of this investigation highlighted a particular microbiota dominated by Treponema spp. present on the skin of DD affected animals and highly different from those microbiotas of healthy skin. The microbiota of DD lesions evolved over the study period and differential bacteria were identified. Further studies are warranted to determine the role of the bacteria composing these microbiotas on lesion onset and outcome.
Myc controls IL-15-driven expansion and translational machinery of NK cells

Myc is a pleiotropic transcription factor involved in cancer, cell proliferation, and metabolism. Its regulation and function in Natural Killer (NK) cells, which are innate cytotoxic lymphocytes important to control viral infections and cancer, remain poorly defined. Here we show that mice deficient for Myc in NK cells presented a severe reduction in these lymphocytes. Myc was required for NK cell development and expansion in response to the key cytokine interleukin (IL)-15, which induced Myc through transcriptional and posttranslational mechanisms. Mechanistically, Myc ablation in vivo largely impacted NK cells’ ribosomagenesis, reducing their translation and expansion capacities. Similar results were obtained by inhibiting MYC in human NK cells. Impairing translation by pharmacological intervention phenocopied the consequences of deleting or blocking MYC in vitro. Notably, mice lacking Myc in NK cells exhibited defective anticancer immunity, which reflected their decreased numbers of mature NK cells exerting suboptimal cytotoxic functions. These results indicate that MYC is a central node in NK cells, connecting IL-15 to translational fitness, expansion, and anticancer immunity.
Mixing by a turbulent plume in a confined stratified region

An experimental and theoretical study of the mixing produced by a plume rising in a confined stratified environment is presented. As a result of the pre-existing stable stratification, the plume penetrates only part way into the region; at an intermediate level it intrudes laterally forming a horizontal layer. As time evolves, this layer of mixed fluid is observed to increase in thickness. The bottom front advects downward in a way analogous to the first front in the filling box of Baines & Turner (1969), while the lateral spreading of the plume occurs at an ever-increasing level and an ascending top front results. We develop a model of this stratified filling box; the model predicts the rate at which the two fronts advance into the environment. It is found that stratification in the environment, when smooth, has no significant influence on the dynamics of the descending front. We show that the rate of rise of the ascending front is determined by the turbulent mixing occurring at the spreading level. Entrainment of environmental fluid from above into the overshooting plume is significant; as a result, a density interface develops at this level. Asymptotically, the system reaches a state in which a bottom convecting layer, with an almost homogeneous density, deepens in a stratified background. The model proposed for this large-time behaviour is based on the simple energetic formulation that a constant fraction of the kinetic energy supplied by the plume, for mixing across the interface, is converted into potential energy of the convective layer. Our experimental results suggest an efficiency of approximately 50 % for this conversion. We discuss our results in the light of previous studies on turbulent penetrative convection and conclude that the theory developed should be valid for an intermediate range of values of the Richardson number characterizing the dynamic conditions at the interface. The model is applied quantitatively to the process of cooling of a room wherein stratification is relevant. The geological problem of replenishment of a magma chamber by a light input of magma is also analysed.
Evaluation of protective shielding thickness for diagnostic radiology rooms: theory and computer simulation.

This work presents the development and evaluation using modern techniques to calculate radiation protection barriers in clinical radiographic facilities. Our methodology uses realistic primary and scattered spectra. The primary spectra were computer simulated using a waveform generalization and a semiempiricalmodel (the Tucker–Barnes–Chakraborty model). The scattered spectra were obtained from published data. An analytical function was used to produce attenuation curves from polycromatic radiation for specified kVp, waveform, and filtration. The results of this analytical function are given in ambient dose equivalent units. The attenuation curves were obtained by application of Archer’s model to computer simulation data. The parameters for the best fit to the model using primary and secondary radiation data from different radiographic procedures were determined. They resulted in an optimized model for shielding calculation for any radiographic room. The shielding costs were about 50% lower than those calculated using the traditional method based on Report No. 49 of the National Council on Radiation Protection and Measurements.
Nonlinear three-mode interactions in a developing mixing layer

A formulation based on the integral energy method is presented for the nonlinear interaction problem between three large-scale coherent modes in a developing, laminar, free shear layer. Both binary and three-mode nonlinear, modal energy and phase interactions are included. The modal evolution and the development of the mean flow are very sensitive to the initial energy contents and phases of the participating modes. A strong nonlinear coupling of the modal phase variations with the variations of the modal energies is shown to exist and is responsible for the rapid reversal of the intermodal energy interactions in favor of the occasionally declining mode. This nonlinear mechanism preserves the higher frequency modes far downstream and is shown to contribute to the appearance of mean flow contraction observed in experiments through local collective return of energy to the mean by all modes. Depending on initial conditions, our results support the arguments of R. A. Petersen and R. C. Clough [“The influence .
Multi-location trials and population-based genotyping reveal high diversity and adaptation to breeding environments in a large collection of red clover

Red clover (Trifolium pratense L.) is an outcrossing forage legume that has adapted to a wide range of climatic and growing conditions across Europe. Red clover is valued for its high yield potential and forage quality. The high amount of genetic diversity present in red clover provides an invaluable, but often poorly characterized resource to improve key traits such as yield, quality, and resistance to biotic and abiotic stresses. In this study, we examined the genetic and phenotypic diversity within a diverse set of 395 diploid red clover accessions via genome wide allele frequency fingerprinting and multi-location field trials across Europe. We found that the genetic structure of accessions mostly reflected their geographic origin and only few cases were detected, where breeders integrated foreign genetic resources into their local breeding pools. Phenotypic performance of accessions in the multi-location field trials revealed a very strong accession x location interaction. Notably, breeding material and cultivars generally performed well at the location where they were developed. Local adaptation was especially prominent in Nordic red clover accessions that showed a distinct adaptation to the growing conditions and cutting regime of the North. Our results confirmed that red clover cultivars were bred from regional ecotypes and show a narrow adaptation to regional conditions. Our study can serve as a valuable basis for identifying interesting material that express the desired characteristics and contribute to the adaptation of red clover to future climatic conditions.