Miracle-dz/UniFAR-FTUs huggingface dataset:
Neurodevelopmental clustering of gene expression identifies lipid metabolism genes associated with neuroprotection and neurodegeneration

APOE variants present the strongest association with sporadic Alzheimer’s Disease. APOE is also highly expressed during neurodevelopment in the Central Nervous System (CNS) and has been shown to be neuroprotective in infancy and gestation. We explored other lipid metabolism genes to determine whether they show a similar neurodevelopmental expression trajectory and are associated with neurodegeneration. APOE was by far the most highly expressed of the lipid metabolism genes in the CNS. Two other genes, Apolipoprotein C1 (APOC1) Glutamate-Ammonia Ligase (GLUL—also known as glutamine synthetase), co-clustered with Apolipoprotein E (APOE) in its developmental trajectory in late gestation through early childhood. These three genes highlight brain structures and developmental time-windows distinct from other lipid metabolism genes. In the CNS they are primarily expressed in astrocytes and are implicated in neuroprotection and neurodegeneration.
A GID E3 ligase assembly ubiquitinates an Rsp5 E3 adaptor and regulates plasma membrane transporters

Cells rapidly remodel their proteomes to align their cellular metabolism to environmental conditions. Ubiquitin E3 ligases enable this response, by facilitating rapid and reversible changes to protein stability, localization, or interaction partners. In S. cerevisiae, the GID E3 ligase regulates the switch from gluconeogenic to glycolytic conditions through induction and incorporation of the substrate receptor subunit Gid4, which promotes the degradation of gluconeogenic enzymes. Here, we show an alternative substrate receptor, Gid10, which is induced in response to changes in temperature, osmolarity and nutrient availability, and regulates the ART-Rsp5 pathway. Art2 levels are elevated upon GID10 deletion, a crystal structure shows the basis for Gid10-Art2 interactions, and Gid10 directs a GID E3 ligase complex to ubiquitinate Art2. We also find that the GID E3 ligase affects the flux of plasma membrane nutrient transporters during heat stress. The data reveal GID as a system of E3 ligases with metabolic regulatory functions outside of glycolysis and gluconeogenesis, controlled by distinct stress-specific substrate receptors.
Metabolomics Analysis of Splenic CD19+ B Cells in Mice Chronically Infected With Echinococcus granulosus sensu lato Protoscoleces

Background: The larval stages of Echinococcus granulosus sensu lato (E. granulosus s.l) infection can alter B cell function and affect host anti-infective immunity, but the underlying mechanism remains unclear. The newly emerging immunometabolism highlights that several metabolites are key factors in determining the fate of immune cells, which provides a new insight for exploring how larval E. granulosus s.l. infection remodels B cell function. This study investigated the metabolomic profiles of B cells in mice infected with E. granulosus s.l. protoscoleces (PSC). Results:Total CD19+ B cells, purified from the spleen of infected mice, showed significantly increased production of IL-6, TNF-α, and IL-10 after exposure to LPS in vitro. Moreover, the mRNA expression of metabolism related enzymes in B cells was remarkably disordered post infection. In addition, differential metabolites were identified in B cells after infection. There were 340 differential metabolites (83 upregulated and 257 downregulated metabolites) identified in the positive ion model, and 216 differential metabolites (97 upregulated and 119 downregulated metabolites) identified in the negative ion mode. Among these, 64 differential metabolites were annotated and involved in 68 metabolic pathways, including thyroid hormone synthesis, the metabolic processes of glutathione, fructose, mannose, and glycerophospholipid. Furthermore, several differential metabolites such as glutathione, taurine, and inosine were validated to regulate the cytokine production in LPS stimulated B cells. Conclusion:Infection with the larval E. granulosus s.l. causes metabolic reprogramming in the intrinsic B cells of mice, which provides the first evidence for understanding the role and mechanism of B cells in parasite anti-infective immunity from the viewpoint of immunometabolism.
The CERN-MEDICIS Isotope Separator Beamline

CERN-MEDICIS is an off-line isotope separator facility for the extraction of radioisotopes from irradiated targets of interest to medical applications. The beamline, between the ion source and the collection chamber, consists of ion extraction and focusing elements, and a dipole magnet mass spectrometer recovered from the LISOL facility in Louvain-la-Neuve. The latter has been modified for compatibility with MEDICIS, including the installation of a window for injecting laser light into the ion source for resonance photo-ionization. Ion beam optics and magnetic field modeling using SIMION and OPERA respectively were performed for the design and characterization of the beamline. The individual components and their optimal configuration in terms of ion beam extraction, mass separation, and ion transport efficiency is described, along with details of the commissioning and initial performance assessment with stable ion beams.
Chemical profile, antioxidant activity and cytotoxic effect of extract from leaves of Erythrochiton brasiliensis Nees & Mart. from different regions of Europe

Abstract The total phenolic content (TPC), total tannin content (TTC) and total flavonoid content (TFC) as well as the antioxidant activity and the cytotoxic effect of the extract from leaves of Erythrochiton brasiliensis Nees & Mart. (Rutaceae) were evaluated. Raw material was collected in different European botanical gardens. Statistical analysis revealed a clear grouping of populations according to their climatic zone. The average TPC, TTC and TFC in tested samples were 35.92 (± 7.11) mg GAE·g–1 DW, 14.98 (± 4.08) mg PyE·g–1 DW and 2.92 (± 0.76) mg QuE·g–1 DW, respectively. The scavenged DPPH and Trolox equivalents determined by EPR spectroscopy were 1.23–4.14 and 0.50–1.44 mmol·g–1 of dry extract, respectively. Thirteen compounds (derivatives of bezoic acid acid and trans-cinnammic acid) were identified in the samples. The flavonoid vitexin was also present as the major component in three investigated samples. The in vitro cytotoxicity test of the extract on Vero cells provided IC50 and IC10 values of 175.6 and 72.5 μg·mL–1, respectively. Incubation of samples with HHV-1 infected Vero cells had no effect on the occurrence of cytopathic effect.
Differential Expression of Immune Response Genes in Asymptomatic Chronic Chagas Disease Patients Versus Healthy Subjects

Infection by the Trypanosoma cruzi parasite causes Chagas disease and triggers multiple immune mechanisms in the host to combat the pathogen. Chagas disease has a variable clinical presentation and progression, producing in the chronic phase a fragile balance between the host immune response and parasite replication that keeps patients in a clinically silent asymptomatic stage for years. Since the parasite is intracellular and replicates within cells, the cell-mediated response of the host adaptive immunity plays a critical role. This function is mainly orchestrated by T lymphocytes, which recognize parasite antigens and promote specific functions to control the infection. However, little is known about the immunological markers associated with this asymptomatic stage of the disease. In this large-scale analysis, the differential expression of 106 immune system-related genes has been analyzed using high-throughput qPCR in T. cruzi antigen-stimulated PBMC from chronic Chagas disease patients with indeterminate form (IND) and healthy donors (HD) from endemic and non-endemic areas of Chagas disease. This analysis revealed that there were no differences in the expression level of most genes under study between healthy donors from endemic and non-endemic areas determined by PCA and differential gene expression analysis. Instead, PCA revealed the existence of different expression profiles between IND patients and HD (p < 0.0001), dependent on the 32 genes included in PC1. Differential gene expression analysis also revealed 23 upregulated genes (expression fold change > 2) and 11 downregulated genes (expression fold change < 0.5) in IND patients versus HD. Enrichment analysis showed that several upregulated genes in IND patients participate in relevant immunological pathways such as antigen-dependent B cell activation, stress induction of HSP regulation, NO2-dependent IL12 pathway in NK cells, and cytokine-inflammatory response. The antigen-specific differential gene expression profile detected in these patients and the relevant immunological pathways that seem to be activated could represent potential biomarkers of the asymptomatic form of Chagas disease, helpful to diagnosis and infection control.
Hippocampal CA1 Neurons Represent Positive Feedback During the Learning Process of an Associative Memory Task

The hippocampus is crucial for forming associations between environmental stimuli. However, it is unclear how neural activities of hippocampal neurons dynamically change during the learning process. To address this question, we developed an associative memory task for rats with auditory stimuli. In this task, the rats were required to associate tone pitches (high and low) and ports (right and left) to obtain a reward. We recorded the firing activity of neurons in rats hippocampal CA1 during the learning process of the task. As a result, many hippocampal CA1 neurons increased their firing rates when the rats received a reward after choosing either the left or right port. We referred to these cells as “reward-direction cells. ” Furthermore, the proportion of the reward-direction cells increased in the middle-stage of learning but decreased after the completion of learning. This result suggests that the activity of reward-direction cells might serve as “positive feedback” signal that facilitates the formation of associations between tone pitches and port choice.
Determinação dos parâmetros de uma seção de testes para o pressurizador do reator nuclear IRIS

An integral, modular and medium size nuclear reactor, known as IRIS, is being developed by Westinghouse and by research centers. IRIS is characterized by having most of its components inside the pressure vessel, eliminating the probability of accidents. Due to its integral configuration, there is no spray system for boron homogenization, which may cause power transients. Thus, boron mixing must be investigated. The aim of this thesis is to establish the conditions under which a test section has to be built for boron dispersion analysis inside IRIS reactor pressurizer. Through Fractional Scaling Analysis, which is a new methodology of similarity, the main parameters for a test section are obtained. By combining Fractional Scaling Analysis with local scaling for the densimetric Froude number and a previously established volumetric scale factor, the values of recirculation orifices, inlet water temperature, time scale factor and recirculation flow for the test section (model) are determined so that boron distribution is well represented in IRIS reactor pressurizer (prototype). Analytical solutions are used so as to validate the adopted methodology and when the results simulated in the model are compared to those that characterize the prototype, the agreement for both systems is absolute. The thermal power also influences boron distribution inside the test section. This power is determined by condensation laws in the vapor region and by suitable correlations for free convection. The fractions for rising inlet recirculation water enthalpy and vapor formation are also considered.
A musculoskeletal finite element model of rat knee joint for evaluating cartilage biomechanics during gait

Abnormal loading of the knee due to injuries or obesity is thought to contribute to the development of osteoarthritis (OA). Small animal models have been used for studying OA progression mechanisms. However, numerical models to study cartilage responses under dynamic loading in preclinical animal models have not been developed. Here we present a musculoskeletal finite element (FE) model of a rat knee joint to evaluate cartilage biomechanical responses during a gait cycle. The rat knee joint geometries were obtained from a 3-D MRI dataset and the boundary conditions regarding loading in the joint were extracted from a musculoskeletal model of the rat hindlimb. The fibril-reinforced poroelastic (FRPE) properties of the rat cartilage were derived from data of mechanical indentation tests. Our numerical results showed the relevance of simulating anatomical and locomotion characteristics in the rat knee joint for estimating tissue responses such as contact pressures, stresses, strains, and fluid pressures. We found that the contact pressure and maximum principal strain were virtually constant in the medial compartment whereas they showed the highest values at the beginning of the gait cycle in the lateral compartment. Furthermore, we found that the maximum principal stress increased during the stance phase of gait, with the greatest values at midstance. We anticipate that our approach serves as a first step towards investigating the effects of gait abnormalities on the adaptation and degeneration of rat knee joint tissues and could be used to evaluate biomechanically-driven mechanisms of the progression of OA as a consequence of joint injury or obesity. Author Summary Osteoarthritis is a disease of the musculoskeletal system which is characterized by the degradation of articular cartilage. Changes in the knee loading after injuries or obesity contribute to the development of cartilage degeneration. Since injured cartilage cannot be reversed back to intact conditions, small animal models have been widely used for investigating osteoarthritis progression mechanisms. Moreover, experimental studies have been complemented with numerical models to overcome inherent limitations such as cost, difficulties to obtain accurate measures and replicate degenerative situations in the knee joint. However, computational models to study articular cartilage responses under dynamic loading in small animal models have not been developed. Thus, here we present a musculoskeletal finite element model of a rat knee joint to evaluate cartilage biomechanical responses during gait. Our computational model considers both the anatomical and locomotion characteristics of the rat knee joint for estimating mechanical responses in the articular cartilage. We suggest that our approach can be used to investigate tissue adaptations based on the mechanobiological responses of the cartilage to prevent the progression of osteoarthritis.
A Genome-Wide Association Study Identifies Candidate Genes Associated With Shell Color in Bay Scallop Argopecten irradians irradians

Molluscan shell color has consistently drawn attention for its abundant diversity and commercial use in shellfish breeding projects. Recently, two new strains of bay scallop (Argopecten irradians irradians) with different shell colors as marked phenotypic traits have been artificially bred to improve their economic values; however, the inheritance mechanism of their shell pigmentation is still unclear. In this study, a genome-wide association study (GWAS) was conducted to determine the genetic basis of shell color in bay scallops utilizing 29,036 high-quality single-nucleotide polymorphisms (SNPs) derived from 80 purple-red (PP) and 80 black-brown (BP) shell color individuals. The result of the GWAS showed that 469 SNPs (p <1.72E−6) significantly associated with shell color were mainly distributed in chromosome 7. The top three SNPs (i.e., chr7-12764003, chr7-13213864, and chr7-11899306) are located in the genic region of G-protein-coupled receptor-like 101 (GRL101), polyketide synthase 1 (PKS1), and phosphoinositide phospholipase C (PLC1), which have been widely reported to be involved in pigmentation. Successfully, the top three SNPs were verified in another non-breeding bay scallop population. Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses obtained 38 GO terms covering 297 genes and aggregating pathways involving 252 annotated genes. Specifically, the expression profiles of the top three identified candidate genes were detected in mantles of PP and BP individuals by real-time quantitative reverse transcription PCR. The significantly higher expression levels of GRL101 (6.43-fold) and PLC1 (6.48-fold) in PP, and PKS1 (12.02-fold) in BP implied that GRL101 and PLC1 potentially functioned in PP shell coloration, and black pigmentation in BP might be principally regulated by PKS1. Our data provide valuable information for deciphering the phenotype differences of shell color in the bay scallop.
Morchella importuna Flavones Improve Intestinal Integrity in Dextran Sulfate Sodium-Challenged Mice

Morchella importuna, as an edible fungus, has various health benefits. However, the effects of M. importuna on intestinal health are rarely investigated. Hence, this study aims to ascertain the influences of flavones from the fruiting bodies of M. importuna (hereinafter abbreviated as MIF) on dextran sulfate sodium (DSS)-induced damage to intestinal epithelial barrier in C57BL/6J mice. In this (14-day) study, 144 C57BL/6J mice were divided into four groups: (1) Control; (2) DSS treatment; (3) DSS treatment + 100 mg/kg MIF (LMIF); (4) DSS treatment + 200 mg/kg MIF (HMIF). On days 8-14, mice in the challenged groups were challenged with 3.5% DSS, while the control group received an equal volume of normal saline. Then, serum and intestinal samples were obtained from all mice. The results showed that MIF ingestion enhanced intestinal integrity in DSS-challenged mice, as evinced by the elevated (p < 0.05) abundances of occludin, claudin-1, and zonula occludens-1 proteins. Meanwhile, MIF ingestion reduced (p < 0.05) the colonic interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) concentrations and increased the superoxide dismutase and catalase activities and Shannon and Simpson indices in DSS-challenged mice. Moreover, MIF ingestion reduced (p < 0.05) the abundance of phospho-nuclear factor (NF)-κB and increased the abundance of phospho-Nrf2 in DSS-challenged mice. Taken together, MIF protects against intestinal barrier injury in C57BL/6J mice via a mechanism that involves inhibiting NF-κB activation and promoting Nrf2 activation, as well as regulating intestinal microbiota.
Relationships Among Trophic Niche Width, Morphological Variation, and Genetic Diversity of Hemiculter leucisculus in China

According to the niche variation hypothesis (NVH), the populations with wider niches are phenotypically more variable than those with narrow niches. Giller expanded the NVH, suggesting that the niche width, morphological variation, and genetic diversity are all positively correlated. However, the hypothesis has been a subject of debate and discussion. In the present study, the NVH was tested by analyzing the relationships among trophic niche width, morphological variation, and genetic diversity of Hemiculter leucisculus, a widespread cyprinid fish. The fish samples were collected from six sites across Haihe, the Yellow, and the Yangtze River basins in China. The relationships among trophic niche width, morphological variation, and genetic diversity were analyzed using Pearson correlation at the inter-population level. Our analysis indicated that trophic niche width is significantly positively correlated with morphological variation, which corroborates the NVH. Morphological variation was significantly correlated to genetic diversity. However, no relationship was observed between trophic niche width and genetic diversity. We inferred that the dietary niche of H. leucisculus might change due to the plastic response toward environmental changes rather than due to the genetic variation. We also suggest that the effects of environment and heredity on the niche of the freshwater fish should be quantified separately in further studies.
Screening of Fungi for Antimycobacterial Activity Using a Medium-Throughput Bioluminescence-Based Assay

There is a real and urgent need for new antibiotics able to kill Mycobacteria, acid-fast bacilli capable of causing multiple deadly diseases. These include members of the Mycobacterium tuberculosis complex, which causes the lung disease tuberculosis (TB) as well as non-tuberculous Mycobacteria (NTM) a growing cause of lung, skin, soft tissue, and other infections. Here we describe a medium-throughput bioluminescence-based pipeline to screen fungi for activity against Mycobacteria using the NTM species Mycobacterium abscessus and Mycobacterium marinum. We used this pipeline to screen 36 diverse fungal isolates from the International Collection of Microorganisms from Plants (ICMP) grown on a wide variety of nutrient-rich and nutrient-poor media and discovered that almost all the tested isolates produced considerable anti-mycobacterial activity. Our data also provides strong statistical evidence for the impact of growth media on antibacterial activity. Chemical extraction and fractionation of a subset of the ICMP isolates revealed that much of the activity we observed may be due to the production of the known anti-mycobacterial compound linoleic acid. However, we have identified several ICMP isolates that retained their anti-mycobacterial activity in non-linoleic acid containing fractions. These include isolates of Lophodermium culmigenum, Pseudaegerita viridis, and Trametes coccinea, as well as an unknown species of Boeremia and an isolate of an unknown genus and species in the family Phanerochaetaceae. Investigations are ongoing to identify the sources of their anti-mycobacterial activity and to determine whether any may be due to the production of novel bioactive compounds.
Bruton’s Tyrosine Kinase-Mediated Signaling in Myeloid Cells Is Required for Protective Innate Immunity During Pneumococcal Pneumonia

Bruton’s tyrosine kinase (Btk) is a cytoplasmic kinase expressed in B cells and myeloid cells. It is essential for B cell development and natural antibody-mediated host defense against bacteria in humans and mice, but little is known about the role of Btk in innate host defense in vivo. Previous studies have indicated that lack of (natural) antibodies is paramount for impaired host defense against Streptococcus (S.) pneumoniae in patients and mice with a deficiency in functional Btk. In the present study, we re-examined the role of Btk in B cells and myeloid cells during pneumococcal pneumonia and sepsis in mice. The antibacterial defense of Btk-/- mice was severely impaired during pneumococcal pneumosepsis and restoration of natural antibody production in Btk-/- mice by transgenic expression of Btk specifically in B cells did not suffice to protect against infection. Btk-/- mice with reinforced Btk expression in MhcII+ cells, including B cells, dendritic cells and macrophages, showed improved antibacterial defense as compared to Btk-/- mice. Bacterial outgrowth in Lysmcre-Btkfl/Y mice was unaltered despite a reduced capacity of Btk-deficient alveolar macrophages to respond to pneumococci. Mrp8cre-Btkfl/Y mice with a neutrophil specific paucity in Btk expression, however, demonstrated impaired antibacterial defense. Neutrophils of Mrp8cre-Btkfl/Y mice displayed reduced release of granule content after pulmonary installation of lipoteichoic acid, a gram-positive bacterial cell wall component relevant for pneumococci. Moreover, Btk deficient neutrophils showed impaired degranulation and phagocytosis upon incubation with pneumococci ex vivo. Taken together, the results of our study indicate that besides regulating B cell-mediated immunity, Btk is critical for regulation of myeloid cell-mediated, and particularly neutrophil-mediated, innate host defense against S. pneumoniae in vivo.