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Progressive familial intrahepatic cholestasis type 3 (PFIC-3) is a rare autosomal recessive cholestatic liver disorder caused by mutations in the ABCB4 gene. The aim of this study was to present the phenotypic and genotypic spectrum of 4 Polish PFIC-3 patients diagnosed in a one-referral centre. The study included 4 patients with cholestasis and pathogenic variants in the ABCB4 gene identified by next-generation sequencing (NGS) of a targeted-gene panel or whole exome sequencing (WES). Clinical, laboratory, histological, and molecular data were collected. Four patients (three males) were identified. The age at first noted clinical signs and symptoms was 6, 2.5, 14, and 2 years respectively; the mean age was 6 years. Those signs and symptoms include pruritus (2 out of 4 patients) and hepatomegaly with splenomegaly (4 out of 4 patients). The age at the time of referral to our centre was 9, 3, 15, and 2.5 years respectively, while the mean age was 7 years. Chronic cholestatic liver disease of unknown aetiology was established in all of them. https://www.selleckchem.com/products/yoda1.html The NGS analysis was performed in all patients at the last follow-up visit. Three novel variants including c.902T>A, p.Met301Lys, c.3279+1G>A, p.?, and c.3524T>A, p.Leu1175His were identified. The time from the first consultation to the final diagnosis was 14, 9, 3, and 1 year respectively; the mean was 6.8 years. A detailed follow-up was presented. The clinical phenotype of PFIC-3 could be variable. The clinical and biochemical diagnosis of PFIC-3 is difficult, thus the NGS study is very useful in making a proper diagnosis. The clinical phenotype of PFIC-3 could be variable. The clinical and biochemical diagnosis of PFIC-3 is difficult, thus the NGS study is very useful in making a proper diagnosis.Tolerance to stress conditions is vital for organismal survival, including bacteria under specific environmental conditions, antibiotics, and other perturbations. Some studies have described common modulation and shared genes during stress response to different types of disturbances (termed as perturbome), leading to the idea of central control at the molecular level. We implemented a robust machine learning approach to identify and describe genes associated with multiple perturbations or perturbome in a Pseudomonas aeruginosa PAO1 model. Using microarray datasets from the Gene Expression Omnibus (GEO), we evaluated six approaches to rank and select genes using two methodologies, data single partition (SP method) or multiple partitions (MP method) for training and testing datasets, we evaluated three classification algorithms (SVM Support Vector Machine, KNN K-Nearest neighbor and RF Random Forest). Gene expression patterns and topological features at the systems level were included to describe the perturbome elements. We were able to select and describe 46 core response genes associated with multiple perturbations in P. aeruginosa PAO1 and it can be considered a first report of the P. aeruginosa perturbome. Molecular annotations, patterns in expression levels, and topological features in molecular networks revealed biological functions of biosynthesis, binding, and metabolism, many of them related to DNA damage repair and aerobic respiration in the context of tolerance to stress. We also discuss different issues related to implemented and assessed algorithms, including data partitioning, classification approaches, and metrics. Altogether, this work offers a different and robust framework to select genes using a machine learning approach.Antibody-antigen interactions are mediated by the same molecular recognition mechanisms as those of an enzyme and its substrate. On this basis, we developed a competitive inhibition kinetic ELISA to measure monoclonal antibody (mAb) inhibition constants. Serially diluted samples of ligand (mAb) and inhibitor (soluble antigen) were incubated to equilibrium in ELISA plates coated with a fixed concentration of antigen (receptor). Plates were washed, and bound mAb measured with antiglobulin-peroxidase. Initial velocity data of receptor-bound mAb at various ligand and inhibitor concentrations were analyzed with enzyme linear competitive inhibition methods by non-linear regression (NLR), linear transformations (Cornish-Bowden, Lineweaver-Burk, Hanes-Woolf, Dixon, Cortés [1/i0.5 vs. Vi/Vmax], Ascenzi [Ks/Vmax/Ks,0/Vmax vs. [I]]) and NLR IC50 plots, to derive mAb inhibition constants (Ki). We obtained similar mAb Ki and Kd values by ELISA and surface plasmon resonance, which confirmed the accuracy of the ELISA method. This competitive inhibition ELISA is a simple (it requires no labeling or prior knowledge of antibody concentration), sensitive (it detects Ki values in the low nanomolar range by conventional colorimetry), and reproducible method with which to calculate mAb inhibition constants.This study aimed to investigate whether Cr(VI) induced tight joint and oxidative damage in the small intestine, as mediated by the nuclear factor erythroid 2-related factor 2 (Nrf2)/reactive oxygen species (ROS)/Notch1 axis crosstalk. Thirty-two ICR mice were obtained and subjected to Cr(VI) via intragastric administration daily for 5 days. Western blot (WB) analysis, enzyme-linked immunosorbent assay (ELISA), immunohistochemistry (IHC) staining, and immunofluorescence (IF) staining were applied to detect small intestinal damage, Nrf2, Notch1, and respective downstream targets in this research. Results showed that Cr(VI) led to the tight joint and oxidative damage in the small intestine of mice. Nrf2 was stimulated, and Notch1 (Notch intracellular domain, NICD1) was activated to translocate into the nucleus and activate an antioxidant action. These findings were validated by WB analysis and IF staining. ROS levels increased as the Cr(VI) concentration increased. The colocalization analysis of Nrf2 and NICD1 implied that a crosstalk between Nrf2 and Notch1 existed. Therefore, this study indicated that the Nrf2/ROS/Notch1 axis crosstalk could aggravate the tight joint and oxidative damage in the small intestine after Cr(VI) treatment.Emerging pollutants represent a group of synthetic or naturally occurring compounds that are not normally monitored within the environment but can enter into the environment and cause different adverse ecological and health effects. This systematic review identified the various emerging pollutants in Nigeria. The following databases, ScienceDirect, PubMed, Google Scholar, and African Journals OnLine (AJOL) were searched to identify studies on pollutants of emerging concerns in Nigeria. A total of 933 articles were identified out of which 30 articles were selected to be eligible for the study. Over 250 emerging pollutants were identified and divided into 9 major groups which are personal care products, pharmaceuticals, industrial chemicals, polycyclic aromatic hydrocarbons, volatile organic compounds, pesticides, mycotoxins, radionuclides and electromagnetic radiations (Gamma radiation) and other pollutants of emerging concerns such as microbes, microplastics, and particulate matter. These pollutants are found in water bodies and underground waters, soils and sediments, biological systems, and ambient air at different concentrations with seasonal variations.
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