PVC-Derived nickel cobalt molybdophosphate (NCMP) composite membrane showed mechanical and thermal stability. The hydrothermal technique was used to synthesize the composite material. The ability to ...control membrane properties by changing the polymer to porous support ratio is a significant advantage of utilizing inorganic. Ion-exchange ability was controlled by chemical characterization TGA, FTIR and SEM with EDX analyses confirming the composition, thermal stability, superficial morphology, porosity, functional groups and ion transport of the composite. The chemical potential was measured using strong electrolytes such as KCl, NaCl, KNO
3
and NaNO
3
. The estimated membrane charge density was calculated for membrane performance. Membrane characteristics like transport number, mobility ratio, and charge efficiency, were determined using the Teorell–Meyer–Sievers theory framework. These characteristics enable the hybrid membrane to be an efficient component in a wide range of electro-membrane execution. Sodium ion extraction and removal efficiency and industrial uses of the NCMP/PVC composite membrane should be investigated.
Bile acids (BAs) are nutrient-responsive hormones that modulate energy balance through cell surface and nuclear receptors. Postprandial plasma BAs have been found to be decreased in obesity.
We aimed ...to determine whether meal-stimulated circulating BA levels are altered by Roux-en-Y gastric bypass (RYGB), an operation that modifies the neurohumoral determinants of food intake and energy expenditure to cause significant and durable weight loss.
Longitudinal study measuring fasting and postprandial plasma BAs before and after RYGB.
Five obese surgical patients and eight lean controls underwent frequent blood sampling after a standard liquid meal. Obese subjects were also tested at 1, 4 and 40 weeks after RYGB. Primary and secondary circulating BAs, as well as their glycine and taurine conjugates, were measured via reverse-phase high-performance liquid chromatography/mass spectroscopy.
We found that postprandial excursion of conjugated BAs was 52.4% lower in obese than in lean individuals by area-under-the-curve (AUC) analysis (378 vs 793 μmol min l(-1), respectively, P<0.05). By 40 weeks after RYGB, the meal-induced rise in conjugated BAs increased by 55.5% to the level of healthy lean controls (378 pre-op vs 850 μmol min l(-) post-op by AUC analyses, P<0.05). In contrast, postprandial concentrations of unconjugated BAs were similar in lean and obese individuals and were not affected by surgery.
In light of the growing evidence that BAs have key roles in glucose, lipid and energy homeostasis, the observation that RYGB normalizes the blunted postprandial circulating BA response in obesity suggests that BAs may contribute to the improvement in meal-related physiology seen after RYGB. Further studies are warranted to examine this hypothesis and to determine the degree to which an augmented BA response to nutrient ingestion may mediate the increased incretin response, brown adipose tissue activation and thermic effect of feeding that has been observed after this operation.
Due to the high genetic heterogeneity of hearing loss (HL), current clinical testing includes sequencing large numbers of genes, which often yields a significant number of novel variants. Therefore, ...the standardization of variant interpretation is crucial to provide consistent and accurate diagnoses. The Hearing Loss Variant Curation Expert Panel was created within the Clinical Genome Resource to provide expert guidance for standardized genomic interpretation in the context of HL. As one of its major tasks, our Expert Panel has adapted the American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines for the interpretation of sequence variants in HL genes. Here, we provide a comprehensive illustration of the newly specified ACMG/AMP HL rules. Three rules remained unchanged, four rules were removed, and the remaining 21 rules were specified. These rules were further validated and refined using a pilot set of 51 variants assessed by curators and disease experts. Of the 51 variants evaluated in the pilot, 37% (19/51) changed category based upon application of the expert panel specified rules and/or aggregation of evidence across laboratories. These HL‐specific ACMG/AMP rules will help standardize variant interpretation, ultimately leading to better care for individuals with HL.
The Hearing Loss Variant Curation Expert panel was created within ClinGen with the goals of standardizing variant interpretation in hearing loss, resolving existing discrepancies in submitted variant classifications in ClinVar and providing expert variant classifications for hearing loss. Here we present specifications of the ACMG/AMP variant interpretation guidelines for hearing loss and the results of a pilot project in which these specifications were applied to 51 variants in the CDH23, COCH, GJB2, KCNQ4, MYO6, MYO7A, SLC26A4, TECTA, and USH2A genes.
Trace chemical detection is important for a wide range of practical applications. Recently emerged two-dimensional (2D) crystals offer unique advantages as potential sensing materials with high ...sensitivity, owing to their very high surface-to-bulk atom ratios and semiconducting properties. Here, we report the first use of Schottky-contacted chemical vapor deposition grown monolayer MoS2 as high-performance room temperature chemical sensors. The Schottky-contacted MoS2 transistors show current changes by 2–3 orders of magnitude upon exposure to very low concentrations of NO2 and NH3. Specifically, the MoS2 sensors show clear detection of NO2 and NH3 down to 20 ppb and 1 ppm, respectively. We attribute the observed high sensitivity to both well-known charger transfer mechanism and, more importantly, the Schottky barrier modulation upon analyte molecule adsorption, the latter of which is made possible by the Schottky contacts in the transistors and is not reported previously for MoS2 sensors. This study shows the potential of 2D semiconductors as high-performance sensors and also benefits the fundamental studies of interfacial phenomena and interactions between chemical species and monolayer 2D semiconductors.
The 2015 ACMG/AMP sequence variant interpretation guideline provided a framework for classifying variants based on several benign and pathogenic evidence criteria, including a pathogenic criterion ...(PVS1) for predicted loss of function variants. However, the guideline did not elaborate on specific considerations for the different types of loss of function variants, nor did it provide decision‐making pathways assimilating information about variant type, its location, or any additional evidence for the likelihood of a true null effect. Furthermore, this guideline did not take into account the relative strengths for each evidence type and the final outcome of their combinations with respect to PVS1 strength. Finally, criteria specifying the genes for which PVS1 can be applied are still missing. Here, as part of the ClinGen Sequence Variant Interpretation (SVI) Workgroup's goal of refining ACMG/AMP criteria, we provide recommendations for applying the PVS1 criterion using detailed guidance addressing the above‐mentioned gaps. Evaluation of the refined criterion by seven disease‐specific groups using heterogeneous types of loss of function variants (n = 56) showed 89% agreement with the new recommendation, while discrepancies in six variants (11%) were appropriately due to disease‐specific refinements. Our recommendations will facilitate consistent and accurate interpretation of predicted loss of function variants.
We provide guidance for PVS1 usage that takes into consideration all aspects of putative loss of function (LoF) variants, including type, location, and annotation, and the disease mechanism of the genes they affect. We demonstrate how the combination of these variant and gene attributes can lead to varied PVS1 strength levels. Finally, we evaluate the refined criterion using > 50 LoF variants in several genes and diseases.
Alveoli, the lung's respiratory units, are tiny sacs where oxygen enters the bloodstream. They are lined by flat alveolar type 1 (AT1) cells, which mediate gas exchange, and AT2 cells, which secrete ...surfactant. Rare AT2s also function as alveolar stem cells. We show that AT2 lung stem cells display active Wnt signaling, and many of them are near single, Wnt-expressing fibroblasts. Blocking Wnt secretion depletes these stem cells. Daughter cells leaving the Wnt niche transdifferentiate into AT1s: Maintaining Wnt signaling prevents transdifferentiation, whereas abrogating Wnt signaling promotes it. Injury induces AT2 autocrine Wnts, recruiting "bulk" AT2s as progenitors. Thus, individual AT2 stem cells reside in single-cell fibroblast niches providing juxtacrine Wnts that maintain them, whereas injury induces autocrine Wnts that transiently expand the progenitor pool. This simple niche maintains the gas exchange surface and is coopted in cancer.
Although single-cell RNA sequencing studies have begun to provide compendia of cell expression profiles
, it has been difficult to systematically identify and localize all molecular cell types in ...individual organs to create a full molecular cell atlas. Here, using droplet- and plate-based single-cell RNA sequencing of approximately 75,000 human cells across all lung tissue compartments and circulating blood, combined with a multi-pronged cell annotation approach, we create an extensive cell atlas of the human lung. We define the gene expression profiles and anatomical locations of 58 cell populations in the human lung, including 41 out of 45 previously known cell types and 14 previously unknown ones. This comprehensive molecular atlas identifies the biochemical functions of lung cells and the transcription factors and markers for making and monitoring them; defines the cell targets of circulating hormones and predicts local signalling interactions and immune cell homing; and identifies cell types that are directly affected by lung disease genes and respiratory viruses. By comparing human and mouse data, we identified 17 molecular cell types that have been gained or lost during lung evolution and others with substantially altered expression profiles, revealing extensive plasticity of cell types and cell-type-specific gene expression during organ evolution including expression switches between cell types. This atlas provides the molecular foundation for investigating how lung cell identities, functions and interactions are achieved in development and tissue engineering and altered in disease and evolution.
The pro-neural transcription factor ASCL1 is a master regulator of neurogenesis and a key factor necessary for the reprogramming of permissive cell types to neurons. Endogenously, ASCL1 expression is ...often associated with neuroblast stem-ness. Moreover, ASCL1-mediated reprogramming of fibroblasts to differentiated neurons is commonly achieved using artificially high levels of ASCL1 protein, where ASCL1 acts as an "on-target" pioneer factor. However, the genome-wide effects of enhancing ASCL1 activity in a permissive neurogenic environment has not been thoroughly investigated. Here, we overexpressed ASCL1 in the neuronally-permissive context of neuroblastoma (NB) cells where modest endogenous ASCL1 supports the neuroblast programme.
Increasing ASCL1 in neuroblastoma cells both enhances binding at existing ASCL1 sites and also leads to creation of numerous additional, lower affinity binding sites. These extensive genome-wide changes in ASCL1 binding result in significant reprogramming of the NB transcriptome, redirecting it from a proliferative neuroblastic state towards one favouring neuronal differentiation. Mechanistically, ASCL1-mediated cell cycle exit and differentiation can be increased further by preventing its multi-site phosphorylation, which is associated with additional changes in genome-wide binding and gene activation profiles.
Our findings show that enhancing ASCL1 activity in a neurogenic environment both increases binding at endogenous ASCL1 sites and also results in additional binding to new low affinity sites that favours neuronal differentiation over the proliferating neuroblast programme supported by the endogenous protein. These findings have important implications for controlling processes of neurogenesis in cancer and cellular reprogramming.
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