FGF12A Regulates Nav1.5 via CaM-regulated and CaM-independent Mechanisms.

Opening of the cardiac voltage-gated Na+ channel (Nav1.5) is responsible for robust depolarization of the cardiac action potential, while inactivation, which rapidly follows, allows for repolarization. Regulation of both the voltage- and time-dependent kinetics of Nav1.

Implementing the Robson Classification for caesarean sections in Pakistan: experience, challenges, and lessons learned.

The Robson Classification System is recognised as a first step for optimising the use of caesarean section and as a strategy for continuous quality improvement in maternal and newborn health. This Viewpoint provides a detailed account of the strategy adopted and lessons learned from a collaborative initiative to institutionalise the Robson Classification into Pakistan's health system. We developed a training package which emphasised capacity building of senior clinicians to act as master trainers.

Interpretable Fine-Grained Phenotypes of Subcellular Dynamics via Unsupervised Deep Learning.

Uncovering fine-grained phenotypes of live cell dynamics is pivotal for a comprehensive understanding of the heterogeneity in healthy and diseased biological processes. However, this endeavor poses significant technical challenges for unsupervised machine learning, requiring the extraction of features that not only faithfully preserve this heterogeneity but also effectively discriminate between established biological states, all while remaining interpretable. To tackle these challenges, a self-training deep learning framework designed for fine-grained and interpretable phenotyping is presented.

Pulsed electric field effect on acrylamide reduction and quality attributes of continuous-style Lamoka potato chips.

Potato chips are a popular snack, well-liked because of their texture-flavor combination. Potato chips are made by frying slices of potato in vegetable oil to achieve a crispy texture. Frying potato slices initiates the Maillard reaction, resulting in chemical changes that enhance taste, color, and texture, but also undesired acrylamides, which are suspected carcinogens.

Arrhythmia-associated calmodulin variants interact with KCNQ1 to confer aberrant membrane trafficking and function.

Missense variants in calmodulin (CaM) predispose patients to arrhythmias associated with high mortality rates ("calmodulinopathy"). As CaM regulates many key cardiac ion channels, an understanding of disease mechanism associated with CaM variant arrhythmias requires elucidating individual CaM variant effects on distinct channels. One key CaM regulatory target is the KCNQ1 (K7.

Arrhythmia-associated Calmodulin Variants Interact with KCNQ1 to Confer Aberrant Membrane Trafficking and Function.

Rationale: Missense variants in calmodulin (CaM) predispose patients to arrhythmias associated with high mortality rates. As CaM regulates several key cardiac ion channels, a mechanistic understanding of CaM variant-associated arrhythmias requires elucidating individual CaM variant effect on distinct channels. One key CaM regulatory target is the KCNQ1 (K 7.

Expression and purification of a cleavable recombinant fortilin from Escherichia coli for structure activity studies.

Complications related to atherosclerosis account for approximately 1 in 4 deaths in the United States and treatment has focused on lowering serum LDL-cholesterol levels with statins. However, approximately 50% of those diagnosed with atherosclerosis have blood cholesterol levels within normal parameters. Human fortilin is an anti-apoptotic protein and a factor in macrophage-mediated atherosclerosis and is hypothesized to protect inflammatory macrophages from apoptosis, leading to subsequent cardiac pathogenesis.

Center of Biomedical Research Excellence in Matrix Biology: Building Research Infrastructure, Supporting Young Researchers, and Fostering Collaboration.

The Center of Biomedical Research Excellence in Matrix Biology strives to improve our understanding of extracellular matrix at molecular, cellular, tissue, and organismal levels to generate new knowledge about pathophysiology, normal development, and regenerative medicine. The primary goals of the Center are to i) support junior investigators, ii) enhance the productivity of established scientists, iii) facilitate collaboration between both junior and established researchers, and iv) build biomedical research infrastructure that will support research relevant to cell-matrix interactions in disease progression, tissue repair and regeneration, and v) provide access to instrumentation and technical support. A Pilot Project program provides funding to investigators who propose applying their expertise to matrix biology questions.

Detection of Erionite and Other Zeolite Fibers in Soil by the Fluidized Bed Preparation Methodology.

Erionite is a zeolite mineral that can occur as fibrous particles in soil. Inhalation exposure to erionite fibers may result in increased risk of diseases, such as mesothelioma. Low level detection of mineral fibers in soils has traditionally been accomplished using polarized light microscopy (PLM) methods to analyze bulk samples providing detection limits of around 0.

Epithelial Smad4 Deletion Up-Regulates Inflammation and Promotes Inflammation-Associated Cancer.

Background & Aims: Chronic inflammation is a predisposing condition for colorectal cancer. Many studies to date have focused on proinflammatory signaling pathways in the colon. Understanding the mechanisms that suppress inflammation, particularly in epithelial cells, is critical for developing therapeutic interventions.

Deleting the TGF-β receptor in proximal tubules impairs HGF signaling.

Transforming growth factor-β (TGF-β) and hepatocyte growth factor (HGF) play key roles in regulating the response to renal injury but are thought to mediate divergent effects on cell behavior. However, how TGF-β signaling alters the response to HGF in epithelia, the key site of HGF signaling in the injured kidney, is not well studied. Contrary to our expectation, we showed that deletion of the TGF-β type II receptor in conditionally immortalized proximal tubule (PT) cells impaired HGF-dependent signaling.

Renal fibrosis is not reduced by blocking transforming growth factor-β signaling in matrix-producing interstitial cells.

Transforming growth factor-β (TGF-β) strongly promotes renal tubulointerstitial fibrosis, but the cellular target that mediates its profibrotic actions has not been clearly identified. While in vitro data suggest that TGF-β-induced matrix production is mediated by renal fibroblasts, the role of these cells in TGF-β-dependent tubulointerstitial fibrosis following renal injury is not well defined. To address this, we deleted the TGF-β type II receptor in matrix-producing interstitial cells using two different inducible Cre models: COL1A2-Cre with a mesenchymal enhancer element and tenascin-Cre that targets medullary interstitial cells, and either the mouse unilateral ureteral obstruction or the aristolochic acid renal injury model.

An in vitro method for estimation of arsenic relative bioavailability in soil.

This report summarizes the results of a study to develop an in vitro bioaccessibility (IVBA) extraction technique for estimating the relative bioavailability (RBA) of arsenic (As) in soil. The study was implemented in several steps. In step 1, key variables in the extraction protocol were identified.

Deamidation alters interactions of beta-crystallins in hetero-oligomers.

Purpose: Cataracts are a major cause of blindness worldwide. A potential mechanism for loss of visual acuity may be due to light scattering from disruption of normal protein-protein interactions. During aging, the lens accumulates extensively deamidated crystallins.

Seroprevalence of human immunodeficiency virus in mental health patients.

In contrast to the published data on Human Immunodeficiency Virus (HIV) infection in parenteral drug abusers, there is a paucity of data on prison inmates and virtually none on psychiatric inpatients. Because our facility serves each of these patients groups, we designed an anonymous seroprevalance study. We tested 1,496 unduplicated sera using sequential enzyme-linked immunosorbent assay (ELISA) and Western blot tests.

The role of bone cells in increasing metaphyseal hard tissue in rapidly growing rats treated with prostaglandin E2.

The skeletal effects of graded doses of prostaglandin E2 (PGE2) given to weanling Sprague-Dawley rats for 3 weeks were investigated to elucidate the role of bone cells in increasing hard tissue mass. Decalcified (3 micron) sections were quantified in the light microscope by point hit and intersect counting using a Merz grid. Hard tissue mass (bone and calcified cartilage) and osteoblast, osteoclast and osteoprogenitor cell numbers were counted in metaphyseal tissue bands 0.

Effects of phytohemagglutinin-P (PHA-P) on bone of the growing rat.

The effects of phytohemagglutinin-P, (PHA-P), a mitogen known to selectively stimulate cells of hematogenous or lymphoid monocytic origin, 25 and 50 mg/kg/day administered for 15 days on proximal tibiae of growing male Sprague-Dawley rats, were studied. The general effect of PHA-P was to decrease the amount of cartilage, hard tissue, and longitudinal growth in the proximal tibial metaphysis. A decrease in longitudinal bone growth, in the number of chondrocytes, in the thickness of cartilage plate, in the metaphyseal mass of hard tissue, in the percentage of calcified cartilage core, and in the number of osteoblasts per mm of bone surface was observed.

An extension of the sign test for replicated measurements.

An extension of the sign test is proposed for the case where there are paired groups or sets of replicated measurements; the individual measurements are unpaired between groups. A class of methods is investigated where the values of the groups of replicates are replaced by summary statistics (exceedances) whose distribution is independent, under the null hypothesis, of the underlying parametric structure. Possible adjustment for discontinuity of the underlying distribution (ties) is discussed and a normal approximation is presented.

Ethane-1-hydroxy-1, 1-diphosphonate (EHDP) effects on incorporation and accumulation of osteoclast nuclei.

Male rats weighing 100 g were injected with vehicle (control group), 0.4 or 4.0 mg/kg/day of ethane-1-hydroxy-1,1-diphosphonate (EHDP).