UTP-dependent Inhibition of Na+ Absorption Requires Activation of PKC in Endometrial Epithelial Cells

The objective of this study was to investigate the mechanism of uridine 5′-triphosphate (UTP)-dependent inhibition of Na+ absorption in porcine endometrial epithelial cells. Acute stimulation with UTP (5 μM) produced inhibition of sodium absorption and stimulation of chloride secretion. Experiments using basolateral membrane–permeabilized cell monolayers demonstrated a reduction in benzamil-sensitive Na+ conductance in the apical membrane after UTP stimulation. The UTP-dependent inhibition of sodium transport could be mimicked by PMA (1 μM). Several PKC inhibitors, including GF109203X and Gö6983 (both nonselective PKC inhibitors) and rottlerin (a PKCδ selective inhibitor), were shown to prevent the UTP-dependent decrease in benzamil-sensitive current. The PKCα-selective inhibitors, Gö6976 and PKC inhibitor 20–28, produced a partial inhibition of the UTP effect on benzamil-sensitive Isc. Inhibition of the benzamil-sensitive Isc by UTP was observed in the presence of BAPTA-AM (50 μM), confirming that activation of PKCs, and not increases in [Ca2+]i, were directly responsible for the inhibition of apical Na+ channels and transepithelial Na+ absorption

CD38/cADPR Signaling Pathway in Airway Disease: Regulatory Mechanisms

Asthma is an inflammatory disease in which proinflammatory cytokines have a role in inducing abnormalities of airway smooth muscle function and in the development of airway hyperresponsiveness. Inflammatory cytokines alter calcium (Ca2+) signaling and contractility of airway smooth muscle, which results in nonspecific airway hyperresponsiveness to agonists. In this context, Ca2+ regulatory mechanisms in airway smooth muscle and changes in these regulatory mechanisms encompass a major component of airway hyperresponsiveness. Although dynamic Ca2+ regulation is complex, phospholipase C/inositol tris-phosphate (PLC/IP3) and CD38-cyclic ADP-ribose (CD38/cADPR) are two major pathways mediating agonist-induced Ca2+ regulation in airway smooth muscle. Altered CD38 expression or enhanced cyclic ADP-ribosyl cyclase activity associated with CD38 contributes to human pathologies such as asthma, neoplasia, and neuroimmune diseases. This review is focused on investigations on the role of CD38-cyclic ADP-ribose signaling in airway smooth muscle in the context of transcriptional and posttranscriptional regulation of CD38 expression. The specific roles of transcription factors NF-kB and AP-1 in the transcriptional regulation of CD38 expression and of miRNAs miR-140-3p and miR-708 in the posttranscriptional regulation and the underlying mechanisms of such regulation are discussed

In situ metal organic framework (ZIF-8) and mechanofusion-assisted MWCNT coating of LiFePO/C composite material for lithium-ion batteries

LiFePO4 is one of the industrial, scalable cathode materials in lithium-ion battery production, due to its cost-effectiveness and environmental friendliness. However, the electrochemical performance of LiFePO4 in high current rate operation is still limited, due to its poor ionic- and electron-conductive properties. In this study, a zeolitic imidazolate framework (ZIF-8) and multiwalled carbon nanotubes (MWCNT) modified LiFePO4/C (LFP) composite cathode materials were developed and investigated in detail. The ZIF-8 and MWCNT can be used as ionic- and electron-conductive materials, respectively. The surface modification of LFP by ZIF-8 and MWCNT was carried out through in situ wet chemical and mechanical alloy coating. The as-synthesized materials were scrutinized via various characterization methods, such as XRD, SEM, EDX, etc., to determine the material microstructure, morphology, phase, chemical composition, etc. The uniform and stable spherical morphology of LFP composites was obtained when the ZIF-8 coating was processed by the agitator [A], instead of the magnetic stirrer [MS], condition. It was found that the (optimum of) 2 wt.% ZIF-8@LFP [A]/MWCNT composite cathode material exhibited outstanding improvement in high-rate performance; it maintained the discharge capacities of 125 mAh g−1 at 1C, 110 mAh g−1 at 3C, 103 mAh g−1 at 5C, and 91 mAh g−1 at 10C. Better cycling stability with capacity retention of 75.82% at 1C for 100 cycles, as compared to other electrodes prepared in this study, was also revealed. These excellent results were mainly obtained because of the improvement of lithium-ion transport properties, less polarization effect, and interfacial impedance of the LFP composite cathode materials derived from the synergistic effect of both ZIF-8 and MWCNT coating materials

Pathogenic and genetic characterization of six Indian populations of Colletotrichum sublineolum, the causal agent of sorghum anthracnose

The pathogenic and genetic characterization of populations of C. sublineolum, the causal agent of anthracnose of sorghum, was investigated in isolates from 6 locations in India. Multi-location field evaluation and greenhouse tests were done on 16 sorghum lines that comprised the International Sorghum Anthracnose Virulence Nursery (ISAVN). The lines were tested in a field trial for 4-5 years (1992-96) at 6 locations: Indore, Surat, Patancheru, Dharwad, Udaipur and Pantnagar. Plants were scored for disease reaction (R/MR/S) and for disease severity (on a 1-9 scale where 1 is no lesions and 9 is >75% leaf area covered with lesions) at the soft-dough stage in the field and at the seedling stage in the greenhouse. Significant (P<0.001) differences were observed for virulence (disease reaction) and aggressiveness (disease severity) across locations (isolates) and sorghum lines both in field and greenhouse tests. In both tests, isolate x sorghum line interactions were highly significant (P<0.001) suggesting that populations of C. sublineolum at these 6 locations were different. A random amplified polymorphic DNA (RAPD) analysis exhibited genetic dissimilarities among the isolates and these were classified into 6 groups

Developmental and Lactational Exposure to Dieldrin Alters Mammary Tumorigenesis in Her2/neu Transgenic Mice

Breast cancer is the most common cancer in Western women and while its precise etiology is unknown, environmental factors are thought to play a role. The organochlorine pesticide dieldrin is a persistent environmental toxicant thought to increase the risk of breast cancer and reduce survival in the human population. The objective of this study was to define the effect of developmental exposure to environmentally relevant concentrations of dieldrin, on mammary tumor development in the offspring. Sexually mature FVB-MMTV/neu female mice were treated with vehicle (corn oil), or dieldrin (0.45, 2.25, and 4.5 µg/g body weight) daily by gavage for 5 days prior to mating and then once weekly throughout gestation and lactation until weaning. Dieldrin concentrations were selected to produce serum levels representative of human background body burdens, occupational exposure, and overt toxicity. Treatment had no effect on litter size, birth weight or the number of pups surviving to weaning. The highest dose of dieldrin significantly increased the total tumor burden and the volume and number of tumors found in the thoracic mammary glands. Increased mRNA and protein expression of the neurotrophin BDNF and its receptor TrkB was increased in tumors from the offspring of dieldrin treated dams. This study indicates that developmental exposure to the environmental contaminant dieldrin causes increased tumor burden in genetically predisposed mice. Dieldrin exposure also altered the expression of BNDF and TrkB, novel modulators of cancer pathogenesis

Height and body-mass index trajectories of school-aged children and adolescents from 1985 to 2019 in 200 countries and territories: a pooled analysis of 2181 population-based studies with 65 million participants

Summary Background Comparable global data on health and nutrition of school-aged children and adolescents are scarce. We aimed to estimate age trajectories and time trends in mean height and mean body-mass index (BMI), which measures weight gain beyond what is expected from height gain, for school-aged children and adolescents. Methods For this pooled analysis, we used a database of cardiometabolic risk factors collated by the Non-Communicable Disease Risk Factor Collaboration. We applied a Bayesian hierarchical model to estimate trends from 1985 to 2019 in mean height and mean BMI in 1-year age groups for ages 5–19 years. The model allowed for non-linear changes over time in mean height and mean BMI and for non-linear changes with age of children and adolescents, including periods of rapid growth during adolescence. Findings We pooled data from 2181 population-based studies, with measurements of height and weight in 65 million participants in 200 countries and territories. In 2019, we estimated a difference of 20 cm or higher in mean height of 19-year-old adolescents between countries with the tallest populations (the Netherlands, Montenegro, Estonia, and Bosnia and Herzegovina for boys; and the Netherlands, Montenegro, Denmark, and Iceland for girls) and those with the shortest populations (Timor-Leste, Laos, Solomon Islands, and Papua New Guinea for boys; and Guatemala, Bangladesh, Nepal, and Timor-Leste for girls). In the same year, the difference between the highest mean BMI (in Pacific island countries, Kuwait, Bahrain, The Bahamas, Chile, the USA, and New Zealand for both boys and girls and in South Africa for girls) and lowest mean BMI (in India, Bangladesh, Timor-Leste, Ethiopia, and Chad for boys and girls; and in Japan and Romania for girls) was approximately 9–10 kg/m2. In some countries, children aged 5 years started with healthier height or BMI than the global median and, in some cases, as healthy as the best performing countries, but they became progressively less healthy compared with their comparators as they grew older by not growing as tall (eg, boys in Austria and Barbados, and girls in Belgium and Puerto Rico) or gaining too much weight for their height (eg, girls and boys in Kuwait, Bahrain, Fiji, Jamaica, and Mexico; and girls in South Africa and New Zealand). In other countries, growing children overtook the height of their comparators (eg, Latvia, Czech Republic, Morocco, and Iran) or curbed their weight gain (eg, Italy, France, and Croatia) in late childhood and adolescence. When changes in both height and BMI were considered, girls in South Korea, Vietnam, Saudi Arabia, Turkey, and some central Asian countries (eg, Armenia and Azerbaijan), and boys in central and western Europe (eg, Portugal, Denmark, Poland, and Montenegro) had the healthiest changes in anthropometric status over the past 3·5 decades because, compared with children and adolescents in other countries, they had a much larger gain in height than they did in BMI. The unhealthiest changes—gaining too little height, too much weight for their height compared with children in other countries, or both—occurred in many countries in sub-Saharan Africa, New Zealand, and the USA for boys and girls; in Malaysia and some Pacific island nations for boys; and in Mexico for girls. Interpretation The height and BMI trajectories over age and time of school-aged children and adolescents are highly variable across countries, which indicates heterogeneous nutritional quality and lifelong health advantages and risks