Proton Pump Activity of Mitochondria-rich Cells : The Interpretation of External Proton-concentration Gradients

We have hypothesized that a major role of the apical H+-pump in mitochondria-rich (MR) cells of amphibian skin is to energize active uptake of Cl− via an apical Cl−/HCO3−-exchanger. The activity of the H+ pump was studied by monitoring mucosal [H+]-profiles with a pH-sensitive microelectrode. With gluconate as mucosal anion, pH adjacent to the cornified cell layer was 0.98 ± 0.07 (mean ± SEM) pH-units below that of the lightly buffered bulk solution (pH = 7.40). The average distance at which the pH-gradient is dissipated was 382 ± 18 μm, corresponding to an estimated “unstirred layer” thickness of 329 ± 29 μm. Mucosal acidification was dependent on serosal pCO2, and abolished after depression of cellular energy metabolism, confirming that mucosal acidification results from active transport of H+. The [H+] was practically similar adjacent to all cells and independent of whether the microelectrode tip was positioned near an MR-cell or a principal cell. To evaluate [H+]-profiles created by a multitude of MR-cells, a mathematical model is proposed which assumes that the H+ distribution is governed by steady diffusion from a number of point sources defining a set of particular solutions to Laplace's equation. Model calculations predicted that with a physiological density of MR cells, the [H+] profile would be governed by so many sources that their individual contributions could not be experimentally resolved. The flux equation was integrated to provide a general mathematical expression for an external standing [H+]–gradient in the unstirred layer. This case was treated as free diffusion of protons and proton-loaded buffer molecules carrying away the protons extruded by the pump into the unstirred layer; the expression derived was used for estimating stationary proton-fluxes. The external [H+]-gradient depended on the mucosal anion such as to indicate that base (HCO3−) is excreted in exchange not only for Cl −, but also for Br− and I−, indicating that the active fluxes of these anions can be attributed to mitochondria-rich cells

Suspected zoonotic transmission of rotavirus group A in Danish adults

SUMMARYGroup A rotaviruses infect humans and a variety of animals. In July 2006 a rare rotavirus strain with G8P[14] specificity was identified in the stool samples of two adult patients with diarrheoa, who lived in the same geographical area in Denmark. Nucleotide sequences of the VP7, VP4, VP6, and NSP4 genes of the identified strains were identical. Phylogenetic analyses showed that both Danish G8P[14] strains clustered with rotaviruses of animal, mainly, bovine and caprine, origin. The high genetic relatedness to animal rotaviruses and the atypical epidemiological features suggest that these human G8P[14] strains were acquired through direct zoonotic transmission events.</jats:p

Imputating missing values in diary records of sun-exposure study

In a sun-exposure study, questionnaires concerning sunhabits were collected from 195 subjects. This paper focuses on the general problem of missing data values, which occurs when some, or even all of the questions have not been answered in a questionnaire. Here, only missing values of low concentration are investigated. We consider and compare two different models for imputating missing values: the Gaussian model and the non-parametric K-Nearest Neighbor model

The Role of Lipophagy in the Development and Treatment of Non-Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) or metabolic (dysfunction) associated liver disease (MAFLD), is, with a global prevalence of 25%, the most common liver disorder worldwide. NAFLD comprises a spectrum of liver disorders ranging from simple steatosis to steatohepatitis, fibrosis, cirrhosis and eventually end-stage liver disease. The cause of NAFLD is multifactorial with genetic susceptibility and an unhealthy lifestyle playing a crucial role in its development. Disrupted hepatic lipid homeostasis resulting in hepatic triglyceride accumulation is an hallmark of NAFLD. This disruption is commonly described based on four pathways concerning 1) increased fatty acid influx, 2) increased de novo lipogenesis, 3) reduced triglyceride secretion, and 4) reduced fatty acid oxidation. More recently, lipophagy has also emerged as pathway affecting NAFLD development and progression. Lipophagy is a form of autophagy (i.e. controlled autolysosomal degradation and recycling of cellular components), that controls the breakdown of lipid droplets in the liver. Here we address the role of hepatic lipid homeostasis in NAFLD and specifically review the current literature on lipophagy, describing its underlying mechanism, its role in pathophysiology and its potential as a therapeutic target

Assessment of the Impact of the Recombinant Porcine Reproductive and Respiratory Syndrome Virus Horsens Strain on the Reproductive Performance in Pregnant Sows

This study assessed the impact of a PRRSV (porcine reproductive and respiratory syndrome virus) recombinant strain (Horsens strain) on the reproductive performance of na&iuml;ve pregnant sows in the last third of gestation. Fifteen sows were included: four negative reproductive controls (NTX), five infected with a PRRSV-1 field strain (Olot/91, T01), and six infected with the recombinant PRRSV-1 strain (Horsens strain, T02). Piglets were monitored until weaning. Reproductive performance was the primary variable. In sows, viremia and nasal shedding (T01 and T02 groups), and, in piglets, viral load in blood and in lungs, as well as macroscopic lung lesions (T01 and T02 groups), were the secondary variables. The reproductive performance results were numerically different between the two challenged groups. Moreover, viral loads in blood were 1.83 &times; 106 &plusmn; 9.05 &times; 106 copies/mL at farrowing, 1.05 &times; 107 &plusmn; 2.21 &times; 107 copies/mL at weaning from piglets born from T01 animals and 1.64 &times; 103 &plusmn; 7.62 &times; 103 copies/mL at farrowing, 1.95 &times; 103 &plusmn; 1.17 &times; 104 copies/mL at weaning from piglets born from T02 sows. Overall, 68.8% of T01 piglets and 38.1% of T02 piglets presented mild lung lesions. In conclusion, the results suggest that Horsens strain is less virulent than the field strain Olot/91 under these experimental conditions

Late regulation of immune genes and microRNAs in circulating leukocytes in a pig model of influenza A (H1N2) infection

MicroRNAs (miRNAs) are a class of short regulatory RNA molecules which are implicated in modulating gene expression. Levels of circulating, cell-associated miRNAs in response to influenza A virus (IAV) infection has received limited attention so far. To further understand the temporal dynamics and biological implications of miRNA regulation in circulating leukocytes, we collected blood samples before and after (1, 3, and 14 days) IAV challenge of pigs. Differential expression of miRNAs and innate immune factor mRNA transcripts was analysed using RT-qPCR. A total of 20 miRNAs were regulated after IAV challenge, with the highest number of regulated miRNAs seen on day 14 after infection at which time the infection was cleared. Targets of the regulated miRNAs included genes involved in apoptosis and cell cycle regulation. Significant regulation of both miRNAs and mRNA transcripts at 14 days after challenge points to a protracted effect of IAV infection, potentially affecting the host’s ability to respond to secondary infections. In conclusion, experimental IAV infection of pigs demonstrated the dynamic nature of miRNA and mRNA regulation in circulating leukocytes during and after infection, and revealed the need for further investigation of the potential immunosuppressing effect of miRNA and innate immune signaling after IAV infection