cGMP-dependent kinase 2, Na/H exchanger NHE3, and PDZ-adaptor NHERF2 co-assemble in apical membrane microdomains.

Aim: Trafficking, membrane retention, and signal-specific regulation of the Na/H exchanger 3 (NHE3) are modulated by the Na/H Exchanger Regulatory Factor (NHERF) family of PDZ-adapter proteins. This study explored the assembly of NHE3 and NHERF2 with the cGMP-dependent kinase II (cGKII) within detergent-resistant membrane microdomains (DRMs, "lipid rafts") during in vivo guanylate cycle C receptor (Gucy2c) activation in murine small intestine.

Methods: Small intestinal brush border membranes (siBBMs) were isolated from wild type, NHE3-deficient, cGMP-kinase II-deficient, and NHERF2-deficient mice, after oral application of the heat-stable Escherichia coli toxin (STa) analog linaclotide.

High self-selection of Ukrainian refugees into Europe: Evidence from Kraków and Vienna.

Almost eight million Ukrainians have fled their country to escape the Russian full-scale invasion. To provide empirical evidence on how beneficiaries of temporary protection who reside in the immediate proximity of Ukraine differ from those who went further and reside in Western European countries, two large-scale rapid-response surveys were conducted in Kraków, Poland, and Vienna, Austria, in spring 2022. Data include information on socio-demographic characteristics, human capital, and return intentions of 472 and 1,094 adult Ukrainian refugees in Poland and Austria, respectively.

SLC26A9 deficiency causes gastric intraepithelial neoplasia in mice and aggressive gastric cancer in humans.

Background: Solute carrier family 26 member (SLC26A9) is a Cl uniporter with very high expression levels in the gastric mucosa. Here, we describe morphological and molecular alterations in gastric mucosa of slc26a9 mice and in selective parietal cell-deleted slc26a9/Atp4b-Cre mice and correlate SLC26A9 expression levels with morphological and clinical parameters in a cohort of gastric cancer (GC) patients.

Methods: The expression patterns of genes related to transport and enzymatic function, proliferation, apoptosis, inflammation, barrier integrity, metaplasia and neoplasia development were studied by immunohistochemistry (IHC), quantitative RT-PCR, in situ hybridization and RNA microarray analysis.

Upregulation of antimicrobial peptide expression in slc26a3-/- mice with colonic dysbiosis and barrier defect.

Genetic defects in SLC26A3 (DRA), an intestinal Cl/HCO exchanger, result in congenital chloride diarrhea (CLD), marked by lifelong acidic diarrhea and a high risk of inflammatory bowel disease. mice serve as a model to understand the pathophysiology of CLD and search for treatment options. This study investigates the microbiota changes in colon, the genotype-related causes for the observed microbiota alterations, its inflammatory potential, as well as the corresponding host responses.

Loss of luminal carbonic anhydrase XIV results in decreased biliary bicarbonate output, liver fibrosis, and cholangiocyte proliferation in mice.

Carbonic anhydrase XIV (Car14) is highly expressed in the hepatocyte, with predominance in the canalicular membrane and its active site in the extracellular milieu. The aim of this study is to determine the physiological relevance of Car14 for biliary fluid and acid/base output, as well as its role in the maintenance of hepatocellular and cholangiocyte integrity. The common bile duct of anesthetized car14 and car14 mice was cannulated and hepatic HCO output was measured by microtitration and bile flow gravimetrically before and during stimulation with intravenously applied tauroursodeoxycholic acid (TUDCA).

Sodium/hydrogen-exchanger-2 modulates colonocyte lineage differentiation.

Aim: The sodium/hydrogen exchanger 2 (NHE2) is an intestinal acid extruder with crypt-predominant localization and unresolved physiological significance. Our aim was to decipher its role in colonic epithelial cell proliferation, differentiation and electrolyte transport.

Methods: Alterations induced by NHE2-deficiency were addressed in murine nhe2 and nhe2 colonic crypts and colonoids, and NHE2-knockdown and control Caco2Bbe cells using pH-fluorometry, gene expression analysis and immunofluorescence.

Hydrokinetic pancreatic function and insulin secretion are moduled by Cl uniporter Slc26a9 in mice.

Aim: Slc26a9 is a member of the Slc26 multifunctional anion transporter family. Polymorphisms in Slc26a9 are associated with an increased incidence of meconium ileus and diabetes in cystic fibrosis patients. We investigated the expression of Slc26a9 in the murine pancreatic ducts, islets and parenchyma, and elucidated its role in pancreatic ductal electrolyte and fluid secretion and endocrine function.

Didn't Plan One but got One: and Parents in the East and the West of Europe.

The realisation rates of short-term childbearing intentions are known to be consistently lower in post-socialist countries than in the rest of Europe. However, the East-West differences in the outcomes of intentions to postpone or forego (further) childbearing have not been previously examined. We employ two panel waves of the Generations and Gender Survey in six countries (three from Eastern and three from Western Europe), and, based on the short- and long-term fertility intentions expressed by respondents at the first survey wave, we classify the births occurring between two waves as intended, sooner-than-intended, or unintended.

Educational Differences in Cohort Fertility Across Sub-national Regions in Europe.

Educational differences in female cohort fertility vary strongly across high-income countries and over time, but knowledge about how educational fertility differentials play out at the sub-national regional level is limited. Examining these sub-national regional patterns might improve our understanding of national patterns, as regionally varying contextual conditions may affect fertility. This study provides for the first time for a large number of European countries a comprehensive account of educational differences in the cohort fertility rate (CFR) at the sub-national regional level.

Deciphering ion transporters, kinases and PDZ-adaptor molecules that mediate guanylate cyclase C agonist-dependent intestinal fluid loss in vivo.

Background: The molecular basis for heat-stable Escherichia coli enterotoxin (STa) action and its synthetic analogue linaclotide is well understood at the enterocyte level. Pharmacologic strategies to prevent STa-induced intestinal fluid loss by inhibiting its effector molecules, however, have achieved insufficient inhibition in vivo.

Aims And Experimental Approach: To investigate whether the currently discussed effector molecules and signaling mechanisms of STa/linaclotide-induced diarrhea have similar relevance in vivo than at the enterocyte level, we studied the effect of 10M of the STa analogue linaclotide on short circuit current (Isc) of chambered isolated jejunal mucosa, and on the in vivo action on fluid transport in a perfused segment of proximal jejunum of anesthetized mice.

Slc26a3 deletion alters pH-microclimate, mucin biosynthesis, microbiome composition and increases the TNFα expression in murine colon.

Aim: SLC26A3 (DRA) mediates the absorption of luminal Cl in exchange for HCO in the distal intestine. Its expression is lost in congenital chloride diarrhoea (CLD) and strongly decreased in the presence of intestinal inflammation. To characterize the consequences of a loss of Slc26a3 beyond disturbed electrolyte transport, colonic mucus synthesis, surface accumulation and composition, pH microclimate, microbiome composition and development of inflammation was studied in slc26a3 mice.

Calcium-sensing receptor regulates intestinal dipeptide absorption via Ca signaling and IK activation.

Although absorption of di- and tripeptides into intestinal epithelial cells occurs via the peptide transporter 1 (PEPT1, also called solute carrier family 15 member 1 (SLC15A1)), the detailed regulatory mechanisms are not fully understood. We examined: (a) whether dipeptide absorption in villous enterocytes is associated with a rise in cytosolic Ca ([Ca ] ), (b) whether the calcium sensing receptor (CaSR) is involved in dipeptide-elicited [Ca ] signaling, and (c) what potential consequences of [Ca ] signaling may enhance enterocyte dipeptide absorption. Dipeptide Gly-Sar and CaSR agonist spermine markedly raised [Ca ] in villous enterocytes, which was abolished by NPS-2143, a selective CaSR antagonist and U73122, an phospholipase C (PLC) inhibitor.

Regional context and realization of fertility intentions: the role of the urban context.

Despite regional variation in fertility, rural-urban differences in the realization of fertility intentions have not been addressed in previous research. This paper analyzes the realization with data from 11 European countries, employing binomial and multinomial logistic regression models, decomposition analyses, and examining the role of contextual factors. The results demonstrate that realization is lower in urban than in rural regions.

Fertility Intentions and Their Realization in Couples: How the Division of Household Chores Matters.

Most research on Europe indicates that a gender-balanced division of family work tends to increase childbearing probabilities, but empirical results vary substantially. The present article proposes explanations for this observed discrepancy. It develops prior research further by (1) studying short-term fertility intentions and their realization within the subsequent 4 years, (2) analyzing the role of the spouses' satisfaction with the division for the effects that the division may have on childbearing, (3) proving a mediation by relationship satisfaction, and (4) considering gender as well as parity as moderators.

Identification of the retrotalar pulley of the Flexor Hallucis Longus tendon.

Functional Hallux Limitus is the expression of the gliding restraint of the Flexor Hallucis Longus (Fhl) tendon, resulting in several painful syndromes. This impingement is located along the tract of the Fhl tendon at the level of its retrotalar tunnel sealed posteriorly by a fibrous pulley. This pulley, although poorly anatomically characterized, has been arthroscopically proven that its presence or resection plays a pivotal clinical role in the biomechanics of the lower leg, being the main restraint to the physiological movement of the Fhl tendon.

Letter to the editor - round table unites to tackle culture change in an effort to improve animal research reporting.

A round table discussion was held during the LAVA-ESLAV-ECLAM conference on Reproducibility of Animal Studies on the 25th of September 2017 in Edinburgh. The aim of the round table was to discuss how to enhance the rate at which the quality of reporting animal research can be improved. This signed statement acknowledges the efforts that participant organizations have made towards improving the reporting of animal studies and confirms an ongoing commitment to drive further improvements, calling upon both academics and laboratory animal veterinarians to help make this cultural change.

Genetic ablation of carbonic anhydrase IX disrupts gastric barrier function via claudin-18 downregulation and acid backflux.

Aim: This study aimed to explore the molecular mechanisms for the parietal cell loss and fundic hyperplasia observed in gastric mucosa of mice lacking the carbonic anhydrase 9 (CAIX).

Methods: We assessed the ability of CAIX-knockout and WT gastric surface epithelial cells to withstand a luminal acid load by measuring the pH of exteriorized gastric mucosa in vivo using two-photon confocal laser scanning microscopy. Cytokines and claudin-18A2 expression was analysed by RT-PCR.