Control of epithelial Na+ channels by CFTR, receptors and kinases

The epithelial Na+ channel (ENaC) is located in the apical membrane of salt (re-) absorbing epithelia in kidney, colon, airways and glandular excretory ducts. In this thesis it is demonstrated that both stimulation of purinergic receptors and activation of the cystic fibrosis transmembrane conductance regulator (CFTR) and other Cl- channels lead to inhibition of epithelial Na+ channels, resulting in reduced Na+ absorption. Activation of purinergic receptors is the starting point for a signalling cascade, leading to inhibition of ENaC via hydrolysis of the phospholipid PIP2. The Na+ channel is also inhibited by stimulation of CFTR- or other Cl- channels, which change the intracellular Cl- concentration upon activation in co-expression experiments. A correlation was found between the degree of ENaC inhibition and the increase in intracellular Cl- concentration. While binding of ENaC to PIP2 keeps the channel in an active state, interference of ENaC with intracelluar Cl- seems inhibitory on ENaC function. To carry out CFTR studies under conditions like in native tissue, two new cell lines were created from MDCK type II cells, which stably express wt-CFTR or its mutant counterpart F508del-CFTR. The cell lines grow as tight monolayers and are therefore suitable for Ussing chamber experiments. CK2 is a constitutively active protein kinase that influences the activity of the channel through its binding and phosphorylation of both beta- and gamma subunits of ENaC. Lack of these phosphorylation sites or dephosphorylation of one of these sites results in a significant attenuation of the activity of the epithelial Na+ channel. It suggests that phosphorylation of both beta- and gammaENaC by CK2 prevents binding of the ubiquitin ligase Nedd4-2 to ENaC. Lack of binding of Nedd4-2 to ENaC may result in both reduced endocytosis and accumulation of ENaC in the cell membrane as well as increase in ENaC activity

India, Water and Sustainable Development

Author's Note: India faces tremendous developmental challenges, both in water and other sectors, in the next couple of decades. My three-month journey in spring 2008 was, at its core, an exploration of the myriad of complexities to providing safe and sustainable water access. I hope the images will lend an insightful introduction to the challenges of the subcontinent and inspire a desire to learn more. Introduction: In February 2008, I took a break from academic studies for three months of real-life study: trying to understand India’s cultural, social and religious constraints to clean water access. The subcontinent has the second largest population in the world, and nearly a quarter of its peoples are lacking access to safe and reliable water. I set out to discover and document this issue. After landing in Delhi, I traveled to Kanpu, Allahabad and Varanasi, all sites along India’s most famous and-arguably-most toxic river because of heavy domestic and industrial pollution. From there, I went south to the Western Ghats and then northeast to the Kolwan Valley, where stories of complex political dynamics lived in every village. Traveling onward to Mumbai, it was a story of socio-economic inequalities. Finally I ended up in Rajasthan, where the biggest issue is also the most basic: there simply is not nearly enough water. Overall, the journey was an eye-opening exploration of India’s biggest challenge in the coming decade: clean and sustainable water access for all of its citizens

Primary Care: On the Front Lines of the Opioid Crisis

This Issue Brief discusses the role of primary care teams in identifying illicit drug use disorders in their patients, the continuum of treatments that they can offer, and opportunities for successful collaboration and integration with specialists. The authors find opportunities exist for increased patient screening and delivering medication-assisted treatment as well as established models for collaboration and integration of opioid treatments

Extremizers of the JJ functional with respect to the d1d_1 metric

In previous work, Darvas-George-Smith obtained inequalities between the large scale asymptotic of the $J$ functional with respect to the $d_1$ metric on the space of toric K\"ahler metrics/rays. In this work we prove sharpness of these inequalities on all toric K\"ahler manifolds, and study the extremizing potentials/rays. On general K\"ahler manifolds we show that existence of radial extremizers is equivalent with the existence of plurisupported currents, as introduced and studied by McCleerey.Comment: Results from an REU project. arXiv admin note: text overlap with arXiv:2101.0258

The Implementation of Service-Oriented Architectures in the German Banking Industry - A Case Study

The concept of Service-oriented Architecture (SOA) is becoming increasingly important not only in research, but also in practice. SOA has emerged as a major topic, especially in regards to the banking industry as it is one of the cutting-edge industries concerning service-orientation. SOA implementation in the German banking industry varies, with some still in the adoption phase and others already in the SOA operations phase. This has specific implications concerning the SOA Readiness as well as the SOA Maturity of German banks. This paper details the research objective, design, and conduction of a case study in the Germany banking industry investigating the SOA Readiness and SOA Maturity of German banks. Different phases such as SOA adoption and SOA operations and the consequences of SOA during Merger & Acquisition (M&A) conduction are analyzed and evaluated. Finally, the preliminary findings are exhibited