Bioelectric-calcineurin signaling module regulates allometric growth and size of the zebrafish fin

AbstractThe establishment of relative size of organs and structures is paramount for attaining final form and function of an organism. Importantly, variation in the proportions of structures frequently underlies adaptive change in morphology in evolution and maybe a common mechanism underlying selection. However, the mechanism by which growth is integrated within tissues during development to achieve proper proportionality is poorly understood. We have shown that signaling by potassium channels mediates coordinated size regulation in zebrafish fins. Recently, calcineurin inhibitors were shown to elicit changes in zebrafish fin allometry as well. Here, we identify the potassium channelkcnk5bas a key player in integrating calcineurin’s growth effects, in part through regulation of the cytoplasmic C-terminus of the channel. We propose that the interaction between Kcnk5b and calcineurin acts as a signaling node to regulate allometric growth. Importantly, we find that this regulation is epistatic to inherent mechanisms instructing overall size as inhibition of calcineurin is able to bypass genetic instruction of size as seen insofand wild-type fins, however, it is not sufficient to re-specify positional memory of size of the fin. These findings integrate classic signaling mediators such as calcineurin with ion channel function in the regulation of size and proportion during growth.</jats:p

Can Unlikely Neanderthal Chloride Channel CLC-2 Gene Variants Provide Insights in Modern Human Infertility?

Background/Aims: Neanderthals, although well adapted to local environments, were rapidly replaced by anatomically modern humans (AMH) for unknown reasons. Genetic information on Neanderthals is limited restricting applicability of standard population genetics. Methods: Here, we apply a novel combination of restricted genetic analyses on preselected physiological key players (ion channels), electrophysiological analyses of gene variants of unclear significance expressed in Xenopus laevis oocytes using two electrode voltage clamp and transfer of results to AMH genetics. Using genetic screening in infertile men identified a loss of CLC-2 associated with sperm deficiency. Results: Increased genetic variation caused functionally impaired Neanderthals CLC-2 channels. Conclusion: Increased genetic variation could reflect an adaptation to different local salt supplies at the cost of reduced sperm density. Interestingly and consistent with this hypothesis, lack of CLC-2 protein in a patient associates with high blood K+ concentration and azoospermia

Molekulare, pharmakologische und evolutionäre Aspekte bei KV_V-Kanal-vermittelten Arrhythmien

Mutationen bei kardialen Ionenkanälen können Auswirkungen auf die Kanalfunktion haben und zu einem modifizierten Herzaktionspotenzial führen. Funktionsstörungen der kardialen Kaliumkanäle K$_V$1.5 und K$_V$7.1 können durch ihre Beteiligung an der Repolarisation des Herzaktionspotenzials lebensbedrohliche Herzrhythmusstörungen auslösen. Ziel dieser Arbeit war die Charakterisierung und Funktionsanalyse von potenziell pathophysiologisch auffälligen Genmutationen der spannungsabhängigen Ionenkanäle K$_V$1.5 und K$_V$7.1 sowie die Identifizierung der Bindestelle des Kalium-Kanalinhibitors JNJ303. Untersuchungen der molekularen Aspekte im K$_V$7.1-Kanal identifizierten die neue $\textit {gain of function}$-Mutation A287T als Schlüsselaminosäure im K$_V$7.1/KCNE1-Kanalkomplex. Die pharmakologischen Aspekte erfassten ein neues Bindemotiv des Inhibitors JNJ303 im K$_V$7.1/KCNE1-Kanal. Untersuchungen der evolutionären Aspekte zeigten Funktionsveränderungen von K$_V$1.5-Mutationen mit hohem arrhythmogenen Potenzial des Neanderthalers

Human eosinophil granulocytes do not express the enzyme arginase.

Human polymorphonuclear PMN constitutively express the enzyme arginase I, which hydrolyzes arginine to ornithine and urea. This arginine consumption has been recognized as a key pathway of myeloid cell-mediated suppression of the adaptive immune system during inflammation, infection, and tumor growth. Eos granulocytes are crucial immunoregulatory and effector cells of allergic inflammation and infections with parasites and helminths and in a variety of tumors. Here, we analyzed if human Eos also express arginase with its potential immunosuppressive consequences. We show that human peripheral blood Eos do not express arginase I or II protein or arginase enzymatic activity. Correspondingly, no metabolism of arginine to ornithine can be detected in Eos-S. Neither Eos apoptosis nor cytokine-mediated cellular activation induces arginase in human Eos in vitro. Finally, we show that arginase activity and protein are also undetectable in Eos of allergic patients from peripheral blood or from BALF activated in vivo during allergic pulmonary inflammation. This work demonstrates a fundamental difference between neutrophil and Eos granulocytes. As Eos are not equipped with the immunosuppressive enzyme arginase, they cannot participate, via arginine limitation, in the suppression of the evolving adaptive immune response in allergy, infections, or tumor immunity

Moving beyond the link between HRM and economic performance : a study on the individual reactions of HR managers and professionals to sustainable HRM

This study contributes to the growing literature on the intersection between human resource management and corporate sustainability (CS) and, in particular, on sustainable human resource management (interpreted here as HRM practices informed by the CS principles, thus aiming at economic, social, environmental and human sustainability simultaneously). In particular, this paper claims that the members of the HR professional community can increase their job satisfaction and decrease their intention to leave by implementing sustainable HRM. In addition, we test for the mediating role played by the meaning that HR professionals and managers attach to HR work. Indeed, when HR professionals and managers are involved in sustainable HRM perceive their job to become more meaningful as it has a broader scope which goes beyond the solely focus on economic performance, and that leads then to higher job satisfaction and lower turnover intention. The study, which is based on 176 questionnaires collected through a cross-country survey, has been developed in partnership between the authors and a leading European association of HR managers and professionals. Our findings, which in general extend the knowledge on the employees' perception of CS-employee attitudes relationships, represent a data-driven argument for a more active role of HRM in developing Sustainable HRM