Confirming the unusual temperature dependence of the electric-field gradient in Zn

The electric-field gradient (EFG) at nuclei in solids is a sensitive probe of the charge distribution. Experimental data, which previously only existed in insulators, have been available for metals with the development of nuclear measuring techniques since about 1970. An early, systematic investigation of the temperature dependence of the EFG in metals, originally based on results for Cd, but then also extended to various other systems, has suggested a proportionality to T 3/2 . However, later measurements in the structurally and electronically similar material Zn, which demonstrated much more complex behavior, were largely ignored at the time. The present experimental effort has confirmed the reliability of this unexpected behavior, which was previously unexplained

A novel role of sphingosine 1-phosphate receptor S1pr1 in mouse thrombopoiesis

Millions of platelets are produced each hour by bone marrow (BM) megakaryocytes (MKs). MKs extend transendothelial proplatelet (PP) extensions into BM sinusoids and shed new platelets into the blood. The mechanisms that control platelet generation remain incompletely understood. Using conditional mutants and intravital multiphoton microscopy, we show here that the lipid mediator sphingosine 1-phosphate (S1P) serves as a critical directional cue guiding the elongation of megakaryocytic PP extensions from the interstitium into BM sinusoids and triggering the subsequent shedding of PPs into the blood. Correspondingly, mice lacking the S1P receptor S1pr1 develop severe thrombocytopenia caused by both formation of aberrant extravascular PPs and defective intravascular PP shedding. In contrast, activation of S1pr1 signaling leads to the prompt release of new platelets into the circulating blood. Collectively, our findings uncover a novel function of the S1P-S1pr1 axis as master regulator of efficient thrombopoiesis and might raise new therapeutic options for patients with thrombocytopenia

Rethinking Land in the Anthropocene: from Separation to Integration

Nur wenn sich unser Umgang mit Land grundlegend ändert, können die Klimaschutzziele erreicht, der dramatische Verlust der biologischen Vielfalt abgewendet und das globale Ernährungssystem nachhaltig gestaltet werden. Der WBGU schlägt fünf exemplarische Mehrgewinnstrategien vor, um Konkurrenzen zwischen Nutzungsansprüchen zu überwinden. Diese sollten durch fünf Governance-Strategien vorangetrieben werden, darunter insbesondere die Setzung geeigneter Rahmenbedingungen, eine Neuorientierung der EUPolitik und die Errichtung von Gemeinschaften gleichgesinnter Staaten.Only if there is a fundamental change in the way we manage land can we reach the targets of climate-change mitigation, avert the dramatic loss of biodiversity and make the global food system sustainable. The WBGU proposes five multiple-benefit strategies illustrating ways of overcoming competition between rival claims to the use of land. These should be promoted by five governance strategies, especially by setting suitable framework conditions, reorienting EU policy and establishing alliances of like-minded states

Perceptions of Equity across Cultures and over Time: A Questionnaire-Experimental Approach

Social choice, Welfare economics, Equity, Justice, Experimental economics, Questionnaire, D63, D64, D71, I38,

Myocardial expression profiles of candidate molecules in patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia compared to those with dilated cardiomyopathy and healthy controls.

BACKGROUND Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is mainly an autosomal dominant disease characterized by fibrofatty infiltration of the right ventricle, leading to ventricular arrhythmias. Mutations in desmosomal proteins can be identified in about half of the patients. The pathogenic mechanisms leading to disease expression remain unclear. OBJECTIVE The purpose of this study was to investigate myocardial expression profiles of candidate molecules involved in the pathogenesis of ARVC/D. METHODS Myocardial messenger RNA (mRNA) expression of 62 junctional molecules, 5 cardiac ion channel molecules, 8 structural molecules, 4 apoptotic molecules, and 6 adipogenic molecules was studied. The averaged expression of candidate mRNAs was compared between ARVC/D samples (n = 10), nonfamilial dilated cardiomyopathy (DCM) samples (n = 10), and healthy control samples (n = 8). Immunohistochemistry and quantitative protein expression analysis were performed. Genetic analysis using next generation sequencing was performed in all patients with ARVC/D. RESULTS Following mRNA levels were significantly increased in patients with ARVC/D compared to those with DCM and healthy controls: phospholamban (P ≤ .001 vs DCM; P ≤ .001 vs controls), healthy tumor protein 53 apoptosis effector (P = .001 vs DCM; P ≤ .001 vs controls), and carnitine palmitoyltransferase 1β (P ≤ .001 vs DCM; P = 0.008 vs controls). Plakophillin-2 (PKP-2) mRNA was downregulated in patients with ARVC/D with PKP-2 mutations compared with patients with ARVC/D without PKP-2 mutations (P = .04). Immunohistochemistry revealed significantly increased protein expression of phospholamban, tumor protein 53 apoptosis effector, and carnitine palmitoyltransferase 1β in patients with ARVC/D and decreased PKP-2 expression in patients with ARVC/D carrying a PKP-2 mutation. CONCLUSION Changes in the expression profiles of sarcolemmal calcium channel regulation, apoptosis, and adipogenesis suggest that these molecular pathways may play a critical role in the pathogenesis of ARVC/D, independent of the underlying genetic mutations

Two-Photon Cross-Correlation Analysis of Intracellular Reactions with Variable Stoichiometry

We successfully demonstrate the effectiveness of two-photon fluorescence cross-correlation spectroscopy (TPCCS) to study the complex binding stoichiometry of calmodulin (CaM) and Ca(2+)/CaM-dependent protein kinase II (CaMKII). Practical considerations are made for developing an intracellular cross-correlation assay, including characterization of the fluorescent molecules involved, calibration procedures of the setup, and optimal measurement conditions. Potential pitfalls and artifacts are discussed, and the complex stoichiometry of the molecular system is accounted for by a new experimental and theoretical framework for TPCCS. Our tailored model accommodates up to 12 red-labeled CaMs binding to a single green-labeled dodecameric CaMKII holoenzyme and accounts for the probability distributions of bound ligand as well as the respective changes in fluorescence emission upon binding. The model was experimentally demonstrated both in solution and in living cells by analyzing the binding of Alexa 633(C2)CaM to eGFP-CaMKII under different biochemical conditions known to induce the basal, activated, and autophosphorylated forms of the enzyme. Key binding parameters, such as binding degree, concentrations of reactants, and binding affinities, were determined under varying conditions with certain assumptions. TPCCS thus offers the unique ability to test our biochemical understanding of protein dynamics in the intracellular milieu