Cardiac glycosides like ouabain are used in the therapy of heart failure and atrial fibrillation. They exert a positive inotropic effect on cardiomyocytes by inhibiting the plasma membrane sodium pump (Na,K-ATPase), decreasing the Ca-extrusion by the sarcolemmal cardiac sodium/calcium exchanger (NCX) and increasing the intracellular Ca-concentration and Ca-release during subsequent contraction cycles.The longer term effects of ouabain treatment on the expression of proteins important for Ca- and Na-homeostasis are not well known and were investigated in this study. Isolated adult rat cardiomyocytes were cultured in the presence or absence of ouabain (30 microM). In these cells, the expression of the Na,K-ATPase, Na,Ca-exchanger (NCX), the sarcoplasmic reticulum Ca-ATPase (SERCA 2a) and phospholamban (PLB) were studied by Western blot. In addition, the contractile function of these cells was studied after electrical stimulation. After 2 days of ouabain treatment immunoreactivity of the NCX was increased significantly relative to control which was set 1 (1.78 +/- 0.16 vs. 1 +/- 0.13; n = 8; P = 0.003) and at day 4 (1.96 +/- 0.35 vs. 1 +/- 0.20; n = 6; P = 0.02). All other proteins (SERCA 2a, PLB and Na,K-ATPase a1 and b1) remained unchanged (n>/= 4). Ouabain treatment increased the fractional shortening of isolated cardiomyocytes at day 0 (1 Hz: 9.64 +/- 0.73 %, n = 24, vs. 7.18 +/- 0.60 %; n = 21; P = 0.01), whereas at day 2 the contractility was unchanged (1 Hz: 7.23 +/- 1.08 %, n = 9 vs. 7.70 +/- 0.63 %; n = 10, P = 0.71). The inhibition of SERCA 2a (10 microM cyclopiazonic acid (CPA)) decreased contractility in both the ouabain treated group and in controls, at day 0 and at day 2. These results show that chronic ouabain treatment increases the protein expression of the NCX. The positive inotropic effect of ouabain can no longer be observed after a chronic treatment for 2 days. Thus, both protein expression and contractile function of the cells are specifically altered by longer term cardiac glycoside exposure. Whether such regulation can be found in human cardiomyocytes and the resulting consequences in the clinical setting remain to be determined.

While global patterns of human genetic diversity are increasingly well characterized, the diversity of human languages remains less systematically described. Here, we outline the Grambank database. With over 400,000 data points and 2400 languages, Grambank is the largest comparative grammatical database available. The comprehensiveness of Grambank allows us to quantify the relative effects of genealogical inheritance and geographic proximity on the structural diversity of the world’s languages, evaluate constraints on linguistic diversity, and identify the world’s most unusual languages. An analysis of the consequences of language loss reveals that the reduction in diversity will be strikingly uneven across the major linguistic regions of the world. Without sustained efforts to document and revitalize endangered languages, our linguistic window into human history, cognition, and culture will be seriously fragmented.

While global patterns of human genetic diversity are increasingly well characterized, the diversity of human languages remains less systematically described. Here we outline the Grambank database. With over 400,000 data points and 2,400 languages, Grambank is the largest comparative grammatical database available. The comprehensiveness of Grambank allows us to quantify the relative effects of genealogical inheritance and geographic proximity on the structural diversity of the world's languages, evaluate constraints on linguistic diversity, and identify the world's most unusual languages. An analysis of the consequences of language loss reveals that the reduction in diversity will be strikingly uneven across the major linguistic regions of the world. Without sustained efforts to document and revitalize endangered languages, our linguistic window into human history, cognition and culture will be seriously fragmented.

Abstract. Estimations were carried out of [3H]thymidine incorporation during culture of isolated porcine thyroid follicles in the presence of standard TSH or epidermal growth factor (EGF) both alone and together with anti-TSH or anti-EGF serum, and of immunoglobulins fractionated from the sera of patients from our endemic goitre area with iodine deficiency. A significant stimulation of thymidine incorporation was exerted by TSH when thyroglobulin was present in the culture medium, and also by EGF. TSH stimulation was abolished by anti-TSH serum, in contrast to the effect of EGF. Anti-EGF serum, on the other hand, blocked the effect of EGF, but not that of TSH. The sera of 20 out of 72 patients (27%) with euthyroid goitre (not operated on) and of ten out of 26 patients (38%) with recurrent euthyroid goitre contained immunoglobulins stimulating thyroid growth (TGI). There was no correlation of TGI with other thyroid antibodies. TGI have to be regarded as a pathogenetic factor of euthyroid goitre also in patients from an endemic region especially in recurrent cases.