High β-1,4-Galactosyltransferase-I expression in peripheral T-lymphocytes is associated with a low risk of relapse in germ-cell cancer patients receiving high-dose chemotherapy with autologous stem cell reinfusion.

Survival of patients with germ-cell cancer (GCC) and primary progression or relapse after cisplatin-based first-line chemotherapy is highly heterogeneous, ranging from close to zero to more than 70%. We investigated β-1,4-Galactosyltransferase-I () expression levels in peripheral lymphocytes in a cohort of 46 testicular cancer patients. enhances immune cell crosstalk via glycosylation of surface molecules. A high expression level of in T-lymphocytes, but not in monocytes, was associated with a lower risk of relapse with a hazard ratio (HR) of 0.66 (95% confidence interval (CI) of HR: 0.45-0.97; = 0.02) upon multivariate Cox regression analysis. Correspondingly, interleukin 10 (IL10), a cytokine released by cytotoxic T-cells, was likewise significantly elevated in T-lymphocytes of non-relapse GCC patients (HR: 0.3; 95% CI of HR: 0.14-0.65; = 0.002). Our data indicate that glycosylation and activation of T-lymphocytes may play a pivotal role in disease control in GCC patients with primary progressive or relapsed disease

Debt sustainability, public investment, and natural resources in developing countries: The DIGNAR model

Policymakers in resource-rich developing countries often face complicated fiscal choices to manage natural resource revenues. While investing resource revenues in public capital may promote economic growth, spending without saving or borrowing against future revenues can expose the economy to debt sustainability risks. This paper presents the Debt, Investment, Growth, and Natural Resources (DIGNAR) model for analyzing the macroeconomic and debt sustainability effects of scaling up public investment in resource-rich developing countries. It captures pervasive problems of these countries that may be aggravated during scaling-ups, including investment inefficiency and limited absorptive capacity. It also allows for flexible fiscal specifications: investment can be jointly financed by resource revenues and debt; a resource fund may be used as a buffer; and distorting fiscal adjustments are subject to feasibility constraints. The application to an average low-income country shows that, when fiscal adjustment is implementable, a delinked public investment approach combined with the resource fund - such that government spending is a-cyclical with respect to resource revenues - can reduce macroeconomic instability relative to a spend-as-you-go approach. However, even with the fund, ambitious frontloading public investment plans combined with more borrowing can induce debt sustainability risks, especially with declining investment efficiency or when future resource revenues turn out to be lower than expected

Struktur und Funktion des tarsalen Haftsystems der Madagaskar-Fauchschabe Grompadorhina portentosa (Blattodea)

The tarsal attachment system of the Madagascar Hissing cockroach Grompadorhinaportentosa (Blattodea, Blaberidae) was analysed with respect to the ultrastructure of its smooth adhesive pads (arolium, euplantula), the chemical composition of its adhesive secretion, and its adhesion and friction performance on surfaces of different roughnesses. Local measurements performed with a nanotribometer showed that, in the non-manipulated euplantulae, friction was clearly increased in the push direction, whereas the arolium of the fore tarsus showed higher friction in the pull direction. The surface of the euplantulae shows an imbricate appearance, whereby the ledges face distally, which might contribute to the observed frictional anisotropyin push direction. The glandular epithelium of both the arolium and the euplantulum releases adhesive secretions into a subcuticular void from which it has to permeate the thick cuticle of the adhesive pads. In the euplantulae, adhesion was one to two orders of magnitude lower than friction. Whereas adhesive tenacity was slightly decreased with depleted secretion, it was considerably increased after artificial application of oily liquids. Our chemical analyses of the secretion suggest a semisolid consistency of the adhesive secretion, which probably facilitates the detachment of the tarsus during locomotion. On nanorough surfaces, the insect appears to benefit from employing emulsions instead of pure oils to avoid excessive friction. Based on our chemical analyses, 12 synthetic heterogeneous adhesive emulsions were prepared. By varying their chemical composition, they could be adjusted to have diverse consistencies. Some of them were able to mimic certain rheological and tribological properties of natural tarsal insect adhesives

A benzodiazepine activator locks K v 7.1 channels open by electro-mechanical uncoupling

Loss-of-function mutations in

Co-expression of YAP and TAZ associates with chromosomal instability in human cholangiocarcinoma

Abstract Background Activation of the oncogene yes-associated protein (YAP) is frequently detected in intrahepatic cholangiocarcinoma (iCCA); however, the expression pattern and the functional impact of its paralogue WW domain-containing transcription regulator 1 (WWTR1; synonym: TAZ) are not well described in different CCA subtypes. Methods Immunohistochemical analysis of YAP and TAZ in iCCA and extrahepatic CCA (eCCA) cohorts was performed. YAP/TAZ shuttling and their functional impact on CCA cell lines were investigated. Target genes expression after combined YAP/TAZ inhibition was analyzed. Results Immunohistochemical analysis of iCCA and eCCA revealed YAP or TAZ positivity in up to 49.2%; however, oncogene co-expression was less frequent (up to 23%). In contrast, both proteins were jointly detectable in most CCA cell lines and showed nuclear/cytoplasmic shuttling in a cell density-dependent manner. Next to the pro-proliferative function of YAP/TAZ, both transcriptional co-activators cooperated in the regulation of a gene signature that indicated the presence of chromosomal instability (CIN). A correlation between YAP and the CIN marker phospho-H2A histone family member X (pH2AX) was particularly observed in tissues from iCCA and distal CCA (dCCA). The presence of the CIN genes in about 25% of iCCA was statistically associated with worse prognosis. Conclusions YAP and TAZ activation is not uncoupled from cell density in CCA cells and both factors cooperatively contribute to proliferation and expression of CIN-associated genes. The corresponding group of CCA patients is characterized by CIN and may benefit from YAP/TAZ-directed therapies