Charakterisierung der molekularen Rolle von BEACH-Proteinen und PKC-Isotypen im Vesikelverkehr

Der autosomal- rezessive Gendefekt des Chediak-Higashi Syndroms in Lyst (lysosmal traffic regulator) zeichnet sich durch eine gestörte zytotoxische Aktivität von T- und NK-Zellen aus. Diese resultiert aus einer fehlgeregelten Exozytose. Der zelluläre Phänotyp ist durch eine abnormale Vergrößerung von Lysosomen, sekretorischen Lysosomen, Melanosomen und sekretorischen Granula charakterisiert. Die Proteine Lyst und FAN (factor associated with neutral sphingomyelinase) gehören zu der Familie der BEACH-Proteine. Als spezifischer Interaktionspartner von FAN war das Protein RACK1 identifiziert worden, welches aktivierte konventionelle PKCs (cPKC) an die Zellmembran rekrutiert. Eine gestörte Membrantranslokation und Membran-assoziierte Aktivität der cPKCs war als ursächlich für die Bildung von Riesenlysosomen und die Defekte der NK-Zellen beschrieben worden. In dieser Arbeit wurde der molekulare Mechanismus untersucht, wie die beiden BEACH-Proteine, Lyst und FAN und das WD-repeat Protein RACK1, sowie Isotypen der PKC zum lysosomalen Vesikeltransport und zur Aktivierung von NK-Zellen beitragen

Language and Linguistics in a Complex World Data, Interdisciplinarity, Transfer, and the Next Generation. ICAME41 Extended Book of Abstracts

This is a collection of papers, work-in-progress reports, and other contributions that were part of the ICAME41 digital conference

Language and Linguistics in a Complex World Data, Interdisciplinarity, Transfer, and the Next Generation. ICAME41 Extended Book of Abstracts

This is a collection of papers, work-in-progress reports, and other contributions that were part of the ICAME41 digital conference

Circulating vaspin is unrelated to insulin sensitivity in a cohort of nondiabetic humans

Objective: To study the association of vaspin with glucose metabolism. Design: Cross-sectional and intervention study. Subjects and methods: The association of serum vaspin with metabolic and anthropometric characteristics was investigated in 108 volunteers. Euglycemic–hyperinsulinemic clamps (EHC) were performed in 83 of the participants. Changes of circulating vaspin levels were additionally studied in a crossover study using 300 min EHC with lipid versus saline infusion (n=10). Results: Neither glucose tolerance status nor insulin sensitivity, both as measured using EHCs and using homeostasis model assessment for insulin resistance (HOMA-IR), was significantly associated with serum vaspin in the cross-sectional study. Furthermore, there was no effect of short-term lipid-induced insulin resistance due to a 300 min intravenous lipid challenge on circulating vaspin. However, circulating vaspin levels were significantly elevated in women using oral contraceptives (OC), both compared to women without OC intake (1.17±0.26 vs 0.52±0.09 ng/ml, P=0.02) and males (1.17±0.26 vs 0.29±0.04 ng/ml, P=0.01). After exclusion of OC using females and stratification according to body mass index (BMI), a significant sexual dimorphism in subjects with a BMI <25 kg/m2 was observed (males 0.21±0.04 ng/ml versus females 0.70±0.16 ng/ml, P=0.009). Conclusion: Our results support the existence of a sexual dimorphism regarding circulating vaspin. The lack of an association of serum vaspin with HOMA-IR and M value indicates, however, no major role for vaspin concerning insulin sensitivity in nondiabetic humans

Microalbuminuria is a major determinant of elevated plasma retinol-binding protein 4 in type 2 diabetic patients

Plasma retinol-binding protein 4 (RBP4) may be a new adipokine linked to obesity-induced insulin resistance and type 2 diabetes. The impact of diabetic nephropathy on plasma RBP4 levels, however, is not known. We tested the hypothesis that microalbuminuria is associated with elevated plasma concentrations of RBP4 in type 2 diabetic subjects. Retinol, its binding protein and transthyretin (TTR) were measured in the plasma and urine of 62 type 2 diabetic subjects, 26 of whom had microalbuminuria. The results were compared to 35 healthy control subjects. Despite no differences in plasma retinol, concentrations of the RBP4 were significantly elevated in plasma of diabetic patients and significantly higher in those with microalbuminuria. The higher plasma levels of the binding protein in subjects with microalbuminuria were accompanied by both significantly elevated plasma TTR and increased urinary levels of RBP4. There were no correlations of plasma-binding protein levels and parameters of insulin resistance. Our study suggests that plasma RBP4 levels in type 2 diabetic patients are affected by incipient nephropathy. Therefore, further studies evaluating RBP4 as a regulator of systemic insulin resistance and type 2 diabetes will need to take renal function into consideration

Prolonged treatment with vitamin D in postmenopausal women with primary hyperparathyroidism

Introduction/background: Vitamin D deficiency further increases circulating parathyroid hormone (PTH) levels in patients with primary hyperparathyroidism (pHPT), with potential detrimental effects on bone mass. Methods: This was an observational clinical study in consecutive conservatively treated postmenopausal women (n=40) with pHPT and coexistent 25-hydroxyvitamin D deficiency (25OHD ≤50 nmol/l (≤20 ng/ml)). Patients who showed an increase in serum 25OHD above the threshold of vitamin D deficiency (>50 nmol/l; n=28) using treatment with various commonly prescribed vitamin D preparations were, for the purposes of statistical analyses, allocated to the treatment group. Patients who were retrospectively identified as having received no treatment with vitamin D and/or remained vitamin D deficient were considered as non-responders/controls (n=12). Adjusted calcium (adjCa), PTH and 25OHD concentrations were monitored in all subjects up to 54 months (mean observation period of 18±2 months). Results: Prolonged increased vitamin D intake, regardless of the source (serum 25OHD, increase from 32.2±1.7 nmol/l at baseline to 136.4±11.6 nmol/l, P0.73). In contrast, serum PTH remained unchanged (15.8±2.6 vs 16.3±1.9 pmol/l, P=0.64) in patients who remained vitamin D deficient, with a significant difference between groups in changes of PTH (P=0.0003). Intrapartial correlation analyses showed an independent negative correlation of changes in 25OHD with PTH levels (r ic=−0.41, P=0.014). Conclusions: Prolonged treatment with vitamin D in various commonly prescribed preparations appeared to be safe and significantly reduced PTH levels by 21%

Lack of Association between the Tagging SNP A+930→G of SOCS3 and Type 2 Diabetes Mellitus: Meta-Analysis of Four Independent Study Populations

BACKGROUND: The suppressor of cytokine signalling 3 (SOCS3) provides a link between cytokine action and their negative consequences on insulin signalling. Thus SOCS3 is a potential candidate gene for type 2 diabetes (T2DM). METHODOLOGY/PRINCIPAL FINDINGS: Based on HapMap we identified the polymorphism A+930-->G (rs4969168) as a haplotype tagging SNP (htSNP) sufficiently covering the genetic variation of the whole gene. We therefore examined the association between rs4969168 within SOCS3 and T2DM in three independent study populations; one prospective case-cohort study and two cross-sectional study populations. Due to the low frequency of individuals being homozygous for the polymorphism a dominant model of inheritance was assumed. The case-cohort study with 2,957 individuals (764 of them with incident T2DM) showed no effect of the polymorphism on diabetes risk (hazard ratio (95%CI): 0.86 (0.66-1.13); p = 0.3). Within the MeSyBePo-study population 325 subjects had T2DM from a total of 1,897 individuals, while the second cross-sectional cohort included 851 cases of T2DM within a total of 1653 subjects. According to the results in the prospective study, no association with T2DM was found (odds ratio (95%CI): 0.78 (0.54-1.12) for MesyBepo and 1.13 (0.90-1.42) for the Leipzig study population). There was also no association with metabolic subtraits such as insulin sensitivity (p = 0.7), insulin secretion (p = 0.8) or the hyperbolic relation of both, the disposition index (p = 0.7). In addition, no evidence for interaction with BMI or sex was found. We subsequently performed a meta-analysis, additionally including the publicly available data from the T2DM-subcohort of the WTCCC (n = 4,855). The overall odds ratio within that meta-analysis was 0.96 (0.88-1.06). CONCLUSIONS/SIGNIFICANCE: There is no strong effect of the common genetic variation within the SOCS3 gene on the development of T2DM

Parameters of Morphosyntactic Variation in Bantu

Bantu languages are fairly uniform in terms of broad typological parameters. However, they have been noted to display a high degree of more fine-grained morphosyntactic micro-variation. In this paper we develop a systematic approach to the study of morphosyntactic variation in Bantu by developing nineteen parameters which serve as the basis for cross-linguistic comparison and which we use for comparing ten southeastern Bantu languages. We address conceptual issues involved in studying morphosyntax along parametric lines and show how the data we have can be used for the quantitative study of language comparison. Although the work reported is a case study in need of expansion, we will show that it nevertheless produces relevant results. © The authors 2007