Lung cancer is one of the leading causes of death worldwide. Among the disease, differentiation between small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) is of huge therapeutic relevance. Novel chemo-therapeutic approaches have been developed for NSCLC, which is known as a largely chemo-resistant tumor group. Clinical studies…
Inherited metabolic disorders mucolipidose (ML) type II/III result from deficiency of a specific transferase, responsible for the formation of mannose-6-phosphat (Man6P)-modified glycoproteins. Without Man6P, the glycoproteins are not destined for lysosomes and escape outside the cells. The deficiency may be overcome by enzyme-replacement therapy…
DNA transposons represent natural gene delivery vehicles that integrate into the host genome via a cut-and-paste mechanism. Their stable insertion thereby provides the basis for long-term expression of transgenes in cells and organisms. Common viral gene transfer vectors give rise to safety concerns and are involved with considerable costs and…
B cells are well-known for their roles in humoral immunity. Recently, a novel role for B cells as potent immunosuppressive cells in vivo has been described. In order to make clinical use of these suppressive features of B cells to suppress immune reactions against auto antigens, therapeutic proteins, gene therapy products and grafts,…
Challenge The Kidney is a vital organ with many multiple functions: besides keeping the homeostasis it is responsible for the generation of essential hormones and vitamins, for some metabolic processes and most importantly for excretion of toxic substances. Unfortunately, following filtration many substances comprised in pharmaceutical compounds…
Challenge Kinins are important mediators in cardiovascular homeostasis, inflammation, and nociception. After ischemic injury, enhanced kinin generation may contribute in processes responsible for tissue healing. By exploiting the gene knockout strategy, our scientists demonstrated that the endogenous B1 signalling is indeed essential for…
Challenge The renin angiotensin system (RAS) is the most important regulator of blood pressure. RAS exerts its regulatory function by eliciting several molecular mechanisms leading to an increase in blood pressure, like vasoconstriction, or sodium retention in the kidney, and is furthermore involved in growth processes. In cardiovascular research,…
Challenge Serotonin [5-hydroxytryptamine (5-HT)], a neurotransmitter in the central nervous system, is known to modulate many behavioural functions such as mood. However, in the periphery it functions as a hormone and regulates vascular tone, gut motility, primary hemostasis and cell-mediated immune responses. Tryptophan hydroxylase (TPH) is the…
The Challenge Blood pressure and circadian rhythmicity of cardiovascular parameters underly many different molecular regulation mechanisms. One system playing a crucial role in the regulation of these mechanisms besides the well known renin-angiotensin system (RAS) is the kallikrein-kinin system (KKS). While RAS exerts its regulatory function in…
Challenge The renin-angiotensin system (RAS) is the most important regulator of blood pressure. Its multiple biological functions include increase in blood pressure, sodium retention in the kidney and regulation of the sympathetic tonus. Angiotensinogen (AOGEN) is mainly expressed by the liver and secreted into the circulation, but also local…
Challenge Hypertension is a widely spread disease responsible for up to 50% of all deaths in the industrialised countries. The most important regulator of blood pressure is the renin angiotensin system (RAS). Besides its function to regulate the blood pressure, it is involved in salt retention in kidney, stimulation of aldosterone synthesis in the…
Challenge Activation of Wnt signaling through ß-catenin/TCF complexes is a key event in the development of various tumors, in particular colorectal and liver tumors. Within the Wnt signaling pathway Conductin induces downregulation of ß-catenin when transiently overexpressed in colon carcinoma cells and is upregulated in colorectal adenomas and…
Challenge Genetically modified animals are essential research tools in modern molecular biology. The chemokine receptor 7 (CCR7) is described as an important regulator of lymphocyte trafficking to and within secondary lymphoid organs, and plays a significant role in organization of the primary immune response, like e.g. in the development of…
Challenge Touch and mechanical pain are first detected at our largest sensory surface, the skin. The cell bodies of sensory neurons that detect such stimuli are located in the dorsal root ganglia, and subtypes of these neurons are specialized to detect specific modalities of mechanical stimuli. Molecular mechanisms involving membrane-associated…
Challenge Kinins are important peptide mediators of a diverse range of physiological and pathological functions of the cardiovascular system and exert their effects by selective activation of two receptors termed B1 and B2. The B1 receptor is activated by metabolites, the synthesis of which are increased during inflammation. The initiation of an…
Challenge Poly(ADP-ribose) polymerase-1 (PARP-1) catalyzes the modification of nuclear enzymes by (ADP-ribosyl)ation. PARP-1 function was first associated with DNA single-stranded break repair, especially in tumor cells, and maintenance of genomic integrity. Accumulating evidence suggests that PARP-1 also plays important roles in other disease…
Challenge The zebrafish is a relevant model system for studying vertebrate development and organogenesis due to its short life cycle and the easiness of isolating large numbers of mutants. For the simplicity of its pronephros it suits especially for the analysis of kidney development. The Wilms tumour protein WT1 is an essential factor for kidney…
Homozygous mice are IL10-deficient and develop spontaneous colitic lesions in the cecum and large intestine as early as 6-8 weeks of age. The severity and age of onset of colitis varies with the donor type and location of the cytokine deficiency colitis susceptibility 1 (Cdcs1) interval. Generally, the C57BL/6 region encompassed byD3Mit348 through…
Mice homozygous for the Il10tm1Cgn targeted mutation are viable and fertile when housed under SPF conditions. Under conventional housing conditions homozygous mutant mice are small in size, anemic, and have chronic enterocolitis. It should be noted that the phenotype of cecocolitis in this strain requires an interaction with an as yet undefined…
Mice homozygous for the Il2rgtm1Cgn targeted mutation are viable and fertile. Mutant mice have hypoplastic thymuses with a 10-fold reduction in the absolute number of lymphocytes. They have a limited number of mature splenic B and T cells, lack NK cells and Peyer's patches, and development of gut-associated intraepithelial lymphocytes is…
