Down-regulation of calpain 9 is linked to hypertensive heart and kidney disease.

Calpains are a family of 14 intracellular calcium-dependent proteases, which have been implicated in cardiovascular diseases. We aimed to analyze specifically the expressional regulation of the different calpain isoforms in hypertensive target organ damage. Using real-time PCR, we found calpain 6 and 9 down-regulated by more than 50% and the endogenous calpain inhibitor calpastatin up-regulated by 225%, respectively, in the hearts of Dahl salt-sensitive rats on a high salt (4% NaCl) compared to normal salt diet. On the protein level, calpain 9 but not calpastatin was regulated in the hypertensive target organs heart and kidney. Moreover, the myocardial expression of calpain 9 protein was inversely linked to left ventricular mass (r= -0.93, p<0.01), and renal expression of calpain 9 protein correlated inversely with albuminuria (r= -0.82, p<0.05). In the aorta, there was no regulation of calpain 9 on the protein level. We conclude that differential regulation of calpain 9 may play a role in hypertensive target organ damage.     

RNA stem–loop enhanced expression of previously non-expressible genes

The key step in bacterial translation is formation of the pre-initiation complex. This requires initial contacts between mRNA, fMet-tRNA and the 30S subunit of the ribosome, steps that limit the initiation of translation. Here we report a method for improving translational initiation, which allows expression of several previously non-expressible genes. This method has potential applications in heterologous protein synthesis and high-throughput expression systems. We introduced a synthetic RNA stem–loop (stem length, 7 bp; ΔG₀ = –9.9 kcal/mol) in front of various gene sequences. In each case, the stem–loop was inserted 15 nt downstream from the start codon. Insertion of the stem–loop allowed in vitro expression of five previously non-expressible genes and enhanced the expression of all other genes investigated. Analysis of the RNA structure proved that the stem–loop was formed in vitro, and demonstrated that stabilization of the ribosome binding site is due to stem–loop introduction. By theoretical RNA structure analysis we showed that the inserted RNA stem–loop suppresses long-range interactions between the translation initiation domain and gene-specific mRNA sequences. Thus the inserted RNA stem–loop supports the formation of a separate translational initiation domain, which is more accessible to ribosome binding.     

Festkolloquium and Symposium "Präadaptation in der Evolution von Pflanze and Tier"

Zum Gelingen dieses Symposiums haben viele entscheidend beigetragen. Tatkräftige Hilfe bei der Organisation habe ich vielen Mitgliedern des Institutes zu verdanken. Stellvertretend für alle sollen nur Frau Dr. C. Gack and meine technische Assistentin, Frau Christine Gutmann , besonders crwähnt werden. Großzügige finanzielle Unterstützung erhielten wir von der Fa. Goedecke (Freiburg) und dem Herder-Verlag (Freiburg).     

Feinstruktur des ventralen mandibulären Muskelrezeptors bei Liposcelis bostrichophilus (Insecta,Psocoptera)

Zusammenfassung Der ventrale Mandibel-Muskelrezeptor wird im Kopf von Liposcelis bostrichophilus (Psocoptera) nachgewiesen. Er zieht, median der Mandibel-Gelenkachse gelegen, vom vorderen Tentorium-Arm zur hinteren Mandibel-Basis und wird also während der Abduktion der Mandibel gedehnt. Der Rezeptor besteht aus einer motorisch und sensorisch innervierten Muskelfaser und 10 bipolaren, multiterminalen Sinneszellen. Einige der Sinneszellen senden ihre Dendriten ins Innere des Rezeptor-Muskels, wo sie sich verzweigen und jeweils an den Z-Scheiben enden. Die übrigen Sinneszellen bilden mit ihren Dendriten ein Bündel, das der Oberfläche des Rezeptor-Muskels anliegt. Nur die ins Innere ziehenden Dendriten weisen in ihren Endigungen Tubularkörper-ähnliche Strukturen auf. Sowohl die Sinneszellen als auch der Rezeptor-Muskel werden von Hüllzell-Wicklungen eng umhüllt.

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Summary The ventral mandibular muscle receptor in the head of Liposcelis bostrichophilus (Psocoptera) is described. It is located median to the mandibular hinge axis, extending from the front tentorium to the dorsal mandibular basis, and is stretched according to the movements of the mandible. The receptor consists of a sensorily and a motor-stimulated muscle fibre and ten bipolar multiterminal neurons. Some of the neurons send their dendrites into the inner part of the receptor muscle, where they branch and terminate at the level of the Z discs. The other neurons build a dendritic bunch, which runs parallel to the muscle fibre surface. Only the dendrites located close to the Z discs show tubular-body-like structures in their terminal ends. The multiterminal neurons and the receptor muscle are covered with glial cells.

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Mit Unterstützung durch die Deutsche Forschungsgemeinschaft     

Decreased cerebral Irp‐1B limits impact of social isolation in wild type and Alzheimer's disease modeled in Drosophila melanogaster

Environmental factors, such as housing conditions and cognitively stimulating activities, have been shown to affect behavioral phenotypes and to modulate neurodegenerative conditions such as Alzheimer's disease (AD). AD is a progressive neurodegenerative disorder affecting cognitive functions. Epidemiological evidence and experimental studies using rodent models have indicated that social interaction reduces development and progression of disease. Drosophila models of Aβ42‐associated AD lead to AD‐like phenotypes, such as long‐term memory impairment, locomotor and survival deficits, while effects of environmental conditions on AD‐associated phenotypes have not been assessed in the fly. Here, we show that single housing reduced survival and motor performance of Aβ42 expressing and control flies. Gene expression analyses of Aβ42 expressing and control flies that had been exposed to different housing conditions showed upregulation of Iron regulatory protein 1B (Irp‐1B) in fly brains following single housing. Downregulating Irp‐1B in neurons of single‐housed Aβ42 expressing and control flies rescued both survival and motor performance deficits. Thus, we provide novel evidence that increased cerebral expression of Irp‐1B may underlie worsened behavioral outcome in socially deprived flies and can additionally modulate AD‐like phenotypes.