[Start-up grants for young scientists in German medical universities : Can the clinical scientist be saved?] / Anschubfinanzierung für junge Wissenschaftler in der Universitätsmedizin in Deutschland : Ist der "clinical scientist" so zu retten?

BACKGROUND: German medical faculties currently have severe financial problems. There is the conflict between financing teaching medical students, inpatient and outpatient costs and supporting basic and applied research. METHODS: Young postdocs can apply for a grant to start research projects to establish techniques on publishing data as a basis for applying for grants from the German Research Foundation or foundations with a critical review system. Successful applicants from the years 1998-2011 were asked to answer a questionnaire. RESULTS: The annual number of applications ranged from 28 to 96 per year. Within the first period of our analysis ranging from 1998 to 2004, a mean number of 69.5 % ± 14.0 % of submitted grant applications were approved annually in comparison to an average approval of 30.9 % ± 11 % in the years 2006-2001. In total 353 projects were funded with a mean amount of money for a project of approximately 18,640 EUR. The mean amount of external grant money following the start-up period was 7.2 times the money initially spent. That is an excellent return of investment. There were no differences between applicants from the department of surgery or department of internal medicine. In the meantime, 56 % of men and 42 % of women have achieved the academic degree university lecturer (privatdozent). Furthermore, 71 % of the participants evaluated this start-up research as supportive for their postdoctoral qualification (habilitation). CONCLUSION: The program for initial investment for young postdocs by internal start-up grants is overall successful.

Diet-dependent alterations of hepatic Scd1 expression are accompanied by differences in promoter methylation.

Obesity and alterations of lipid homeostasis are hallmarks of the metabolic syndrome and largely influenced by the dietary conditions of the individual. Although heritability is considered to be a major risk factor, the almost 40 candidate genes identified by genome-wide association studies (GWAS) so far account for only 5-10% of the observed variance in BMI in human subjects. Alternatively, diet-induced changes of epigenetic gene regulation might be involved in disturbed lipid homeostasis and weight development. The aim of this study was to investigate how a high-carbohydrate diet (HCD; 70 kcal% from carbohydrates, 10 kcal% from fat) or a high-fat diet (HFD; 20 kcal% from carbohydrates, 60 kcal% from fat) affects hepatic expression of genes involved in fatty acid metabolism and if these alterations are correlated to changes in promoter methylation. Expression of stearoyl-CoA desaturase 1 (Scd1) was lower in livers from HFD-fed C57BL/6 J mice compared to HCD-fed animals and correlated inversely with the degree of DNA methylation at 2 distinct, adjacent CpG sites in the Scd1 promoter. In contrast, expression of transcription factors peroxisome proliferator activated receptor alpha and gamma (Ppara, Pparg), and sterol regulatory element binding transcription factor 1 (Srebf1) was not affected. The degree of hepatic Scd1 promoter methylation at these CpG sites correlated positively to fat mass and serum leptin levels, whereas serum ghrelin levels were inversely correlated with methylation at both CpG sites. Taken together, hepatic expression of Scd1 is differentially affected by carbohydrate- and lipid content of the diet. These differences in Scd1 expression are associated with altered promoter methylation, indicating that diets affect lipid metabolism in the liver via epigenetic mechanisms.

Exercise and cardiac performance capacity in rats with partial sympathectomy.

This study was undertaken to examine maximal oxygen uptake (VO2 max) and heart rate (HR) during exercise, in situ derived cardiac contractile capacity, and Ca2+ regulation of cardiac myofibril ATPase in normal female rats and in rats with partial sympathectomy (SYMX) induced by chronic injections of guanethidine. Also, normal control (NC) rats were studied during exercise with and without the beta 1-blocking drug atenolol. The results show that SYMX did not have any effect on Ca2+-regulated cardiac myofibril ATPase activity. Also similar cardiac functional capacity, as reflected in left ventricular pressure development and +dP/dtmax, was observed for both groups when the heart was stressed by either exogenous norepinephrine or maximal afterload (aortic constriction). Exercise VO2 max was reduced by 15% (P less than 0.05) in the SYMX compared to the NC group. Although this reduction in VO2 max corresponded to a parallel reduction in HRmax, NC rats with cardiac beta-blockade attained normal VO2 max even though their exercise HRmax was below the SYMX group. These findings suggest that normal rats with attenuated HR and contractility have a better capacity to acutely maintain VO2 max during exercise than rats with chemical sympathectomy.

Exercise capacity and cardiac function of rats with drug-induced cardiac enlargement.

A study was undertaken to determine if sustained administration of isoproterenol (ISO) alters biochemical and functional properties of hearts and the submaximal and maximal exercise capacity of rodents. Compared with sham-treated controls of the same age, sex, and body weight, 4 wk of ISO (0.2--0.4 mg/kg sc) produced an approximate 30% increase in combined ventricle wet weight (P less than 0.001). Respiratory capacity of homogenates, total muscle protein concentration, and actomyosin and myofibril ATPase of heart muscle of the ISO-treated group were the same as in the control group. Various cardiac function parameters in situ, obtained under control conditions and in response to tyramine-induced norepinephrine release, were similar for the two groups. ISO-treated rats had slightly greater endurance for running submaximally on a treadmill than the control rats (P less than 0.10), but their maximal capacity to utilize oxygen (VO2max) was not different from controls. These findings suggest that rodent hearts moderately enlarged by relatively low doses of isoproterenol possess normal metabolic and functional capacity. However, this cardiac enlargement had no apparent effect on maximal exercise performance of the whole animal.

Effects of physical training and thyroxine on rodent cardiac functional and biochemical properties.

The effects of 8 weeks of interval running and of 14 days of thyroxine treatment were studied on selected cardiac functional and biochemical parameters of contraction in both female guinea pigs and rats. Relative to their respective sendentary-control groups, both trained groups demonstrated typical exercise adaptations of resting bradycardia and of increases in skeletal muscle oxidative enzymes and relative heart mass (P less than 0.05). Myosin ATPase, Ca2+ regulated myofibril ATPase, and + dP/dt max were at least two-fold higher in rats compared to guinea pigs (P less than 0.001). Physical training did not augment any of these parameters in either species under the experimental conditions studied. However, biochemical and functional indices of intrinsic cardiac contractility in guinea pigs were increased by injections of thyroxine; whereas, the same treatment regimen was without effect on the rats. These findings suggest that chronic running does not alter the intrinsic cardiac contractility state in either species. Also, exercise doesn't change the thyroid state of the guinea pig to a level sufficient to affect cardiac function.

Exercise capacity and cardiac function in trained and untrained thyroid-deficient rats.

This study was undertaken to ascertain the extent that impairments in a) the oxidative capacity of skeletal muscle, b) cardiac functional and biochemical correlates of contractile capacity, and c) maximal oxygen consumption (VO2 max) can be reversed in thyroid-deficient (TD) female rats subjected to an 8-wk physical training (running) program. Compared with a normal control (NC) group, thyroid deficiency caused reductions in the following: VO2 max (-32%), skeletal muscle homogenate respiratory capacity (-50%), cardiac myosin ATPase (-58%), and in situ-derived ventricular dP/dt max (-58%) (P < 0.001). The training program restored to within normal limits skeletal muscle oxidative capacity and VO2 max, but it did not improve cardiac myosin ATPase, Ca2+ regulation of myofibril ATPase, and dP/dt max relative to TD sedentary rats. However, the heart weight-to-body weight ratio was highest among the three groups in the TD trained group. These findings suggest that maximal oxygen utilization capacity of TD rats can be normalized by physical training, even though intrinsic contractile capacity of the heart could not.