Thermal noise limitations to force measurements with torsion pendulums: Applications to the measurement of the Casimir force and its thermal correction

A general analysis of thermal noise in torsion pendulums is presented. The specific case where the torsion angle is kept fixed by electronic feedback is analyzed. This analysis is applied to a recent experiment that employed a torsion pendulum to measure the Casimir force. The ultimate limit to the distance at which the Casimir force can be measured to high accuracy is discussed, and in particular the prospects for measuring the thermal correction are elaborated upon.Comment: one figure, five pages, to be submitted to Phys Rev

Micronutrient supplementation affects DNA methylation in male gonads with potential intergenerational epigenetic inheritance involving the embryonic development through glutamate receptor-associated genes

Background DNA methylation has an important role in intergenerational inheritance. An increasing number of studies have reported evidence of germline inheritance of DNA methylation induced by nutritional signals in mammals. Vitamins and minerals as micronutrients contribute to growth performance in vertebrates, including Atlantic salmon (Salmo salar), and also have a role in epigenetics as environmental factors that alter DNA methylation status. It is important to understand whether micronutrients in the paternal diet can influence the offspring through alterations of DNA methylation signatures in male germ cells. Results Here, we show the effect of micronutrient supplementation on DNA methylation profiles in the male gonad through a whole life cycle feeding trial of Atlantic salmon fed three graded levels of micronutrient components. Our results strongly indicate that micronutrient supplementation affects the DNA methylation status of genes associated with cell signalling, synaptic signalling, and embryonic development. In particular, it substantially affects DNA methylation status in the promoter region of a glutamate receptor gene, glutamate receptor ionotropic, NMDA 3A-like (grin3a-like), when the fish are fed both medium and high doses of micronutrients. Furthermore, two transcription factors, histone deacetylase 2 (hdac2) and a zinc finger protein, bind to the hyper-methylated site in the grin3a-like promoter. An estimated function of hdac2 together with a zinc finger indicates that grin3a-like has a potential role in intergenerational epigenetic inheritance and the regulation of embryonic development affected by paternal diet. Conclusions The present study demonstrates alterations of gene expression patterns and DNA methylation signatures in the male gonad when Atlantic salmon are fed different levels of micronutrients. Alterations of gene expression patterns are of great interest because the gonads are supposed to have limited metabolic activities compared to other organs, whereas alterations of DNA methylation signatures are of great importance in the field of nutritional epigenetics because the signatures affected by nutrition could be transferred to the next generation. We provide extensive data resources for future work in the context of potential intergenerational inheritance through the male germline

Micronutrient supplementation affects transcriptional and epigenetic regulation of lipid metabolism in a dose-dependent manner

Micronutrients (vitamins and minerals) have been less well studied compared to macronutrients (fats, proteins, and carbohydrates) although they play important roles in growth, metabolism, and maintenance of tissues. Hence, there is growing interest to understand the influence of micronutrients across various aspects in nutritional research. In the last two decades, aquaculture feeds have been shifted to containing more plant-based materials to meet the increasing demand and maintain the sustainability in the industry. In cultured fish, changing raw materials in feeds alters the requirement levels of micronutrients. A recent whole life cycle feeding trial of Atlantic salmon (Salmo salar) with graded levels of micronutrient packages has concluded that the levels of several B-vitamins and microminerals need to be increased from the current recommendation levels for optimal growth and fish welfare when plant-based diets are used. Here, we show the effect of micronutrient supplementation on transcriptional and epigenetic regulation by using liver samples from the same feeding trial. Specifically, our aim is to reveal the mechanisms of altered cell metabolism, which results in improved growth performance by micronutrient surpluses, at gene expression and DNA methylation levels. Our results strongly indicate that micronutrient supplementation suppresses gene expression in lipid metabolism in a dose-dependent manner and broadly affects DNA methylation in cell adhesion and cell signalling. In particular, it increases DNA methylation levels on the acetyl-CoA carboxylase alpha promoter in a concentration-dependent manner, which further suggests that acetyl-CoA carboxylase alpha is an upstream epigenetic regulator controlling its downstream lipid biosynthesis activities. This study demonstrates a comprehensive analysis to reveal an important role of micronutrients in lipid metabolism through epigenetic control of gene expression

Different expressions of trypsin and chymotrypsin in relation to growth in Atlantic salmon (Salmo salar L.)

The expressions of trypsin and chymotrypsin in the pyloric caeca of Atlantic salmon (Salmo salar L.) were studied in three experiments. Two internal (trypsin phenotypes, life stages) and three common external factors (starvation, feeding, temperatures) influencing growth rates were varied. Growth was stimulated by increased temperature and higher feeding rate, and it was depressed during starvation. The interaction between trypsin phenotype and start-feeding temperature affected specific activity of trypsin, but not of chymotrypsin. Trypsin specific activity and the activity ratio of trypsin to chymotrypsin (T/C ratio) increased when growth was promoted. Chymotrypsin specific activity, on the other hand, increased when there was a reduction in growth rate whereas fish with higher growth had higher chymotrypsin specific activity resulting in lower T/C ratio value. During a rapid growth phase, trypsin specific activity did not correlate with chymotrypsin specific activity. On the other hand, a relationship between specific activities of trypsin and chymotrypsin could be observed when growth declined, such as during food deprivation. Trypsin is the sensitive key protease under conditions favouring growth and genetically and environmentally affected, while chymotrypsin plays a major role when growth is limited or depressed. Trypsin specific activity and the T/C ratio value are shown to be important factors in the digestion process affecting growth rate, and could be applicable as indicators for growth studies of fish in captive cultures and in the wild, especially when food consumption rate cannot be measured

Practical guidelines for rigor and reproducibility in preclinical and clinical studies on cardioprotection

The potential for ischemic preconditioning to reduce infarct size was first recognized more than 30 years ago. Despite extension of the concept to ischemic postconditioning and remote ischemic conditioning and literally thousands of experimental studies in various species and models which identified a multitude of signaling steps, so far there is only a single and very recent study, which has unequivocally translated cardioprotection to improved clinical outcome as the primary endpoint in patients. Many potential reasons for this disappointing lack of clinical translation of cardioprotection have been proposed, including lack of rigor and reproducibility in preclinical studies, and poor design and conduct of clinical trials. There is, however, universal agreement that robust preclinical data are a mandatory prerequisite to initiate a meaningful clinical trial. In this context, it is disconcerting that the CAESAR consortium (Consortium for preclinicAl assESsment of cARdioprotective therapies) in a highly standardized multi-center approach of preclinical studies identified only ischemic preconditioning, but not nitrite or sildenafil, when given as adjunct to reperfusion, to reduce infarct size. However, ischemic preconditioning—due to its very nature—can only be used in elective interventions, and not in acute myocardial infarction. Therefore, better strategies to identify robust and reproducible strategies of cardioprotection, which can subsequently be tested in clinical trials must be developed. We refer to the recent guidelines for experimental models of myocardial ischemia and infarction, and aim to provide now practical guidelines to ensure rigor and reproducibility in preclinical and clinical studies on cardioprotection. In line with the above guideline, we define rigor as standardized state-of-the-art design, conduct and reporting of a study, which is then a prerequisite for reproducibility, i.e. replication of results by another laboratory when performing exactly the same experiment