Reduced caloric intake and periodic fasting independently contribute to metabolic effects of caloric restriction

Caloric restriction (CR) has positive effects on health and longevity. CR in mammals implements time‐restricted (TR) feeding, a short period of feeding followed by prolonged fasting. Periodic fasting, in the form of TR or mealtime, improves metabolism without reduction in caloric intake. In order to understand the relative contribution of reduced food intake and periodic fasting to the health benefits of CR, we compared physiological and metabolic changes induced by CR and TR (without reduced food intake) in mice. CR significantly reduced blood glucose and insulin around the clock, improved glucose tolerance, and increased insulin sensitivity (IS). TR reduced blood insulin and increased insulin sensitivity, but in contrast to CR, TR did not improve glucose homeostasis. Liver expression of circadian clock genes was affected by both diets while the mRNA expression of glucose metabolism genes was significantly induced by CR, and not by TR, which is in agreement with the minor effect of TR on glucose metabolism. Thus, periodic fasting contributes to some metabolic benefits of CR, but TR is metabolically different from CR. This difference might contribute to differential effects of CR and TR on longevity.     

Modulation of haloperidol induced electrophysiological alterations on cardiac action potential by various risk factors and gender difference

Haloperidol (HPL), well known antipsychotic drug can induce a marked QT prolongation and polymorphic arrhythmias. In this study we evaluated the influence of various induced risk factors such as electrolyte imbalance (hypokalemia and hypomagnesemia), gender difference, low pacing frequency, ischemia reperfusion insult on electrophysiological effect by haloperidol on electrically driven action potentials recorded from guinea pig papillary muscle. The doses of HPL ranging from 1 to 16 μM were used in this investigation. Action potentials (APs) were elicited electrically and recorded by classical microelectrode technique. HPL caused dose dependent prolongation of APD₉₀ the final stage of repolarization, increased triangulation, and led into dispersion of action potential, conduction delay and conduction block. Magnitude of the effect of haloperidol was amplified significantly by most of the risk factors. Among the various risk factors, electrolyte imbalance (hypokalemia, hypomagnesemia) caused more amplification of HPL effect. Most of the risk factors amplified prolongation of APD₉₀ by HPL. This effect is mainly due to the influence of these electrolytes and sex hormone on various ion channels involved in the repolarization phase of cardiac AP. This is the first report which provides an experimental evidence of amplification of electrophysiological effects of HPL in the presence of various risk factors.     

Hepatocytes of Wistar and Sprague Dawley rats differ significantly in their central metabolism

Wistar and Sprague‐Dawley (SD) rats are most commonly used experimental rats. They have similar genetic background and are therefore, not discriminated in practical research. In this study, we compared metabolic profiles of Wistar and SD rat hepatocytes from middle (6 months) and old (23 months) age groups. Principle component analysis (PCA) on the specific uptake and production rates of amino acids, glucose, lactate and urea indicated clear differences between Wistar and SD rat hepatocytes. SD rat hepatocytes showed higher uptake rates of various essential and non‐essential amino acids, particularly in early culture phases (0‐12 h) compared to later phases (12‐24 h). SD hepatocytes seem to be more sensitive to isolation procedure and in vitro culture requiring more amino acids for cellular maintenance and repair. Major differences between Wistar and SD rat hepatocytes were observed for glucose and branched chain amino acid metabolism. We conclude that the observed differences in the central carbon metabolism of isolated hepatocytes from these two rats should be considered when using one or the other rat type in studies on metabolic effects or diseases such as diabetes or obesity.     

Substitution of Glutamate Residue by Lysine in the Dimerization Domain Affects DNA Binding Ability of HapR by Inducing Structural Deformity in the DNA Binding Domain

HapR has been given the status of a high cell density master regulatory protein in Vibrio cholerae. Though many facts are known regarding its structural and functional aspects, much still can be learnt from natural variants of the wild type protein. This work aims at investigating the nature of functional inertness of a HapR natural variant harboring a substitution of a conserved glutamate residue at position 117 which participates in forming a salt bridge by lysine (HapR_V2G-E¹¹⁷K). Experimental evidence presented here reveals the inability of this variant to interact with various cognate promoters by in vitro gel shift assay. Furthermore, the elution profiles of HapR_V2G-E¹¹⁷K protein along with the wild type functional HapR_V2G in size-exclusion chromatography as well as circular dichroism spectra did not reflect any significant differences in its structure, thereby indicating the intactness of dimer in the variant protein. To gain further insight into the global shape of the proteins, small angle X-ray scattering analysis (SAXS) was performed. Intriguingly, increased radius of gyration of HapR_V2G-E¹¹⁷K of 27.5 Å in comparison to the wild type protein from SAXS data analyses implied a significant alteration in the global shape of the dimeric HapR_V2G-E¹¹⁷K protein. Structure reconstruction brought forth that the DNA binding domains were substantially “parted away” in this variant. Taken together, our data illustrates that substitution of the conserved glutamate residue by lysine in the dimerization domain induces separation of the two DNA binding domains from their native-like positioning without altering the dimeric status of HapR variant.     

Correction to: External Supplement of Impulsive Micromanager Trichoderma Helps in Combating CO2 Stress in Rice Grown Under FACE

Plant Molecular Biology Reporter - The original version of this article unfortunately contained missing information at author’s affiliations. The affiliation address of the author’s...