Cellular and Molecular Life Sciences

In neonatal rat ventricular myocytes pretreatment with pertussis toxin did not affect 1 μM (−)-norepinephrine stimulation of inositol phosphates or myocardial cell hypertrophy as measured either by protein radiolabelling or by myocardial cell protein content. Thus guanine nucleotide protein (s) ADP-ribosylated by pertussis toxin do not play a role in twoα 1-adrenoceptor-mediated processes, phosphatidylinositide turnover and induction of myocardial cell hypertrophy.

Sex differences in human health and disease can range from undetectable to profound. Differences in brain tumor rates and outcome are evident in males and females throughout the world and regardless of age. These observations indicate that fundamental aspects of sex determination can impact the biology of brain tumors. It is likely that optimal personalized approaches to the treatment of male and female brain tumor patients will require recognizing and understanding the ways in which the biology of their tumors can differ. It is our view that sex-specific approaches to brain tumor screening and care will be enhanced by rigorously documenting differences in brain tumor rates and outcomes in males and females, and understanding the developmental and evolutionary origins of sex differences. Here we offer such an integrative perspective on brain tumors. It is our intent to encourage the consideration of sex differences in clinical and basic scientific investigations.

Skin acts as a barrier between the environment and internal organs and performs functions that are critical for the preservation of body homeostasis. In mammals, a complex network of circadian clocks and oscillators adapts physiology and behavior to environmental changes by generating circadian rhythms. These rhythms are induced in the central pacemaker and peripheral tissues by similar transcriptional–translational feedback loops involving clock genes. In this work, we investigated the presence of functional oscillators in the human skin by studying kinetics of clock gene expression in epidermal and dermal cells originating from the same donor and compared their characteristics. Primary cultures of fibroblasts, keratinocytes, and melanocytes were established from an abdominal biopsy and expression of clock genes following dexamethasone synchronization was assessed by qPCR. An original mathematical method was developed to analyze simultaneously up to nine clock genes. By fitting the oscillations to a common period, the phase relationships of the genes could be determined accurately. We thereby show the presence of functional circadian machinery in each cell type. These clockworks display specific periods and phase relationships between clock genes, suggesting regulatory mechanisms that are particular to each cell type. Taken together, our data demonstrate that skin has a complex circadian organization. Oscillators are present not only in fibroblasts but also in epidermal keratinocytes and melanocytes and are likely to act in coordination to drive rhythmic functions within the skin.

Calorie restriction has been known for many decades to extend the life span of rodents. Since the more recent discovery that a long-term reduction in nutrient intake also extends life span in nearly every invertebrate model organism used for aging research, the mechanisms behind the longevity benefits of this intervention have been under intense scrutiny. While models have been developed in yeast, worms, and flies, the molecular mechanisms governing life span extension by calorie restriction remain controversial, resulting in great anticipation of mammalian studies testing these models. Here we discuss the links between nutrient reduction and enhanced longevity with emphasis on evolutionarily conserved nutrient response signaling.