Characterization of bimodal chronotype and its association with sleep: A population-based study

The circadian system coordinates internal events in a daily schedule to make sure that the body systems are synchronized to environmental time and internal cues. One important behavioral aspect of the circadian system is the chronotype. It is usually assessed through subjective questionnaires, being the Horne-Ostberg Morningness–Eveningness Questionnaire (MEQ) one of the most used. It classifies individuals into three major categories: morning, evening, and intermediate types. Recently, it has been hypothesized the existence of a fourth chronotype, the bimodal type, through an algorithm derived from the MEQ responses. Bimodals answer as morning-types in some questions, and as evening-types in others, resulting in an intermediate total score. To better characterize this phenotype, the present study aimed to detect and characterize the frequency of the bimodal chronotype in the EPISONO, a large population-based cohort, as well as to verify the association between bimodality and sleep parameters and genetic variation in the PER3 gene. Of the 1,042 individuals who participated of the EPISONO, 857 had MEQ filled correctly. We found that 16% of our sample were bimodal types. We observed that bimodal individuals were significantly younger and had lower body mass index. The association between PER3 VNTR genotype and gender with bimodal chronotype was not significant. However, we found an association between bimodality and Epworth Sleepiness Scale (EES) and apnea-hypopnea index (AHI). We did not find a statistically significant difference between bimodals and intermediate non-bimodals for the studied variables. Lastly, it was observed that the most significant predictors for bimodal chronotype were female gender, AHI, and EES. In conclusion, the present work provides more evidence that the bimodal type might have to be considered when classifying chronotype and its association with young age and sleepiness may be due to the influence of social and environmental factors.     

P elements in the saltans group of Drosophila: a new evaluation of their distribution and number of genomic insertion sites

Few are studies on P elements that have addressed the saltans group. These studies had shown that species from the cordata and elliptica subgroups were devoid of any discernible P homologous sequences, while species from the parasaltans, sturtevanti, and saltans subgroups all contain P element sequences. Our analyses showed the presence of one to 15 P element insertion sites in species of the saltans group, including Drosophila neocordata and Drosophila emarginata (cordata and elliptica subgroups, respectively). From these species, only those from the parasaltans, sturtevanti, and saltans subgroups harbor canonical P elements and, only those of the last two subgroups seem to harbor putative full-sized elements. Due to the low similarity of the sequences found in D. neocordata and D. emarginata to those earlier described, we suggest that these sequences might be rudimental P element derivatives that were present in the ancestral of the subgenus Sophophora.     

PrPc on the road: trafficking of the cellular prion protein

The glycosylphosphatidylinositol (GPI)-anchored cellular prion protein (PrPc) has a fundamental role in prion diseases. Intracellular trafficking of PrPc is important in the generation of protease resistant PrP species but little is known of how endocytosis affects PrPc function. Here, we discuss recent experiments that have illuminated how PrPc is internalized and what are the possible destinations taken by the protein. Contrary to what would be expected for a GPI-anchored protein there is increasing evidence that clathrin-mediated endocytosis and classical endocytic organelles participate in PrPc trafficking. Moreover, the N-terminal domain of PrPc may be involved in sorting events that can direct the protein during its intracellular journey. Indeed, the concept that the GPI-anchor determines PrPc trafficking has been challenged. Cellular signaling can be triggered or be regulated by PrPc and we suggest that endocytosis of PrPc may influence signaling in several ways. Definition of the processes that participate in PrPc endocytosis and intracellular trafficking can have a major impact on our understanding of the mechanisms involved in PrPc function and conversion to protease resistant conformations.     

Diphenyl diselenide reverses cadmium-induced oxidative damage on mice tissues

The concept that selenium-containing molecules may be better antioxidants than classical antioxidants, has led to the design of synthetic organoselenium compounds. In the present investigation subchronic deleterious effects of cadmium-intoxication in mice and a possible protective effect of diphenyl diselenide (PhSe)2 (5 micromol/kg) were studied. Male adult Swiss albino mice (25-35 g) received CdCl2 (10 micromol/kg, subcutaneously), five times/week, for 4 weeks. A number of toxicological parameters in blood, liver, kidney, spleen and brain of mice were examined including delta-aminolevulinic acid dehydratase (delta-ALA-D) activity, lipid peroxidation and ascorbic acid content, the parameters that indicate tissue damage such as plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea, creatinine and lactate dehydrogenase (LDH) were also determined. The results demonstrated that cadmium caused inhibition of delta-ALA-D activity in liver (24%), kidney (33%) and spleen (73%) and (PhSe)2 therapy was effective in restoring enzyme activity in all tissues. A reduction in ascorbic acid content was observed in kidney (11%) and spleen (10.7%) of cadmium-treated mice and (PhSe)2 was only effective in improving this reduction in kidney. An increase of lipid peroxidation induced by cadmium was noted in liver (29%) and brain (28%) tissues and (PhSe)2 therapy was effective in restoring TBARS levels in both tissues. We also observed an increase on plasma LDH (1.99-times), AST (1.93-times) and ALT (4.24-times) activities. (PhSe)2 therapy was effective in restoring AST activity at control level. (PhSe)2 did not present toxic effects when plasma parameters were evaluated. The results suggest that the administration of an antioxidant (PhSe)2, during cadmium intoxication may provide beneficial effects by reducing oxidative stress in tissues.     

Air pressure effects on biomass yield of two different Kluyveromyces strains

The use of air pressure as a way of improving oxygen transfer in aerobic bioreactors was investigated. To compare the air pressure effects with traditional air bubbled cultures, experiments using a pressure reactor and a stirred flask, with the same oxygen transfer rate, were made. Kluyveromyces marxianus is an important industrial yeast and some of it show a “Kluyver effect” for lactose: even under oxygen limited growth conditions, certain disaccharides that support aerobic, respiratory growth, are not fermented. This study deals with the effect of increased pressure on the physiological behavior of two Kluyveromyces strains: K. marxianus ATCC10022 is a lactose-fermenting strain, whereas K. marxianus CBS 7894 has a Kluyver-effect for lactose. For K. marxianus ATCC10022 an air pressure increase of 2 bar led to a 3-fold increase in biomass yield. When air pressure increased an enhancement of ethanol oxidation of cell yeasts was also observed. Batch cultures of K. marxianus CBS 7894 exhibited different growth behaviour. Its metabolism was always oxidative and ethanol was never produced. With the increase in air pressure, it was possible to increase the productivity in biomass of K. marxianus CBS 7894. As a response to high oxygen concentrations, due to the increase in oxygen partial pressure, oxidative stress in the cells was also studied. Antioxidant defences, such as superoxide dismutase, catalase, and glutathione reductase, were at high activity levels, suggesting that these yeast strains could tolerate the increased pressures applied.     

Cathepsin-L influences the expression of extracellular matrix in lymphoid organs and plays a role in the regulation of thymic output and of peripheral T cell number

Nackt mice, which are deficient in cathepsin-L (CTSL), show an early impairment during positive selection in the context of class II MHC molecules and as a consequence, the percentage and absolute number of CD4(+) thymocytes are significantly decreased. In this study, we show that lymph nodes from nackt mice are hypertrophied, showing normal absolute numbers of CD4(+) T cells and marked increases in the number of CD8(+) T lymphocytes. Basal proliferative levels are increased in the CD4(+) but not in the CD8(+) population. Lymph node T cells show increases in the expression of alpha(5), alpha(6), and beta(1) integrin chains. These alterations correlate with increases in the expression of extracellular matrix (ECM) components in lymph nodes. Interestingly, laminin, fibronectin, and collagen I and IV are markedly decreased in nackt thymus which shows an augmented output of CD8(+) cells. These results demonstrate that a mutation in the Ctsl gene influences the levels of ECM components in lymphoid organs, the thymic output, and the number of T cells in the periphery. They further raise the possibility that, by regulating the level of expression of ECM components in lymphoid organs, CTSL is able to broadly affect the immune system.     

Morphological and physiological changes in Saccharomyces cerevisiae by oxidative stress from hyperbaric air

Increase in air or oxygen pressure in microbial cell cultures can cause oxidative stress and consequently affect cell physiology and morphology. The behaviour of Saccharomyces cerevisiae grown under hyperbaric atmospheres of air and pure oxygen was studied. A limit of 1.0 MPa for the air pressure increase (i.e. 0.21 MPa of oxygen partial pressure) in a fed-batch culture of S. cerevisiae was established. Values of 1.5 MPa air pressure and 0.32 MPa pure oxygen pressure strongly inhibited the metabolic activity and the viability of the cells. Also, morphological changes were observed, especially cell-size distribution and the genealogical age profile. Pressure caused cell compression and an increase in number of aged cells. These effects were attributed to oxygen toxicity since similar results were obtained using air or oxygen, if oxygen partial pressure was equal to or higher than 0.32 MPa. The activity of the antioxidant enzymes, catalase and superoxide dismutase (SOD) (cytosolic and mitochondrial isoformes) indicated that the enzymes have different roles in oxidative stress cell protection, depending on other factors that affect the cell physiological state.