Short-term hypergravity influences NGF and BDNF expression, and mast cell distribution in the lungs and heart of adult male mice

In this study we investigate the effects of short-term hypergravity on lung and heart neurotrophins and mast cell distribution. Our results showed that brain derived-neurotrophic factor (BDNF) protein and mRNA expression are increased in the lungs of mice exposed to hypergravity while in the heart hypergravity causes a marked reduction in BDNF mRNA expression, and a decrease in BDNF protein. Compared to controls, nerve growth factor (NGF) protein was expressed more in the heart of rotated mice. These observations demonstrate that altered hypergravity can affect, though differentially, the local expression of NGF and BDNF proteins and their mRNAs in the lung and heart and indicates that short-term exposure to hypergravity causes a marked increase in BDNF, but not in NGF in the lungs of adult mice. Moreover, mast cells, which are NGF-producing cells and implicated in cardiac and respiratory activity, increased in number in proximity to blood vessels in the heart and in lung airway epithelium of rotated mice. This study indicates that hypergravity influences cardiovascular and respiratory tissue and suggests a neurotrophin involvement in the reaction to this environmental exposure.     

Distribution of apelin,the endogenous ligand of the APJ receptor,in the lizard <Emphasis Type="Italic">Podarcis sicula</Emphasis>

Summary Apelin is a novel bioactive peptide that has been isolated from bovine stomach extracts and identified as the endogenous ligand for the APJ receptor. Although the main physiological functions of apelin have not yet been clarified, it is known that apelin is involved in the regulation of blood pressure, central control of body fluid homeostasis and the modulation of immune response. In order to investigate the distribution of apelin in reptiles, we have performed an immunohistochemical analysis on tissues of the lizard Podarcis sicula. The peptide was found to be widely distributed, although its cellular localization differed in the various organs examined. A strong immunopositivity was found in the heart, stomach and intestine. In the spleen, an intense apelin immunopositivity was restricted to a discrete number of cells scattered throughout the red pulp and co-localized with immunoglobulin kappa and lambda chains, suggesting an analogous function of this peptide in immune responses also in reptiles. Intriguingly, apelin immunoreactivity was discretely localized in endothelial cells in the lung and thyroid gland. In the light of these data, we conclude that apelin may have multiple functions in reptiles.     

Volume Contents

Volume Contents

Volume Contents     

Sensation seeking in fathers: the impact on testosterone and paternal investment

Paternal care is associated with a reduced likelihood of engaging in competitive or mating behavior and an increased likelihood of providing protection when necessary. Over recent years, there has been increasing evidence to assume that the steroid testosterone (T) in men might reflect the degree of mating effort. In line with this, decreased T levels were shown in fathers compared to non-fathers and it was suggested that paternal care, and most behavior positively associated with T, might be incompatible with each other. Independently, the personality trait sensation seeking (SS) has been related to mating behavior and also to elevated T in men. Aiming to integrate these different lines of research in a longitudinal approach, we explored the impact of SS on T levels in the context of the transition to fatherhood. Thirty-seven fathers and 38 men without children but in committed, romantic relationships (controls) were recruited. At two time points (for fathers: four weeks prior to (t1) and eight weeks after birth (t2)), all subjects repeatedly collected saliva samples for T measurement, filled in a protocol of activities during the course of these days and completed an online questionnaire. In line with our hypotheses, the results show significantly lower aggregated (AUC-T) T levels in fathers compared with non-fathers. Furthermore, moderation analyses revealed a significant interaction between group and SS at t2, with the lowest T levels in low SS fathers. These data suggest that adaptation processes of the transition to fatherhood are influenced by individual differences in personality traits.     

Beneficial effects of curcumin on GFAP filament organization and down-regulation of GFAP expression in an in vitro model of Alexander disease

Heterozygous mutations of the GFAP gene are responsible for Alexander disease, a neurodegenerative disorder characterized by intracytoplasmic Rosenthal fibers (RFs) in dystrophic astrocytes. In vivo and in vitro models have shown co-localization of mutant GFAP proteins with the small heat shock proteins (sHSPs) HSP27 and alphaB-crystallin, ubiquitin and proteasome components. Results reported by several recent studies agree on ascribing an altered cytoskeletal pattern to mutant GFAP proteins, an effect which induces mutant proteins accumulation, leading to impaired proteasome function and autophagy induction. On the basis of the protective role shown by both these small heat shock proteins (sHSPs), and on the already well established neuroprotective effects of curcumin in several diseases, we have investigated the effects of this compound in an in vitro model of Alexander disease, consisting in U251-MG astrocytoma cells transiently transfected with a construct encoding for GFAP carrying the p.R239C mutation in frame with the reporter green fluorescent protein (GFP). In particular, depending on the dose used, we have observed that curcumin is able to induce both HSP27 and alphaB-crystallin, to reduce expression of both RNA and protein of endogenous GFAP, to induce autophagy and, finally, to rescue the filamentous organization of the GFAP mutant protein, thus suggesting a role of this spice in counteracting the pathogenic effects of GFAP mutations.     

Effect of size and heterogeneity of samples on biomarker discovery: synthetic and real data assessment

Motivation

The identification of robust lists of molecular biomarkers related to a disease is a fundamental step for early diagnosis and treatment. However, methodologies for the discovery of biomarkers using microarray data often provide results with limited overlap. These differences are imputable to 1) dataset size (few subjects with respect to the number of features); 2) heterogeneity of the disease; 3) heterogeneity of experimental protocols and computational pipelines employed in the analysis. In this paper, we focus on the first two issues and assess, both on simulated (through an in silico regulation network model) and real clinical datasets, the consistency of candidate biomarkers provided by a number of different methods.

Methods

We extensively simulated the effect of heterogeneity characteristic of complex diseases on different sets of microarray data. Heterogeneity was reproduced by simulating both intrinsic variability of the population and the alteration of regulatory mechanisms. Population variability was simulated by modeling evolution of a pool of subjects; then, a subset of them underwent alterations in regulatory mechanisms so as to mimic the disease state.

Results

The simulated data allowed us to outline advantages and drawbacks of different methods across multiple studies and varying number of samples and to evaluate precision of feature selection on a benchmark with known biomarkers. Although comparable classification accuracy was reached by different methods, the use of external cross-validation loops is helpful in finding features with a higher degree of precision and stability. Application to real data confirmed these results.     

Responsiveness to 6-n-propylthiouracil (PROP) is associated with salivary levels of two specific basic proline-rich proteins in humans

Thiourea tasting can be predictive of individual differences in bitter taste responses, general food preferences and eating behavior, and could be correlated with saliva chemical composition. We investigated the possible relationship between PROP bitter taste responsiveness and the salivary proteome in subjects genotyped for TAS2R38 and gustin gene polymorphisms. Taste perception intensity evoked by PROP and NaCl solutions was measured in sixty-three volunteers (21 males, 42 females, age 25±3 y) to establish their PROP taster status, and 24 PROP super-tasters and 21 nontasters were selected to participate in the study. TAS2R38 and gustin gene molecular analysis were performed using PCR techniques. Qualitative and quantitative determination of salivary proteins was performed by HPLC-ESI-MS before and after PROP taste stimulation. PROP super-tastings was strongly associated with the 'taster' variant (PAV haplotype) of TAS2R38 and the A allele of rs2274333 polymorphism in the gustin gene and nontasting was associated with the minor alleles at both loci. ANOVA revealed that basal levels of II-2 and Ps-1 proteins, belonging to the basic proline-rich protein (bPRPs) family, were significantly higher in PROP super-taster than in nontaster un-stimulated saliva, and that PROP stimulation elicited a rapid increase in the levels of these same proteins only in PROP super-taster saliva. These data show for the first time that responsiveness to PROP is associated with salivary levels of II-2 peptide and Ps-1 protein, which are products of the PRB1 gene. These findings suggest that PRB1, in addition to TAS2R38 and gustin, could contribute to individual differences in thiourea sensitivity, and the expression of the PROP phenotype as a complex genetic trait.