Inflammation and Hras signaling control epithelial–mesenchymal transition during skin tumor progression

Epithelial–mesenchymal transition (EMT) is thought to be an important, possibly essential, component of the process of tumor dissemination and metastasis. About 20%–30% of Hras mutant mouse skin carcinomas induced by chemical initiation/promotion protocols have undergone EMT. Reduced exposure to TPA-induced chronic inflammation causes a dramatic reduction in classical papillomas and squamous cell carcinomas (SCCs), but the mice still develop highly invasive carcinomas with EMT properties, reduced levels of Hras and Egfr signaling, and frequent Ink4/Arf deletions. Deletion of Hras from the mouse germline also leads to a strong reduction in squamous tumor development, but tumors now acquire activating Kras mutations and exhibit more aggressive metastatic properties. We propose that invasive carcinomas can arise by different genetic and biological routes dependent on exposure to chronic inflammation and possibly from different target cell populations within the skin. Our data have implications for the use of inhibitors of inflammation or of Ras/Egfr pathway signaling for prevention or treatment of invasive cancers.     

Longitudinal associations of physical fitness and body mass index with academic performance

No studies have analyzed the longitudinal associations of change in physical fitness components and obesity with academic performance. The aim of the study was to examine longitudinal associations of changes in physical fitness components and body mass index with academic performance among youth, and whether the physical fitness components are moderators of the longitudinal association between obesity and academic performance in youth. Longitudinal analyses (2 years) included 1802 youths. Physical fitness components were assessed following the ALPHA health‐related fitness test battery. Academic performance was assessed via school records. Youth in the persistently high cardiorespiratory fitness and motor ability categories (ie, fit at baseline and at 2‐year follow‐up) had higher academic performance at follow‐up than those in the persistently low category. Further, youth with normal weight at baseline and overweight/obesity at follow‐up had lower academic performance scores at follow‐up compared to those with normal weight. Also, cardiorespiratory fitness may ameliorate the negative influence of excess body mass index on academic performance at follow‐up. Promoting physical activity programs at school that include both aerobic exercise and motor tasks to improve physical fitness and reduce body mass index may not only improve physical health, but also contribute toward successful academic development.     

Patients with paroxysmal nocturnal hemoglobinuria have a high frequency of peripheral-blood T cells expressing activating isoforms of inhibiting superfamily receptors

Patients with paroxysmal nocturnal hemoglobinuria (PNH) have a large clonal population of blood cells deriving from hematopoietic stem cells (HSCs) deficient in glycosylphosphatidylinositol (GPI)-anchored surface molecules. A current model postulates that PNH arises through negative selection against normal HSCs exerted by autoreactive T cells, whereas PNH HSCs escape damage. We have investigated the inhibitory receptor superfamily (IRS) system in 13 patients with PNH. We found a slight increase in the proportion of T cells expressing IRS. In contrast to what applies to healthy donors, the engagement of IRS molecules on T cells from patients with PNH elicited a powerful cytolytic activity in a redirected killing assay, indicating that these IRSs belong to the activating type. This was confirmed by clonal analysis: 50% of IRS+ T-cell clones in patients with PNH were of the activating type, while only 5% were of the activating type in healthy donors. Moreover, the ligation of IRS induces (1) production of tumor necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma) and (2) brisk cytolytic activity against cells bearing appropriate IRS counter-ligands. In addition, these IRS+ T cells show natural killer (NK)-like cytolytic activity to which GPI- cells were less sensitive than GPI+ cells. Thus, T cells with NK-like features, expressing the activating isoforms of IRS, may include effector cells involved in the pathogenesis of PNH.     

Proteins of the S100 family regulate the oligomerization of p53 tumor suppressor

S100B protein is elevated in the brains of patients with early stages of Alzheimer's disease and Down's syndrome. S100A4 is correlated with the development of metastasis. Both proteins bind to p53 tumor suppressor. We found that both S100B and S100A4 bind to the tetramerization domain of p53 (residues 325-355) only when exposed in lower oligomerization states and so they disrupt the tetramerization of p53. In addition, S100B binds to the negative regulatory and nuclear localization domains, which results in a very tight binding to p53 protein sequences that exposed the tetramerization domain in their C terminus. Because the trafficking of p53 depends on its oligomerization state, we suggest that S100B and S100A4 could regulate the subcellular localization of p53. But, the differences in the way these proteins bind to p53 could result in S100B and S1004 having different effects on p53 function in cell-cycle control.     

Dispersion of γ-Alumina Nano-Sized Spherical Particles in a Calamitic Liquid Crystal. Study and Optimization of the Confinement Effects

We report an experimental study on confined systems formed by butyloxybenzylidene octylaniline liquid crystal (4O.8) + γ-alumina nanoparticles. The effects of the confinement in the thermal and dielectric properties of the liquid crystal under different densities of nanoparticles is analyzed by means of high resolution Modulated Differential Scanning Calorimetry (MDSC) and broadband dielectric spectroscopy. First, a drastic depression of the N-I and SmA-N transition temperatures is observed with confinement, the more concentration of nanoparticles the deeper this depression is, driving the nematic range closer to the room temperature. An interesting experimental law is found for both transition temperatures. Second, the change in shape of the heat capacity peaks is quantified by means of the full width half maximum (FWHM). Third, the confinement does not noticeably affect the molecular dynamics. Finally, the combination of nanoparticles and the external applied electric field tends to favor the alignment of the molecules in metallic cells. All these results indicate that the confinement of liquid crystals by means of γ-alumina nanoparticles could be optimum for liquid crystal-based electrooptic devices.     

Cadmium toxicity and its relationship with disturbances in the cytoskeleton,cell cycle and chromosome stability

Ecotoxicology - This study aimed to investigate the mode of action of cadmium (Cd) toxicity at cell level, especially at early stages of plant exposure. Tomato seedlings were cultivated in growth...