Biological aspects of mTOR in leukemia

The mammalian target of rapamycin (mTOR) is a central processor of intra-and extracellular signals, regulating many fundamental cellular processes such as metabolism, growth, proliferation, and survival. Strong evidences have indicated that mTOR dysregulation is deeply implicated in leukemogenesis. This has led to growing interest in the development of modulators of its activity for leukemia treatment. This review intends to provide an outline of the principal biological and molecular functions of mTOR. We summarize the current understanding of how mTOR interacts with microRNAs, with components of cell metabolism, and with controllers of apoptotic machinery. Lastly, from a clinical/translational perspective, we recapitulate the therapeutic results in leukemia, obtained by using mTOR inhibitors as single agents and in combination with other compounds

Superconductivity in Sr2RuO4-Sr3Ru2O7 eutectic crystals

Superconducting behavior has been observed in the Sr2RuO4-Sr3Ru2O7 eutectic system as grown by the flux-feeding floating zone technique. A supercurrent flows across a single interface between Sr2RuO4 and Sr3Ru2O7 areas at distances that are far beyond those expected in a conventional proximity scenario. The current-voltage characteristics within the Sr3Ru2O7 macrodomain, as extracted from the eutectic, exhibit signatures of superconductivity in the bilayered ruthenate. Detailed microstructural, morphological and compositional analyses address issues on the concentration and the size of Sr2RuO4 inclusions within the Sr3Ru2O7 matrix. We speculate on the possibility of inhomogeneous superconductivity in the eutectic Sr3Ru2O7 and exotic pairing induced by the Sr2RuO4 inclusions.Comment: Pages 4, figures 3, submitted to Phys. Rev. Let

A study on the sexual and contraception behaviours of the pre-university students in Puglia (South-Italy)

Introduction. The aim of the present study is to determine attitude and associated factors towards the use of methods of protection/contraception. Methods. In August 2008, a study was carried out using a self-administered standardised anonymous questionnaire. It was administered to school-leavers who were attending a study course at Bari University. Results. The total number of questionnaires returned was 1091, the average age of the interviewed subjects was 19.6. Those declaring to have had sexual intercourse at least once was 88%. Of those sexually active, the average age at first intercourse was 16.8, and 75.2% stated that they had used some form of contraception on this occasion. The condom was the most popular method employed, followed by withdrawal and by contraceptive pills. Around 20% of the interviewees indicated that they used emergency post-coital contraception. Discussion. The study results emphasise the importance of an effective teaching of the aspects of sex and relationship education before puberty

Paramagnetic effect in YBaCuO grain boundary junctions

A detailed investigation of the magnetic response of YBaCuO grain boundary Josephson junctions has been carried out using both radio-frequency measurements and Scanning SQUID Microscopy. In a nominally zero-field-cooled regime we observed a paramagnetic response at low external fields for 45 degree asymmetric grain boundaries. We argue that the observed phenomenology results from the d-wave order parameter symmetry and depends on Andreev bound states.Comment: To be published in Phys. Rev.

Influence of Topological Edge States on the Properties of Al/Bi2Se3/Al Hybrid Josephson Devices

In superconductor-topological insulator-superconductor hybrid junctions, the barrier edge states are expected to be protected against backscattering, to generate unconventional proximity effects, and, possibly, to signal the presence of Majorana fermions. The standards of proximity modes for these types of structures have to be settled for a neat identification of possible new entities. Through a systematic and complete set of measurements of the Josephson properties we find evidence of ballistic transport in coplanar Al-Bi2Se3-Al junctions that we attribute to a coherent transport through the topological edge state. The shunting effect of the bulk only influences the normal transport. This behavior, which can be considered to some extent universal, is fairly independent of the specific features of superconducting electrodes. A comparative study of Shubnikov - de Haas oscillations and Scanning Tunneling Spectroscopy gave an experimental signature compatible with a two dimensional electron transport channel with a Dirac dispersion relation. A reduction of the size of the Bi2Se3 flakes to the nanoscale is an unavoidable step to drive Josephson junctions in the proper regime to detect possible distinctive features of Majorana fermions.Comment: 11 pages, 14 figure

Metabolic reprogramming promotes myogenesis during aging

Sarcopenia is the age-related progressive loss of skeletal muscle mass and strength finally leading to poor physical performance. Impaired myogenesis contributes to the pathogenesis of sarcopenia, while mitochondrial dysfunctions are thought to play a primary role in skeletal muscle loss during aging. Here we studied the link between myogenesis and metabolism. In particular, we analyzed the effect of the metabolic modulator trimetazidine (TMZ) on myogenesis in aging. We show that reprogramming the metabolism by TMZ treatment for 12 consecutive days stimulates myogenic gene expression in skeletal muscle of 22-month-old mice. Our data also reveal that TMZ increases the levels of mitochondrial proteins and stimulates the oxidative metabolism in aged muscles, this finding being in line with our previous observations in cachectic mice. Moreover, we show that, besides TMZ also other types of metabolic modulators (i.e., 5-Aminoimidazole-4-Carboxamide Ribofuranoside-AICAR) can stimulate differentiation of skeletal muscle progenitors in vitro. Overall, our results reveal that reprogramming the metabolism stimulates myogenesis while triggering mitochondrial proteins synthesis in vivo during aging. Together with the previously reported ability of TMZ to increase muscle strength in aged mice, these new data suggest an interesting non-invasive therapeutic strategy which could contribute to improving muscle quality and neuromuscular communication in the elderly, and counteracting sarcopenia

Traumatic experiences in childhood and adolescence: a meta-analysis of prospective studies assessing risk for psychosis

Evidence of the association between traumatic experiences and psychosis are uncertain with respect to temporal order, clinical outcomes and the role of the age and genetic liability. The aim of the present meta-analysis was to explore the temporal relationship between the development of psychosis and traumatic exposure using prospective studies and to examine the role of moderation factors on overall effect sizes. Studies were identified by searching Embase-Ovid, PsycINFO (EBSCO), Pubmed, Scopus, Web of Science databases, and yielded an initial total of 9016 papers, leaving finally 23 after the screening process. Three sets of meta-analyses estimated the risk of developing psychotic experiences or full clinical psychosis by having experienced maltreatment by an adult or bullying by peers or parental death, using the random-effects model. Bullying by peers (OR = 2.28 [1.64, 4.34]), maltreatment by an adult (OR = 2.20 [1.72, 2.81]) and parental death (OR = 1.24 [1.06, 1.44]) all increased the risk of psychosis. Moderator analysis showed that negative effects of bullying were detected especially in those with genetic liability for psychosis and exposure to multiple trauma types; studies with higher prevalence of males showed a stronger risk for those exposed to parental death. No significant meta-regression was found between the risk of developing a full clinical psychosis or a psychotic experience. Lack of studies hampered the results about the age of trauma occurrence. The cumulative effect of being bullied from peers and experiencing other adversities during childhood and/or adolescence, together with genetic liability for psychosis, appears to confer the highest risk for developing psychotic symptoms later in life