GALNT2 mRNA levels are associated with serum triglycerides in humans

Atherogenic dyslipidemia, characterized by high triglycerides (TG) and low high density lipoprotein (HDL)-cholesterol levels, is a feature of patients with insulin resistance, obesity, and type 2 diabetes (T2D) [1] and plays a major role in shaping the risk of cardiovascular disease. Both TG and HDL-cholesterol serum concentrations are under the control of both environmental factors and up to 95 genetic loci, unraveled by a very large genome-wide association study (GWAs) in approximately 100,000 individuals [2]. Among these loci is GALNT2, which encode for ppGal-NAc-T2, involved in O-linked glycosylation. Similarly, studies in rodents have shown that liver GALNT2 expression modulates HDL-cholesterol concentrations [2]. Based on such studies, it is conceivable that GALNT2 expression changes play a role on TG and/or HDL-cholesterol levels. To gain further insights about this hypothesis, GALNT2 expression was measured in peripheral white blood cells (PWBC), from 224 individuals with a wide range of TG and HDL-cholesterol levels, as well as other metabolic parameters and clinical conditions

THE ROLE OF PHYSICAL EDUCATION AND CORPOREALITY IN THE INCLUSION PROCESS: AN EXPLORATORY STUDY WITH SPECIAL NEEDS TEACHERS IN TRAINING

It was decided to carry out an exploratory study aimed at investigating the opinions of 100 teachers specializing in special educational needs at the University of Naples “Suor Orsola Benincasa”, in relation to the aspect of corporeality and motor education as an essential dimension in the inclusive process to be implemented in the school context. 100 semi-structured on-line interviews were held. It was decided to carry out an analysis of the content of the interviews (Krippendorff, 2013) adopting the Grounded Theory (Glaser & Strauss, 1967) as the theoretical and methodological substrate, with specifc reference to the constructivist-epistemological paradigm (Charmaz, 2005). The qualitative analysis was supported by the use of Nvivo software (Richards, 1999). The corpus of the interviews was subjected to content analysis (Krippendorff, 2013). The qualitative analysis of the corpus of the interviews highlights the need for providing postgraduate teachers with more specifc training in the feld of physical education, particularly in its inclusive purpose. While recognizing the importance of physical education in the integral formation of the person, the teachers declared themselves not very competent and, above all, that they would not put into practice actions concerning the motor dimension in their teaching activity

Inkjet Printing of Two-dimensional Materials for Flexible Optoelectronics

During this Thesis work, I focused on the synthesis, characterization and ink-jet printing of Layered Material-based inks produced by liquid phase exfoliation (LPE), a top-down approach for the production of LMs that has been receiving a great attention since it is particularly suitable for scaling-up and applications at the industrial levels. I synthesized LPE-produced graphene-based inks in NMP and MoS2-based inks in IPA, that were then characterized morphologically using several techniques. First, the concentration of the as-produced inks was estimated by absorption spectroscopy; then, Raman spectroscopy was exploited to analyze the quality and the number of layers of the flakes dispersed in the ink, while transmission electron microscopy (TEM) was instead used to determine their lateral size. Finally, rheological analysis was carried out to measure the viscosity of the ink to be ink-jet printed. Inkjet printing of the as-obtained inks was then performed on flexible Polyamide 6 on thin polyethylene terephthalate PET-foils. Rectangular stripes were printed, that were then characterized both optically and electrically. The surface topography was analyzed by means of optical and scanning electron microscopy (SEM). Atomic force microscopy (AFM) was exploited to measure the thickness of the printed stripes, estimated as 500 nm for graphene (N=48 printing steps) and 800 nm for MoS2 (N=60 printing steps). Furthermore, Raman spectroscopy was carried out on the printed stripes to monitor the quality of the printed flakes, which were not affected by the printing process. Before the electrical measurements, the printed stripes were first pressed and then annealed in order to remove residual solvent that may negatively affect the electrical conductivity of the as-prepared samples. 4-wire resistance measurements before and after such treatments have shown that this approach enabled to reduce the resistance of the printed stripes from hundred kOhm to few kOhm. Finally, I have carried out some endurance tests on the printed stripes. The electrical resistance of the stripes easily recovers after mechanical stresses such as traction (up to a 5% normalized strain) or low-frequency protracted strain (registering a 0.4% and 0.7% increase in electric resistance after 36,000 and 72,000 bending cycles respectively). These preliminary results show the potentiality of this approach for the realization of fully-printed conductive components for flexible optoelectronics. Photoconductivity tests with 532 nm laser excitation were then performed at different incident power. From the responsivity, an external quantum efficiency up to 0.001 was obtained. Although there is plenty of room for optimization and the results can be considered preliminary,they may pave the way towards the development of printed heterostructures

The secondary metabolite euplotin c induces apoptosis-like death in the marine ciliated protist euplotes vannus

The sesquiterpenoid euplotin C is a secondary metabolite produced by the ciliated protist Euplotes crassus and provides a mechanism for damping populations of potential competitors. Indeed, E. crassus is virtually resistant to its own product while different non-producer species representing an unbiased sample of the marine, interstitial, ciliate diversity are sensitive. For instance, euplotin C exerts a marked disruption of different homeostatic mechanisms in Euplotes vannus. We demonstrate by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay that euplotin C quickly decreases viability and mitochondrial function of E. vannus with a very high efficacy and at micromolar potency. In addition, euplotin C induces apoptosis in E. vannus as 4,6-diamino-2-phenylindole and Terminal Transferase dUTP Nick End Labeling staining show the rapid condensation and fragmentation of nuclear material in cells treated with euplotin C. These effects occur without detectable permeabilisation or rupture of cell membranes and with no major changes in the overall morphology, although some traits, such as vacuolisation and disorganised microtubules, can be observed by transmission electron microscopy. In particular, E. vannus show profound changes of the mitochondrial ultrastructure. Finally, we also show that caspase activity in E. vannus is increased by euplotin C. These data elucidate the pro-apoptotic role of euplotin C and suggest a mechanism for its impact on natural selection.L'articolo è disponibile sul sito dell'editore http://onlinelibrary.wiley.com

Chromogranin A: From Laboratory to Clinical Aspects of Patients with Neuroendocrine Tumors

Background. Neuroendocrine tumors (NETs) are characterized by having behavior and prognosis that depend upon tumor histology, primary site, staging, and proliferative index. The symptoms associated with carcinoid syndrome and vasoactive intestinal peptide tumors are treated with octreotide acetate. The PROMID trial assesses the effect of octreotide LAR on the tumor growth in patients with well-differentiated metastatic midgut NETs. The CLARINET trial evaluates the effects of lanreotide in patients with nonfunctional, well-, or moderately differentiated metastatic enteropancreatic NETs. Everolimus has been approved for the treatment of advanced pancreatic NETs (pNETs) based on positive PFS effects, obtained in the treated group. Sunitinib is approved for the treatment of patients with progressive gastrointestinal stromal tumor or intolerance to imatinib, because a randomized study demonstrated that it improves PFS and overall survival in patients with advanced well-differentiated pNETs. In a phase II trial, pasireotide shows efficacy and tolerability in the treatment of patients with advanced NETs, whose symptoms of carcinoid syndrome were resistant to octreotide LAR. An open-label, phase II trial assesses the clinical activity of long-acting repeatable pasireotide in treatment-naive patients with metastatic grade 1 or 2 NETs. Even if the growth of the neoplasm was significantly inhibited, it is still unclear whether its antiproliferative action is greater than that of octreotide and lanreotide. Because new therapeutic options are needed to counter the natural behavior of neuroendocrine tumors, it would also be useful to have a biochemical marker that can be addressed better in the management of these patients. Chromogranin A is currently the most useful biomarker to establish diagnosis and has some utility in predicting disease recurrence, outcome, and efficacy of therapy

Cytotoxic effects and apoptotic signalling mechanisms of the sesquiterpenoid euplotin C, a secondary metabolite of the marine ciliate Euplotes crassus, in tumour cells

Most antitumour agents with cytotoxic properties induce apoptosis. The lipophilic compound euplotin C, isolated from the ciliate Euplotes crassus, is toxic to a number of different opportunistic or pathogenic microorganisms, although its mechanism of action is currently unknown. We report here that euplotin C is a powerful cytotoxic and pro-apoptotic agent in mouse AtT-20 and rat PC12 tumour-derived cell lines. In addition, we provide evidence that euplotin C treatment results in rapid activation of ryanodine receptors, depletion of Ca2+ stores in the endoplasmic reticulum (ER), the release of cytochrome c from the mitochondria, activation of caspase-12, and activation of caspase-3, leading to apoptosis. Intracellular Ca2+ overload is an early event which induces apoptosis and is parallelled by ER stress and the release of cytochrome c, whereas caspase-12 may be activated by euplotin C at a later stage in the apoptosis pathway. These events, either independently or concomitantly, lead to the activation of the caspase-3 and its downstream effectors, triggering the cell to undergo apoptosis. These results demonstrate that euplotin C may be considered for the design of cytotoxic and pro-apoptotic new drugs.L'articolo è disponibile sul sito dell'editore http://www.springerlink.com

Directional Fluorescence Spectral Narrowing in All-Polymer Microcavities Doped with CdSe/CdS Dot-in-Rod Nanocrystals

We report on the fluorescence properties of high optical quality all-polymer planar microcavities embedding core 12shell dot-in-rod CdSe/CdS nanocrystals. Properly tuned microcavities allow a 10-fold sharpening of the nanocrystals fluorescence spectrum, resulting in a reduction of the bandwidth from 24 to 2.4 nm, which corresponds to a quality factor larger than 250. A 5-fold peak photoluminescence intensity enhancement is measured, while the overall number of emitted photons is reduced. Time-resolved photoluminescence and quantum yield for microcavities and suitable references show the presence of two decays related to differences in nanocrystal size distribution. The slower decay rate, which becomes faster when the nanocrystals are embedded into the microcavity, is assigned to longer nanorods with emission spectrally overlapped to the cavity mode. Conversely, the short-living component, which is assigned to an impurity of shorter nanorods, remains unaffected by the microcavity

The energy sensor AMPK regulates Hedgehog signaling in human cells through a unique Gli1 metabolic checkpoint

Hedgehog signaling controls proliferation of cerebellar granule cell precursors (GCPs) and its aberrant activation is a leading cause of Medulloblastoma, the most frequent pediatric brain tumor. We show here that the energy sensor AMPK inhibits Hh signaling by phosphorylating a single residue of human Gli1 that is not conserved in other species.Studies with selective agonists and genetic deletion have revealed that AMPK activation inhibits canonical Hh signaling in human, but not in mouse cells. Indeed we show that AMPK phosphorylates Gli1 at the unique residue Ser408, which is conserved only in primates but not in other species. Once phosphorylated, Gli1 is targeted for proteasomal degradation. Notably, we show that selective AMPK activation inhibits Gli1-driven proliferation and that this effect is linked to Ser408 phosphorylation, which represents a key metabolic checkpoint for Hh signaling.Collectively, this data unveil a novel mechanism of inhibition of Gli1 function, which is exclusive for human cells and may be exploited for the treatment of Medulloblastoma or other Gli1 driven tumors