c-Flip KO fibroblasts display lipid accumulation associated with endoplasmic reticulum stress

c-Flip proteins are well-known apoptosis modulators. They generally contribute to tissue homeostasis maintenance by inhibiting death-receptor-mediated cell death. In the present manuscript, we showthat c-Flip knock-out (KO) mouse embryonic fibroblasts (MEFs) kept in culture under starvation conditions gradually modify their phenotype and accumulate vacuoles, becoming progressively larger according to the duration of starvation. Large vacuoles are present in KO MEFs though not in WT MEFs, and are Oil Red-O positive, which indicates that they represent lipid droplets. Western blot experiments reveal that, unlikeWTMEFs, KOMEFs express high levels of the lipogenic transcription factor PPAR-γ. Lipid droplet accumulation was found to be associated with endoplasmic reticulum (ER) stress activation and autophagic modulation valuated by means of BIP increase, LC3 lipidation and AMP-activated protein kinase (AMPK) phosphorylation, and p62 accumulation. Interestingly, XBP-1, an ER stress-induced lipogenic transcription factor, was found to preferentially localize in the nucleus rather than in the cytoplasm of KO MEFs. These data demonstrate that, upon starvation, c-Flip affects lipid accumulation, ER stress and autophagy, thereby pointing to an important role of c-Flip in the adaptive response and ER stress response programs under both normal and pathological conditions

Cancer microenvironment and endoplasmic reticulum stress response

Different stressful conditions such as hypoxia, nutrient deprivation, pH changes, or reduced vascularization, potentially able to act as growth-limiting factors for tumor cells, activate the unfolded protein response (UPR). UPR is therefore involved in tumor growth and adaptation to severe environments and is generally cytoprotective in cancer. The present review describes the molecular mechanisms underlying UPR and able to promote survival and proliferation in cancer. The critical role of UPR activation in tumor growth promotion is discussed in detail for a few paradigmatic tumors such as prostate cancer and melanoma

Heterostyly in Goniolimon italicum (Plumbaginaceae), endemic to Abruzzo (central Apennines, Italy)

Goniolimon italicum is an endemic species to central Apennines (Italy). Here we provide the first report of heterostyly in this species. Two morphological types were identified: an S-morph with stamen filaments longer than gynoecia, stigmas with a papillate surface and finely reticulated pollen grains with very small spinules (Type B); and an L-morph with stamen filaments shorter than gynoecia, stigmas with a cob pattern and coarsely reticulated pollen grains with small spinules (Type A). Two new locations of G. italicum were found and are here reported

Effects of ionizing radiation sterilization on microparticulate drug delivery systems based on poly-alfa-hydroxyacids: an overview.

Ionizing radiation treatment is particularly advantageous as a sterilization technique for polymeric drug delivery systems. In recent years several authors have investigated this topic with interesting and sometimes controversial results. This overview was aimed at gathering and critically discussing the studies performed on the effect of ionizing radiation sterilization on microparticulate drug delivery systems made of poly-α- hydroxyacids. The results reported in the literature showed that ionizing radiation always led to a decrease in poly-α-hydroxyacids molecular weight. This effect was strictly related to irradiation dose, irradiation conditions, and depended on the starting polymer molecular weight. The presence of a drug and/or an additive inside the polymeric micromatrix could affect polymer behavior upon irradiation and consequently drug release behavior. Electron paramagnetic resonance (EPR) and electron-nuclear double resonance (ENDOR) proved to be useful techniques to elucidate the radiolytic mechanisms and the drug /polymer interaction upon irradiation

Changes in PGE2 signaling after submandibulectomy alter post–tooth extraction socket healing

Saliva is very important to oral health, and a salivary deficit has been shown to bring serious problems to oral health. There is scant information about the mechanisms through which salivary glands participate in post–tooth extraction socket healing. Therefore, the aim of the present study was to investigate the effect of submandibulectomy (SMx), consisting of the ablation of submandibular and sublingual glands (SMG and SLG, respectively), on PGE2 signaling and other bone regulatory molecules, such as OPG and RANKL, involved in tooth extraction socket healing. Male Wistar rats, 70 g body weight, were assigned to an experimental (subjected to SMx) or a control group (sham operated). One week later, the animals in both groups underwent bilateral extraction of the first mandibular molars. The effect of SMx on different stages of socket healing after tooth extraction (7, 14, and 30 days) was studied by evaluating some parameters of inflammation, including PGE2 and its receptors, and of bone metabolism, as well as by performing bone biomechanical studies. SMx increased TNFα and PGE2 content as well as cyclooxygenase-II (COX-II) expression in tooth socket tissue at almost all the studied time points. SMx also had an effect on mRNA expression of PGE2 receptors at the different time points, but did not significantly alter osteoprotegerin (OPG) and RANKL mRNA expression at any of the studied time points. In addition, an increase in bone mass density was observed in SMx rats compared with matched controls, and the structural and mechanical bone properties of the mandibular socket bone were also affected by SMx. Our results suggest that the SMG/SLG complex regulates cellular activation and differentiation by modulating the production of molecules intervening in tooth extraction socket repair, including the PGE2 signaling system, which would therefore account for the higher density and resistance of the newly formed bone in SMx rat.Fil: Mohn, Claudia Ester. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Odontología. Cátedra de Fisiología; ArgentinaFil: Troncoso, Gastón Rodolfo. Universidad de Buenos Aires. Facultad de Odontología. Cátedra de Fisiología; ArgentinaFil: Bozzini, Clarisa. Universidad de Buenos Aires. Facultad de Odontología. Cátedra de Fisiología; ArgentinaFil: Conti, María Inés. Universidad de Buenos Aires. Facultad de Odontología. Cátedra de Fisiología; ArgentinaFil: Fernández Solari, José Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Odontología. Cátedra de Fisiología; ArgentinaFil: Elverdín, Juan Carlos. Universidad de Buenos Aires. Facultad de Odontología. Cátedra de Fisiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentin

Variaciones de nitrógeno liviano y nitratos producidos por los distintos manejos del cultivo de maíz en suelos argiudoles

p.335-343En suelos argiudoles de la provincia de Buenos Aires, se realizaron distintos ensayos para cuantificar el ritmo de mineralización del nitrógeno liviano y la producción de nitratos obtenida. Las variables usadas fueron diferentes manejos sobre un cultivo de maíz, sistemas de labranza y fertilización. El orden de la mineralización del nitrógeno liviano al finalizar el ciclo vegetal sigue la tendencia general de arada con cincel menos que arada con reja y ésta menos que arada de desfonde. En nitratos se evidencia un comportamiento similar en los diferentes manejos y lugares, con máximos de producción en septiembre-octubre y bruscas disminuciones en diciembre. El agregado de fertilizante (UREA) tiene influencia disminuyendo la mineralización de nitrógeno liviano y aumentando la producción de nitratos

Methodological evolutions of Raman spectroscopy in art and archaeology

During the last decades, Raman spectroscopy has grown from research laboratories to a well-established approach that is increasingly often used in archaeometry and conservation science

Role of energetic ions in the growth of fcc and {\omega} crystalline phases in Ti films deposited by HiPIMS

Titanium (Ti), due to its excellent properties, is widely exploited in thin film technology that usually leads to the production of {\alpha}-phase (hcp) Ti films. In this work, we investigate the phase evolution of Ti films deposited by varying type and energy of the film-forming species. To investigate different plasma species environments, films with different thicknesses are grown by using conventional Direct Current Magnetron Sputtering (DCMS) and High Power Impulse Magnetron Sputtering (HiPIMS). Furthermore, HiPIMS depositions with different substrate bias voltage US (0 V, -300 V and -500 V) are performed to investigate different ion energy ranges. Microstructure, morphology and residual stress of the deposited films, as well as the DCMS and HiPIMS plasma composition, are analysed with different characterization techniques. The DCMS samples exhibit the Ti {\alpha}-phase only and show a tensile residual stress decreasing with thickness. As far as HiPIMS samples are concerned, a compressive-tensile-compressive (CTC) behavior is observed for residual stresses as thickness increases. Specifically, films deposited in low energy ion conditions (US =0 V) show the presence of the Ti fcc phase up to a maximum thickness of about 370 nm. Differently, films deposited under high energy conditions (US = -300 V and -500 V) show the nucleation of the Ti {\omega}-phase for thicknesses greater than 260 and 330 nm, respectively. The formation of these unusual Ti phases is discussed considering the different deposition conditions.Comment: This project has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (ENSURE grant agreement No. 647554

Survey on broiler pre-slaughter mortality in a commercial abattoir of central Italy

The pre-slaughter mortality was investigated on broilers, in the Mediterranean climate condition, considering the most significant risk factors as the journey length, waiting time, season and the space allowance in cages. At first, the pre-slaughter mortality was studied considering the totality of birds and then by examining in detail three broiler categories: large, medium and small size. The average dead on arrival (DOA) recorded on the totality of birds throughout the year was 0.38% and the values obtained in winter, spring, summer and autumn were 0.52, 0.48, 0.31 and 0.22%, respectively. The mortality rate observed during the year was 0.52, 0.47 and 0.31% for large, medium and small broilers, respectively. In all three groups, the maximum values of mortality were obtained in winter, whereas the minimum ones were recorded in autumn, spring and summer for large, medium, and small size birds, respectively. The increase of journey length could cause a higher mortality rate whereas the increase of the waiting time in the facilities at controlled environmental conditions did not seem to be a risk factor, but rather a mean to reduce the number of dead animals (all P < 0.05). It is concluded that the resistance to the hostile weather conditions, long journeys and extended waiting times was strongly related with the body weight of broilers; therefore, the planning of the slaughtering activity should consider this aspect, in order to avoid animal suffering and the economic loss