Gasdermin pores permeabilize mitochondria to augment caspase-3 activation during apoptosis and inflammasome activation.

Gasdermin E (GSDME/DFNA5) cleavage by caspase-3 liberates the GSDME-N domain, which mediates pyroptosis by forming pores in the plasma membrane. Here we show that GSDME-N also permeabilizes the mitochondrial membrane, releasing cytochrome c and activating the apoptosome. Cytochrome c release and caspase-3 activation in response to intrinsic and extrinsic apoptotic stimuli are significantly reduced in GSDME-deficient cells comparing with wild type cells. GSDME deficiency also accelerates cell growth in culture and in a mouse model of melanoma. Phosphomimetic mutation of the highly conserved phosphorylatable Thr6 residue of GSDME, inhibits its pore-forming activity, thus uncovering a potential mechanism by which GSDME might be regulated. Like GSDME-N, inflammasome-generated gasdermin D-N (GSDMD-N), can also permeabilize the mitochondria linking inflammasome activation to downstream activation of the apoptosome. Collectively, our results point to a role of gasdermin proteins in targeting the mitochondria to promote cytochrome c release to augment the mitochondrial apoptotic pathway

Status of the BMV experiment

In this contribution we present the status of the BMV experiment whose goal is to measure the vacuum magnetic birefringence

Spatial distribution and partitioning of organophosphates pesticide in water and sediment from Sarno River and Estuary, Southern Italy

The organophosphates pesticide (OPP) pollution in the Sarno River and its environmental impact on the Gulf of Naples (Tyrrhenian Sea, Central Mediterranean Sea) were estimated. Nine selected OPPs (diazinon, dimethoate, malathion, chlorpyrifos, dichlorvos, fenitrothion, methidathion, tolclofos-methyl, azinphos-methyl) were determined in the water dissolved phase (DP), suspended particulate matter (SPM) and sediment samples. Total OPP concentrations ranged from 5.58 to 39.25 ng L−1 in water (as the sum of the DP and SPM) and from 0.19 to 3.98 ng g−1 in sediment samples. Contaminant discharges of OPPs into the sea were calculated in about 48,064.08 g year−1, showing that this river should account as one of the main contribution sources of OPPs to the Tyrrhenian Sea

Effect of Heat Treatment of 316L Stainless Steel Produced by Selective Laser Melting (SLM)

Selective Laser Melting (SLM) shows a big potential within additive manufacturing of metals. The competitive mechanical properties compared to conventional processes as well as the geometry freedom are the main advantages of SLM. 316L stainless steel has been investigated in previous works regarding microstructure and mechanical properties. However, the influence of heat treatments has not been fully reported yet. This work studies the influence of different heat treatments applied to 316L stainless steel produced by SLM. The microstructure evolution was investigated for different conditions. Tensile, Charpy and hardness tests were performed on the as built and heat treated samples.Mechanical Engineerin

Distribution and biology of the Blackmouth catshark Galeus melastomus in the Strait of Sicily (Central Mediterranean Sea)

The Blackmouth catshark, Galeus melastomus, Rafinesque, 1810 (Carcharhiniformes; Scyliorhinidae), is a common, although at present discarded, by- catch of the bottom trawl fisheries in the Strait of Sicily. Given its ecological interest, data gathered in experimental bottom trawl surveys were analysed in order to describe its distribution and main biological traits. The Blackmouth catshark was sampled almost exclusively on the upper slope (200-800), showing the highest frequency of occurrence (69-100%), biomass (BI; 10-85 kg*km-2) and density (DI; 54-506 N*km-2) indexes in the deeper (501-800m) grounds. Individual size (total length, TL, mm) were between 70-590 and 90-510 in females and males, respectively. The sex ratio (SR) was around 0.5. The SR by size showed a gradual decrease till 450 mm class size, followed by an increase up 1 after 500 mm. Virginal/immature specimens represented the bulk of the samples in both females (77%) and males (65%); the length at 50% of sexual maturity (Lm50%) and corresponding maturity range (Lm25% - Lm75% ) was 433 (423-443) and 380 (366-394) mm, respectively

Obesity and bone loss at menopause: The role of sclerostin

Background. Peripheral fat tissue is known to positively influence bone health. However, evidence exists that the risk of non-vertebral fractures can be increased in postmenopausal women with obesity as compared to healthy controls. The role of sclerostin, the SOST gene protein product, and body composition in this condition is unknown. Methods. We studied 28 severely obese premenopausal (age, 44.7 \ub1 3.9 years; BMI, 46.0 \ub1 4.2 kg/m2 ) and 28 BMI-matched post-menopausal women (age, 55.5 \ub1 3.8 years; BMI, 46.1 \ub1 4.8 kg/m2 ) thorough analysis of bone density (BMD) and body composition by dual X-ray absorptiometry (DXA), bone turnover markers, sclerostin serum concentration, glucose metabolism, and a panel of hormones relating to bone health. Results. Postmenopausal women harbored increased levels of the bone turnover markers CTX and NTX, while sclerostin levels were non-significantly higher as compared to premenopausal women. There were no differences in somatotroph, thyroid and adrenal hormone across menopause. Values of lumbar spine BMD were comparable between groups. By contrast, menopause was associated with lower BMD values at the hip (p < 0.001), femoral neck (p < 0.0001), and total skeleton (p < 0.005). In multivariate regression analysis, sclerostin was the strongest predictor of lumbar spine BMD (p < 0.01), while menopausal status significantly predicted BMD at total hip (p < 0.01), femoral neck (p < 0.001) and total body (p < 0.05). Finally, lean body mass emerged as the strongest predictor of total body BMD (p < 0.01). Conclusions. Our findings suggest a protective effect of obesity on lumbar spine and total body BMD at menopause possibly through mechanisms relating to lean body mass. Given the mild difference in sclerostin levels between pre-and postmenopausal women, its potential actions in obesity require further investigation

Patterns of sexualised recreational drug use and its association with risk behaviours and sexual health outcomes in men who have sex with men in London, UK: a comparison of cross-sectional studies conducted in 2013 and 2016

Objective: London has one of the highest identified prevalence of chemsex (sexualised recreational drug use) among men who have sex with men (MSM) in Europe. We examine MSM’s patterns of chemsex and its association with HIV/STI risk behaviours, STI diagnoses, and sexual healthcare-seeking behaviours, including if HIV testing behaviour met UK national guidelines (3-monthly if engaging in chemsex). Methods: Cross-sectional survey data from 2013 (n=905) and 2016 (n=739) were collected using anonymous, self-administered questionnaires from MSM recruited in commercial gay venues in London, UK. Descriptive and multivariable analyses, stratified by self-reported HIV status, were conducted. Adjusted prevalence ratios (aPR) with 95% confidence intervals (CI) were calculated. Results: Comparing the 2013 and 2016 surveys; chemsex prevalence in the past year remained stable, in both HIV-negative/unknown-status MSM (20.9% in 2013 vs 18.7% in 2016, p=0.301) and HIV-positive MSM (41.6% in 2013 vs 41.7% in 2016, p=0.992). Combined 2013-2016 data showed that compared to other MSM, those reporting chemsex were more likely to report HIV/STI risk behaviours, including condomless anal intercourse with serodifferent HIV-status partners (HIV-negative/unknown-status men: aPR 2.36, 95% CI 1.68-3.30; HIV-positive men: aPR 4.19, 95% CI 1.85-9.50), and STI diagnoses in the past year (HIV-negative/unknown-status men: aPR 2.10, 95% CI 1.64-2.69; HIV-positive men: aPR 2.56, 95% CI 1.57-4.20). 69.0% of HIV-negative/unknown-status men reporting chemsex attended sexual health clinics and 47.6% had tested for HIV more than once in the past year. Conclusions: Chemsex in London MSM remained stable but high, particularly among HIV-positive men. Irrespective of HIV status, chemsex was associated with engagement in HIV/STI risk behaviours. Frequency of HIV testing in the past year among HIV-negative/unknown-status men was below national recommendations. Promoting combination prevention strategies, including 3-monthly HIV/STI testing, access to PrEP/ART, and behavioural interventions among MSM reporting chemsex, remain vital to address sexual health inequalities in MSM

Cell cultures harbouring constructs of different pig promoter polymorphisms show different transcriptional efficiency in gene reporter systems

AbstractProduction traits variability among and within breeds, differences among developmental stages or the response to different environments are in part due to genetic factors that affect gene expression. Within the context of an Italian FIRB project, whose objective is to identify genes and molecular mechanisms affecting meat quality and production traits in pig, we studied the promoter regions of candidate genes selected on the basis of their physiological role in animal tissue development or composition. Genomic DNA was isolated from liver or muscle tissue of individuals belonging to Large White and Casertana breed. PCR primers were designed to amplify 5' upstream region of SCD (Stearoyl-CoA Desaturase), LDLR (Low Density Lipoprotein Receptor), LEP (Leptin), MSTN (Myostatin), ACTA1 (Alpha-actin) and HFABP (Heart Fatty Acid Binding Protein) genes using sequences available at NCBI. A total of 19 single nucleotide polymorphisms (SNPs) not previously described were characterised. Some haplotypes, harbou..

Dichotomy between the hole and electrons behavior in the multiband FeSe probed by ultra high magnetic fields

Magnetoresistivity \r{ho}xx and Hall resistivity \r{ho}xy in ultra high magnetic fields up to 88T are measured down to 0.15K to clarify the multiband electronic structure in high-quality single crystals of superconducting FeSe. At low temperatures and high fields we observe quantum oscillations in both resistivity and Hall effect, confirming the multiband Fermi surface with small volumes. We propose a novel and independent approach to identify the sign of corresponding cyclotron orbit in a compensated metal from magnetotransport measurements. The observed significant differences in the relative amplitudes of the quantum oscillations between the \r{ho}xx and \r{ho}xy components, together with the positive sign of the high-field \r{ho}xy , reveal that the largest pocket should correspond to the hole band. The low-field magnetotransport data in the normal state suggest that, in addition to one hole and one almost compensated electron bands, the orthorhombic phase of FeSe exhibits an additional tiny electron pocket with a high mobility.Comment: Latex, 4 pages (2 figures, 1 table), and supplemental materia