Human aquaporin-11 guarantees efficient transport of H2O2 across the endoplasmic reticulum membrane

Hydrogen peroxide (H2O2) is an essential second intracellular messenger. To reach its targets in the cytosol, H2O2 must cross a membrane, a feat that requires aquaporins (AQP) endowed with 'peroxiporin' activity (AQP3, AQP8, AQP9). Here, we exploit different organelle-targeted H2O2-sensitive probes to show that also AQP11 efficiently conduits H2O2. Unlike other peroxiporins, AQP11 is localized in the endoplasmic reticulum (ER), accumulating partly in mitochondrial-associated ER membranes (MAM). Its downregulation severely perturbs the flux of H2O2 through the ER, but not through the mitochondrial or plasma membranes. These properties make AQP11 a potential regulator of ER redox homeostasis and signaling.This work was supported in part through grants from the Associazione Italiana Ricerca sul Cancro (IG 2016-18824 to R.S.), the Fondazione Cariplo (2015-0591 to R.S.), and the Telethon (GGP15059 to R.S.). A.R. was supported by local funds from the University of Ferrara and the Italian Ministry of Health (GR-2016-02364602). Italian Association for Cancer Research (AIRC, IG-18624), Telethon (GGP11139B), and local funds from the University of Ferrara to P.P

A persulfidation-based mechanism controls aquaporin-8 conductance

Upon engagement of tyrosine kinase receptors, nicotinamide adenine dinucleotide phosphate (NADPH)-oxidases release H2O2 in the extracellular space. We reported previously that aquaporin-8 (AQP8) transports H2O2 across the plasma membrane and is reversibly gated during cell stress, modulating signal strength and duration. We show that AQP8 gating is mediated by persulfidation of cysteine 53 (C53). Treatment with H2S is sufficient to block H2O2 entry in unstressed cells. Silencing cystathionine beta-synthase (CBS) prevents closure, suggesting that this enzyme is the main source of H2S. Molecular modeling indicates that C53 persulfidation displaces a nearby histidine located in the narrowest part of the channel. We propose that H2O2 molecules transported through AQP8 sulfenylate C53, making it susceptible to H2S produced by CBS. This mechanism tunes H2O2 transport and may control signaling and limit oxidative stress.This work was supported in part through grants from the Associazione Italiana Ricerca sul Cancro (IG 2016-18824 to R.S. and IG 2016-15434 to A.R.), the Fondazione Cariplo (2015-0591 to R.S.), the Ministero della Salute (PE-2011-02352286 to R.S. and RF-2013-02354880 to G.M.), the Telethon (GGP15059 to R.S.), and the "Cinque per mille"; (to A.R.). G.P.B. was supported by an Emmy Noether grant 1668/1-1 from the Deutsche Forschungsgemeinschaft

Temporal variability and effect of environmental variables on airborne bacterial communities in an urban area of Northern Italy

Despite airborne microorganisms representing a relevant fraction of atmospheric suspended particles, only a small amount of information is currently available on their abundance and diversity and very few studies have investigated the environmental factors influencing the structure of airborne bacterial communities. In this work, we used quantitative PCR and Illumina technology to provide a thorough description of airborne bacterial communities in the urban area of Milan (Italy). Forty samples were collected in 10-day sampling sessions, with one sessionper season.Themeanbacterialabundancewasabout104 ribosomal operons perm3 of air andwas lower inwinter than in the other seasons. Communitieswere dominated by Actinobacteridae, Clostridiales, Sphingobacteriales and fewproteobacterial orders (Burkholderiales, Rhizobiales, Sphingomonadales andPseudomonadales).Chloroplastswere abundant in all samples. Ahigher abundanceof Actinobacteridae,which are typical soil-inhabiting bacteria, and a lower abundance of chloroplasts in samples collected on cold days were observed. The variation in community composition observed within seasons was comparable to that observed between seasons, thus suggesting that airborne bacterial communities showlarge temporal variability, even between consecutive days. The structure of airborne bacterial communities therefore suggests that soil and plants are the sources which contribute most to the airborne communities of Milan atmosphere, but the structure of the bacterial community seems to depend mainly on the source of bacteria that predominates in a given period of time

Elastocaloric Properties of Polycrystalline Samples of NiMnGaCu Ferromagnetic Shape Memory Alloy under Compression: Effect of Improvement of Thermoelastic Martensitic Transformation

Shape memory alloys (SMAs) and ferromagnetic shape memory alloys (FeSMAs) have recently attracted interest for solid state refrigeration applications. Among NiMnGa-based quaternary systems, NiMnGaCu exhibits an interesting giant magnetocaloric effect thanks to the overlapping of the temperatures related to the magnetic transition and the thermoelastic martensitic transformation (TMT); in particular, for compositions with Cu content of approximately 6 at%. In the present work, we investigated the improvement effect of TMT on the total entropy change (ΔS) in the elastocaloric performances of polycrystalline Ni50Mn18.5Cu6.5Ga25 at% alloy samples, just above room temperature. We report an extensive calorimetric and thermomechanical characterization to explore correlations between microstructural properties induced by the selected thermal treatment and elastocaloric response, aiming at providing the basis to develop more efficient materials based on this quaternary system. Both ΔT and ΔS values obtained from mechanical curves at different temperatures and strain recovery tests under fixed load vs. T were considered. Maximum values of ΔS = 55.9 J/KgK and ΔT = 4.5 K were attained with, respectively, a stress of 65 MPa and strain of 4%. The evaluation of the coefficient of performance (COP) was carried out from a cyclic test

Carpals and epiphyses of radius and ulna as age indicators using longitudinal data: a Bayesian approach

The aim of this study is to develop a new formula for age estimation in a longitudinal study of a sample from the radiological collection of wrist bones of growing infants, children, and adolescents recorded at the Burlington Growth Centre. A sample of 82 individuals (43 boys and 39 girls), aged between 3 and 16 years, were analyzed with a total of 623 X-rays of left hand-wrist bones by measuring the area of carpal bones and epiphyses of the ulna and radius (Bo) and carpal area (Ca). The intra-class correlation coefficient (ICC) and its 95% confidence interval were used to evaluate intra-observer agreement. Hierarchical Bayesian calibration has been adopted to exceed the bias deriving from the classical regression approach used for age estimation in forensic disciplines, since it tends to overestimate or underestimate the age of the individuals. Calibration distributions of the dataset obtained by the evaluation of BoCa (the ratio of Bo and Ca) suggested mean absolute errors (MAE) of 1.07 and 1.34 years in boys and girls, respectively. The mean interquartile range (MIQR) was 1.7 and 2.42 years in boys and girls, respectively. The respective bias of the estimates was βERR = - 0.025 and - 0.074. Furthermore, a correspondence between different BoCa values and estimated age with its standard deviation (SD) was calculated for boys and girls, respectively. In conclusion, the Bayesian calibration method appears to be suitable for assessing both age and its distribution in subadults, according to hand-wrist maturity. Furthermore, it can easily incorporate other age predictors, obtaining a distribution of the subjects with multivariate predictors

Stress Regulates Aquaporin-8 Permeability to Impact Cell Growth and Survival

Aquaporin-8 (AQP8) allows the bidirectional transport of water and hydrogen peroxide across biological membranes. Depending on its concentration, H2O2 exerts opposite roles, amplifying growth factor signaling in physiological conditions, but causing severe cell damage when in excess. Thus, H2O2 permeability is likely to be tightly controlled in living cells. AIMS: In this study, we investigated whether and how the transport of H2O2 through plasma membrane AQP8 is regulated, particularly during cell stress. RESULTS: We show that diverse cellular stress conditions, including heat, hypoxia, and ER stress, reversibly inhibit the permeability of AQP8 to H2O2 and water. Preventing the accumulation of intracellular reactive oxygen species (ROS) during stress counteracts AQP8 blockade. Once inhibition is established, AQP8-dependent transport can be rescued by reducing agents. Neither H2O2 nor water transport is impaired in stressed cells expressing a mutant AQP8, in which cysteine 53 had been replaced by serine. Cells expressing this mutant are more resistant to stress-, drug-, and radiation-induced growth arrest and death. INNOVATION AND CONCLUSION: The control of AQP8-mediated H2O2 transport provides a novel mechanism to regulate cell signaling and survival during stress

Assessment of second (I2M) and third (I3M) molar indices for establishing 14 and 16 legal ages and validation of the Cameriere's I3M cut-off for 18 years old in Chilean population

AIMS:The evaluation of the cutoff value of I3M = 0.08 for discriminating black South African minors from adults, and its relationship with chronological age. MATERIAL AND METHODS:A sample of 833 panoramic radiographs of healthy black South African subjects (500 females and 333 males), in the age range of 14 to 24 years (mean age 17.67 years in females and 17.42 years in males), was retrospectively evaluated. RESULTS:ICC values were 99.10% (95% CI 97.70 to 99.70%) and 99.20% (95% CI 98.00 to 99.60%), for the intra- and inter-observer reliability, respectively. I3M decreased as the real age gradually increased in both sexes. According to the logistic regression model, the variable sex was not significant when the probability that an individual is 18 years or older was calculated. The I3M = 0.08 was valuable in discriminating between adults and minors. The overall accuracy (ACC = fraction of accurately classified subjects) is 0.90 (95% CI 0.87-0.91); the proportion of correctly classified subjects (Se = sensitivity) is 0.80 (95% CI 0.76-0.84), and specificity (Sp) is 0.95 (95% CI 0.93-0.97). The PPV (predictive positive value) is 0.96 (95% CI 0.95-0.97), and the negative predictive value is 0.76 (95% CI 0.72-0.80). CONCLUSION:The results show that I3M is a valuable method to distinguish subjects who are around legal adult age in South Africa