Identification and characterization of dysregulated P-element induced wimpy testis-interacting RNAs in head and neck squamous cell carcinoma.

It is clear that alcohol consumption is a major risk factor in the pathogenesis of head and neck squamous cell carcinoma (HNSCC); however, the molecular mechanism underlying the pathogenesis of alcohol-associated HNSCC remains poorly understood. The aim of the present study was to identify and characterize P-element-induced wimpy testis (PIWI)-interacting RNAs (piRNAs) and PIWI proteins dysregulated in alcohol-associated HNSCC to elucidate their function in the development of this cancer. Using next generation RNA-sequencing (RNA-seq) data obtained from 40 HNSCC patients, the piRNA and PIWI protein expression of HNSCC samples was compared between alcohol drinkers and non-drinkers. A separate piRNA expression RNA-seq analysis of 18 non-smoker HNSCC patients was also conducted. To verify piRNA expression, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed on the most differentially expressed alcohol-associated piRNAs in ethanol and acetaldehyde-treated normal oral keratinocytes. The correlation between piRNA expression and patient survival was analyzed using Kaplan-Meier estimators and multivariate Cox proportional hazard models. A comparison between alcohol drinking and non-drinking HNSCC patients demonstrated that a panel of 3,223 piRNA transcripts were consistently detected and differentially expressed. RNA-seq analysis and in vitro RT-qPCR verification revealed that 4 of these piRNAs, piR-35373, piR-266308, piR-58510 and piR-38034, were significantly dysregulated between drinking and non-drinking cohorts. Of these four piRNAs, low expression of piR-58510 and piR-35373 significantly correlated with improved patient survival. Furthermore, human PIWI-like protein 4 was consistently upregulated in ethanol and acetaldehyde-treated normal oral keratinocytes. These results demonstrate that alcohol consumption may cause dysregulation of piRNA expression in HNSCC and in vitro verifications identified 4 piRNAs that may be involved in the pathogenesis of alcohol-associated HNSCC

Étude de la contamination par les métaux lourds du champ d'épandage des eaux usées de la ville de Marrakech (Maroc)

La bioconcentration du Zn, Cu et Cd a été étudiée chez Melanopsis praemorsa L. (Gastéropode prosobranche) provenant de deux sites d'une khettara située dans le champ d'épandage des eaux usées de la ville de Marrakech. Les khettaras représentent un système d'irrigation traditionnel que l'on trouve dans certaines zones arides et semi-arides de la région ouest-paléarctique. L'eau est mise à jour par drainage de la nappe phréatique. Le degré de contamination de ce gastéropode s'avère très élevé et les teneurs métalliques augmentent de l'hiver à l'été. Les causes de la variabilité des concentrations métalliques chez les gastéropodes des deux stations ont été recherchées par des expériences de transplantation, et par des dosages de métaux au niveau du sédiment, de la spirogyre et du périphyton installé sur des substrats artificiels. Les résultats obtenus montrent que les différences entre les concentrations métalliques accumulées par les Melanopsis dans les deux stations pourraient être attribuées à la spéciation du métal dans l'eau. D'autres facteurs peuvent être mis en cause et méritent d'être précisés.Molluscs are well known for their capacity to bioaccumulate heavy metals from water or sediments. This study involves an evaluation of the contamination level of the undergroud and surface waters from a specific irrigation system known as a « khetarra », located near the town of Marrakech (Morocco). Khettaras represent a traditional systern by means ofwhich the ground water is drained to the surface and then can be used as drinking water or for irrigation in some arid and semi-arid areas. The bioindicator chosen was the gasteropod Melanopsispraemorca L. Two stations (Kl and K2) were investigated in a khettara located in spreading Marrakech waste water. The contamination of soils and water by heavy metals, eipecially Zn, Cu and Cd was first described by EL MEZD1 (1985) and SEDKI(1990).The studied khettara (1500 m. in length) is contaminated in two different ways: first by infiltration of waste water from the Seguia system and secondly directly by over-flow and escape of a main common sewer which crosses over the khetarra between the Kl andK2 stations.At each station, sediment peripbyton, Spirogyra and M. praemorsa were sampled in different seasons. Each sample was prepared for analysis (S.A.A. varian 475.AA) according to the method described by COSSON (1987). Flame atomization was chosen for Zn and Cu, the grafite furnace for Cd.The main results concern the level of contamination, with a comparison between Kl and K2 stations, the variation in contamination according to the seasons, the dilferent routes of contamination, namely through water or by the trophic chaîn (periphfion and Spirogyra).The degree of contamination in M. praemona is signifïcatively higher at the Kl station, with the following ranking: Zn> Cu> Cd (fig. 2, 3 and 4). Compared with other literature data: FORSTNER et al., 1981; RADA, 1985; COSSON, 1987; PIP, 1992, the upper concentrations are the highest.The metal concentrations increase from winter to summer, with significant differences between winter and spring or summer values at Kl for Zn, Cu, Cd; the same distinction, but only for Zn and Cd at K2 station.The causes of variation in metal concentrations in the gasteropods from the two sites were investigated,by in situ cotransplantation experiences and by measuring metaflic concentrations in sediments, periphyton and Spirogyra. Results show that differences in gasteropod metal concentrations between sites appear to be related to differences in aqueous metal speciation. The data concerning the food chain show that metallic concentrations are higher for periphyton and, Spirogyra living at Kl station, this according to the data for M. praemorsa.In contrast, the level of contamination in sediments is higher at K2 station. The most probable hypothesis is that organic and suspended matter, present at a higher level in this station, bind the heary metals and reduce their bioavailability.The cotransplantation between Kl and K2 stations shows that the individuals transferred from Kl to K2 station for 15 days cease to bioaccumulate Zn and Cd. A detoxification process occurs for these two metals but not for Cu, which continues to increase; thus, bioavailability of different metals at the same station is not equivalent. On the other hand the individuals transferred from K2 to Kl station do not increase their Zn, Cu or Cd concentrations even after 30 days. Concerning this fact FRAZIER and GEORGE (1983) suggest the possibility of an adaptation to initial conditions.It seems that many other factors influence metal bioaccumulation and merit further study, e.g.: the size and the age of individuals, the biological cycle with the period of reproduction ; the interaction of abiotic factors: T°, salinity, dissolved orygen, turbidity, lighting

Alcohol-dysregulated miR-30a and miR-934 in head and neck squamous cell carcinoma.

BackgroundAlcohol consumption is a well-established risk factor for head and neck squamous cell carcinoma (HNSCC); however, the molecular mechanisms by which alcohol promotes HNSCC pathogenesis and progression remain poorly understood. Our study sought to identify microRNAs that are dysregulated in alcohol-associated HNSCC and investigate their contribution to the malignant phenotype.MethodUsing RNA-sequencing data from 136 HNSCC patients, we compared the expression levels of 1,046 microRNAs between drinking and non-drinking cohorts. Dysregulated microRNAs were verified by qRT-PCR in normal oral keratinocytes treated with biologically relevant doses of ethanol and acetaldehyde. The most promising microRNA candidates were investigated for their effects on cellular proliferation and invasion, sensitivity to cisplatin, and expression of cancer stem cell genes. Finally, putative target genes were identified and evaluated in vitro to further establish roles for these miRNAs in alcohol-associated HNSCC.ResultsFrom RNA-sequencing analysis we identified 8 miRNAs to be significantly upregulated in alcohol-associated HNSCCs. qRT-PCR experiments determined that among these candidates, miR-30a and miR-934 were the most highly upregulated in vitro by alcohol and acetaldehyde. Overexpression of miR-30a and miR-934 in normal and HNSCC cell lines produced up to a 2-fold increase in cellular proliferation, as well as induction of the anti-apoptotic gene BCL-2. Upon inhibition of these miRNAs, HNSCC cell lines exhibited increased sensitivity to cisplatin and reduced matrigel invasion. miRNA knockdown also indicated direct targeting of several tumor suppressor genes by miR-30a and miR-934.ConclusionsAlcohol induces the dysregulation of miR-30a and miR-934, which may play crucial roles in HNSCC pathogenesis and progression. Future investigation of the alcohol-mediated pathways effecting these transformations will prove valuable for furthering the understanding and treatment of alcohol-associated HNSCC

Charge transfer and Fermi level shift in p-doped single-walled carbon nanotubes

The electronic properties of p-doped single-walled carbon nanotube (SWNT) bulk samples were studied by temperature-dependent resistivity and thermopower, optical reflectivity, and Raman spectroscopy. These all give consistent results for the Fermi level downshift (Delta E(F)) induced by doping. We find Delta E(F) approximate to 0.35 eV and 0.50 eV for concentrated nitric and sulfuric acid doping respectively. With these values, the evolution of Raman spectra can be explained by variations in the resonance condition as E(F) moves down into the valence band. Furthermore, we find no evidence for diameter-selective doping, nor any distinction between doping responses of metallic and semiconducting tubes

Bulk and boundary zero-bias anomaly in multi-wall carbon nanotubes

We compute the tunneling density of states of doped multi-wall nanotubes including disorder and electron-electron interactions. A non-conventional Coulomb blockade reflecting nonperturbative Altshuler-Aronov-Lee power-law zero-bias anomalies is found, in accordance with recent experimental results. The presence of a boundary implies a universal doubling of the boundary exponent in the diffusive limit.Comment: 4 pages, to appear in PRL (revised version

First assessment of pollution impact at Essaouira coast (Morocco) using biotic and abiotic parameters and the red algae Ellisolandia elongata as potential bioindicator of organic pollution

Environmental pollutants might significantly affect the ecological integrity of coastal waters. Biological indicators like seaweeds have been used globally to assess water pollution. In the present work, the seaweed Ellisolandia elongata was used to evaluate the pollution status in coastal waters around Essaouira city. Three sites were chosen: One as reference station (S1) and two polluted ones (S2 and S3). Seaweed biodiversity, physiologic parameters of E. elongata, as well as, abiotic parameters were studied. Results showed that at the polluted stations, seaweed biodiversity was significantly lower than in S1. However, the concentrations of Total Suspended Solids, Electrical Conductivity, Biological Oxygen Demand, Chemical Oxygen Demand, Ammonium, and Orthophosphates at S2 were significantly higher than at S1. Metal content of E. elongata remained below detection limit at all stations except for Zn and Cu at S2 considered the most polluted station. With respect to the physiologic parameters, Proline, Glycine Betaine and Polyphenol contents at S2 were above, whereas, Chlorophyll a content and axis length were below those determined at the reference station. From the results it can be concluded that seaweed E. elongata could be a good indicator to determine organic pollution in marine ecosystem

Synthesis of pH-responsive hydrogel based on PVP grafted with crotonic acid for controlled drug delivery

In the present study polyvinylpyrrolidone (PVP) was grafted with crotonic acid (CrA) in order to obtain novel hydrogels which are pH – responsive. The grafting was performed by mixing the polymer solution with various concentrations of CrA and applying gamma radiation at different doses. The effects of the preparation conditions such as the irradiation dose and CrA concentration on the gelation process and swelling of the synthesized copolymer were investigated. The hydrogel system was used as carrier for a model drug, ketoprofen, the release behaviour of the drug from the hydrogel was monitored in two different release media (pH 1 and pH 7.2), and released amounts of ketoprofen were followed up spectrophotometrically. The release was low in the acidic medium compared to a better and extended release in the neutral medium suggesting the possibility of using this hydrogel as potential drug carrier to allow targeted release in the intestinal medium