Total Mercury Levels In The Coastal Environment Of Qatar (Arabian Gulf)

The levels of total Mercury (t-Hg) were determined in various segments of the marine environment of Qatar. Several coastal stations, both on the East as well as the West coast of Qatar were worked for t-Hg in seawater, sediments and biological matrices. Nearly 20 stations were worked within the EEZ of Qatar, on the east coast, wherein seawater samples were collected at different depths for t-Hg along with surface sediments and resident biota. Seawater samples were not filtered and results given are for total dissolved Hg. Sediment samples were analyzed for leachable as well as t-Hg contents. A wide range of 22-198 ng/L values were obtained for the seawater samples, 0.098-317 ug/g dry wt. in sediments and 0.008-0.093 ug/g dry wt. in biota were measured. The leachable fractions amounted to a range of 3-18% of the t-Hg in sediments. The results do not indicate any elevated levels but are discussed in the light of the geographical distribution of stations and sampling sites with respect to their location and possible input sources

Multi-ancestry genome-wide association analyses improve resolution of genes and pathways influencing lung function and chronic obstructive pulmonary disease risk

Lung-function impairment underlies chronic obstructive pulmonary disease (COPD) and predicts mortality. In the largest multi-ancestry genome-wide association meta-analysis of lung function to date, comprising 580,869 participants, we identified 1,020 independent association signals implicating 559 genes supported by ≥2 criteria from a systematic variant-to-gene mapping framework. These genes were enriched in 29 pathways. Individual variants showed heterogeneity across ancestries, age and smoking groups, and collectively as a genetic risk score showed strong association with COPD across ancestry groups. We undertook phenome-wide association studies for selected associated variants as well as trait and pathway-specific genetic risk scores to infer possible consequences of intervening in pathways underlying lung function. We highlight new putative causal variants, genes, proteins and pathways, including those targeted by existing drugs. These findings bring us closer to understanding the mechanisms underlying lung function and COPD, and should inform functional genomics experiments and potentially future COPD therapies

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

الطحالب البحرية ككاشفات حيوية لمستويات التلوث في الخليج العربي

The extensive distribution of several marine macroalgal species makes them a potential bioindicator tool for monitoring existing levels of different types of marine pollutants in the region. The present work illustrates the importance of a few widely distributed species of marine algae in depicting the levels of some toxic heavy metals and hydrocarbons along the Qatari and Saudi Arabian shores. Results indicate a strong bioaccumulation potential in these species for both heavy metals and hydrocarbons. A similar monitoring scheme using these identified species could very well be extended to other areas in the Gulf in order to form a comprehensive monitoring plan for the region. This field study also highlights the potential for removal of pollutants by algae as they are washed ashore in large quantities in the region.التوزيع المكثف لعدد من الطحالب البحرية في الخليج يلعب درراً كبيراً في استخدامها ككاشفات حيوية لرصد، تركيزات بعض الملوثات في المنطقة . وتوضح الدراسة الحالية أهمية تواجد وانتشار بعض أجناس الطحالب في تقدير مستويات بعض الفلزات الثقيلة والهيدروكرلونات البترولية حول السواحل القطرية والسعودية . أبرزت النتائج تراكم تلك الملوثات في هذه الأجناس بصورة واضحة وكذلك امكانية تطبيق برنامج رصد مكثف مشابه في أماكن أخرى بمنطقة الخليج . كما ألقت الدراسة الضوء على أهمية التخلص الطبيعي من الملوثات البحرية عند انجراف الطحالب بعد موتها بكميات كبيرة على شواطىء المنطقة

Targeting Wnt/EZH2/microRNA-708 signaling pathway inhibits neuroendocrine differentiation in prostate cancer

Prostate cancer (PC) castration resistance has been linked to the differentiation of PC luminal cells into hormone-refractory neuroendocrine (NE) cells. However, the molecular mechanisms controlling the emergence of lethal NE prostate cancer (NEPC) remain unclear. The present study aimed to investigate the mechanisms underlying the transition from prostate adenocarcinoma to NEPC. The microRNA miR-708 was involved in NE differentiation and was downregulated in NEPC cells and tumor specimens. miR-708 targeted Sestrin-3 to inhibit Forkhead Box O1 (FOXO1) phosphorylation, resulting in apoptosis of prostate adenocarcinoma cells and AKT-inactivated NEPC cells, the latter of which was consistent with the progression of tumor xenografts in mice under miR-708 treatment. In silico analysis of PC and NEPC tumor specimens suggested that the polycomb repressive complex subunit Enhancer of zeste homolog 2 (EZH2) was particularly overexpressed in NEPC. Notably, EZH2 bound to the miR-708 promoter and induced its silencing in NEPC. Inhibition of EZH2 prevented NE differentiation of PC cells. EZH2 expression was regulated by both Cyclin Dependent Kinase 1 (CDK1) and Wnt signaling. Silencing transcription factor 4 (TCF4), as a key protein in Wnt signaling, prevented NEPC formation. These results provide a molecular basis for the roles of miR-708 and EZH2 in NE differentiation in PC and highlight a new paradigm in NEPC formation and survival.Other Information Published in: Cell Death Discovery License: https://creativecommons.org/licenses/by/4.0See article on publisher's website: http://dx.doi.org/10.1038/s41420-019-0218-y</p