Browsing by Subject "ZINC"

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  • Arar, Sharif; Al-Hunaiti, Afnan; Masad, Mohanad H.; Maragkidou, Androniki; Wraith, Darren; Hussein, Tareq (2019)
    In this study, we performed elemental analysis for floor dust samples collected in Jordanian microenvironments (dwellings and educational building). We performed intercorrelation and cluster analysis between the elemental, polyaromatic hydrocarbon (PAH), and microorganism concentrations. In general, the educational building workshops had the highest elemental contamination. The age of the dwelling and its occupancy played a role on the elemental contamination level: older and more occupied dwellings had greater contamination. The elemental contamination at a dwelling entrance was observed to be higher than in the living room. We found exceptionally high concentrations for Fe and Mn in the educational workshop and additionally, Hg, Cr, and Pb concentrations exceeded the limits set by the Canadian Council of Ministers of the Environment. According to the cluster analysis, we found three major groups based on location and contamination. According to the enrichment factor (EF) assessment, Al, Co, Mn, Ti, and Ba had EF <2 (i.e., minimal enrichment) whereas P, S, Pb, Sb, Mo, Zn, Hg, and Cu had EF > 40 (i.e., extremely enriched). In contrast, Ca and P were geogenically enriched. Furthermore, significant Spearman correlations indicated nine subgroups of elemental contamination combined with PAHs and microbes.
  • Safdar, Luqman Bin; Almas, Fakhrah; Rehman, Attiq Ur; Umer, Muhammad Jawad; Shah, Syed Mashab Ali; Uddin, Siraj; Ashfaq, Shomaila; Rahman, Hamid Ur; Quraishi, Umar Masood (2020)
    Excess Ni intake has harmful implications on human health, which include chronic bronchitis, reduced lung function, and cancer of lung and nasal sinuses. Like other toxic metals, higher Ni accumulation in grains leads to excess intake by humans when the contaminated grains are consumed as food. There is little information about the genetic factors that regulate Ni uptake in plants. To investigate genetic architecture of Ni uptake in leaf and translocation to grain, we performed a genome-wide association study with genotyping from 90 K array in a historical bread wheat diversity panel from Pakistan. We observed that Ni toxicity caused more than 50 % reductions in biological yield and grain yield, other agronomic traits were also partly or severely affected. Genetic association study helped identify 23 SNP-trait associations involved in Ni uptake in leaf and translocation to grains. These 23 SNPs covered 15 genomic loci at chromosomes 1A, 2D, 3B, 4A and 4B of wheat. The favorable alleles of these SNPs were randomly distributed in subpopulations indicating no selection pressure for this trait during breeding improvement. These regions had 283 low-confidence and 248 high-confidence protein coding genes. Among these, 156 were annotated using databases of wheat and closely related grass species. Since there is no previous report on genetic information of Ni uptake and translocation, these results provide sufficient grounds for further research of candidate genes and varietal development.
  • Ward, Heather A.; Whitman, Julia; Muller, David C.; Johansson, Mattias; Jakszyn, Paula; Weiderpass, Elisabete; Palli, Domenico; Fanidi, Anouar; Vermeulen, Roel; Tjonneland, Anne; Hansen, Louise; Dahm, Christina C.; Overvad, Kim; Severi, Gianluca; Boutron-Ruault, Marie-Christine; Affret, Aurelie; Kaaks, Rudolf; Fortner, Renee; Boeing, Heiner; Trichopoulou, Antonia; La Vecchia, Carlo; Kotanidou, Anastasia; Berrino, Franco; Krogh, Vittorio; Tumino, Rosario; Ricceri, Fulvio; Panico, Salvatore; Bueno-de-Mesquita, H. Bas; Peeters, Petra H.; Nost, Therese Haugdahl; Sandanger, Torkjel M.; Ramon Quiros, Jose; Agudo, Antonio; Rodriguez-Barranco, Miguel; Larranaga, Nerea; Maria Huerta, Jose; Ardanaz, Eva; Drake, Isabel; Brunnstrom, Hans; Johansson, Mikael; Grankvist, Kjell; Travis, Ruth C.; Freisling, Heinz; Stepien, Magdalena; Merritt, Melissa A.; Riboli, Elio; Cross, Amanda J. (2019)
    Background Epidemiological studies suggest that haem iron, which is found predominantly in red meat and increases endogenous formation of carcinogenic N-nitroso compounds, may be positively associated with lung cancer. The objective was to examine the relationship between haem iron intake and lung cancer risk using detailed smoking history data and serum cotinine to control for potential confounding. Methods In the European Prospective Investigation into Cancer and Nutrition (EPIC), 416,746 individuals from 10 countries completed demographic and dietary questionnaires at recruitment. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for incident lung cancer (n = 3731) risk relative to haem iron, non-haem iron, and total dietary iron intake. A corresponding analysis was conducted among a nested subset of 800 lung cancer cases and 1489 matched controls for whom serum cotinine was available. Results Haem iron was associated with lung cancer risk, including after adjustment for details of smoking history (time since quitting, number of cigarettes per day): as a continuous variable (HR per 0.3 mg/1000 kcal 1.03, 95% CI 1.00-1.07), and in the highest versus lowest quintile (HR 1.16, 95% CI 1.02-1.32; trend across quintiles: P = 0.035). In contrast, non-haem iron intake was related inversely with lung cancer risk; however, this association attenuated after adjustment for smoking history. Additional adjustment for serum cotinine did not considerably alter the associations detected in the nested case-control subset. Conclusions Greater haem iron intake may be modestly associated with lung cancer risk.
  • Local Burden Dis Diarrhoea; Wiens, Kirsten E.; Lindstedt, Paulina A.; Blacker, Brigette F.; Meretoja, Tuomo J.; Shiri, Rahman (2020)
    Background Oral rehydration solution (ORS) is a form of oral rehydration therapy (ORT) for diarrhoea that has the potential to drastically reduce child mortality; yet, according to UNICEF estimates, less than half of children younger than 5 years with diarrhoea in low-income and middle-income countries (LMICs) received ORS in 2016. A variety of recommended home fluids (RHF) exist as alternative forms of ORT; however, it is unclear whether RHF prevent child mortality. Previous studies have shown considerable variation between countries in ORS and RHF use, but subnational variation is unknown. This study aims to produce high-resolution geospatial estimates of relative and absolute coverage of ORS, RHF, and ORT (use of either ORS or RHF) in LMICs. Methods We used a Bayesian geostatistical model including 15 spatial covariates and data from 385 household surveys across 94 LMICs to estimate annual proportions of children younger than 5 years of age with diarrhoea who received ORS or RHF (or both) on continuous continent-wide surfaces in 2000-17, and aggregated results to policy-relevant administrative units. Additionally, we analysed geographical inequality in coverage across administrative units and estimated the number of diarrhoeal deaths averted by increased coverage over the study period. Uncertainty in the mean coverage estimates was calculated by taking 250 draws from the posterior joint distribution of the model and creating uncertainty intervals (UIs) with the 2 center dot 5th and 97 center dot 5th percentiles of those 250 draws. Findings While ORS use among children with diarrhoea increased in some countries from 2000 to 2017, coverage remained below 50% in the majority (62 center dot 6%; 12 417 of 19 823) of second administrative-level units and an estimated 6 519 000 children (95% UI 5 254 000-7 733 000) with diarrhoea were not treated with any form of ORT in 2017. Increases in ORS use corresponded with declines in RHF in many locations, resulting in relatively constant overall ORT coverage from 2000 to 2017. Although ORS was uniformly distributed subnationally in some countries, within-country geographical inequalities persisted in others; 11 countries had at least a 50% difference in one of their units compared with the country mean. Increases in ORS use over time were correlated with declines in RHF use and in diarrhoeal mortality in many locations, and an estimated 52 230 diarrhoeal deaths (36 910-68 860) were averted by scaling up of ORS coverage between 2000 and 2017. Finally, we identified key subnational areas in Colombia, Nigeria, and Sudan as examples of where diarrhoeal mortality remains higher than average, while ORS coverage remains lower than average. Interpretation To our knowledge, this study is the first to produce and map subnational estimates of ORS, RHF, and ORT coverage and attributable child diarrhoeal deaths across LMICs from 2000 to 2017, allowing for tracking progress over time. Our novel results, combined with detailed subnational estimates of diarrhoeal morbidity and mortality, can support subnational needs assessments aimed at furthering policy makers' understanding of within-country disparities. Over 50 years after the discovery that led to this simple, cheap, and life-saving therapy, large gains in reducing mortality could still be made by reducing geographical inequalities in ORS coverage. Copyright (c) 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.
  • Takamiya, Masanari; Xu, Feng; Suhonen, Heikki; Gourain, Victor; Yang, Lixin; Nga Yu Ho, [Tuntematon]; Helfen, Lukas; Schroeck, Anne; Etard, Christelle; Grabher, Clemens; Rastegar, Sepand; Schlunck, Guenther; Reinhard, Thomas; Baumbach, Tilo; Straehle, Uwe (2016)
    Altered levels of trace elements are associated with increased oxidative stress that is eventually responsible for pathologic conditions. Oxidative stress has been proposed to be involved in eye diseases, including cataract formation. We visualized the distribution of metals and other trace elements in the eye of zebrafish embryos by micro X-ray fluorescence (mu-XRF) imaging. Many elements showed highest accumulation in the retinal pigment epithelium (RPE) of the zebrafish embryo. Knockdown of the zebrafish brown locus homologues tyrp1a/b eliminated accumulation of these elements in the RPE, indicating that they are bound by mature melanosomes. Furthermore, albino (slc45a2) mutants, which completely lack melanosomes, developed abnormal lens reflections similar to the congenital cataract caused by mutation of the myosin chaperon Unc45b, and an in situ spin trapping assay revealed increased oxidative stress in the lens of albino mutants. Finally transplanting a wildtype lens into an albino mutant background resulted in cataract formation. These data suggest that melanosomes in pigment epithelial cells protect the lens from oxidative stress during embryonic development, likely by buffering trace elements.
  • Heikkilä, Aki (Helsingfors universitet, 2015)
    Lead molecule search is the first part of drug design. This process can be done using computerized docking of ligands into target proteins. Usually this requires expensive software and powerful computer systems specifically made for the process. There are however some programs that are available for free and can be run on home computers. The purpose of this Master's Thesis was to see how these free software can be used for the task of docking and also to create a method or a guideline for such work. Protein kinase C (PKC), a popular target for drug design, was chosen as a target of inhibitor design. PKC is part of a larger family of serine/threonine kinases and formed of 10 isoforms all with different effects on cellular functions. The large amount of related kinases and the similarities in their sequences make finding selective inhibitors a difficult process. Homology models of all PKC isoforms in three known conformations solved by x-ray diffraction (pdb: 1XJD, 2I0E and 3A8W) were created using Modeller. Into these models a set of possible ligands from the free database of molecules ZINC was docked using Autodock Vina utilizing a script created for docking multiple ligands into multiple targets. The dockings resulted in some interesting results. Six molecules were recognized as possible lead molecules for further research. None of these molecules had any patents or previous results of protein kinase inhibition connected to them. The most interesting result was the finding that coluracetam, a nootropic drug of the racetam family, might be a protein kinase inhibitor. Racetams are usually considered drugs that lead to PKC activation. It has been proposed that inhibitors may prolong the lifetime of kinases in the cells leading to increased activity in the long term. In our opinion coluracetam might prove to be a good tool for studying the complex way kinase activity is modulated. The methods and scripts used in this work will be released for free use.
  • Patrikainen, Maarit; Pan, Peiwen; Kulesskaya, Natalia; Voikar, Vootele; Parkkila, Seppo (2014)