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Evana N. Abdulaziz Tristan A. Bell Bazlur Rashid Mina L. Heacock Tarik Begic Owen S. Skinner Mohammad A. Yaseen Luke H. Chao Vamsi K. Mootha Antonio J. Pierik Valentin Cracan 《The Journal of biological chemistry》2022,298(8)
Microaerophilic pathogens such as Giardia lamblia, Entamoeba histolytica, and Trichomonas vaginalis have robust oxygen consumption systems to detoxify oxygen and maintain intracellular redox balance. This oxygen consumption results from H2O-forming NADH oxidase (NOX) activity of two distinct flavin-containing systems: H2O-forming NOXes and multicomponent flavodiiron proteins (FDPs). Neither system is membrane bound, and both recycle NADH into oxidized NAD+ while simultaneously removing O2 from the local environment. However, little is known about the specific contributions of these systems in T. vaginalis. In this study, we use bioinformatics and biochemical analyses to show that T. vaginalis lacks a NOX–like enzyme and instead harbors three paralogous genes (FDPF1–3), each encoding a natural fusion product between the N-terminal FDP, central rubredoxin (Rb), and C-terminal NADH:Rb oxidoreductase domains. Unlike a “stand-alone” FDP that lacks Rb and oxidoreductase domains, this natural fusion protein with fully populated flavin redox centers directly accepts reducing equivalents of NADH to catalyze the four-electron reduction of oxygen to water within a single polypeptide with an extremely high turnover. Furthermore, using single-particle cryo-EM, we present structural insights into the spatial organization of the FDP core within this multidomain fusion protein. Together, these results contribute to our understanding of systems that allow protozoan parasites to maintain optimal redox balance and survive transient exposure to oxic conditions. 相似文献
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Chen Chen John Wang Jeff Kwong JinHee Kim Aaron van Donkelaar Randall V. Martin Perry Hystad Yushan Su Eric Lavigne Megan Kirby-McGregor Jay S. Kaufman Tarik Benmarhnia Hong Chen 《CMAJ》2022,194(20):E693
Background:The tremendous global health burden related to COVID-19 means that identifying determinants of COVID-19 severity is important for prevention and intervention. We aimed to explore long-term exposure to ambient air pollution as a potential contributor to COVID-19 severity, given its known impact on the respiratory system.Methods:We used a cohort of all people with confirmed SARS-CoV-2 infection, aged 20 years and older and not residing in a long-term care facility in Ontario, Canada, during 2020. We evaluated the association between long-term exposure to fine particulate matter (PM2.5), nitrogen dioxide (NO2) and ground-level ozone (O3), and risk of COVID-19-related hospital admission, intensive care unit (ICU) admission and death. We ascertained individuals’ long-term exposures to each air pollutant based on their residence from 2015 to 2019. We used logistic regression and adjusted for confounders and selection bias using various individual and contextual covariates obtained through data linkage.Results:Among the 151 105 people with confirmed SARS-CoV-2 infection in Ontario in 2020, we observed 8630 hospital admissions, 1912 ICU admissions and 2137 deaths related to COVID-19. For each interquartile range increase in exposure to PM2.5 (1.70 μg/m3), we estimated odds ratios of 1.06 (95% confidence interval [CI] 1.01–1.12), 1.09 (95% CI 0.98–1.21) and 1.00 (95% CI 0.90–1.11) for hospital admission, ICU admission and death, respectively. Estimates were smaller for NO2. We also estimated odds ratios of 1.15 (95% CI 1.06–1.23), 1.30 (95% CI 1.12–1.50) and 1.18 (95% CI 1.02–1.36) per interquartile range increase of 5.14 ppb in O3 for hospital admission, ICU admission and death, respectively.Interpretation:Chronic exposure to air pollution may contribute to severe outcomes after SARS-CoV-2 infection, particularly exposure to O3.By November 2021, COVID-19 had caused more than 5 million deaths globally1 and more than 29 400 in Canada.2 The clinical manifestations of SARS-CoV-2 infection range from being asymptomatic to multiple organ failure and death. Identifying risk factors for COVID-19 severity is important to better understand etiological mechanisms and identify populations to prioritize for screening, vaccination and medical treatment. Risk factors for severity of COVID-19 include male sex, older age, pre-existing medical conditions and being from racialized communities.3–5 More recently, ambient air pollution has been implicated as a potential driver of COVID-19 severity.6–10Long-term exposure to ambient air pollution, a major contributor to global disease burden,11 could increase the risk of severe COVID-19 outcomes by several mechanisms. Air pollutants can reduce individuals’ pulmonary immune responses and antimicrobial activities, boosting viral loads.8 Air pollution can also induce chronic inflammation and overexpression of the alveolar angiotensin-converting enzyme 2 (ACE) receptor,7 the key receptor that facilitates SARS-CoV-2 entry into cells.12,13 Exposure to air pollution contributes to chronic conditions, such as cardiovascular disease, that are associated with unfavourable COVID-19 prognosis, possibly owing to persistent immune activation and excessive amplification of cytokine development.10 Thus, greater exposure to long-term air pollution may lead to severe COVID-19 outcomes.Reports exist of positive associations between long-term exposure to particulate matter with diameters equal to or smaller than 2.5 or 10 μm (PM2.5 and PM10), ground-level ozone (O3) and nitrogen dioxide (NO2), and metrics of COVID-19 severity (e.g., mortality and case fatality rate).8–10 However, most studies to date have used ecological and cross-sectional designs, owing to limited access to individual data, which leads to ambiguity in interpreting the results, thus hindering their influence on policy. 6,14 Ecological designs do not allow for disentangling the relative impacts of air pollution on individual susceptibility to infection and disease severity.14 Residual confounding by factors such as population mobility and social interactions is also problematic. Therefore, a cohort study with data on individuals with SARS-CoV-2 is a more appropriate design.6,14 Studies that have used individual data were conducted in specific subpopulations15,16 or populations with few severe cases,17 or had limited data on individual exposure to air pollutants.18 In Canada, 1 ecological study found a positive association between long-term exposure to PM2.5 and COVID-19 incidence,19 but no published study has explored the association between air pollution and COVID-19 severity.We aimed to examine the associations between long-term exposure to 3 common air pollutants (PM2.5, NO2 and O3) and key indicators of COVID-19 severity, including hospital admission, intensive care unit (ICU) admission and death, using a large prospective cohort of people with confirmed SARS-CoV-2 infection in Ontario, Canada, in 2020. The air contaminants PM2.5, NO2 and O3 are regularly monitored by the Canadian government, and are key pollutants that are considered when setting air-quality policies. They originate from varying sources (NO2 is primarily emitted during combustion of fuel, O3 is primarily formed in air by chemical reactions of nitrogen oxides and volatile organic compounds, and PM2.5 can be emitted during combustion or formed by reactions of chemicals like sulphur dioxide and nitrogen oxides in air) and they may affect human health differently.20,21,22 相似文献
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The purpose of this study was to assess whole blood selenium levels of 300 healthy adults living in four selected areas of the west of Algeria. Selenium was measured using differential pulse cathodic stripping voltammetry with a detection limit of 29.20 μg/L. The mean of whole blood selenium concentrations was 85.65 ± 21.60 μg/L ranging between 30.90 and 144.04 μg/L. This concentration did not vary significantly (P > 0.05) in relation to the gender of the subject, with concentrations of 87.75 ± 21.30 μg/L in men and 83.95 ± 21.60 μg/L in women group. Individuals older than 60 years had a whole blood selenium concentration significantly lower than the rest of the population. However, the measured selenium concentrations in the residential areas were not statistically different (P > 0.05). A total of 32 (10.70%) individuals exhibited whole blood selenium level below 60 μg/L. These results are similar to those of some European countries but are much lower than data observed in USA or seleniferous regions. 相似文献
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Mohamed-Elamir F. Hegazy Tarik A. Mohamed Fathy F. Abdel-Latif Mansour S. Alsaid Abdelaaty A. Shahat Paul W. Paré 《Phytochemistry letters》2013,6(3):383-386
Chemical investigations of the soft coral Sarcophyton trocheliophorum, has led to the isolation of six cembranoids, two of which are new, Trochelioid A (1) and B (2), and one, 16-oxosarcophytonin E (3) isolated from nature for the first time. Additionally, two have been isolated from S. trocheliophorum for the first time (4 and 6). Structures were elucidated by employing extensive NMR and HR-FAB-MS experimentation. 相似文献
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Weaam Ebrahim Amal H. Aly Attila Mándi Victor Wray El Mokhtar Essassi Tarik Ouchbani Rachid Bouhfid Wenhan Lin Peter Proksch Tibor Kurtán Abdessamad Debbab 《Chirality》2013,25(4):250-256
Three new polyketides (-)-1 , (+)-1 , and 2 ) were isolated from the EtOAc extract of the fungus Embellisia eureka, an endophyte of the Moroccan plant Cladanthus arabicus (Asteraceae). The structures of these new compounds were determined on the basis of one- and two-dimensional NMR spectroscopy as well as by high-resolution mass spectrometry. The absolute configurations of (-)-1 , (+)-1 , and 2 were determined by TDDFT ECD calculations of solution conformers, online HPLC-ECD analysis, and the modified Mosher method. Chirality 25:250–256, 2013. © 2013 Wiley Periodicals, Inc. 相似文献
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Tarik Asselah Alex J. Thompson Robert Flisiak Manuel Romero-Gomez Diethelm Messinger Georgios Bakalos Mitchell L. Shiffman 《PloS one》2016,11(3)
Background
Access to direct-acting antiviral agents (DAAs) is restricted in some settings; thus, the European Association for the Study of the Liver recommends dual peginterferon/ribavirin (PegIFN/RBV) therapy wherever DAAs are unavailable. HCV genotype (GT) 3 infection is now the most difficult genotype to eradicate and PegIFN/RBV remains an effective option. The goal of this study was to devise a simple predictive score to identify GT3 patients with a high probability of achieving a sustained virologic response (SVR) with PegIFN alfa-2a/RBV therapy.Methods
Relationships between baseline characteristics and SVR were explored by multiple logistic regression models and used to develop a simple scoring system to predict SVR using data from 1239 treatment-naive GT3 patients who received PegIFN alfa-2a/RBV for 24 weeks in two large observational cohort studies.Results
The score was validated using a database of 473 patients. Scores were assigned for six factors as follows: age (years) (≤40: 2 points; >40 but ≤55: 1); bodyweight (kg) (<70: 2; ≥70 but <90: 1); no cirrhosis/transition to cirrhosis (2); ALT ≤2.5 x ULN (1); platelets (109/L) (>200: 2; ≥100 but <200: 1); HCV RNA (<400,000 IU/mL: 1). The points are summed to arrive at a score ranging from 0‒10 where higher scores indicate higher chances of SVR; 141, 123, 203, 249, 232, and 218 patients had total scores of 0‒4, 5, 6, 7, 8, and 9–10, respectively, among whom SVR rates were 45%, 62%, 72%, 76%, 84%, and 89%. Among 622 patients who had scores of 6‒10 and HCV RNA <50 IU/mL by treatment week 4 the SVR rate was 86% (532/622).Conclusions
A simple baseline scoring system involving age, bodyweight, cirrhosis status, ALT level, platelet count and HCV RNA level can be used to identify treatment-naive Caucasian patients with HCV GT3 infection with a high probability of SVR with PegIFN alfa-2a/RBV therapy. 相似文献10.
Tarik?S.K.M.?RabieEmail author Richard?P.M.A.?Crooijmans Mireille?Morisson Joanna?Andryszkiewicz Jan?J.?van der?Poel Alain?Vignal Martien?A.M.?Groenen 《Mammalian genome》2004,15(7):560-569
The mapping resolution of the physical map for chicken Chromosome 4 (GGA4) was improved by a combination of radiation hybrid (RH) mapping and bacterial artificial chromosome (BAC) mapping. The ChickRH6 hybrid panel was used to construct an RH map of GGA4. Eleven microsatellites known to be located on GGA4 were included as anchors to the genetic linkage map for this chromosome. Based on the known conserved synteny between GGA4 and human Chromosomes 4 and X, sequences were identified for the orthologous chicken genes from these human chromosomes by BLAST analysis. These sequences were subsequently used for the development of STS markers to be typed on the RH panel. Using a logarithm of the odds (LOD) threshold of 5.0, nine linkage groups could be constructed which were aligned with the genetic linkage map of this chromosome. The resulting RH map consisted of the 11 microsatellite markers and 50 genes. To further increase the number of genes on the map and to provide additional anchor points for the physical BAC map of this chromosome, BAC clones were identified for 22 microsatellites and 99 genes. The combined RH and BAC mapping approach resulted in the mapping of 61 genes on GGA4 increasing the resolution of the chicken–human comparative map for this chromosome. This enhanced comparative mapping resolution enabled the identification of multiple rearrangements between GGA4 and human Chromosomes 4q and Xp. 相似文献