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- Figlioli, G, et al.
(author)
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The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer
- 2019
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In: NPJ breast cancer. - : Springer Science and Business Media LLC. - 2374-4677. ; 5, s. 38-
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Journal article (peer-reviewed)abstract
- Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM−/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors.
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- Bazargan-Hejazi, Shahrzad, et al.
(author)
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The Burden of Road Traffic Injuries in Iran and 15 Surrounding Countries : 1990-2016
- 2018
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In: Archives of Iranian Medicine. - 1029-2977 .- 1735-3947. ; 21:12, s. 556-565
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Journal article (peer-reviewed)abstract
- BACKGROUND: The Global Burden of Disease (GBD) Study provides estimates of deaths, years of life lost (YLL), years of life lived with disability (YLD), and disability-adjusted life years (DALYs) due to 249 causes of death, 315 diseases and injuries, and 79 behavioral, environmental, occupational, and metabolic risk factors in 195 countries, territories, and regions by sex and 20 age categories in 195 countries and regions since 1990. In this study, we aimed to present the burden of road traffic injuries (RTIs) in Iran and 15 surrounding countries in 1990-2016.METHODS: The standard Cause of Death Ensemble modeling (CODEm) is used to estimate deaths due to all causes of injury by age, sex, country and year. A range of 27 causes is used for estimating non-fatal health outcomes based on inpatient and outpatient datasets using DisMod-MR 2.0. Disability-adjusted life years (DALYs) estimate quantify the total burden of years lost due to premature death or disability and was computed by summing the fatal burden and non-fatal burden associated with a cause (i.e., YLL+YLD).RESULTS: In 2016, age-standardized transport injuries in Iran accounted for 35.6 (UI: 29.64-43.44) deaths per 100000 compared to 60.8 (UI: 51.04-72.49) in 1990. Transport injury became the fourth leading cause of death in Iran in 2016, up from the 5th leading cause of death in 1990. The burden of RTIs was mainly caused by motor vehicles and motorcycles and mostly affected the economically productive age groups (15-49), males and children, especially those at school age. Afghanistan with 59.14 deaths (52.09-66.8) and UAE with 53.71 deaths (36.59-72.77) had the largest transport injury death rates per 100000. From 1990 to 2016, Iran had -2.06 annual percent change in transport death rates. The lowest annual percent change is reported for Turkmenistan at -3.43. While Pakistan, UAE and Qatar had the highest annual percent change in transport injury. Across all countries, the observed-to-expected ratios for transport injury death rates varied considerably in 2016.The UAE had the largest age-standardized ratios of observed-to-expected rate (2.93), followed by Oman (2.39), Saudi Arabia (2.23), Afghanistan (2.04) and Iran (1.95).CONCLUSIONS: RTIs continue to be a public health burden in Iran and its neighboring countries, even though, there is evidence for decline in RTIs across all countries except Pakistan. The most frequent sub-causes of death and injury are the motor vehicle, motorcycle, and pedestrian injuries. The most vulnerable road users are children and young adults.
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- Biurrun, Idoia, et al.
(author)
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Benchmarking plant diversity of Palaearctic grasslands and other open habitats
- 2021
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In: Journal of Vegetation Science. - Oxford : John Wiley & Sons. - 1100-9233 .- 1654-1103. ; 32:4
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Journal article (peer-reviewed)abstract
- Journal of Vegetation Science published by John Wiley & Sons Ltd on behalf of International Association for Vegetation Science.Aims: Understanding fine-grain diversity patterns across large spatial extents is fundamental for macroecological research and biodiversity conservation. Using the GrassPlot database, we provide benchmarks of fine-grain richness values of Palaearctic open habitats for vascular plants, bryophytes, lichens and complete vegetation (i.e., the sum of the former three groups). Location: Palaearctic biogeographic realm. Methods: We used 126,524 plots of eight standard grain sizes from the GrassPlot database: 0.0001, 0.001, 0.01, 0.1, 1, 10, 100 and 1,000 m2 and calculated the mean richness and standard deviations, as well as maximum, minimum, median, and first and third quartiles for each combination of grain size, taxonomic group, biome, region, vegetation type and phytosociological class. Results: Patterns of plant diversity in vegetation types and biomes differ across grain sizes and taxonomic groups. Overall, secondary (mostly semi-natural) grasslands and natural grasslands are the richest vegetation type. The open-access file ”GrassPlot Diversity Benchmarks” and the web tool “GrassPlot Diversity Explorer” are now available online (https://edgg.org/databases/GrasslandDiversityExplorer) and provide more insights into species richness patterns in the Palaearctic open habitats. Conclusions: The GrassPlot Diversity Benchmarks provide high-quality data on species richness in open habitat types across the Palaearctic. These benchmark data can be used in vegetation ecology, macroecology, biodiversity conservation and data quality checking. While the amount of data in the underlying GrassPlot database and their spatial coverage are smaller than in other extensive vegetation-plot databases, species recordings in GrassPlot are on average more complete, making it a valuable complementary data source in macroecology. © 2021 The Authors.
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- Cornelius Chukwu, Eugenia, et al.
(author)
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Engineered Aldolases Catalyzing Stereoselective Aldol Reactions Between Aryl-Substituted Ketones and Aldehydes
- 2023
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In: Catalysis Science & Technology. - : Royal Society of Chemistry. - 2044-4753 .- 2044-4761.
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Journal article (peer-reviewed)abstract
- An A129G/R134V/S166G triple mutant of fructose 6-phosphate aldolase (FSA) from Escherichia coli was further engineered with the goal to generate new enzyme variants capable of catalyzing aldol reactions between aryl substituted ketones and aldehydes. Residues L107 and L163 were subjected to saturation mutagenesis and the resulting library of FSA variants was screened for catalytic activity with 2-hydroxyacetophenone and phenylacetaldehyde as substrates. A selection of aldolase variants was identified that catalyze the synthesis of 2,3-dihydroxy-1,4-diphenylbutanone. The most active enzyme variants contained an L163C substitution. An L107C/L163C variant was further tested for activity with substituted phenylacetaldehydes, and was shown to afford the production of the corresponding diphenyl substituted butanones with good diastereoselectivities (anti : syn dr of 10 to 30) and reasonable to good enantioselectivities of syn enantiomers (er of 5 to 25).
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