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tality compared with plasma cell disorder or myeloma (2·41, [1·08-5·38]; p=0·033) in autologous HSCT recipients. Recipients of autologous and allogeneic HSCT who develop COVID-19 have poor overall survival. These data emphasise the need for stringent surveillance and aggressive treatment measures in HSCT recipients who develop COVID-19. American Society of Hematology; Leukemia and Lymphoma Society; National Cancer Institute; National Heart, Lung and Blood Institute; National Institute of Allergy and Infectious Diseases; National Institutes of Health; National Cancer Institute; Health Resources and Services Administration; Office of Naval Research. American Society of Hematology; Leukemia and Lymphoma Society; National Cancer Institute; National Heart, Lung and Blood Institute; National Institute of Allergy and Infectious Diseases; National Institutes of Health; National Cancer Institute; Health Resources and Services Administration; Office of Naval Research.Effectively managing farming to meet food demand is vital for the future of biodiversity.1,2 Increasing yields on existing farmland can allow the abandonment (sparing) of low-yielding areas that subsequently recover as secondary forest.2-5 A key question is whether such "secondary sparing" conserves biodiversity more effectively than retaining wildlife-friendly habitat within farmland ("land sharing"). Focusing on the Colombian Choco-Andes, a global hotspot of threatened biodiversity,6 and on cattle farming, we examined the outcomes of secondary sparing and land sharing via simulated scenarios that maintained constant landscape-wide production and equal within-pasture yield (1) for species and functional diversity of dung beetles and birds; (2) for avian phylogenetic diversity; and (3) across different stages of secondary forest regeneration, relative to spared primary forests. Sparing older secondary forests (15-30 years recovery) promotes substantial species, functional, and phylogenetic (birds only) diversity benefits for birds and dung beetles compared to land sharing. Species of conservation concern had higher occupancy estimates under land-sparing compared to land-sharing scenarios. Spared secondary forests accumulated equivalent diversity to primary forests for dung beetles within 15 years and within 15-30 years for birds, highlighting the need for longer term protection to maximize the biodiversity gains of secondary sparing. Promoting the recovery and protection of large expanses of secondary forests under the land-sparing model provides a critical mechanism for protecting tropical biodiversity, with important implications for concurrently assisting in the delivery of global targets to restore 350 million hectares of forested landscapes.7,8.Detyrosination of the α-tubulin C-terminal tail is a post-translational modification (PTM) of microtubules that is key for many biological processes.1 Although detyrosination is the oldest known microtubule PTM,2-7 the carboxypeptidase responsible for this modification, VASH1/2-SVBP, was identified only 3 years ago,8,9 precluding genetic approaches to prevent detyrosination. Studies examining the cellular functions of detyrosination have therefore relied on a natural product, parthenolide, which is widely believed to block detyrosination of α-tubulin in cells, presumably by inhibiting the activity of the relevant carboxypeptidase(s).10 Parthenolide is a sesquiterpene lactone that forms covalent linkages predominantly with exposed thiol groups; e.g., on cysteine residues.11-13 Using mass spectrometry, we show that parthenolide forms adducts on both cysteine and histidine residues on tubulin itself, in vitro and in cells. Parthenolide causes tubulin protein aggregation and prevents the formation of microtubules. In contrast to epoY, an epoxide inhibitor of VASH1/2-SVBP,9 parthenolide does not block VASH1-SVBP activity in vitro. Lastly, we show that epoY is an efficacious inhibitor of microtubule detyrosination in cells, providing an alternative chemical means to block detyrosination. Collectively, our work supports the notion that parthenolide is a promiscuous inhibitor of many cellular processes and suggests that its ability to block detyrosination may be an indirect consequence of reducing the polymerization-competent pool of tubulin in cells. Ambient air pollution is a major environmental cause of morbidity and mortality worldwide. Cities are generally hotspots for air pollution and disease. However, the exact extent of the health effects of air pollution at the city level is still largely unknown. We aimed to estimate the proportion of annual preventable deaths due to air pollution in almost 1000 cities in Europe. We did a quantitative health impact assessment for the year 2015 to estimate the effect of air pollution exposure (PM and NO ) on natural-cause mortality for adult residents (aged ≥20 years) in 969 cities and 47 greater cities in Europe. We retrieved the cities and greater cities from the Urban Audit 2018 dataset and did the analysis at a 250 m grid cell level for 2015 data based on the global human settlement layer residential population. https://www.selleckchem.com/products/aminoguanidine-hydrochloride.html We estimated the annual premature mortality burden preventable if the WHO recommended values (ie, 10 μg/m for PM and 40 μg/m for NO ) were achieved and if air pollution concentrations wetry of Science and Innovation, Internal ISGlobal fund. There has been a considerable increase in thyroid cancer incidence among adults in several countries in the past three decades, attributed primarily to overdiagnosis. We aimed to assess global patterns and trends in incidence and mortality of thyroid cancer in children and adolescents, in view of the increased incidence among adults. We did a population-based study of the observed incidence (in 49 countries and territories) and mortality (in 27 countries) of thyroid cancer in children and adolescents aged 0-19 years using data from the International Incidence of Childhood Cancer Volume 3 study database, the WHO mortality database, and the cancer incidence in five continents database (CI5plus; for adult data [age 20-74 years]). We analysed temporal trends in incidence rates, including absolute changes in rates, and the strength of the correlation between incidence rates in children and adolescents and in adults. We calculated the average annual number of thyroid cancer deaths and the age-standardised mortality rates for children and adolescents.
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