Oxygenated Aromatic Compounds are Important Precursors of Secondary Organic Aerosol in Biomass Burning Emissions

Biomass burning is the largest combustion-related source of volatile organic compounds (VOCs) to the atmosphere. We describe the development of a state-of-the-science model to simulate the photochemical formation of secondary organic aerosol (SOA) from biomass-burning emissions observed in dry (RH <20%) environmental chamber experiments. The modeling is supported by (i) new oxidation chamber measurements, (ii) detailed concurrent measurements of SOA precursors in biomass-burning emissions, and (iii) development of SOA parameters for heterocyclic and oxygenated aromatic compounds based on historical chamber experiments. We find that oxygenated aromatic compounds, including phenols and methoxyphenols, account for slightly less than 60% of the SOA formed and help our model explain the variability in the organic aerosol mass (R² = 0.68) and O/C (R² = 0.69) enhancement ratios observed across 11 chamber experiments. Despite abundant emissions, heterocyclic compounds that included furans contribute to ∼20% of the total SOA. The use of pyrolysis-temperature-based or averaged emission profiles to represent SOA precursors, rather than those specific to each fire, provide similar results to within 20%. Our findings demonstrate the necessity of accounting for oxygenated aromatics from biomass-burning emissions and their SOA formation in chemical mechanisms

Статеві особливості метаболізму міокарда в динаміці розвитку експериментального гіпертиреозу

В экспериментах на половозрелых самцах и самках крыс исследовано активность перекисного окислення липидов, антиоксидантной защиты и энергообразования в динамике развития тироксиновой кардиомиопатии, которую моделировали введением L-тироксина (500 мг/кг, внутрижелудочно, ежедневно). В миокарде желудочков через 5, 10 и 15 дней с начала эксперимента определяли содержание диеновых и триеновых коньюгат (ДК, ТК), ТБК-активных продуктов (ТБК-АП), активность супероксиддисмутазы (СОД), каталазы, глутатионпероксидазы (ГП) и глутатионредуктазы (ГР), сукцинатдегидрогеназы (СДГ), цитохромоксидазы (ЦО). Установили, что гипертироксинемия визывала накопление в миокарде желудочков крыс ДК, ТК и ТБК-АП, что в самок было более существенным, чем у самцов, несмотря на большую активность ГП та ГР. Недостаточная протекторная эффективность ферментов системы глутатиона была результатом значительного угнетения активности СОД и каталазы, что свидетельствовало о существенном накоплении активных форм кислорода. Активность энергообразования в таких условиях уменьшалась, о чем свидетельствовало угнетение активности СДГ, которое было аналогичным в самцов и самок, и ЦО, что было более существенным в самок. Полученные результаты свидетельствуют о том, что развитие тироксиновой кардиомиопатии вызывает существенный метаболический дисбаланс в миокарде желудочков самок крыс, что разрешает ожидать болем интенсивные структурные нарушения.Lipid peroxidation, antioxidant protection and energy production were studied in adult male and female rats with thyroxin cardiomyopathy, which simulated by introduction of L-thyroxine (500 mg / kg, intraperitoneally, daily). In the myocardium of the ventricles after 5, 10 and 15 days from the start of the experiment determined the content of diene and triene conjugate (DC, TC), TBA-active metabolits (TBA-am), activity of superoxide dismutase (SOD), catalase, glutathione peroxidase (GP) and glutathione reductase (GR), succinate dehydrogenase (SDH), cytochrome oxidase (CO). Found that hyperthyroxinemia caused accumulation in myocardium of the ventricles DC, TC and TBA-am mostly in females despite the higher activity of GP and GR. Lack of protective effects of glutathione system enzymes resulted from significant inhibition of SOD and catalase, indicating a significant accumulation of reactive species of oxygen. Activity of the energy production in these conditions decreased. That was proved by the inhibition of SDH in myocardium both sex animals and CO mostly in females. We conclude that the development of thyroxin cardiomyopathy causes metabolic disbalance in myocardium of the ventricles mostly in female rats, which can results in more intense structural damage

Mapping the human genetic architecture of COVID-19

The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-191,2, host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases3–7. They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease

ATP and MO25 alpha regulate the conformational state of the STRAD alpha pseudokinase and activation of the LKB1 tumour suppressor

The conformation of the pseudokinase STRADα, which is regulated by binding to ATP and to the scaffolding protein MO25α, is key to the activiation of the LKB1 tumor suppressor complex