Incorporation of isolated chromosomes and induction of hypoxanthine phosphoribosyltransferase in Chinese hamster cells.

Evidence is presented for the uptake of radioactive-labeled isolated Chinese hamster chromosomes following incubation with Chinese hamster cells. Metaphases were found which contained radioactive labeled chromosomes in a very low frequency, and in some of the labeled chromosomes only one chromatid was labeled. Incubation of hypoxanthine phosphoribosyltransferas (HPRT)-deficient Chinese hamster cells with chromosomes isolated from HPRT+ Chinese hamster or human cells resulted in the appearance of HPRT+ cells. Clones derived from these cells were isolated in HAT medium. Cells in mitosis during incubation with the chromosomes yielded thr-e times more HPRT+ clones than did cells in interphase. The intraspecies combination involving recipient cells and chromosomes from Chinese hamster origin yielded significantly higher numbers of HPRT+ clones than did the interspecies system using human chromsomes and Chinese hamster recipient cells (5 X 10(-5) and 6 X 10(-6) respectively). Electrophoresis of HPRT from Chinese hamster cells treated with human chromosomes revealed the pattern of the human enzyme.     

Conformation of the common purine (β) ribosides in solution: further evidence for a correlation between N-S state of the ribose moiety and syn-anti equilibrium

The solution conformations of adenosine, guanosine and inosine in liquid ND₃ have been determined by NMR. Comparison of the Karplus analysis of the proton HR spectra of the ribose moiety obtained in this solvent with the data from aqueous solutions of A and I proves that the conformations of the nucleosides are very similar in both liquids. From the analysis of the vicinal coupling constants of the ring protons it has been deduced that the S state C(2′)-endo is slightly preferred. The mole fraction in S approximates 0.6 for all three nucleosides. C-13 relaxation measurements have been applied in the determination of the correlation times for rotational diffusion. Only at temperatures below −40‡ C is the pseudorotation of the furanoside ring slowed down sufficiently for it not to contribute to the measured relaxation rates. From NOE studies and T¹ measurements on the individual protons it is derived that the N, C(3′)-endo, form of the ribose is correlated with an anti conformation of the base (Y≈210‡ to 220‡) and the S, C(2′)-endo, form of the ribose with a syn conformation of the base (Y≈30‡ to 50‡). The glycosyl torsion angles derived for the two conformations of A, G, and I are equal within the limits of accuracy.     

Microphotometry of rat liver nucleoproteins during the cell cycle, and comparison of diploid nuclei in the G2 period with tetraploid nuclei.

The following facts were established with a microphotometric investigation of isolated nuclei from rat liver in different stages of the cell cycle. During the mitotic wave occurring in the liver of newborn animals after injection of casein it was found that the naphtol yellow S (NYS) protein content of the nuclei increases about 30% during the G1-period. A second increase of around 70% was established during the S-phase whereas no increase could be observed during the G2-phase. An indication for the existence of a "critical protein mass" of the nuclei before the onset of the S-phase could be observed. The protein content of diploid nuclei in the G1-phase of adult animals is about 50% higher than in newborns. This makes it probable that there is no significant difference in the NYS-protein content of diploid nuclei in the G2-period and tetraploid nuclei of adult rats. No differences were observed between diploid nuclei in the G2-period of newborn rats and tetraploid nuclei of adult rats in their Fastgreen histon, RNA and SH plus SS content. The only criterion to distinguish between G2 nuclei and tetraploid nuclei seems to be the number of nucleoli, but this is rather unreliable.     

Activity of prostaglandin E, F, A and B on sphincter, dilator and ciliary muscle preparations of the cat eye

Both sphincter and dilator muscle preparations of the cat iris contract to prostaglandins; F_2α and E₂ are the most potent and A₁ and B₁ the least. Ciliary muscle strips relax to PG's provided that the strips are precontracted. E₁, E₂ and often F_2α are more potent relaxants than the remaining PG's. The effects of PG's are not altered by α or β blockade nor by atropine; however, propranolol blocks the PG induced relaxation of the ciliary muscle. The effects of PG's on the sphincter are antagonized by catecholamines; but the latter act synergistically in contracting the dilator and in relaxing the ciliary muscle. Indomethacin markedly potentiates the effects of PG's on all three muscle preparations.     

Association between long-term exposure to ambient air pollution and COVID-19 severity: a prospective cohort study

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 (PM_2.5), 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 PM_2.5 (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 (PM_2.5 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 subpopulations^15,16 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 PM_2.5 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 (PM_2.5, 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 PM_2.5, 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 PM_2.5 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     

Common regulation of apoptosis signaling induced by CD95 and the DNA-damaging stimuli etoposide and gamma-radiation downstream from caspase-8 activation.

The death receptor CD95 (APO-1/Fas), the anticancer drug etoposide, and gamma-radiation induce apoptosis in the human T cell line Jurkat. Variant clones selected for resistance to CD95-induced apoptosis proved cross-resistant to etoposide- and radiation-induced apoptosis, suggesting that the apoptosis pathways induced by these distinct stimuli have critical component(s) in common. The pathways do not converge at the level of CD95 ligation or caspase-8 signaling. Whereas caspase-8 function was required for CD95-mediated cytochrome c release, effector caspase activation, and apoptosis, these responses were unaffected in etoposide-treated and irradiated cells when caspase-8 was inhibited by FLIPL. Both effector caspase processing and cytochrome c release were inhibited in the resistant variant cells as well as in Bcl-2 transfectants, suggesting that, in Jurkat cells, the apoptosis signaling pathways activated by CD95, etoposide, and gamma-radiation are under common mitochondrial control. All three stimuli induced ceramide production in wild-type cells, but not in resistant variant cells. Exogenous ceramide bypassed apoptosis resistance in the variant cells, but not in Bcl-2-transfected cells, suggesting that apoptosis signaling induced by CD95, etoposide, and gamma-radiation is subject to common regulation at a level different from that targeted by Bcl-2.