Lysinonorleucine cross-link formation in alpha amino heptenoic acid-substituted peptide derivatives

Studies on the cross-linking of a tripeptide (t-butyloxycarbonyl-L -alanyl-D ,L -2-amino-6-heptenoyl-L -alanine methyl ester) have shown that it is possible to form specific cross-links in good yields through Schiff base formation of the ε amino group of lysine. The heptenoic acid residue has been ozonized to an aldehyde and condensed with the ε amino of lysine in the compounds alpha-t-butyloxycarbonyl-L -alanyl-L -lysine methyl ester and alpha-t-butyloxycarbonyl-L -lysine methyl ester to form the cross-link, lysinonorleucine. This compound has been stabilized by reduction with sodium borohydride and quantitated on the amino acid analyzer. This technique converts from 60 to 98% of the available aldehyde to lysinonorleucine.     

Perturbation of the chemotactic tumbling of bacteria

The bacterial sensing system has been studied on three levels. First, a quantitative method has been devised for measuring the “action spectrum” of the bacterium in response to a sudden addition of attractant. Second, a technique has been developed for the rapid isolation of mutants defective in the transmission part of the sensing system. Third, a study of the effects of light on the transmission system reveals two components, one which generates tumbling and another which inhibits it.     

Relationship of macromolecular synthesis to competence induction in a group H streptococcus.

Group H streptococcus strain Wicky, which was induced to competence for genetic transformation with competence factor (CF) derived from a related strain, displayed reduced rates of ribonucleic acid (RNA) and peptidoglycan synthesis. Pulse-labeling studies revealed that the inhibition of both RNA and peptidoglycan synthesis was maximal at the peak of competence and decreased as competence declined. These studies indicated that competence induction had only a slight effect on the rate of protein synthesis. Trypsin inactivation of CF prevented the reductions in synthesis normally elicited by CF preparations. If the addition of trypsin was delayed until 5 min after the addition of CF, competence induction and decreased synthesis of RNA and peptidoglycan were again apparent. Thus, the alterations in the synthesis of these macromolecules appeared to be related to the induction of competence. Further studies indicated that the apparent reductions in biosynthesis were not caused by decreased uptake of the labeled precursors by intact Wicky cells. In addition, these effects were probably not the result of turnover of macromolecules induced by CF. The lack of turnover of labeled peptidoglycan suggested that competence induction may not involve an autolysin.     

Cerebral function before and after carotid endarterectomy.

Twenty men had their cerebral function measured preoperatively and three months after carotid endarterectomy using the Halstead-Reitan neuropsychological test battery. Thirteen patients were cerebrally impaired preoperatively, but 12 of them improved appreciably after surgery. Changes in internal carotid arterial blood flow measured preoperatively showed no significant correlation with the improvement in neuropsychological status. We think that carotid endarterectomy carries an even better prophylaxis for the brain as a whole than had been thought.     

Using genetic variation to disentangle the complex relationship between food intake and health outcomes

Diet is considered as one of the most important modifiable factors influencing human health, but efforts to identify foods or dietary patterns associated with health outcomes often suffer from biases, confounding, and reverse causation. Applying Mendelian randomization in this context may provide evidence to strengthen causality in nutrition research. To this end, we first identified 283 genetic markers associated with dietary intake in 445,779 UK Biobank participants. We then converted these associations into direct genetic effects on food exposures by adjusting them for effects mediated via other traits. The SNPs which did not show evidence of mediation were then used for MR, assessing the association between genetically predicted food choices and other risk factors, health outcomes. We show that using all associated SNPs without omitting those which show evidence of mediation, leads to biases in downstream analyses (genetic correlations, causal inference), similar to those present in observational studies. However, MR analyses using SNPs which have only a direct effect on the exposure on food exposures provided unequivocal evidence of causal associations between specific eating patterns and obesity, blood lipid status, and several other risk factors and health outcomes.     

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     

Improved protein identification through the use of unstained gels

In this work, a method for improved protein identification of low-abundance proteins using unstained gels, in combination with robotics and matrix-assisted laser desorption/ionization tandem mass spectrometry, has been developed and evaluated. Omitting the silver-staining process resulted in increased protein identification scores, an increase in the number of peptides observed in the MALDI mass spectrum, and improved quality of the tandem mass spectrometry data.     

Wetland conservation and sustainable use under global change: a tropical Australian case study using magpie geese

Imminent shifts in environmental parameters due to climatic change might have profound ramifications for wetlands listed under the Ramsar convention. Although the exact mechanisms by which global change will affect these systems are not known, models that simulate component drivers, particularly at a broad spatial scale, can nevertheless allow for more informed conservation decision making. Such general inference is particularly needed for wetlands across the tropics, where less knowledge and fewer resources are available to mitigate the impacts on important conservation sites. Here we develop a case study of wetland loss to sea level rise across tropical north Australia (including Ramsar‐listed sites), and link these to a metapopulation model for a keystone endemic waterbird, the magpie goose Anseranas semipalmata. We projected published models on sea level rise through to the year 2400, and found a non‐linear trajectory of inundation up to 20 m above present levels. Digital elevation models were used to simulate sea level rise and the spatially differentiated loss of wetland habitat used by geese. Range retraction was linked to decline in ecological carrying capacity, and we coupled wetland‐specific habitat loss projections to a spatially explicit demographic metapopulation model. Additionally, we included alternate harvest strategies based on present‐day estimates of indigenous and non‐indigenous offtake of geese, and examined the synergy between wetland loss and hunting on extinction risk. Our results suggest that Australia's once‐abundant and widespread magpie goose will be reduced to a fragmented population of just a few thousand individuals within the next 200–300 yr. Harvest could continue for some time, up to a “tipping point” at around 5% loss of current wetland habitat, after which the decline of geese is rapid. Given the inexorable nature of sea level rise, short‐ to medium‐term conservation of waterbirds across Ramsar wetlands must prepare for adaptive wetland management, such as through buffer‐placement, and ongoing monitoring of harvest.