The role of lysines in Euglena cytochrome c-552. Chemical modification studies.

2-Hydroxy(p-hydroxyphenyl)-acetaldoxime, the alternative precursor to p-hydroxyphenylacetonitrile in dhurrin biosynthesis, was synthesized and its effectiveness as a substrate was examined in a microsomal enzyme system from sorghum seedlings. The hydroxyaldoxime was slowly converted to p-hydroxymandelonitrile when compared with p-hydroxyphenylacetonitrile and p-hydroxyphenylacetaldoxime. Moreover, radioactivity from [U-¹⁴C]tyrosine was efficiently incorporated by trapping experiments into both the nitrile and aldoxime, but not into the hydroxyaldoxime. The reaction products formed on hydroxylation of the nitrile by the microsomal enzyme were identified as p-hydroxybenzaldehyde, HCN, and H₂O. Under anaerobic conditions, the nitrile was produced from the aldoxime and accumulated without undergoing hydroxylation. These results establish p-hydroxyphenylacetonitrile and not 2-hydroxy(p-hydroxyphenyl)-acetaldoxime as the intermediate in the conversion of p-hydroxyphenylacetaldoxime to p-hydroxymandelonitrile in dhurrin biosynthesis.     

The role of the lysines in the alkaline heme-linked ionization of ferric cytochrome c.

Phage ?¹⁵ adsorbed at a low temperature (or by short-time incubation) to the outer surface of $\text{Salmonella}\text{anatum}$ gathers on further incubation at a high temperature to a certain region where the inner and outer membranes may join. This was demonstrated by separating the inner and outer membranes of the cells in sucrose gradient after addition of ³⁵S-labeled ?¹⁵ to the cells. Radioactivity adsorbed at 4° was first recovered mainly with the dense outer membrane but disappeared by further incubation at 35° within 5 min. Instead, the radioactivity was recovered with the membrane fraction which had intermediate density. Such phage translocation was not observed when phage ?¹⁵ was added to a $\text{pep}\text{mutant of}\text{S.}\text{anatum}$ to which the phage can adsorb but fail to infect. A host range mutant phage which can infect the $\text{pep}$ mutant migrated to the intermediate dense region.     

Outcomes in patients with and without disability admitted to hospital with COVID-19: a retrospective cohort study

Background:Disability-related considerations have largely been absent from the COVID-19 response, despite evidence that people with disabilities are at elevated risk for acquiring COVID-19. We evaluated clinical outcomes in patients who were admitted to hospital with COVID-19 with a disability compared with patients without a disability.Methods:We conducted a retrospective cohort study that included adults with COVID-19 who were admitted to hospital and discharged between Jan. 1, 2020, and Nov. 30, 2020, at 7 hospitals in Ontario, Canada. We compared in-hospital death, admission to the intensive care unit (ICU), hospital length of stay and unplanned 30-day readmission among patients with and without a physical disability, hearing or vision impairment, traumatic brain injury, or intellectual or developmental disability, overall and stratified by age (≤ 64 and ≥ 65 yr) using multivariable regression, controlling for sex, residence in a long-term care facility and comorbidity.Results:Among 1279 admissions to hospital for COVID-19, 22.3% had a disability. We found that patients with a disability were more likely to die than those without a disability (28.1% v. 17.6%), had longer hospital stays (median 13.9 v. 7.8 d) and more readmissions (17.6% v. 7.9%), but had lower ICU admission rates (22.5% v. 28.3%). After adjustment, there were no statistically significant differences between those with and without disabilities for in-hospital death or admission to ICU. After adjustment, patients with a disability had longer hospital stays (rate ratio 1.36, 95% confidence interval [CI] 1.19–1.56) and greater risk of readmission (relative risk 1.77, 95% CI 1.14–2.75). In age-stratified analyses, we observed longer hospital stays among patients with a disability than in those without, in both younger and older subgroups; readmission risk was driven by younger patients with a disability.Interpretation:Patients with a disability who were admitted to hospital with COVID-19 had longer stays and elevated readmission risk than those without disabilities. Disability-related needs should be addressed to support these patients in hospital and after discharge.

A successful public health response to the COVID-19 pandemic requires accurate and timely identification of, and support for, high-risk groups. There is increasing recognition that marginalized groups, including congregate care residents, racial and ethnic minorities, and people experiencing poverty, have elevated incidence of COVID-19.^1,2 Older age and comorbidities such as diabetes are also risk factors for severe COVID-19 outcomes.^3,4 One potential high-risk group that has received relatively little attention is people with disabilities.The World Health Organization estimates there are 1 billion people with disabilities globally.⁵ In North America, the prevalence of disability is 20%, with one-third of people older than 65 years having a disability.⁶ Disabilities include physical disabilities, hearing and vision impairments, traumatic brain injury and intellectual or developmental disabilities.^5,6 Although activity limitations experienced by people with disabilities are heterogeneous,^5,6 people with disabilities share high rates of risk factors for acquiring COVID-19, including poverty, residence in congregate care and being members of racialized communities.^7–9 People with disabilities may be more reliant on close contact with others to meet their daily needs, and some people with disabilities, especially intellectual developmental disabilities, may have difficulty following public health rules. Once they acquire SARS-CoV-2 infection, people with disabilities may be at risk for severe outcomes because they have elevated rates of comorbidities.¹⁰ Some disabilities (e.g., spinal cord injuries and neurologic disabilities) result in physiologic changes that increase vulnerability to respiratory diseases and may mask symptoms of acute respiratory disease, which may delay diagnosis.^11–13 There have also been reports of barriers to high-quality hospital care for patients with disabilities who have COVID-19, including communication issues caused by the use of masks and restricted access to support persons.^14–17Some studies have suggested that patients with disabilities and COVID-19 are at elevated risk for severe disease and death, with most evaluating intellectual or developmental disability.^13,18–26 Yet, consideration of disability-related needs has largely been absent from the COVID-19 response, with vaccine eligibility driven primarily by age and medical comorbidity, limited accommodations made for patients with disabilities who are in hospital, and disability data often not being captured in surveillance programs.^14–17 To inform equitable pandemic supports, there is a need for data on patients with a broad range of disabilities who have COVID-19. We sought to evaluate standard clinical outcomes in patients admitted to hospital with COVID-19²⁷ (i.e., in-hospital death, intensive care unit [ICU] admission, hospital length of stay and unplanned 30-d readmission) for patients with and without a disability, overall and stratified by age. We hypothesized that patients with a disability would have worse outcomes because of a greater prevalence of comorbidities,¹⁰ physiologic characteristics that increase morbidity risk^11–13 and barriers to high-quality hospital care.^14–17     

Origin, distribution and 3D-modeling of Gr-EXPB1, an expansin from the potato cyst nematode Globodera rostochiensis

Southern analysis showed that Gr-EXPB1, a functional expansin from the potato cyst nematode Globodera rostochiensis, is member of a multigene family, and EST data suggest expansins to be present in other plant parasitic nematodes as well. Homology modeling predicted that Gr-EXPB1 domain 1 (D1) has a flat beta-barrel structure with surface-exposed aromatic rings, whereas the 3D structure of Gr-EXPB1-D2 was remarkably similar to plant expansins. Gr-EXPB1 shows highest sequence similarity to two extracellular proteins from saprophytic soil-inhabiting Actinobacteria, and includes a bacterial type II carbohydrate-binding module. These results support the hypothesis that a number of pathogenicity factors of cyst nematodes is of procaryotic origin and were acquired by horizontal gene transfer.     

Synthetic multifunctional pores that open and close in response to chemical stimulation

Studies on synthetic multifunctional pores with external and internal active sites for ligand gating and noncompetitive blockage are presented, with emphasis on the contribution of external ligands to the characteristics of pore. A comparison between different synthetic multifunctional pores reveals that the location of functional groups in rigid-rod beta-barrel pores is precisely reflected in the function: molecular recognition at the outer barrel surface results in pore opening, while molecular recognition at the inner barrel surface results in pore closing. Negligible nonspecific leakage, disappearance of pH gating, inhibition of intervesicular pore transfer, and maybe also the flickering of currents of single open pores characterize external ligands as adhesive cushions that liberate the pore from lateral pressure exerted by the surrounding membrane. Refined molecular models show good agreement with pore design and experimental facts with regard to function.     

Losartan inhibits cellular uptake of oxidized LDL by monocyte-macrophages from hypercholesterolemic patients

Angiotensin II (Ang II) and oxidized LDL (Ox-LDL) are risk factors for atherosclerosis, and both of them contribute to macrophage cholesterol accumulation, the hallmark of early atherosclerosis. As Ang II was shown to increase macrophage uptake of Ox-LDL, we investigated the effect of losartan, an Ang II receptor antagonist with antiatherogenic properties, on the cellular uptake of Ox-LDL by human monocyte-derived macrophages (HMDM) from hypercholesterolemic patients. Eight normotensive hypercholesterolemic patients were treated with losartan (50 mg/day) for a period of 4 weeks. Losartan therapy did not significantly affect the degradation of native LDL by the patients' HMDM. However, losartan therapy significantly reduced HMDM uptake of Ox-LDL as shown by a 78% reduction in Ox-LDL cell-association and a 21% reduction in Ox-LDL degradation. CD36 (an Ox-LDL receptor) mRNA expression in HMDM obtained after losartan treatment was decreased by 54% compared to HMDM obtained before treatment. The ability of losartan to inhibit HMDM CD36 mRNA expression and, hence, Ox-LDL uptake and macrophage foam cell formation is probably related to the blockage of Ang II binding to the cell surface and thus to the prevention of Ang II atherogenic effects.     

Kinetics of thermal inactivation of catalase in the presence of additives

The kinetics of catalase inactivation in buffer-free aqueous solutions within the temperature range 30–60 °C in the absence or presence of hydrogen peroxide was investigated and discussed taking into account the effect of NaCl, ethane-1,2-diol, propane-1,2,3-triol and sucrose, additives expected to increase the enzyme thermostability. Using the kinetic extended curves obtained by measuring the substrate absorbance in time and an isoconversional method, several simple kinetic models most frequently encountered in literature were fitted to the experimental data. The best model for inactivation was chosen on the basis of several statistical criteria. The half-times of inactivation and the activation energies were also reported and discussed.     

Selective distribution of oxysterols in atherosclerotic lesions and human plasma lipoproteins

The presence of oxidized sterols (oxysterols) in human serum and lesions has been linked to the initiation and progression of atherosclerosis. Data concerning the origin, identity and quantity of oxysterols in biological samples are controversial and inconsistent. This inconsistency may arise from different analytical methods or handling conditions used by different investigators. In the present study, oxysterol levels and distribution were analyzed by an optimized GC-MS method, in human atherosclerotic coronary and carotid lesions, in atherosclerotic apolipoprotein E deficient mice (E° mice) and in native and in vitro oxidized human low and high density lipoproteins. Oxysterol levels were analyzed with a limit of detection of 0.06 – 0.24 ng, with 25-hydroxycholesterol (25-OH) being the least sensitive. In human coronary and carotid lesions, obtained from endatherectomic samples, 27-hydroxycholesterol (27-OH) was the major oxysterol, with about 85% as sterols esterified to fatty acids. While total cholesterol and oxysterols levels were similar in both kinds of human lesions, oxysterol distribution was significantly different. In coronary lesions the mean levels of 27-OH and 7β-hydroxycholesterol (7β-OH) were 38% and 20% of total oxysterols, whereas in carotid lesions their mean levels were 66% and 5%, respectively. Unlike in human aortic lesions, 27-OH was entirely absent in E° mice, whereas the level of 7α-hydroxycholesterol (7α-OH) was 28% of the total oxysterols, vs. 5% in human coronary lesions. As 27-OH is an enzymatic product of cholesterol oxidation, this finding may indicate that such an enzymatic process does not take place in E° mice.