Palmitoylation of Desmoglein 2 Is a Regulator of Assembly Dynamics and Protein Turnover.

Desmosomes are prominent adhesive junctions present between many epithelial cells as well as cardiomyocytes. The mechanisms controlling desmosome assembly and remodeling in epithelial and cardiac tissue are poorly understood. We recently identified protein palmitoylation as a mechanism regulating desmosome dynamics. In this study, we have focused on the palmitoylation of the desmosomal cadherin desmoglein-2 (Dsg2) and characterized the role that palmitoylation of Dsg2 plays in its localization and stability in cultured cells. We identified two cysteine residues in the juxtamembrane (intracellular anchor) domain of Dsg2 that, when mutated, eliminate its palmitoylation. These cysteine residues are conserved in all four desmoglein family members. Although mutant Dsg2 localizes to endogenous desmosomes, there is a significant delay in its incorporation into junctions, and the mutant is also present in a cytoplasmic pool. Triton X-100 solubility assays demonstrate that mutant Dsg2 is more soluble than wild-type protein. Interestingly, trafficking of the mutant Dsg2 to the cell surface was delayed, and a pool of the non-palmitoylated Dsg2 co-localized with lysosomal markers. Taken together, these data suggest that palmitoylation of Dsg2 regulates protein transport to the plasma membrane. Modulation of the palmitoylation status of desmosomal cadherins can affect desmosome dynamics

Associations between dietary flavonoids and retinal microvasculature in older adults

Purpose In this study, we assessed whether there are independent associations between dietary total flavonoid intake and major flavonoid classes with retinal arteriolar and venular calibre. Methods Blue Mountains Eye Study participants aged 49+ years who had complete data on diet and retinal vessel measures were analysed (n = 2821). Dietary intake was assessed using a semi-quantitative Food-Frequency Questionnaire (FFQ). Flavonoid content of foods in the FFQ was estimated using the US Department of Agriculture Flavonoid, Isoflavone and Proanthocyanidin databases. Fundus photographs were taken and retinal vascular calibre was measured using validated computer-assisted techniques. The associations of intake of dietary flavonoids with retinal vessel calibre were examined in linear regression models and general linear model. Results The highest quartile of intake was compared with the lowest quartile using multivariable-adjustment models. Participants with the highest proanthocyanidin intake had narrower retinal venules (223.9 ± 0.62 versus 226.5 ± 0.63, respectively; Ptrend = 0.01); and the highest isoflavone intake was associated with wider retinal arterioles (188.1 ± 0.55 versus 186.3 ± 0.56, respectively; Ptrend = 0.01). The highest apple/pear consumption (a dietary source of catechin) was associated with narrower retinal venules (223.8 ± 0.57 versus 226.1 ± 0.52; Ptrend = 0.01) and wider retinal arterioles (187.9 ± 0.51 versus 186.2 ± 0.51; Ptrend = 0.02). Further, participants who were in the highest versus lowest quartile of chocolate consumption had ~ 2.1 μm narrower retinal venules (multivariable-adjusted P = 0.03). Conclusions This study shows that higher intakes of specific flavonoid subclasses are associated with a favourable retinal microvascular profile. Greater consumption of flavonoid-rich apples/pears and chocolate was also associated with beneficial variations in retinal vascular calibre

Associations between intake of dietary flavonoids and 10-year incidence of age-related hearing loss

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. Dietary flavonoids are vasoactive phytochemicals with promising anti-inflammatory properties. We aimed to assess the associations between baseline intakes of six commonly consumed flavonoid subclasses and 10-year incidence of age-related hearing loss. At baseline, 1691 participants aged 50+ years had information on dietary intakes and hearing status. Hearing loss was defined as the pure-tone average of frequencies 0.5, 1.0, 2.0, and 4.0 kHz \u3e 25 dB hearing level (HL). Dietary data were collected through a semi-quantitative food frequency questionnaire. The flavonoid content of foods was estimated using US databases. During the 10-year follow-up, 260 (31.6%) new cases of hearing loss (incident) were observed. After multivariable adjustment, participants in the fourth versus first quartile (reference group) of intake of dietary isoflavone had 36% lower risk of incident hearing loss after 10 years: odds ratios (OR) 0.64 (95% confidence intervals, CI, 0.42–0.99); p-value for trend = 0.03. Nonsignificant associations were observed between the other five flavonoid subclasses and 10-year incidence of hearing loss. Our findings do not support the hypothesis that the intake of dietary flavonoids protect against long-term risk of hearing loss. The association with isoflavone intake needs to be confirmed by other population-based studies

Comparison of four dietary pattern indices in Australian baby boomers: Findings from the Busselton Healthy Ageing Study

The assessment of dietary patterns comprehensively represents the totality of the diet, an important risk factor for many chronic diseases. This study aimed to characterise and compare four dietary pattern indices in middle-aged Australian adults. In 3458 participants (55 % female) from the Busselton Healthy Ageing Study (Phase Two), a validated food frequency questionnaire was used to capture dietary data between 2016 and 2022. Four dietary patterns [Australian Dietary Guideline Index 2013 (DGI-2013); the Mediterranean Diet Index (MedDiet); the Literature-based Mediterranean Diet Index (Lit-MedDiet); and the EAT-Lancet Index], were calculated and compared by measuring total and sub-component scores, and concordance (ρc). Cross-sectional associations between the dietary indices and demographic, lifestyle, and medical conditions were modelled with linear regression and restricted cubic splines. Participants had the highest standardised scores for the DGI-2013 followed by the EAT-Lancet Index and the MedDiet, with the lowest standardised scores observed for the Lit-MedDiet. The DGI-2013 had the lowest agreement with the other scores (ρc ≤ 0.47). These findings indicate that the diets included in this Australian cohort align more closely with the Australian Dietary Guidelines than with the other international dietary patterns, likely due to the wide variation of individual food group weightings in the construction of these indices

How effective are face coverings in reducing transmission of COVID-19?

In the COVID-19 pandemic, among the more controversial issues is the use of face coverings. To address this we show that the underlying physics ensures particles with diameters & 1 $\mu$m are efficiently filtered out by a simple cotton or surgical mask. For particles in the submicron range the efficiency depends on the material properties of the masks, though generally the filtration efficiency in this regime varies between 30 to 60 % and multi-layered cotton masks are expected to be comparable to surgical masks. Respiratory droplets are conventionally divided into coarse droplets (> 5-10 $\mu$m) responsible for droplet transmission and aerosols (< 5-10 $\mu$m) responsible for airborne transmission. Masks are thus expected to be highly effective at preventing droplet transmission, with their effectiveness limited only by the mask fit, compliance and appropriate usage. By contrast, knowledge of the size distribution of bioaerosols and the likelihood that they contain virus is essential to understanding their effectiveness in preventing airborne transmission. We argue from literature data on SARS-CoV-2 viral loads that the finest aerosols (< 1 $\mu$m) are unlikely to contain even a single virion in the majority of cases; we thus expect masks to be effective at reducing the risk of airborne transmission in most settings.Comment: 5 pages + references, 3 figure

Spitzer Secondary Eclipse Observations of Five Cool Gas Giant Planets and Empirical Trends in Cool Planet Emission Spectra

In this work we present Spitzer 3.6 and 4.5 micron secondary eclipse observations of five new cool (<1200 K) transiting gas giant planets: HAT-P-19b, WASP-6b, WASP-10b, WASP-39b, and WASP-67b. We compare our measured eclipse depths to the predictions of a suite of atmosphere models and to eclipse depths for planets with previously published observations in order to constrain the temperature- and mass-dependent properties of gas giant planet atmospheres. We find that the dayside emission spectra of planets less massive than Jupiter require models with efficient circulation of energy to the night side and/or increased albedos, while those with masses greater than that of Jupiter are consistently best-matched by models with inefficient circulation and low albedos. At these relatively low temperatures we expect the atmospheric methane to CO ratio to vary as a function of metallicity, and we therefore use our observations of these planets to constrain their atmospheric metallicities. We find that the most massive planets have dayside emission spectra that are best-matched by solar metallicity atmosphere models, but we are not able to place strong constraints on metallicities of the smaller planets in our sample. Interestingly, we find that the ratio of the 3.6 and 4.5 micron brightness temperatures for these cool transiting planets is independent of planet temperature, and instead exhibits a tentative correlation with planet mass. If this trend can be confirmed, it would suggest that the shape of these planets' emission spectra depends primarily on their masses, consistent with the hypothesis that lower-mass planets are more likely to have metal-rich atmospheres.Comment: 16 pages, 14 figures, accepted for publication in Ap

Cruciferous and allium vegetable intakes are inversely associated with 15‐year atherosclerotic vascular disease deaths in older adult women

Background Higher vegetable intake is consistently associated with lower atherosclerotic vascular disease (ASVD) events. However, the components responsible and mechanisms involved are uncertain. Nonnutritive phytochemicals may be involved. The objective of this study was to investigate the associations of total vegetable intake and types of vegetables grouped according to phytochemical constituents with ASVD mortality. Methods and Results The cohort consisted of 1226 Australian women aged 70 years and older without clinical ASVD or diabetes mellitus at baseline (1998). Vegetable intakes were calculated per serving (75 g/d) and were also classified into prespecified types relating to phytochemical constituents. ASVD‐related deaths were ascertained from linked mortality data. During 15 years (15 947 person‐years) of follow‐up, 238 ASVD‐related deaths occurred. A 1‐serving increment of vegetable intake was associated with a 20% lower hazard of ASVD‐related death (multivariable‐adjusted hazard ratio, 0.80; 95% confidence interval, 0.69–0.94 [P=0.005]). In multivariable‐adjusted models for vegetable types, cruciferous (per 10‐g/d increase: hazard ratio, 0.87; 95% confidence interval, 0.81–0.94 [PP=0.003]) vegetables were inversely associated with ASVD‐related deaths. The inclusion of other vegetable types, as well as lifestyle and cardiovascular risk factors, did not alter these associations. Yellow/orange/red (P=0.463), leafy green (P=0.063), and legume (P=0.379) vegetables were not significant. Conclusions Consistent with current evidence, higher cruciferous and allium vegetable intakes were associated with a lower risk of ASVD mortality. In addition, cruciferous and allium vegetables are recognized to be a good source of several nonnutritive phytochemicals such as organosulfur compounds. Clinical Trial Registration URL: http://www.anzctr.org.au. Unique identifier: ACTRN12617000640303

Vegetable diversity, injurious falls, and fracture risk in older women: A prospective cohort study

The importance of vegetable diversity for the risk of falling and fractures is unclear. Our objective was to examine the relationship between vegetable diversity with injurious falling and fractures leading to hospitalization in a prospective cohort of older Australian women (n = 1429, ≥70 years). Vegetable diversity was quantified by assessing the number of different vegetables consumed daily. Vegetable intake (75 g servings/day) was estimated using a validated food frequency questionnaire at baseline (1998). Over 14.5 years, injurious falls (events = 568, 39.7%), and fractures (events = 404, 28.3%) were captured using linked health records. In multivariable-adjusted Cox regression models, women with greater vegetable diversity (per increase in one different vegetable/day) had lower relative hazards for falls (8%; p = 0.02) and fractures (9%; p = 0.03). A significant interaction between daily vegetable diversity (number/day) and total vegetable intake (75 g servings/day) was observed for falls (pinteraction = 0.03) and fractures (pinteraction \u3c 0.001). The largest benefit of higher vegetable diversity were observed in the one third of women with the lowest vegetable intake (\u3c2.2 servings/day; falls HR 0.83 95% CI (0.71–0.98); fractures HR 0.74 95% CI (0.62–0.89)). Increasing vegetable diversity especially in older women with low vegetable intake may be an effective way to reduce injurious fall and fracture risk

Dietary nitrate intake is associated with muscle function in older women

Background In younger individuals, dietary nitrate supplementation has been shown to improve short‐term vascular and muscle function. The role of higher habitual nitrate intake as part of a typical diet on muscle function in ageing has not been investigated. A cross‐sectional study of relationships between dietary nitrate and measures of muscle function in older community‐dwelling Australian women (n = 1420, ≥70 years) was undertaken. Methods Participants completed a semi‐quantitative food frequency questionnaire assessing dietary intake over the previous year. Total nitrate from vegetables and non‐vegetable sources was calculated from a validated instrument that quantified the nitrate content of food recorded within the food frequency questionnaire. Handgrip strength and timed‐up‐and‐go (TUG) were assessed, representing muscle strength and physical function, respectively. Cut‐points for weak grip strength (kg) and slow TUG (\u3e10.2 s) were selected due to their association with adverse outcomes. Linear and logistic regressions were used to examine the relationship between total nitrate intake and muscle function measures. Results Mean ± standard deviation (SD) total nitrate intake was 79.5 ± 31.2 mg/day, of which 84.5% came from vegetables. Across the unadjusted tertiles of nitrate intake (P= 0.027) and faster TUG (per second, β −0.27, P = 0.001). The proportion of women with weak grip strength (kg) or slow TUG (\u3e10.2 s) was 61.0% and 36.9%, respectively. Each SD higher nitrate intake (31.2 mg/day) was associated with lower odds for weak grip strength (OR 0.84, 95% CI 0.74–0.95, P = 0.005) and slow TUG (OR 0.86, 95% CI 0.76–0.98, P = 0.021). Compared with women in the lowest tertile of nitrate intake, women in the highest nitrate intake tertile had lower odds for weak grip strength (OR 0.65, 95% CI 0.49–0.87, Ptrend=0.004) and slow TUG (OR 0.72, 95% CI 0.53–0.97, Ptrend = 0.044). Conclusions This investigation highlights potential benefits of nitrate‐rich diets on muscle strength and physical function in a large cohort of older women. Considering poor muscle strength and physical function is associated with a range of adverse health outcomes such as falling, fractures, cardiovascular disease, and mortality, increasing dietary nitrate, especially though vegetable consumption may be an effective way to limit age‐related declines in muscle function