Search

A study describing the H, C and N backbone and side chain chemical shift assignments and secondary structure of Skint-1 a prototypic member of a family of mouse genes, of which Skint-1 is involved in the development of the dendritic epidermal T cell (DETC) subset of γδ T cells. [ABSTRACT FROM AUTHOR]

Protecting, establishing and managing biodiverse semi-natural habitats is one strategy within the concept of ecological intensification of agriculture that supports insect pollinator abundance and diversity in agroecosystems. However, without accounting for species-level relationships between insects, crops and non-crop vegetation, diverse semi-natural habitats may not lead to improved crop pollination, and could create pest reservoirs. Possibly thousands of non-bee insect species contribute to global crop pollination, but research has largely focussed on bees. Thus, key information to best manage habitats that target wider crop pollinator diversity and abundance is lacking. We demonstrate the concept of designing mixed species native plantings (a type of semi-natural habitat) based on plant-insect interactions to increase abundance and diversity of non-bee and bee crop pollinators in an intensively managed agricultural landscape. We used existing refereed and grey literature to identify and anticipate interactions between pollinators, natural enemies and pests with native plants and crop species to design and establish plantings on three farms. We anticipated the designed plantings would support 21 pollinating species, 20 of which were verified in observational surveys 5 years post-establishment. While anticipated bee-plant species interactions were largely confirmed, actual networks of the non-bee pollinators, were larger and more complex than expected, indicating the plantings were particularly effective in supporting these interactions. Most immature life-stages of non-bee pollinators were not directly supported by plantings and separate strategies should consider larval requirements. Presenting the plant-pollinator networks to relevant industries has been a powerful tool for incentivising their support for designed habitats on farms. [ABSTRACT FROM AUTHOR]

Objective: To examine depressed affect, somatic complaints, and positive affect as longitudinal predictors of fluid, crystallized and global cognitive performance in the Kuakini Honolulu-Asia Aging Study (HAAS), a large prospective cohort study of Japanese-American men., Methods: We assessed 3,088 dementia-free Kuakini-HAAS participants aged 71-93 (77.1 ± 4.2) years at baseline (1991-1993). Depressive symptoms were evaluated by the Center for Epidemiologic Studies Depression (CES-D) Scale. Baseline CES-D depression subscales (depressed and positive affects; somatic complaints) were computed. The Cognitive Abilities Screening Instrument (CASI) measured cognitive performance on a 100-point scale; fluid and crystallized cognitive abilities were derived from CASI factor analysis. Cognition was also evaluated at 4 follow-up examinations over a 20-year period. Multiple regression assessed baseline CES-D subscales as predictors of cognitive change. The baseline covariates analyzed were CASI, age, education, prevalent stroke, APOE ε4 presence, and the longevity-associated FOXO3 genotype., Results: Cross-sectionally, baseline CES-D subscales were related to cognitive measures; e.g., higher depressed affect was associated with lower crystallized ability (β = -0.058, p ≤ 0.01), and somatic complaints were linked to poorer fluid ability (β = -0.045, p ≤ 0.05) and to worse global cognitive function as measured by total CASI score (β = -0.038, p ≤ 0.05). However, depression subscales did not significantly or consistently predict fluid ability, crystallized ability, or global cognitive performance over time., Conclusion: Psychological and physical well-being were associated with contemporaneous but not subsequent cognitive functioning. Assessment of depressive symptoms may identify individuals who are likely to benefit from interventions to improve mood and somatic health and thereby maintain or enhance cognition., Competing Interests: Declaration of competing interest The authors report no conflicts with any product mentioned or concept discussed in this article., (Copyright © 2024. Published by Elsevier B.V.)

Systemic immunity plays an important role in cancer immune surveillance and response to therapy, but little is known about the immune status of children with solid cancers. We performed a high-dimensional single-cell analysis of systemic immunity in 50 treatment-naive pediatric cancer patients, comparing them to age-matched healthy children. Children with cancer had a lower frequency of peripheral NK cells, which was not due to tumor sequestration, had lower surface levels of activating receptors and increased levels of the inhibitory NKG2A receptor. Furthermore, the natural killer (NK) cells of pediatric cancer patients were less mature and less cytotoxic when tested in vitro . Culture of these NK cells with interleukin-2 restored their cytotoxicity. Collectively, our data show that NK cells in pediatric cancer patients are impaired through multiple mechanisms and identify rational strategies to restore their functionality., Competing Interests: The authors declare no competing interests., (© 2024 The Author(s).)

Objectives: The purpose of this study was to evaluate a cross-lagged panel model of general cognition and functional abilities over 13 years. The goal was to determine whether general cognitive abilities predict or precede functional decline versus functional abilities predicting cognitive decline. Methods: The sample included 3508 men (71-93 years of age at baseline) of the Kuakini Honolulu-Asia Aging Study who were tested repeatedly using a global cognitive test and an assessment of functional capacity. Education and age served as covariates. Cross-lagged models were tested, assessing stationarity of stability and cross-lags. Results: The overall model fit the data well. Cognitive scores had better stability than functional abilities and predicted functional abilities more strongly than functional abilities predicted cognitive scores over time. The strength of all cross-lags increased over time. Discussion: These longitudinal data show that cognitive scores predicted functional decline in a population-based study of older men.

Forthcoming advances in geroscience will influence the health span of current and future generations and generate both challenges and opportunities for those approaching or reaching retirement ages. The resulting changes in the life course will influence those reaching stages in life that are commonly associated with retirement. How people plan for that later phase of life is critical-especially given that current approaches to planning are either nonexistent or outdated. In this review, we show how advances in applied genetics can yield valuable information for individuals that are facing the challenges and opportunities that will accompany anticipated advances in geroscience and their unique influence on the life span and health span of current and future generations., (Copyright © 2023 Cold Spring Harbor Laboratory Press; all rights reserved.)

Background: Accurate assessment of fat intake is essential to examine relationships between diet and disease risk. However, estimating individual intakes of fat quantity by dietary assessment is difficult., Objective: We assessed the association of plasma phospholipid fatty acid levels with dietary intake of fatty acids in the INTERMAP/INTERLIPID study, conducted with a standardized protocol., Methods: The study participants were 1339 men and women ages 40-59 years from five Japanese populations one from Hawaii; four from Japan. Fatty acid intake was estimated from four standardized 24-hour dietary recalls. Plasma phospholipid fatty acid composition was analyzed by gas chromatography. We illustrated the relationship between intake and circulating fatty acid levels using Spearman's rank-correlation coefficients, mean, and median values., Results: Spearman's rank-correlation coefficients between intake (g/d) and circulating fatty acid levels (µg/ml) were -0.03 to 0.21 for saturated fatty acids and monounsaturated fatty acids and -0.04 to 0.32 for trans fatty acids. The coefficients for essential n-3 and n-6 fatty acids were moderate to high, especially for eicosapentaenoic acid (EPA), 0.60; docosahexaenoic acid (DHA), 0.41; and EPA+DHA, 0.51. The circulating levels and intake of marine-derived n-3 fatty acids showed a linear association, at least for the intake of EPA+DHA up to 2.1 g/d., Conclusion: We observed high correlation between intake and circulating levels of marine-derived n-3 fatty acids in participants from Japanese and Japanese-American populations with high and low fish intake. Plasma phospholipid marine-derived n-3 fatty acid measurements are a simple and reliable biomarker for assessing dietary intake., Competing Interests: Declaration of Competing Interest The authors have no conflicts., (Copyright © 2022. Published by Elsevier Inc.)

Seventy five percent of the world's food crops benefit from insect pollination. Hence, there has been increased interest in how global change drivers impact this critical ecosystem service. Because standardized data on crop pollination are rarely available, we are limited in our capacity to understand the variation in pollination benefits to crop yield, as well as to anticipate changes in this service, develop predictions, and inform management actions. Here, we present CropPol, a dynamic, open, and global database on crop pollination. It contains measurements recorded from 202 crop studies, covering 3,394 field observations, 2,552 yield measurements (i.e., berry mass, number of fruits, and fruit density [kg/ha], among others), and 47,752 insect records from 48 commercial crops distributed around the globe. CropPol comprises 32 of the 87 leading global crops and commodities that are pollinator dependent. Malus domestica is the most represented crop (32 studies), followed by Brassica napus (22 studies), Vaccinium corymbosum (13 studies), and Citrullus lanatus (12 studies). The most abundant pollinator guilds recorded are honey bees (34.22% counts), bumblebees (19.19%), flies other than Syrphidae and Bombyliidae (13.18%), other wild bees (13.13%), beetles (10.97%), Syrphidae (4.87%), and Bombyliidae (0.05%). Locations comprise 34 countries distributed among Europe (76 studies), North America (60), Latin America and the Caribbean (29), Asia (20), Oceania (10), and Africa (7). Sampling spans three decades and is concentrated on 2001-2005 (21 studies), 2006-2010 (40), 2011-2015 (88), and 2016-2020 (50). This is the most comprehensive open global data set on measurements of crop flower visitors, crop pollinators and pollination to date, and we encourage researchers to add more datasets to this database in the future. This data set is released for non-commercial use only. Credits should be given to this paper (i.e., proper citation), and the products generated with this database should be shared under the same license terms (CC BY-NC-SA)., (© 2021 The Ecological Society of America.)

Background: Few studies have compared factors related to cognitive function among people with similar genetic backgrounds but different lifestyles., Objective: We aimed to identify factors related to lower cognitive scores among older Japanese men in two genetically similar cohorts exposed to different lifestyle factors., Methods: This cross-sectional study of community-dwelling Japanese men aged 71-81 years included 2,628 men enrolled in the Kuakini Honolulu-Asia Aging Study based in Hawaii and 349 men in the Shiga Epidemiological Study of Subclinical Atherosclerosis based in Japan. We compared participant performance through Cognitive Abilities Screening Instrument (CASI) assessment in Hawaii (1991-1993) and Japan (2009-2014). Factors related to low cognitive scores (history of cardiovascular disease, cardiometabolic factors, and lifestyle factors) were identified with questionnaires and measurements. Multivariable logistic regression analysis was used to calculate the adjusted odds ratios (ORs) of a low (< 82) CASI score based on different factors., Results: CASI scores were lower in Hawaii than in Japan [21.2%(n = 556) versus 12.3%(n = 43), p < 0.001], though this was not significant when adjusted for age and educational attainment (Hawaii 20.3%versus Japan 17.9%, p = 0.328). History of stroke (OR = 1.65, 95%confidence interval = 1.19-2.29) was positively associated with low cognitive scores in Hawaii. Body mass index ≥25 kg/m2 tended to be associated with low cognitive scores in Japan; there was a significant interaction between the cohorts., Conclusion: Cognitive scores differences between cohorts were mostly explained by differences in educational attainment. Conversely, cardiovascular diseases and cardiometabolic factors differentially impacted cognitive scores among genetically similar older men exposed to different lifestyle factors.

Background and Aim: Few studies have examined the association of long-chain n-3 polyunsaturated fatty acids (LCn-3PUFAs) with the measures of atherosclerosis in the general population. This study aimed to examine the relationship of total LCn-3PUFAs, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) with aortic calcification., Methods and Results: In a multiethnic population-based cross-sectional study of 998 asymptomatic men aged 40-49 years (300 US-White, 101 US-Black, 287 Japanese American, and 310 Japanese in Japan), we examined the relationship of serum LCn-3PUFAs to aortic calcification (measured by electron-beam computed tomography and quantified using the Agatston method) using Tobit regression and ordinal logistic regression after adjusting for potential confounders. Overall 56.5% participants had an aortic calcification score (AoCaS) > 0. The means (SD) of total LCn-3PUFAs, EPA, and DHA were 5.8% (3.3%), 1.4% (1.3%), and 3.7% (2.1%), respectively. In multivariable-adjusted Tobit regression, a 1-SD increase in total LCn-3PUFAs, EPA, and DHA was associated with 29% (95% CI = 0.51, 1.00), 9% (95% CI = 0.68, 1.23), and 35% (95% CI = 0.46, 0.91) lower AoCaS, respectively. Results were similar in ordinal logistic regression analysis. There was no significant interaction between race/ethnicity and total LCn-3PUFAs, EPA or DHA on aortic calcification., Conclusions: This study showed the significant inverse association of LCn-3PUFAs with aortic calcification independent of conventional cardiovascular risk factors among men in the general population. This association appeared to be driven by DHA but not EPA., (Copyright © 2019 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background: Recently, high-density lipoprotein particles (HDL-P) have been found to be more strongly inversely associated with coronary artery disease (CAD) risk than their counterpart, HDL cholesterol (HDL-C). Given that lifestyle is among the first targets in CAD prevention, we compared the associations of HDL-P and HDL-C with selected lifestyle factors., Methods and results: We examined 789 Japanese participants of the INTERLIPID Study: men (n=386) and women (n=403) aged 40-59 years in 1996-1998. Participants treated for dyslipidemias were excluded. Lifestyle factors included alcohol intake, smoking amount, and body mass index (BMI). Multivariable linear regression was used for cross-sectional analyses of these factors with HDL-P, HDL-C, HDL-P size subclasses (small, medium and large) and mean HDL-P size. In men, higher alcohol intake was associated with higher HDL-P and higher HDL-C. The associations of alcohol, however, were strongest with HDL-P. A higher smoking amount tended to be associated with lower HDL-P and HDL-C. In contrast, BMI was not associated with HDL-P, but was strongly inversely associated with HDL-C. While alcohol intake favored larger mean HDL-P size, smoking and BMI favored a lipid profile with smaller HDL-P subclasses and overall smaller mean HDL-P size. Similar, but generally weaker results were observed in women., Conclusions: Although both HDL-P and HDL-C are parameters of HDL, they have different associations with alcohol, smoking and BMI.

Previous studies have shown that walking is associated with increased longevity and a reduced risk of cardiovascular and age-related diseases. Whether walking benefits individuals with diabetes who are at high risk of coronary heart disease (CHD) remains to be determined. The objective of this study is to examine the association between walking and risk of CHD among elderly men with and without diabetes. Walking data was assessed in 2732 men aged 71 to 93 years participating in the Honolulu Heart Program from 1991-1993. Study participants were initially without disabilities and free of prevalent CHD. Men were then followed for incident CHD for up to 7 years. For men with diabetes who walked <0.25 miles/day, the age-adjusted incidence of CHD was significantly higher than in men without diabetes (27.1 vs. 12.7/1000 person years, p = 0.026). In contrast when distance walked was >1.5 miles/day, incidence of CHD was similar in men with and without diabetes (12.2 vs. 9.1/1000 person-years, p = 0.46). While risk of CHD declined significantly with increasing walking distance in men with diabetes after age and risk factor adjustment ( p = 0.043, p = 0.025), associations in those without diabetes were weaker ( p = 0.070, p = 0.10). These findings suggest that among elderly men with diabetes who are capable of physical activity, walking reduces CHD risk to levels similar to when diabetes is absent. Walking is an easy, safe and accessible form of physical activity that may have marked health benefits for elderly men with diabetes., Competing Interests: Conflicts of Interest: The authors declare no conflicts of interest.

Data presented in this article are supplementary data to our primary article 'Association of Alcohol Consumption and Aortic Calcification in Healthy Men Aged 40-49 Years for the ERA JUMP Study' [1]. In this article, we have presented supplementary tables showing the independent association of alcohol consumption with coronary artery calcification using Tobit conditional regression and ordinal logistic regression.

Objective: The aim of this study was to investigate the association between anthropometric measurements of sarcopenic obesity and all-cause mortality., Methods: The study included 2309 Japanese-American men ages 71 to 93 y. Mortality data were available for up to 24 y of follow-up. Sarcopenic obesity defined by three patterns of obesity indexes (body mass index [BMI], percent body fat [%BF] and waist circumference [WC]) and skeletal muscle index estimated by anthropometric measurements., Results: Of the 2309 participants, 2210 deaths were reported during the mean follow-up period of 11.7 y. Risk for death was significantly increased with sarcopenia after adjusting for baseline age, lifestyle variables, hypertension, diabetes, and cognitive scores (hazard ratio [HR], 1.26; 95% confidence interval [CI], 1.15-1.38). Risk for death was significantly decreased with obesity using WC and %BF to define obesity, but not BMI. Risk for death also was significantly increased in the sarcopenia group compared with the optimal group, regardless of which pattern of obesity indexes (BMI, %BF, and WC) was used. Risk for death was significantly increased in sarcopenic obesity defined by WC (HR, 1.19; 95% CI, 1.02-1.38), borderline in the BMI-defined group, and not significant in the %BF-defined group., Conclusion: All-cause mortality was increased in men with sarcopenic obesity defined by WC, but not BMI and %BF. Sarcopenia was a stronger predictor of all-cause mortality in this cohort >70 y of age. These results suggest that anthropometric definitions for sarcopenia and sarcopenic obesity are clinically useful as a predictor of all-cause mortality., (Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background and Aims: Several studies have reported a significant inverse association of light to moderate alcohol consumption with coronary heart disease (CHD). However, studies assessing the relationship between alcohol consumption and atherosclerosis have reported inconsistent results. The current study was conducted to determine the relationship between alcohol consumption and aortic calcification., Methods: We addressed the research question using data from the population-based ERA-JUMP Study, comprising of 1006 healthy men aged 40-49 years, without clinical cardiovascular diseases, from four race/ethnicities: 301 Whites, 103 African American, 292 Japanese American, and 310 Japanese in Japan. Aortic calcification was assessed by electron-beam computed tomography and quantified using the Agatston method. Alcohol consumption was categorized into four groups: 0 (non-drinkers), ≤1 (light drinkers), >1 to ≤3 (moderate drinkers) and >3 drinks per day (heavy drinkers) (1 drink = 12.5 g of ethanol). Tobit conditional regression and ordinal logistic regression were used to investigate the association of alcohol consumption with aortic calcification after adjusting for cardiovascular risk factors and potential confounders., Results: The study participants consisted of 25.6% nondrinkers, 35.3% light drinkers, 23.5% moderate drinkers, and 15.6% heavy drinkers. Heavy drinkers [Tobit ratio (95% CI) = 2.34 (1.10, 4.97); odds ratio (95% CI) = 1.67 (1.11, 2.52)] had significantly higher expected aortic calcification score compared to nondrinkers, after adjusting for socio-demographic and confounding variables. There was no significant interaction between alcohol consumption and race/ethnicity on aortic calcification., Conclusions: Our findings suggest that heavy alcohol consumption may be an independent risk factor for atherosclerosis., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The C-type lectin domain containing group 14 family members CLEC14A and CD93 are proteins expressed by endothelium and are implicated in tumour angiogenesis. CD248 (alternatively known as endosialin or tumour endothelial marker-1) is also a member of this family and is expressed by tumour-associated fibroblasts and pericytes. Multimerin-2 (MMRN2) is a unique endothelial specific extracellular matrix protein that has been implicated in angiogenesis and tumour progression. We show that the group 14 C-type lectins CLEC14A, CD93 and CD248 directly bind to MMRN2 and only thrombomodulin of the family does not. Binding to MMRN2 is dependent on a predicted long-loop region in the C-type lectin domain and is abrogated by mutation within the domain. CLEC14A and CD93 bind to the same non-glycosylated coiled-coil region of MMRN2, but the binding of CD248 occurs on a distinct non-competing region. CLEC14A and CD248 can bind MMRN2 simultaneously and this occurs at the interface between endothelium and pericytes in human pancreatic cancer. A recombinant peptide of MMRN2 spanning the CLEC14A and CD93 binding region blocks CLEC14A extracellular domain binding to the endothelial cell surface as well as increasing adherence of human umbilical vein endothelial cells to the active peptide. This MMRN2 peptide is anti-angiogenic in vitro and reduces tumour growth in mouse models. These findings identify novel protein interactions involving CLEC14A, CD93 and CD248 with MMRN2 as targetable components of vessel formation.

Arterial stiffness is established as an independent predictor of cardiovascular morbidity and mortality. The objective was to prospectively evaluate association of aortic calcification burden with progression of arterial stiffness in population-based samples of healthy middle-aged men from ERA JUMP cohort (Electron-Beam Computed Tomography and Risk Factor Assessment in Japanese and US Men in the Post-World War II Birth Cohort). Men (n=635) aged 40 to 49 years (207 white American, 45 black American, 142 Japanese American, and 241 Japanese in Japan) were examined at baseline and 4 to 7 years later. Aortic calcification was evaluated from level of aortic arch to iliac bifurcation. Arterial stiffness progression was measured as annual change in brachial-ankle pulse wave velocity. Multivariable-adjusted general linear models were applied to investigate associations of longitudinal change in aortic calcification with arterial stiffness progression in participants overall, as well as in subgroups without or with prevalent aortic calcification at baseline. Annual change in aortic calcification was positively and significantly associated with arterial stiffness progression. In participants with annual changes in aortic calcium score of ≤0, 1 to 10, 11 to 100, and >100, the adjusted means (SD) for the annual change in brachial-ankle pulse wave velocity were 3.8 (2.2), 7.2 (2.2), 12.2 (1.8), and 15.6 (2.6) cm/s, respectively (P for trend <0.01) adjusted for baseline aortic calcification, arterial stiffness, and standard cardiovascular risk factors. Arterial stiffness was associated with the incidence of aortic calcification over the follow-up period among participants without aortic calcification (n=297) and with an increase in aortic calcification among participants with prevalent aortic calcification at baseline (n=388). Our findings suggest aortic calcification may be causally linked to arterial stiffness., Competing Interests: 6. Conflict of Interests: None, (© 2016 American Heart Association, Inc.)

Objective: Although a significant positive association of vitamin D deficiency with coronary heart disease has been demonstrated in cross-sectional as well as prospective studies, only a few studies have examined the association of vitamin D deficiency with subclinical atherosclerosis. We examined whether vitamin D deficiency is associated with subclinical atherosclerosis, as measured by coronary artery calcification (CAC) in asymptomatic adults., Methods: In a population-based cross-sectional study, 195 men aged 40 to 49 years without cardiovascular disease were randomly selected (98 Caucasian and 97 Japanese American men). Liquid chromatography-tandem mass spectrometry was utilized to measure serum vitamin D. CAC was examined by electron beam computed tomography using standardized protocols and read centrally at the University of Pittsburgh using Agatston's methods. To investigate an association between vitamin D deficiency (defined as 25-hydroxyvitamin D [25(OH)D] < 20 ng/mL) and CAC (defined as Agatston score ≥ 10), we utilized multivariable logistic regression models., Results: Prevalence of CAC and vitamin D deficiency was 27.2% and 10.3%, respectively. Participants with CAC were significantly older, had significantly higher body mass index (BMI), and had higher rates of smoking. Those with CAC were 3.31 times likely to be vitamin D deficient, after adjusting for traditional cardiovascular risk factors (odds ratio [OR] = 3.31, 95% confidence interval [CI], 1.12-9.77)., Conclusions: In this population-based study of healthy middle-aged men, vitamin D deficiency had a significant positive association with the presence of CAC.

Background: Worldwide, the US accounts for a large proportion of journals related to public health. Although the American Public Health Association (APHA) includes 54 affiliated regional and state associations, little is known about their capacity to support public health scholarship. The aim of this study is to assess barriers and facilitators to operation of state journals for the dissemination of local public health research and practices., Methods: A mixed methods approach will be used to complete the 12-month study. Affiliate websites will be accessed through the APHA membership portal to evaluate organizational infrastructure and ascertain the presence/absence of a journal. The leader of each affiliate will be contacted via email containing a link to a 12-question on-line survey to collect his/her perceptions of scholarly journals and the publication of local health data. To determine barriers and facilitators to publication of local public health findings, 30-minute semi-structured telephone interviews will focus on the infrastructure of the association, perceptions of the leader about the journal (if in place), and its operation., Anticipated Results: We anticipate that 54 affiliate websites will be reviewed to complete the extraction checklist, that 74% of affiliate leaders will respond to the survey, and that 11 semi-structured interviews will be conducted. A limited number of state/regional public health associations will operate journals and a small percentage of those without journals may express an interest in implementing them. Barriers to operation of journals may include lack of resources (i.e., personnel, funding), and low prioritization of publication of state and local public health findings. Facilitators may include strong affiliate-academic relationships, affiliate leadership with experience in publications, and affiliate relationships with state and local departments of health., Conclusions: The research proposed in this protocol may stimulate other state public health associations and other academic public health programs to follow suit; it would not be the first time that an observational research study served as an intervention.

Background: C-reactive protein (CRP) and many fatty acids (FAs) have been linked to cardiovascular disease. Associations of serum CRP with FAs in different populations have not been established., Methods: Participants were 926 men aged 40-49 (2002-2006) from a population-based sample; 310 Whites from Pennsylvania, U.S., 313 Japanese from Shiga, Japan, and 303 Japanese Americans from Hawaii, U.S. Serum CRP (mg/L) was measured using immunosorbent assay while serum FAs (%) were measured using capillary-gas-liquid chromatography., Results: Whites had CRP (mg/L) levels higher than Japanese with Japanese Americans in-between (age-adjusted geometric mean "GM" 0.96, 0.38, 0.66, respectively). Whites had also higher levels of total n-6 FAs (%) and trans fatty acids (TFAs) but lower levels of marine-derived n-3 FAs compared to Japanese (41.78 vs. 35.05, 1.04 vs. 0.58, and 3.85 vs. 9.29, respectively). Japanese Americans had FAs levels in-between the other two populations. Whites had significant inverse trends between CRP and tertiles of total n-6 FAs (GM 1.20, 0.91 and 0.80; p=0.002) and marine-derived n-3 FAs (GM 1.22, 1.00 and 0.72; p<0.001) but a significant positive trend with TFAs (GM 0.80, 0.95 and 1.15; p=0.007). Japanese had a significant inverse trend between CRP and only total n-6 FAs (GM 0.50, 0.35 and 0.31; p<0.001). Japanese Americans had CRP associations with n-3 FAs, n-6 FAs, and TFAs similar to but weaker than Whites., Conclusions: With the exception of consistent inverse association of CRP with total n-6 FAs, there are considerable variations across the three populations in the associations of CRP with different FAs.

Objectives: To study the association between total and differential white blood cell (WBC) count and incident stroke in an older Asian population., Design: Prospective population-based study with 8 years of follow-up., Setting: The Honolulu Heart Program, Oahu, Hawaii., Participants: Japanese-American men aged 71 to 93 who were free of stroke and had baseline WBC counts measured in 1991-93 (N=3,342)., Measurements: Participants were divided into quartiles of total and differential WBC count for analysis and were followed for incident stroke (thromboembolic and hemorrhagic (hemorrhagic)) for 8 years using data from a comprehensive hospital surveillance system., Results: Age-adjusted incident stroke rates increased significantly with increasing WBC quartile (Q1, 7.68; Q2, 9.04; Q3, 9.26; Q4, 14.10 per 1,000 person-years of follow-up, P=.001). Hazard ratios (HRs) for stroke for each quartile of total and differential WBC count were obtained using Cox regression analysis, with the lowest quartile as the reference group. After full adjustment, including age; cardiovascular risk factors; fibrinogen; prevalent coronary heart disease, cancer, or chronic obstructive pulmonary disease, and nonsteroidal anti-inflammatory drug use, HRs were 1.62 (95% confidence interval (CI)=1.04-2.52, P=.03) in the highest quartile of total WBC and 2.19 (95% CI=1.41-3.39, P<.001) in the highest quartile of neutrophil counts. Significant associations were also seen for thromboembolic but not for hemorrhagic strokes. No significant associations were found between lymphocyte or monocyte counts and incident stroke or subtypes., Conclusion: In elderly Japanese-American men, higher total WBC and neutrophil counts were independent predictors of overall stroke, as well as thromboembolic stroke., (© 2015, Copyright the Authors Journal compilation © 2015, The American Geriatrics Society.)

Unlabelled: Baseline risk factors were associated with fractures that developed after 29-31 years among Japanese-American men. Hip fracture risk increased with increasing BMI (28% increase for 1 U increase), physical activity (7% increase for 1 U increase), and was decreased with increasing arm girth (27% decrease for 1 U increase)., Purpose: The objective of this study was to identify risk factors among Japanese-American men aged 45-68 years at baseline that were associated with prevalence and incidence of fractures at advanced age., Methods: We used baseline information from Honolulu Heart Program (HHP) and Honolulu-Asia Aging Study (HAAS). The HHP was a prospective study with primary focus on risk factors for cardiovascular disease. A cohort of 8,006 men of Japanese ancestry aged 45-68 years residing on Oahu was recruited in 1965 and followed for 31 years. The HAAS started in 1991 in conjunction with the HHP with a focus on age-related health conditions. Self-reported hip, spine, and forearm fracture prevalence was ascertained in 1991-1993 among 3,845 men aged 71-93 years. Incidence was obtained during the period (1994-1999) among 2,737 men aged 74-98 years. Poisson regression models were used to determine multi-variable adjusted prevalence and incidence ratios for fracture., Results: Incident hip fracture was directly associated with baseline body mass index (BMI) and physical activity, and inversely associated with left upper arm girth. Incident spine fracture was directly associated with baseline age. Prevalent hip fracture was directly associated with baseline pack-years of smoking. Prevalent spine fracture was inversely associated with baseline education, and directly associated with standing height and use of medication for diabetes. Prevalent forearm fracture was inversely associated with baseline age, and directly associated with education., Conclusions: Results indicated that multiple baseline demographic lifestyle and anthropometric characteristics predict fracture risk at advanced age. In addition, associations varied by fracture location.

Certain micronutrients are protective against cognitive decline. We examined whether there is any uniform pattern of circulating micronutrients cross-culturally that are associated with successful cognitive aging. For the U.S. sample, we used the stored serum/plasma of 115 participants, collected in Oregon, USA. The Okinawa sample consisted of 49 participants selected using similar inclusion criteria as the Oregon sample, from the Keys to Optimal Cognitive Aging Project. All participants were aged 85 years and older without cognitive impairment. We found that the Okinawan elders used fewer vitamin supplements but had similar levels of vitamin B(12) and α-tocopherol, lower folate and γ-tocopherol, compared with Oregonian elders. That is, we did not find a uniform pattern of circulating micronutrients, suggesting that micronutrients other than those examined here or other lifestyle factors than nutrition could play an important role in achieving successful cognitive aging.

Models and frameworks to guide "sustainable mobility" of personal transportation lack definitive quantitative targets. This paper defines sustainable mobility targets for US light-duty vehicles (LDVs) to help stabilize atmospheric carbon dioxide concentrations at 450 or 550 ppm. The Intergovernmental Panel on Climate Change carbon stabilization pathways are used to equitably distribute future carbon dioxide emissions to the US. Allowable US emissions are then allocated to the LDV sector according to the current share of national emissions. Average on-road LDV well-to-wheel carbon emissions must be reduced from 160 g/mile (2002) to 20 g/mile by 2050 to contribute to a 450 ppm CO2 goal. Strategies to reduce LDV greenhouse gas emissions include reducing travel demand, improving average fuel economy, and utilizing low-carbon ethanol. Simulations using EIA modeling parameters indicate that average LDV fuel economy must reach 136 mpg, cellulosic ethanol must make up over 83% of fuel market share, or annual LDV travel demand must be reduced by about 53% by 2050 to help meet LDV greenhouse gas targets based on a 450 ppm CO2 stabilization goal. Recent federal energy security policy and plug-in hybrid technology programs may also help meet LDV carbon emission targets in the short term by reducing gasoline use, but an aggressive combination of strategies will be needed to keep vehicle CO2 in line with an emissions target to 2050.

The CD1 family of proteins has evolved to bind a range of endogenous and foreign lipids and present these at the cell surface for antigen-specific recognition by T cells. The distinct intracellular trafficking pathways of CD 1 molecules indicate that collectively, they have the potential to survey the endocytic system widely for antigen, consistent with a role in the presentation of lipids derived from intracellular microbial pathogens. In keeping with this idea, CDla, CDlb, CDlc and CDld have now been shown to present foreign lipid antigens derived from mycobacteria, Gram-negative bacteria and also protozoan species to T cells. These antigens are extremely diverse chemically, and include naturally occurring lipopeptide, glycolipid and phospholipid structures that are distinct from mammalian lipids. CD1-restricted mycobacterial lipids defined to date derive from the highly complex microbial cell envelope. They play a variety of physiological roles for the microbe, including formation of the plasma membrane and protective cell wall and as metabolic intermediates in iron-scavenging pathways. In each case, alkyl chains of CD 1-restricted lipid antigens are accommodated within a deep hydrophobic groove in the membrane-distal alphal-alpha2 domains of the CD1 molecule, with hydrophilic elements solvent-exposed and accessible for recognition by the T cell receptor. Variation in the number, length and saturation of alkyl chains, and the precise chemistry and chirality of the lipid headgroup, clearly exert dominant influences on antigenicity, mediated by effects on CD1 binding and T cell receptor recognition. In the context of structural studies of CD1-lipid complexes, these data suggest that the CD1 isoforms have evolved binding specificities for different classes of foreign lipids, and strongly support a model for antigen recognition involving fine discrimination of lipid headgroup components by the alpha beta T cell receptor. In this review, we summarise our current knowledge of foreign lipid antigens bound by CD 1, focusing on the roles their distinct structural features play in presentation and T cell antigen recognition, and their likely function in antimicrobial T cell responses.

Background: Remnant-like particles have been proposed as a new risk factor for coronary heart disease (CHD). This is the first long-term prospective investigation of the relationship between remnant-like particles and a cardiovascular disease outcome in healthy men., Methods and Results: A cohort of 1156 Japanese-American men aged 60 to 82 from the Honolulu Heart Program was followed for 17 years. During that period 164 incident cases of CHD were identified. In multivariate Cox regression analyses, baseline remnant-like particle cholesterol (RLP-C) and triglyceride (RLP-TG) levels were significantly related to CHD incidence independently of nonlipid cardiovascular risk factors and of total cholesterol or high-density and low-density lipoprotein cholesterol levels. Total triglyceride levels were an independent predictor of CHD incidence. However, in models including RLP and triglyceride level simultaneously, neither variable was significant when adjusted for the other. This finding can be attributed to the strong correlation between RLP-C and RLP-TG levels and total triglycerides. When individuals with normal triglyceride levels (n=894) were separated from those with elevated triglycerides (n=260), the association between RLPs and CHD relative risk was only significant for the group with elevated triglyceride levels., Conclusions: RLP levels predicted CHD incidence independently of nonlipid risk factors and of total cholesterol or high-density and low-density lipoprotein cholesterol levels. However, RLP levels did not provide additional information about CHD incidence over and above total triglyceride levels. Therefore, this study does not support the need for testing of remnants in men if measures of fasting triglycerides are available.

Ig-like transcript 4 (ILT4) (also known as leukocyte Ig-like receptor 2, CD85d, and LILRB2) is a cell surface receptor expressed mainly on myelomonocytic cells, whereas ILT2 (also known as leukocyte Ig-like receptor 1, CD85j, and LILRB1) is expressed on a wider range of immune cells including subsets of natural killer and T cells. Both ILTs contain immunoreceptor tyrosine-based inhibitory receptor motifs in their cytoplasmic tails that inhibit cellular responses by recruiting phosphatases such as SHP-1 (Src homology 2 domain containing tyrosine phosphatase 1). Although these ILTs have been shown to recognize a broad range of classical and nonclassical human MHC class I molecules (MHCIs), their precise binding properties remain controversial. We have used surface plasmon resonance to analyze the interaction of soluble forms of ILT4 and ILT2 with several MHCIs. Although the range of affinities measured was quite broad (Kd = 2-45 microM), some interesting differences were observed. ILT2 generally bound with a 2- to 3-fold higher affinity than ILT4 to the same MHCI. Furthermore, ILT2 and ILT4 bound to HLA-G with a 3- to 4-fold higher affinity than to classical MHCIs, suggesting that ILT/HLA-G recognition may play a dominant role in the regulation of natural killer, T, and myelomonocytic cell activation. Finally, we show that ILT2 and ILT4 effectively compete with CD8 for MHCI binding, raising the possibility that ILT2 modulates CD8+ T cell activation by blocking the CD8 binding as well as by recruiting inhibitory molecules through its immunoreceptor tyrosine-based inhibitory receptor motif.

NKG2D is a potent activating receptor on natural killer cells, T cells, and macrophages. Mouse NKG2D interacts with two cell surface ligands related to class I MHC molecules: RAE1 and H60. We used soluble versions of NKG2D, RAE1, and H60 to characterize their interactions. RAE1 and H60 each bind NKG2D with nanomolar affinities, indicating tighter binding than most cell surface immune interactions, but NKG2D binds to H60 with approximately 25-fold higher affinity than to RAE1. RAE1 and H60 compete directly for occupancy of NKG2D, and, thus, NKG2D can be occupied by only one ligand at a time. The NKG2D-H60 interaction is more temperature dependent and makes greater use of electrostatic interactions than the NKG2D-RAE1 interaction. The distinct thermodynamic profiles provide insights into the different molecular mechanisms of the binding interactions.

Human immunodeficiency virus type-1 (HIV-1) cytotoxic T lymphocyte (CTL) epitopes have largely been defined in Caucasian populations infected with clade B virus. Identification of potentially protective CTL epitopes in non-B clade-infected African subjects is important for vaccine development. In a study of CTL responses in clade A-infected Gambians, using cytotoxicity, interferon-gamma (IFN-gamma) enzyme-linked immunospot (ELISpot) and HLA-B53-peptide tetramer assays, we identified three HLA-B53-restricted epitopes in HIV-1 gag p24. CTL specific for an epitope in a highly immunogenic region of the p24 protein showed no cross-reactivity to other HIV-1 clades. Two of the epitopes would not have been predicted from the peptide-binding motif due to the absence of a proline anchor at position 2. Structural analysis of HLA-B53 and its relative, HLA B35, enabled us to re-define the peptide-binding motif to include other P2 anchors. These results demonstrate the value of combined immunological and structural analyses in defining novel CTL epitopes and have implications for HIV-1 vaccine design.

The major histocompatibility complex (MHC) class I homolog, MICA, is a stress-inducible ligand for NKG2D, a C-type lectin-like activating immunoreceptor. The crystal structure of this ligand-receptor complex that we report here reveals an NKG2D homodimer bound to a MICA monomer in an interaction that is analogous to that seen in T cell receptor-MHC class I protein complexes. Similar surfaces on each NKG2D monomer interact with different surfaces on either the alpha1 or alpha2 domains of MICA. The binding interactions are large in area and highly complementary. The central section of the alpha2-domain helix, disordered in the structure of MICA alone, is ordered in the complex and forms part of the NKG2D interface. The extensive flexibility of the interdomain linker of MICA is shown by its altered conformation when crystallized alone or in complex with NKG2D.

The cell surface molecules CD4 and CD8 greatly enhance the sensitivity of T-cell antigen recognition, acting as "co-receptors" by binding to the same major histocompatibility complex (MHC) molecules as the T-cell receptor (TCR). Here we use surface plasmon resonance to study the binding of CD8alphaalpha to class I MHC molecules. CD8alphaalpha bound the classical MHC molecules HLA-A*0201, -A*1101, -B*3501, and -C*0702 with dissociation constants (K(d)) of 90-220 microm, a range of affinities distinctly lower than that of TCR/peptide-MHC interaction. We suggest such affinities apply to most CD8alphaalpha/classical class I MHC interactions and may be optimal for T-cell recognition. In contrast, CD8alphaalpha bound both HLA-A*6801 and B*4801 with a significantly lower affinity (>/=1 mm), consistent with the finding that interactions with these alleles are unable to mediate cell-cell adhesion. Interestingly, CD8alphaalpha bound normally to the nonclassical MHC molecule HLA-G (K(d) approximately 150 microm), but only weakly to the natural killer cell receptor ligand HLA-E (K(d) >/= 1 mm). Site-directed mutagenesis experiments revealed that variation in CD8alphaalpha binding affinity can be explained by amino acid differences within the alpha3 domain. Taken together with crystallographic studies, these results indicate that subtle conformational changes in the solvent exposed alpha3 domain loop (residues 223-229) can account for the differential ability of both classical and nonclassical class I MHC molecules to bind CD8.

A method to produce alphabeta T-cell receptors (TCRs) in a soluble form suitable for biophysical analysis was devised involving in vitro refolding of a TCR fusion protein. Polypeptides corresponding to the variable and constant domains of each chain of a human and a murine receptor, fused to a coiled coil heterodimerization motif from either c-Jun (alpha) or v-Fos (beta), were overexpressed separately in Escherichia coli. Following recovery from inclusion bodies, the two chains of each receptor were denatured, and then refolded together in the presence of denaturants. For the human receptor, which is specific for the immunodominant influenza A HLA-A2-restricted matrix epitope (M58-66), a heterodimeric protein was purified in milligram yields and found to be homogeneous, monomeric, antibody-reactive, and stable at concentrations lower than 1 microM. Using similar procedures, analogous results were obtained with a murine receptor specific for an influenza nucleoprotein epitope (366-374) restricted by H2-Db. Production of these receptors has facilitated a detailed analysis of viral peptide-Major Histocompatibility Complex (peptide-MHC) engagement by the TCR using both surface plasmon resonance (SPR) and, in the case of the human TCR, isothermal titration calorimetry (ITC) (Willcox et al., 1999). The recombinant methods described should enable a wide range of TCR-peptide-MHC interactions to be studied and may also have implications for the production of other heterodimeric receptor molecules.