Publications

A previous study, using capillary electrophoresis (CE) [J. Am. Chem. Soc.2008, 130, 17384–17393], reported that six discrete complexes of ubiquitin (UBI) and sodium dodecyl sulfate (SDS) form at different concentrations of SDS along the pathway to unfolding of UBI in solutions of SDS. One complex (which formed between 0.8 and 1.8 mM SDS) consisted of native UBI associated with approximately 11 molecules of SDS. The current study used CE and 15N/13C–1H heteronuclear single quantum coherence (HSQC) NMR spectroscopy to identify residues in folded UBI that associate specifically with SDS at 0.8–1.8 mM SDS, and to correlate these associations with established biophysical and structural properties of this well-characterized protein. The ability of the surface charge and hydrophobicity of folded UBI to affect the association with SDS (at concentrations below the CMC) was studied, using CE, by converting lys-ε-NH3+ to lys-ε-NHCOCH3 groups. According to CE, the acetylation of lysine residues inhibited the binding of 11 SDS ([SDS] < 2 mM) and decreased the number of complexes of composition UBI-(NHAc)8·SDSn that formed on the pathway of unfolding of UBI-(NHAc)8 in SDS. A comparison of 15N–1H HSQC spectra at 0 mM and 1 mM SDS with calculated electrostatic surface potentials of folded UBI (e.g., solutions to the nonlinear Poisson–Boltzmann (PB) equation) suggested, however, that SDS binds preferentially to native UBI at hydrophobic residues that are formally neutral (i.e., Leu and Ile), but that have positive electrostatic surface potential (as predicted from solutions to nonlinear PB equations); SDS did not uniformly interact with residues that have formal positive charge (e.g., Lys or Arg). Cationic functional groups, therefore, promote the binding of SDS to folded UBI because these groups exert long-range effects on the positive electrostatic surface potential (which extend beyond their own van der Waals radii, as predicted from PB theory), and not because cationic groups are necessarily the site of ionic interactions with sulfate groups. Moreover, SDS associated with residues in native UBI without regard to their location in α-helix or β-sheet structure (although residues in hydrogen-bonded loops did not bind SDS). No correlation was observed between the association of an amino acid with SDS and the solvent accessibility of the residue or its rate of amide H/D exchange. This study establishes a few (of perhaps several) factors that control the simultaneous molecular recognition of multiple anionic amphiphiles by a folded cytosolic protein.

&lt;p&gt; &lt;/p&gt; &lt;p&gt;&lt;strong&gt;OBJECTIVE &lt;/strong&gt;The present study aims to prospectively examine the association between post-diagnosis low carbohydrate diet (LCD) patterns and mortality among individuals with type 2 diabetes (T2D).&lt;/p&gt; &lt;p&gt;&lt;strong&gt;RSEARCH DESIGN AND METHODS &lt;/strong&gt;Among participants with incident diabetes identified in the Nurses’ Health Study and Health Professionals Follow-Up Study, an overall total low carbohydrate diet score (TLCDS) was calculated based on the percentage of energy as total carbohydrates. In addition, vegetable (VLCDS), animal (ALCDS), healthy (HLCDS), and unhealthy LCDS (ULCDS) were further derived that emphasized different sources and quality of macronutrients. Multivariable-adjusted Cox model were used to assess the association between the LCDS and mortality.&lt;/p&gt; &lt;p&gt;&lt;strong&gt;RESULTS &lt;/strong&gt;Among 10,101 incident T2D cases contributing 139,407 person-years during follow-up, we documented 4,595 deaths of which 1,389 cases were attributed to cardiovascular disease (CVD) and 881 to cancer. The pooled multivariable-adjusted hazard ratios (HRs, 95% CIs) of total mortality per 10 points increment of post-diagnosis LCDS were 0.87 (0.82,0.92) for TLCDS, 0.76 (0.71,0.82) for VLCDS, and 0.78 (0.73,0.84) for HLCDS. Both VLCDS and HLCDS were also associated with significantly lower CVD and cancer mortality. Each 10 points increase of TLCDS, VLCDS, and HLCDS from pre-diagnosis to post-diagnosis period was associated with 12% (7%, 17%), 25% (19%, 30%), and 25% (19%, 30%) lower total mortality, respectively. No significant associations were observed for ALCDS and ULCDS. &lt;/p&gt; &lt;p&gt;&lt;strong&gt;CONCLUSIONS&lt;/strong&gt; Among people with T2D, greater adherence to LCD patterns that emphasize high quality sources of macronutrients was significantly associated with lower total, cardiovascular, and cancer mortality. &lt;/p&gt;

OBJECTIVE To examine the association of plasma alkylresorcinol metabolite 3-(3,5-dihydroxyphenyl)-1-propanoic acid (DHPPA), a biomarker of whole-grain wheat and rye intake, with type 2 diabetes (T2D) and impaired glucose regulation (IGR) in a Chinese population. RESEARCH DESIGN AND METHODS A total of 1,060 newly diagnosed T2D patients, 736 newly diagnosed IGR patients, and 1,443 control subjects with normal glucose tolerance were recruited in the case-control study. Plasma DHPPA concentrations were determined by high-performance liquid chromatography–tandem mass spectroscopy. Multivariate logistic regression analysis was used to evaluate the independent association of plasma DHPPA concentrations with the likelihood of T2D and IGR. RESULTS After adjustment for age, sex, BMI, and family history of diabetes, the odds ratios (95% CI) of T2D and IGR were 0.57 (0.45, 0.73) and 0.66 (0.50, 0.85), respectively, comparing the lowest with the highest quartile of plasma DHPPA concentrations. Further adjustment for current smoking status, current alcohol consumption, physical activity, history of hypertension, and educational level did not change the observed association materially. Similar results were also obtained in T2D and IGR groups combined. The inverse association of plasma DHPPA with T2D persisted in stratified analyses according to age, sex, BMI, current smoking status, current alcohol consumption, physical activity, family history of diabetes, and history of hypertension. CONCLUSIONS These findings suggested that higher plasma DHPPA concentrations were associated with lower odds of T2D and IGR. Further studies are warranted to confirm these findings in prospective cohorts.

ABSTRACT Purpose An inverse association between physical activity (PA) and risk of CHD has been seen in many studies, but evidence for benefits of PA after myocardial infarction (MI) in reducing mortality is limited. Methods Using data from the Health Professionals Follow-up Study cohort, we followed male survivors of MI. Short- and long-term changes in PA from before to after MI were calculated, and participants without ambulation impairment were classified into maintained low, decreased, increased, or maintained high PA categories. Cox models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for mortality across PA and PA change categories. Results During a mean of 14 yr of follow-up of 1651 incident nonfatal MI cases, we documented 678 deaths, 307 were due to cardiovascular disease. The adjusted HR for all-cause mortality comparing ≥21 with ≤1.5 MET·wk −1 of PA before MI was 0.73 (95% CI = 0.59–0.89, P trend = 0.03). Compared with men who maintained low PA before and after MI, men who maintained high PA had a 39% (95% CI = 25–50) lower risk of all-cause mortality, and those who had a long-term increase in PA from before to after MI had a 27% (95% CI = 6–43) lower risk. Walking for ≥30 min·d −1 after MI was associated with a 29% lower mortality (HR = 0.71, 95% CI = 0.58–0.84), independent of walking pace, and walking pace after MI was inversely associated with mortality (HR = 0.67, 95% CI = 0.49–0.92). Conclusions Maintaining a high PA or having a long-term increase in PA from before to after MI was associated with lower mortality among male MI survivors. Walking time and walking pace after MI were each inversely associated with mortality.

OBJECTIVE The metabolic syndrome (MetS) is defined as concomitant disorders of lipid and glucose metabolism, central obesity, and high blood pressure, with an increased risk of type 2 diabetes and cardiovascular disease. This study tests whether common genetic variants with pleiotropic effects account for some of the correlated architecture among five metabolic phenotypes that define MetS. RESEARCH DESIGN AND METHODS Seven studies of the STAMPEED consortium, comprising 22,161 participants of European ancestry, underwent genome-wide association analyses of metabolic traits using a panel of ∼2.5 million imputed single nucleotide polymorphisms (SNPs). Phenotypes were defined by the National Cholesterol Education Program (NCEP) criteria for MetS in pairwise combinations. Individuals exceeding the NCEP thresholds for both traits of a pair were considered affected. RESULTS Twenty-nine common variants were associated with MetS or a pair of traits. Variants in the genes LPL, CETP, APOA5 (and its cluster), GCKR (and its cluster), LIPC, TRIB1, LOC100128354/MTNR1B, ABCB11, and LOC100129150 were further tested for their association with individual qualitative and quantitative traits. None of the 16 top SNPs (one per gene) associated simultaneously with more than two individual traits. Of them 11 variants showed nominal associations with MetS per se. The effects of 16 top SNPs on the quantitative traits were relatively small, together explaining from ∼9% of the variance in triglycerides, 5.8% of high-density lipoprotein cholesterol, 3.6% of fasting glucose, and 1.4% of systolic blood pressure. CONCLUSIONS Qualitative and quantitative pleiotropic tests on pairs of traits indicate that a small portion of the covariation in these traits can be explained by the reported common genetic variants.

An elastomeric device converts a constant input pressure into multiple oscillating, temporally offset output pressures.

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMonolayers on disordered substrates: self-assembly of alkyltrichlorosilanes on surface-modified polyethylene and poly(dimethylsiloxane)Gregory S. Ferguson, Manoj K. Chaudhury, Hans A. Biebuyck, and George M. WhitesidesCite this: Macromolecules 1993, 26, 22, 5870–5875Publication Date (Print):October 1, 1993Publication History Published online1 May 2002Published inissue 1 October 1993https://pubs.acs.org/doi/10.1021/ma00074a007https://doi.org/10.1021/ma00074a007research-articleACS PublicationsRequest reuse permissionsArticle Views1141Altmetric-Citations140LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts

<h3>Introduction</h3> Forced vital capacity (FVC) is a powerful predictor of mortality, more than airflow obstruction (Burney <i>et al</i>. Thorax 2011;66:49–54). FVC is associated with systemic inflammation as well as with cardiovascular disease and diabetes. Given that systemic inflammation is also associated with cardiovascular disease and diabetes, systemic inflammation could explain the observed association between FVC and cardiometabolic markers. Here, we examined the association between FVC, cardiometabolic markers and systemic inflammation in 3,731 individuals belonging to the Northern Finland Birth Cohort 1966. <h3>Methods</h3> Using linear regression, we examined the association between i) cardiometabolic markers (systolic blood pressure, diastolic blood pressure, LDL cholesterol, triglycerides, fasting glucose, insulin and HOMA-IR) and inflammatory markers (C-reactive protein (CRP) and white blood cell count (WBC)), ii) FVC and inflammatory markers, and iii) FVC and cardiometabolic markers. We then tested whether the association between FVC and cardiometabolic markers could be explained by systemic inflammation, by adjusting the linear regression models of FVC on each cardiometabolic marker for the two inflammatory markers. <h3>Results</h3> Increasing levels of inflammatory markers were associated with a decrease in FVC, -12mL per mg/L of CRP (95% confidence interval (CI): -17 to -7 mL) and -17 mL per 10⁹ cells/L of WBC (95% CI: -28 to -7 mL), and with increasing levels of the cardiometabolic markers. FVC also decreased with increasing levels of cardiometabolic markers (Table, column 1) and adjusting these associations for the inflammatory markers did not substantially alter them (Table, column 2). <h3>Conclusion</h3> The association between FVC and cardiometabolic markers is not explained by variation in inflammatory markers, as measured by CRP and WBC. However, due to the cross-sectional nature of the analysis, no inference can be made with regard to the directionality of the associations.

Introduction: Higher Mediterranean diet (MED) intake has been associated with lower risk of cardiovascular disease (CVD) but limited data is available about the underlying molecular mechanisms of t...