Plasma PLP Concentration and Depressive Symptomatology, over time, in older Latino Adults

Background: Low vitamin B-6 status has been linked to depressive symptomatology. However, most studies have been cross-sectional and may not have controlled for relevant confounders. Few studies have examined this association in Latino populations at high risk for major depression. Design: We used two-level hierarchical linear regression models (HLM) for continuous outcomes. Level-1 data included three measures of participant’s depressive symptomatology collected at baseline, 2y follow-up and 5y follow-up. Participants constituted level-2 data. Vitamin B-6 was associated with depressive symptomatology across these time points. Objective: We examined the longitudinal association of vitamin B-6 status with depressive symptomatology across 3 time points over ~ 5-7 y in a cohort of older Puerto Rican adults, a population previously identified to be at high risk for depressive symptomatology and clinical depression. Results: Plasma pyridoxyl-5’-phosphate (PLP) concentration, a time-varying predictor, was significantly associated with depressive symptomatology. Study participants with PLP deficiency, vs. optimal PLP, had higher baseline depressive symptoms (22±14, vs. 20±13); this differential remained constant over time and persisted after controlling for age, sex, education, BMI, smoking and alcohol use, other relevant nutritional factors, perceived stress, stressful life events and allostatic load; and use of antidepressant medication. However, PLP concentration was not associated with the rate of change in depressive symptomatology over time. Conclusions: Suboptimal plasma PLP is associated with higher depressive symptomatology in older Puerto Rican adults and this appears to persist over time. Our data suggest that identification and treatment of vitamin B-6 deficiency may be a useful preventive and intervention approach in this population

Disparities in allele frequencies and population differentiation for 101 disease-associated single nucleotide polymorphisms between Puerto Ricans and Non-Hispanic Whites

BACKGROUND. Variations in gene allele frequencies can contribute to differences in the prevalence of some common complex diseases among populations. Natural selection modulates the balance in allele frequencies across populations. Population differentiation (FST) can evidence environmental selection pressures. Such genetic information is limited in Puerto Ricans, the second largest Hispanic ethnic group in the US, and a group with high prevalence of chronic disease. We determined allele frequencies and population differentiation for 101 single nucleotide polymorphisms (SNPs) in 30 genes involved in major metabolic and disease-relevant pathways in Puerto Ricans (n = 969, ages 45–75 years) and compared them to similarly aged non-Hispanic whites (NHW) (n = 597). RESULTS. Minor allele frequency (MAF) distributions for 45.5% of the SNPs assessed in Puerto Ricans were significantly different from those of NHW. Puerto Ricans carried risk alleles in higher frequency and protective alleles in lower frequency than NHW. Patterns of population differentiation showed that Puerto Ricans had SNPs with exceptional FST values in intronic, non-synonymous and promoter regions. NHW had exceptional FST values in intronic and promoter region SNPs only. CONCLUSION. These observations may serve to explain and broaden studies on the impact of gene polymorphisms on chronic diseases affecting Puerto Ricans.National Institutes of Health, National Institutes on Aging (P01AG02394, P01AG023394-SI); National Insitutes of Health (53-K06-5-10); US Department of Agriculture Research Service (58-1950-9-001, 58-1950-7-707); National Institutes of Health & Heart, Lung, and Blood Institute (U 01 HL72524, Genetic and Environmental Determinants of Triglycerides, HL54776

THE VARIABLE GENOMIC ARCHITECTURE OF ISOLATION BETWEEN HYBRIDIZING SPECIES OF HOUSE MICE

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75350/1/EVO_846_sm_FigS3A.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/75350/2/EVO_846_sm_legend.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/75350/3/EVO_846_sm_FigS4.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/75350/4/j.1558-5646.2009.00846.x.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/75350/5/EVO_846_sm_FigS1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/75350/6/EVO_846_sm_FigS2.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/75350/7/EVO_846_sm_FigS3B.pd

Two types of shock in the hotspot of the giant quasar 4C74.26: a high-resolution comparison from Chandra, Gemini & MERLIN

New Chandra observations have resolved the structure of the X-ray luminous southern hotspot in the giant radio quasar 4C74.26 into two distinct features. The nearer one to the nucleus is an extremely luminous peak, extended some 5 kpc perpendicular to the orientation of the jet; 19 kpc projected further away from the central nucleus than this is a fainter X-ray arc having similar symmetry. This arc is co-spatial with near-IR and optical emission imaged with Gemini, and radio emission imaged with MERLIN. The angular separation of the double shock structure (itself ~19 kpc or 10 arcsec in size) from the active nucleus which fuels them of ~550 kpc is a reminder of the challenge of connecting "unidentified" hard X-ray or Fermi sources with their origins.Comment: In press at MNRA

Patterns of beverages consumed and risk of incident kidney disease

© 2019 by the American Society of Nephrology. Background and objectives Selected beverages, such as sugar-sweetened beverages, have been reported to influence kidney disease risk, although previous studies have been inconsistent. Further research is necessary to comprehensively evaluate all types of beverages in association with CKD risk to better inform dietary guidelines. Design, setting, participants, & measurements We conducted a prospective analysis in the Jackson Heart Study, a cohort of black men and women in Jackson, Mississippi. Beverage intake was assessed using a food frequency questionnaire administered at baseline (2000–2004). Incident CKD was defined as onset of eGFR\u3c60 ml/min per 1.73 m 2 and ≥30% eGFR decline at follow-up (2009–13) relative to baseline among those with baseline eGFR ≥60 ml/min per 1.73 m 2 . Logistic regression was used to estimate the association between the consumption of each individual beverage, beverage patterns, and incident CKD. Beverage patterns were empirically derived using principal components analysis, in which components were created on the basis of the linear combinations of beverages consumed. Results Among 3003 participants, 185 (6%) developed incident CKD over a median follow-up of 8 years. At baseline, mean age was 54 (SD 12) years, 64% were women, and mean eGFR was 98 (SD 18) ml/min per 1.73 m 2 . After adjusting for total energy intake, age, sex, education, body mass index, smoking, physical activity, hypertension, diabetes, HDL cholesterol, LDL cholesterol, history of cardiovascular disease, and baseline eGFR, a principal components analysis–derived beverage pattern consisting of higher consumption of soda, sweetened fruit drinks, and water was associated with significantly greater odds of incident CKD (odds ratio tertile 3 versus 1 =1.61; 95% confidence interval, 1.07 to 2.41). Conclusions Higher consumption of sugar-sweetened beverages was associated with an elevated risk of subsequent CKD in this community-based cohort of black Americans

Platelet endothelial cell adhesion molecule-1 inhibits platelet response to thrombin and von Willebrand factor by regulating the internalization of glycoprotein Ib via AKT/glycogen synthase kinase-3/dynamin and integrin αIIbβ3

OBJECTIVE: Platelet endothelial cell adhesion molecule-1 (PECAM-1) regulates platelet response to multiple agonists. How this immunoreceptor tyrosine-based inhibitory motif-containing receptor inhibits G protein-coupled receptor-mediated thrombin-induced activation of platelets is unknown. APPROACH AND RESULTS: Here, we show that the activation of PECAM-1 inhibits fibrinogen binding to integrin αIIbβ3 and P-selectin surface expression in response to thrombin (0.1-3 U/mL) but not thrombin receptor-activating peptides SFLLRN (3×10(-7)-1×10(-5) mol/L) and GYPGQV (3×10(-6)-1×10(-4) mol/L). We hypothesized a role for PECAM-1 in reducing the tethering of thrombin to glycoprotein Ibα (GPIbα) on the platelet surface. We show that PECAM-1 signaling regulates the binding of fluorescein isothiocyanate-labeled thrombin to the platelet surface and reduces the levels of cell surface GPIbα by promoting its internalization, while concomitantly reducing the binding of platelets to von Willebrand factor under flow in vitro. PECAM-1-mediated internalization of GPIbα was reduced in the presence of both EGTA and cytochalasin D or latrunculin, but not either individually, and was reduced in mice in which tyrosines 747 and 759 of the cytoplasmic tail of β3 integrin were mutated to phenylalanine. Furthermore, PECAM-1 cross-linking led to a significant reduction in the phosphorylation of glycogen synthase kinase-3β Ser(9), but interestingly an increase in glycogen synthase kinase-3α pSer(21). PECAM-1-mediated internalization of GPIbα was reduced by inhibitors of dynamin (Dynasore) and glycogen synthase kinase-3 (CHIR99021), an effect that was enhanced in the presence of EGTA. CONCLUSIONS: PECAM-1 mediates internalization of GPIbα in platelets through dual AKT/protein kinase B/glycogen synthase kinase-3/dynamin-dependent and αIIbβ3-dependent mechanisms. These findings expand our understanding of how PECAM-1 regulates nonimmunoreceptor signaling pathways and helps to explains how PECAM-1 regulates thrombosis

Terrainbento 1.0: a Python package for multi-model analysis in long-term drainage basin evolution

Models of landscape evolution provide insight into the geomorphic history of specific field areas, create testable predictions of landform development, demonstrate the consequences of current geomorphic process theory, and spark imagination through hypothetical scenarios. While the last 4 decades have brought the proliferation of many alternative formulations for the redistribution of mass by Earth surface processes, relatively few studies have systematically compared and tested these alternative equations. We present a new Python package, terrainbento 1.0, that enables multi-model comparison, sensitivity analysis, and calibration of Earth surface process models. Terrainbento provides a set of 28 model programs that implement alternative transport laws related to four process elements: hillslope processes, surface-water hydrology, erosion by flowing water, and material properties. The 28 model programs are a systematic subset of the 2048 possible numerical models associated with 11 binary choices. Each binary choice is related to one of these four elements &ndash; for example, the use of linear or nonlinear hillslope diffusion. Terrainbento is an extensible framework: base classes that treat the elements common to all numerical models (such as input/output and boundary conditions) make it possible to create a new numerical model without reinventing these common methods. Terrainbento is built on top of the Landlab framework such that new Landlab components directly support the creation of new terrainbento model programs. Terrainbento is fully documented, has 100 % unit test coverage including numerical comparison with analytical solutions for process models, and continuous integration testing. We support future users and developers with introductory Jupyter notebooks and a template for creating new terrainbento model programs. In this paper, we describe the package structure, process theory, and software implementation of terrainbento. Finally, we illustrate the utility of terrainbento with a benchmark example highlighting the differences in steady-state topography between five different numerical models.</p

A randomised controlled trial of blood pressure self-monitoring in the management of hypertensive pregnancy. OPTIMUM-BP:A feasibility trial

Objective: To assess the feasibility of a blood pressure self-monitoring intervention for managing pregnancy hypertension. Study design: OPTIMUM-BP was an unmasked randomised controlled trial comparing a self-monitoring of blood pressure (SMBP) intervention versus usual care for the management of pregnancy hypertension. Women with chronic (CH) or gestational hypertension (GH) from 4 UK centres were randomised (2:1) intervention to control. Self-monitoring involved daily home blood pressure (BP) measurements, with recording via study diary or telemonitoring. Clinicians were invited to use the home readings in clinical and antihypertensive titration decisions. Main outcomes: The primary outcomes were recruitment, retention, adherence and persistence with the intervention. Results: Women from four UK centres were randomised: 158/222 (71%) of those approached agreed, comprising: 86 women with chronic hypertension (55 SMBP, 31 control) and 72 with gestational hypertension (49 SMBP, 23 control) of whom outcome data were available from 154 (97%) and were included in the analysis. The median (IQR) number of days with home BP readings per week were 5.5 (3.1–6.5) for those with chronic hypertension and 6.1 (4.5–6.7) with gestational hypertension. Participants persisted with the intervention for 80% or more of their time from enrolment until delivery in 86% (43/50) and 76% (38/49) of those with chronic and gestational hypertension respectively. Recorded clinic and study BPs were similar for both groups. Conclusions: This is the first randomised investigation of BP self-monitoring for the management of pregnancy hypertension and indicates that a large RCT would be feasible.</p

Dietary Intake of n-6 Fatty Acids Modulates Effect of Apolipoprotein A5 Gene on Plasma Fasting Triglycerides, Remnant Lipoprotein Concentrations, and Lipoprotein Particle Size

Background— Apolipoprotein A5 gene (APOA5) variation is associated with plasma triglycerides (TGs). However, little is known about whether dietary fat modulates this association. Methods and Results— We investigated the interaction between APOA5 gene variation and dietary fat in determining plasma fasting TGs, remnant-like particle (RLP) concentrations, and lipoprotein particle size in 1001 men and 1147 women who were Framingham Heart Study participants. Polymorphisms –1131T>C and 56C>G, representing 2 independent haplotypes, were analyzed. Significant gene–diet interactions between the –1131T>C polymorphism and polyunsaturated fatty acid (PUFA) intake were found (PG polymorphism. The –1131C allele was associated with higher fasting TGs and RLP concentrations (P6% of total energy). No heterogeneity by sex was found. These interactions showed a dose-response effect when PUFA intake was considered as a continuous variable (P<0.01). Similar interactions were found for the sizes of VLDL and LDL particles. Only in carriers of the –1131C allele did the size of these particles increase (VLDL) or decrease (LDL) as PUFA intake increased (P<0.01). We further analyzed the effects of n-6 and n-3 fatty acids and found that the PUFA–APOA5 interactions were specific for dietary n-6 fatty acids. Conclusions— Higher n-6 (but not n-3) PUFA intake increased fasting TGs, RLP concentrations, and VLDL size and decreased LDL size in APOA5 –1131C carriers, suggesting that n-6 PUFA–rich diets are related to a more atherogenic lipid profile in these subjects.Corella Piquer, Maria Dolores, [email protected]