The temporal control of CONSTANS (CO) expression and activity is a key mechanism in photoperiodic flowering in Arabidopsis. FLAVIN-BINDING, KELCH REPEAT, F-BOX 1 (FKF1) protein regulates CO transcription, although the molecular mechanism is unknown. We demonstrate here that FKF1 controls the stability of a Dof transcription factor, CYCLING DOF FACTOR 1 (CDF1). FKF1 physically interacts with CDF1, and CDF1 protein is more stable in fkf1 mutants. Plants with elevated levels of CDF1 flower late and have reduced expression of CO. CDF1 and CO are expressed in the same tissues, and CDF1 binds to the CO promoter. Thus, FKF1 controls daily CO expression in part by degrading CDF1, a repressor of CO transcription.

Objective To estimate the prevalence, types and sociodemographic and biobehavioral correlates of antinuclear antibodies (ANA) in the United States (U.S.). Methods Cross-sectional analysis of 4,754 individuals from the National Health and Nutrition Examination Survey (NHANES) 1999–2004. ANA by indirect immunofluorescence, including cellular staining patterns and specific autoantibody reactivities by immunoprecipitation in those with ANA. Results ANA prevalence in the U.S. population ages 12 years and older was 13.8% (95% CI, 12.2% to 15.5%). ANA increased with age (P = 0.01) and were more prevalent among females than males (17.8% vs. 9.6%, P < 0.001), with the female to male ratio peaking at 40–49 years of age. ANA prevalence was modestly higher in African Americans than whites (adjusted prevalence odds ratio [POR], 1.30; 95% CI, 1.00 to 1.70). Remarkably, ANA were less common in overweight and obese (adjusted POR, 0.74; 95% CI, 0.59 to 0.94) individuals than persons of normal weight. No significant associations were seen with education, family income, alcohol use, smoking history, serum levels of cotinine or C-reactive protein. In ANA-positive individuals, nuclear patterns were seen in 84.6%, cytoplasmic patterns in 21.8%, and nucleolar patterns in 6.1%, and the most common specific autoantibodies were anti-Ro (3.9%) and anti-Su (2.4%). Conclusion These findings suggest that over 32 million persons in the U.S. have ANA and the prevalence is higher among females, older individuals, African Americans and those with normal weight. These data will serve as a useful baseline for future investigations of predictors and changes in ANA prevalence over time.

Diabetes is the dominant risk factor for a high (> or =1.40) ABI. Occlusive PAD is highly prevalent in subjects with high ABI, and these subjects should be considered as PAD-equivalent.

BACKGROUND Prostate cancer (PCa) affects more than 190,000 men each year with ~10% of men diagnosed at ≤ 55 years, i.e., early onset (EO) PCa. Based on historical findings for other cancers, EO PCa likely reflects a stronger underlying genetic etiology. METHODS We evaluated the association between EO PCa and previously identified single nucleotide polymorphisms (SNPs) in 754 Caucasian cases from the Michigan Prostate Cancer Genetics Project (mean 49.8 years at diagnosis), 2,713 Caucasian controls from Illumina’s iControlDB database and 1,163 PCa cases diagnosed at >55 years from the Cancer Genetic Markers of Susceptibility Study (CGEMS). RESULTS Significant associations existed for 13 of 14 SNPs (rs9364554 on 6q25, rs10486567 on 7p15, rs6465657 on 7q21, rs6983267 on 8q24, rs1447295 on 8q24, rs1571801 on 9q33, rs10993994 on 10q11, rs4962416 on 10q26, rs7931342 on 11q13, rs4430796 on 17q12, rs1859962 on 17q24.3, rs2735839 on 19q13, and rs5945619 on Xp11.22, but not rs2660753 on 3p12). EO PCa cases had a significantly greater cumulative number of risk alleles (mean 12.4) than iControlDB controls (mean 11.2; p=2.1×10−33) or CGEMS cases (mean 11.9; p=1.7 × 10−5). Notably, EO PCa cases had a higher frequency of the risk allele than CGEMS cases at 11 of13 associated SNPs, with significant differences for five SNPs. EO PCa cases diagnosed at <50 (mean 12.8) also had significantly more risk alleles than those diagnosed at 50–55 years (mean 12.1; p = 0.0003). CONCLUSIONS These results demonstrate the potential for identifying PCa-associated genetic variants by focusing on the subgroup of men diagnosed with EO disease.

Objectives To determine in patients with peripheral arterial disease (PAD) whether novel biomarkers improve prediction of cardiovascular disease (CVD) mortality and total mortality. Background Whether novel biomarkers improve risk prediction of mortality beyond standard CVD risk markers in PAD patients, and whether any such prediction differs with length of follow-up, remains controversial. Methods A cohort of 397 patients were referred to a vascular lab had PAD diagnosed by non-invasive testing. 58% also had coronary or cerebrovascular disease at baseline. Predictors of total, CVD, and non-CVD mortality were assessed with Cox proportional hazards models, and the incremental value of predictors were evaluated with both the C-statistic and the integrated discrimination improvement (IDI) index. Results Total mortality was 11 % at 2 years of follow-up and 65 % at an average of 7 years of follow-up (maximum 11.4 years). At 2 years, hs-CRP was a strong and significant predictor of mortality, with a hazard ratio (HR) of 1.56 per standard deviation, p=.006. However, at full follow-up standard CVD risk markers were significant (age, sex, ankle-brachial index [ABI], other CVD, and hypertension), but hs-CRP no longer showed a significant relationship HR = 1.12, p = .11. None of the other biomarkers studied showed a significant independent association with mortality. Hs-CRP improved the C-statistic and the IDI beyond standard risk markers at 2 years, but not at full follow-up. Conclusions Hs-CRP was a strong predictor of short-term mortality in this cohort of PAD patients, while standard risk markers were better at predicting longer-term mortality.