APC/C-mediated degradation of dsRNA-binding protein 4 (DRB4) involved in RNA silencing.

Background: Selective protein degradation via the ubiquitin-26S proteasome is a major mechanism underlying DNA replication and cell division in all Eukaryotes. In particular, the APC/C (Anaphase Promoting Complex or Cyclosome) is a master ubiquitin protein ligase (E3) that targets regulatory proteins for degradation allowing sister chromatid separation and exit from mitosis. Interestingly, recent work also indicates that the APC/C remains active in differentiated animal and plant cells.

Calf muscle characteristics, strength measures, and mortality in peripheral arterial disease: a longitudinal study.

Objectives: This study analyzed whether lower calf muscle density and poorer upper and lower extremity strength are associated with higher mortality rates in men and women with peripheral arterial disease (PAD).

Background: Men and women with lower extremity PAD have lower calf muscle density and reduced lower extremity strength compared with individuals without PAD.

Methods: At baseline, participants underwent measurement of calf muscle density with computed tomography in addition to knee extension power and isometric knee extension, plantar flexion, and hand grip strength measures.

Fetuin-A is inversely associated with coronary artery calcification in community-living persons: the Multi-Ethnic Study of Atherosclerosis.

Background: Fetuin-A is a hepatic secretory protein that inhibits arterial calcification in vitro. The association of fetuin-A with coronary arterial calcification (CAC) in the general population is uncertain.

Methods: Among 2457 community-living individuals without cardiovascular disease (CVD), we measured serum fetuin-A concentrations by ELISA and evaluated the cross-sectional association of fetuin-A with CAC prevalence (any vs none) and severity; on follow-up 3.

Higher body mass index is associated with more adverse changes in calf muscle characteristics in peripheral arterial disease.

Objective: This study investigated whether higher body mass index (BMI) is associated with more adverse lower extremity muscle characteristics at baseline and more adverse changes in muscle over time among participants with lower extremity peripheral arterial disease (PAD).

Methods: This was a longitudinal, observational study of 425 men and women with PAD and 261 without PAD. Computed tomography was used to measure calf muscle characteristics at baseline and every 2 years.

Progression of asymptomatic peripheral artery disease over 1 year.

The pathophysiology and time course of an individual converting from asymptomatic peripheral artery disease (PAD) to symptomatic claudication is unclear. The objectives of this study were: (1) to characterize the extent of atherosclerotic disease in individuals with an abnormal ankle-brachial index (ABI), but without claudication; and over 1 year of follow-up to (2) evaluate the progression of PAD using ultrasound imaging, (3) determine changes in the ABI and leg pain symptoms, and (4) correlate PAD progression with changes in the ABI and leg symptoms. We hypothesized that PAD progression would be associated with the development of claudication and changes in the ABI, 6-minute walk distance (6-MWD), and walking quality of life.

Genetic determinants of the ankle-brachial index: a meta-analysis of a cardiovascular candidate gene 50K SNP panel in the candidate gene association resource (CARe) consortium.

Background: Candidate gene association studies for peripheral artery disease (PAD), including subclinical disease assessed with the ankle-brachial index (ABI), have been limited by the modest number of genes examined. We conducted a two stage meta-analysis of ∼50,000 SNPs across ∼2100 candidate genes to identify genetic variants for ABI.

Methods And Results: We studied subjects of European ancestry from 8 studies (n=21,547, 55% women, mean age 44-73 years) and African American ancestry from 5 studies (n=7267, 60% women, mean age 41-73 years) involved in the candidate gene association resource (CARe) consortium.

Associations of noninvasive measures of arterial compliance and ankle-brachial index: the Multi-Ethnic Study of Atherosclerosis (MESA).

Background: The association between measures of arterial compliance and peripheral arterial disease (PAD) is unclear. Early changes in arterial wall compliance could be a useful marker of patients at high risk for developing lower extremity atherosclerosis.

Methods: We used linear and logistic regression models on baseline data from 2,803 female and 2,558 male participants in the Multi-Ethnic Study of Atherosclerosis (MESA) to study associations between tonometry-derived baseline measures of arterial compliance (large artery compliance (C1) and small artery compliance (C2)) and the baseline ankle-brachial index (ABI), as well as change in the ABI over ~3 years of follow-up.

Antithrombotic therapy in peripheral artery disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines.

Background: This guideline focuses on antithrombotic drug therapies for primary and secondary prevention of cardiovascular disease as well as for the relief of lower-extremity symptoms and critical ischemia in persons with peripheral arterial disease (PAD).

Methods: The methods of this guideline follow those described in Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines in this supplement.

Results: The most important of our 20 recommendations are as follows.

Association between chromosome 9p21 variants and the ankle-brachial index identified by a meta-analysis of 21 genome-wide association studies.

Background: Genetic determinants of peripheral arterial disease (PAD) remain largely unknown. To identify genetic variants associated with the ankle-brachial index (ABI), a noninvasive measure of PAD, we conducted a meta-analysis of genome-wide association study data from 21 population-based cohorts.

Methods And Results: Continuous ABI and PAD (ABI ≤0.

GIGAS CELL1, a novel negative regulator of the anaphase-promoting complex/cyclosome, is required for proper mitotic progression and cell fate determination in Arabidopsis.

Increased cellular ploidy is widespread during developmental processes of multicellular organisms, especially in plants. Elevated ploidy levels are typically achieved either by endoreplication or endomitosis, which are often regarded as modified cell cycles that lack an M phase either entirely or partially. We identified GIGAS CELL1 (GIG1)/OMISSION OF SECOND DIVISION1 (OSD1) and established that mutation of this gene triggered ectopic endomitosis.

Lower extremity nerve function, calf skeletal muscle characteristics, and functional performance in peripheral arterial disease.

Objectives: To determine whether poor lower extremity nerve function is associated with less-favorable calf muscle characteristics and greater functional impairment in people with and without peripheral arterial disease (PAD).

Design: Cross-sectional.

Setting: Three Chicago-area medical centers.

Calcified atherosclerosis in different vascular beds and the risk of mortality.

Objective: The goal of this study was to determine differences in risks for total and cause-specific mortality related to calcified atherosclerosis in different vascular beds.

Methods And Results: A total of 4544 patients underwent computed tomography scans that were interrogated for calcium in different vascular beds. Mortality assessment was conducted by death certificate adjudication.

Association of pulse pressure, arterial elasticity, and endothelial function with kidney function decline among adults with estimated GFR >60 mL/min/1.73 m(2): the Multi-Ethnic Study of Atherosclerosis (MESA).

Background: The association of subclinical vascular disease and early declines in kidney function has not been well studied.

Study Design: Prospective cohort study.

Setting & Participants: Multi-Ethnic Study of Atherosclerosis (MESA) participants with estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.

The downward shift of the aortic bifurcation, a possible marker for vascular aging.

Purpose: Radiographers in both clinical and research settings utilize lumbar vertebral landmarks (i.e. L5/S1) on scout films to guide imaging of the abdominal aorta.

Association of body mass index with peripheral arterial disease in older adults: the Cardiovascular Health Study.

The authors hypothesized that the absence of cross-sectional associations of body mass index (BMI; weight (kg)/height (m)(2)) with peripheral arterial disease (PAD) in prior studies may reflect lower weight among persons who smoke or have poor health status. They conducted an observational study among 5,419 noninstitutionalized residents of 4 US communities aged ≥ 65 years at baseline (1989-1990 or 1992-1993). Ankle brachial index was measured, and participants reported their history of PAD procedures.

Family history of peripheral artery disease is associated with prevalence and severity of peripheral artery disease: the San Diego population study.

Objectives: The purpose of this study was to determine the association of family history of peripheral artery disease (PAD) with PAD prevalence and severity.

Background: PAD is a significant public health problem. Shared genetic and environmental factors may play an important role in the development of PAD.

Association of self-reported race/ethnicity and genetic ancestry with arterial elasticity: the Multi-Ethnic Study of Atherosclerosis (MESA).

African Americans have a disproportionate burden of hypertension compared with white, whereas data on Hispanics is less well-defined. Mechanisms underlying these differences are unclear, but could be in part because of ancestral background and vascular function. We studied 660 African Americans and 635 Hispanics from the Multi-Ethnic Study of Atherosclerosis (MESA) with complete data on genetic ancestry, pulse pressure (PP), and large and small arterial elasticity (LAE, SAE).

The association of bone density and calcified atherosclerosis is stronger in women without dyslipidemia: the multi-ethnic study of atherosclerosis.

We tested whether the association between bone mineral density (BMD) and coronary artery calcification (CAC) varies according to dyslipidemia in community-living individuals. Between 2002 and 2005, 305 women and 631 men (mean age of 64 years), who were not taking lipid-lowering medications or estrogen were assessed for spine BMD, CAC, and total (TC), HDL- and LDL-cholesterol and triglycerides. Participants were a random sample from the Multi-Ethnic Study of Atherosclerosis (MESA) without clinical cardiovascular disease.

Superficial femoral artery plaque and functional performance in peripheral arterial disease: walking and leg circulation study (WALCS III).

Objectives: We studied associations of magnetic resonance imaging measurements of plaque area and relative percent lumen reduction in the proximal superficial femoral artery with functional performance among participants with peripheral arterial disease.

Background: The clinical significance of directly imaged plaque characteristics in lower extremity arteries is not well established.

Methods: A total of 454 participants with an ankle brachial index <1.

Association of lipoprotein-associated phospholipase A(2) and endothelial function in the Multi-Ethnic Study of Atherosclerosis (MESA).

Mechanisms underlying the role of lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) in atherosclerotic development are not completely understood. We evaluated the relationship of Lp-PLA(2) with endothelial dysfunction, an early manifestation of atherosclerosis, in a cohort without known clinical cardiovascular disease. A total of 2809 participants in the Multi-Ethnic Study of Atherosclerosis underwent plasma Lp-PLA(2) mass and activity measurement and brachial artery flow-mediated vasodilation testing.

Poorer clock draw test scores are associated with greater functional impairment in peripheral artery disease: the Walking and Leg Circulation Study II.

We hypothesized that, in the absence of clinically recognized dementia, cognitive dysfunction measured by the clock draw test (CDT) is associated with greater functional impairment in men and women with peripheral artery disease (PAD). Participants were men and women aged 60 years and older with Mini-Mental Status Examination scores ≥ 24 with PAD (n = 335) and without PAD (n = 234). We evaluated the 6-minute walk test, 4-meter walking velocity at usual and fastest pace, the Short Physical Performance Battery (SPPB), and accelerometer-measured physical activity.

Greater sedentary hours and slower walking speed outside the home predict faster declines in functioning and adverse calf muscle changes in peripheral arterial disease.

Objectives: In participants with peripheral arterial disease (PAD), we determined whether more sedentary behavior and slower outdoor walking speed were associated with faster functional decline and more adverse changes in calf muscle characteristics over time.

Background: Modifiable behaviors associated with faster functional decline in lower-extremity PAD are understudied.

Methods: Participants were 384 men and women with an ankle brachial index <0.

Pulmonary function is associated with distal aortic calcium, not proximal aortic distensibility. MESA lung study.

Forced expiratory volume in one second strongly predicts mortality from cardiovascular disease. FEV(1) has been associated with aortic stiffness a strong independent predictor of cardiovascular mortality. However, the anatomical site and possible mechanisms linking aortic stiffness and lung function are unknown.