We report an improved draft nucleotide sequence of the 2.3-gigabase genome of maize, an important crop plant and model for biological research. Over 32,000 genes were predicted, of which 99.8% were placed on reference chromosomes. Nearly 85% of the genome is composed of hundreds of families of transposable elements, dispersed nonuniformly across the genome. These were responsible for the capture and amplification of numerous gene fragments and affect the composition, sizes, and positions of centromeres. We also report on the correlation of methylation-poor regions with Mu transposon insertions and recombination, and copy number variants with insertions and/or deletions, as well as how uneven gene losses between duplicated regions were involved in returning an ancient allotetraploid to a genetically diploid state. These analyses inform and set the stage for further investigations to improve our understanding of the domestication and agricultural improvements of maize.

Background The purpose of this study was to determine whether patients with heart failure and a preserved ejection fraction (HFpEF) have an increase in passive myocardial stiffness and the extent to which discovered changes are dependent on changes in extracellular matrix fibrillar collagen and/or cardiomyocyte titin. Methods and Results Seventy patients undergoing coronary artery bypass grafting underwent an echocardiogram, plasma biomarker determination, and intra-operative left ventricular (LV) epicardial anterior wall biopsy. Patients were divided into 3 groups: referent control (n=17, no hypertension or diabetes), hypertension (HTN) without(-) HFpEF (n=31), and HTN with(+) HFpEF (n=22). One or more of the following studies were performed on the biopsies: passive stiffness measurements to determine total, collagen-dependent and titin-dependent stiffness (differential extraction assay), collagen assays (biochemistry or histology), or titin isoform and phosphorylation assays. Compared with controls, patients with HTN(-)HFpEF had no change in LV end diastolic pressure (LVEDP), myocardial passive stiffness, collagen, or titin phosphorylation but had an increase in biomarkers of inflammation (CRP, sST2, TIMP-1). Compared with both control and HTN(-)HFpEF, patients with HTN(+)HFpEF had increased LVEDP, left atrial volume, NT-proBNP, total, collagen-dependent and titin-dependent stiffness, insoluble collagen, increased titin phosphorylation on PEVK S11878(S26), reduced phosphorylation on N2B S4185(S469), and increased biomarkers of inflammation. Conclusions Hypertension in the absence of HFpEF, did not alter passive myocardial stiffness. Patients with HTN(+)HFpEF had a significant increase in passive myocardial stiffness; collagen-dependent and titin-dependent stiffness were increased. These data suggest that the development of HFpEF is dependent on changes in both collagen and titin homeostasis.

Importance Iron deficiency is present in approximately 50% of patients with heart failure with reduced left ventricular ejection fraction (HFrEF) and is an independent predictor of reduced functional capacity and mortality. However, the efficacy of inexpensive, readily available oral iron supplementation in heart failure is unknown. Objective To test whether therapy with oral iron improves peak exercise capacity in patients with HFrEF and iron deficiency. Design, Setting, and Participants Phase 2, double-blind, placebo-controlled randomized clinical trial of patients with HFrEF (<40%) and iron deficiency, defined as serum ferritin level between 15–100 ng/ml or serum ferritin 101-299 ng/ml with transferrin saturation (Tsat) <20%. Patients were enrolled between September 2014 and November 2015 at 23 US sites. Interventions Oral iron polysaccharide (n = 111) or placebo (n = 114), 150 mg twice daily for 16 weeks. Main Outcomes and Measures The primary endpoint was a change in peak oxygen uptake (VO2), from baseline to 16 weeks. Secondary endpoints included changes in six minute walk distance; plasma NT-pro BNP levels; and health status as assessed by Kansas City Cardiomyopathy Questionnaire (KCCQ, range 0-100, higher scores reflect better quality of life). Results Among 225 randomized patients (median age 63 years, 36% women) 203 completed the study. The median baseline peak VO2 was 1196 ml/min (887, 1448 ml/min) in the oral iron group and 1167 ml/min (887, 1449 ml/min) in the placebo group. The primary endpoint, change in peak VO2, did not significantly differ between the oral iron and placebo groups (+23 ml/min vs −2 ml/min; difference, 21 ml/min [95% CI, −34 to +76]; P=.46). Similarly, at 16 weeks there were no significant differences between treatment groups in changes in 6-minute walk distance (−13, −32 to 6m), NT-pro BNP levels (159, −280 to 599 pg/ml), KCCQ Score (1, −2.4 to 4.4) or time to first adverse event (hazard ratio 0.85, 0.56 to 1.31), all p>0.05. Conclusion Among patients with HFrEF with iron deficiency, high-dose oral iron did not improve exercise capacity over 16 weeks. These results do not support use of oral iron supplementation in patients with HFrEF.

The present study does not provide evidence to support a meaningful change in clinical outcomes for HF patients receiving SCS. (Determining the Feasibility of Spinal Cord Neuromodulation for the Treatment of Chronic Heart Failure [DEFEAT-HF]; NCT01112579).

LeWinter. Skeletal muscle myofibrillar protein metabolism in heart failure: relationship to immune activation and functional capacity. Am J Physiol Endocrinol Metab 288: E685-E692, 2005. First published November 23, 2004; doi:10.1152/ajpendo.00444.2004.-Chronic heart failure is characterized by changes in skeletal muscle that contribute to physical disability. Most studies to date have investigated defects in skeletal muscle oxidative capacity. In contrast, less is known about how heart failure affects myofibrillar protein metabolism. Thus we examined the effect of heart failure on skeletal muscle myofibrillar protein metabolism, with a specific emphasis on changes in myosin heavy chain (MHC) protein content, synthesis, and isoform distribution in 10 patients with heart failure (63 Ϯ 3 yr) and 11 controls (70 Ϯ 3 yr). In addition, we examined the relationship of MHC protein metabolism to inflammatory markers and physical function. Although MHC and actin protein content did not differ between groups, MHC protein content decreased with increasing disease severity in heart failure patients (r ϭ Ϫ0.748, P Ͻ 0.02), whereas actin protein content was not related to disease severity. No difference in MHC protein synthesis was found between groups, and MHC protein synthesis rates were not related to disease severity. There were, however, relationships between C-reactive protein and both MHC protein synthesis (r ϭ Ϫ0.442, P ϭ 0.05) and the ratio of MHC to mixed muscle protein synthesis (r ϭ Ϫ0.493, P Ͻ 0.03). Heart failure patients showed reduced relative amounts of MHC I (P Ͻ 0.05) and a trend toward increased MHC IIx (P ϭ 0.06). In regression analyses, decreased MHC protein content was related to decreased exercise capacity and muscle strength in heart failure patients. Our results demonstrate that heart failure affects both the quantity and isoform distribution of skeletal muscle MHC protein.The fact that MHC protein content was related to both exercise capacity and muscle strength further suggests that quantitative alterations in MHC protein may have functional significance. sarcopenia; cardiac cachexia; myosin heavy chain isoform; cytokine; actin RESEARCH OVER THE PAST TWO DECADES has identified an important role for skeletal muscle in reduced functional capacity in heart failure patients. Several abnormalities intrinsic to skeletal muscle, including muscle atrophy (7, 30) and diminished oxidative capacity (35), have been cited as factors contributing to physical disability. The mechanisms underlying these defects and their contribution to exercise intolerance and reduced muscle strength, however, remain unclear. The majority of studies that have examined the effect of heart failure on skeletal muscle have focused on oxidative capacity and/or mitochondrial function. In contrast, less is known about the impact of heart failure on myofibrillar proteins and their relationship to reduced functional capacity.Protein is the primary structural and functional macromolecule in skeletal muscle. From both quantitative and funct...