Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Dietary protein intake does not modulate daily myofibrillar protein synthesis rates of loss of muscle mass and function during short-term immobilization in young men : a randomized controlled trial

Background Short-term (<1 wk) muscle disuse lowers daily myofibrillar protein synthesis (MyoPS) rates resulting in muscle mass loss. The understanding of how daily dietary protein intake influences such muscle deconditioning requires further investigation. Objectives To assess the influence of graded dietary protein intakes on daily MyoPS rates and the loss of muscle mass during 3 d of disuse. Methods Thirty-three healthy young men (aged 22 ± 1 y; BMI = 23 ± 1 kg/m2) initially consumed the same standardized diet for 5 d, providing 1.6 g protein/kg body mass/d. Thereafter, participants underwent a 3-d period of unilateral leg immobilization during which they were randomly assigned to 1 of 3 eucaloric diets containing relatively high, low, or no protein (HIGH: 1.6, LOW: 0.5, NO: 0.15 g protein/kg/d; n = 11 per group). One day prior to immobilization participants ingested 400 mL deuterated water (D2O) with 50-mL doses consumed daily thereafter. Prior to and immediately after immobilization upper leg bilateral MRI scans and vastus lateralis muscle biopsies were performed to measure quadriceps muscle volume and daily MyoPS rates, respectively. Results Quadriceps muscle volume of the control legs remained unchanged throughout the experiment (P > 0.05). Immobilization led to 2.3 ± 0.4%, 2.7 ± 0.2%, and 2.0 ± 0.4% decreases in quadriceps muscle volume (P 0.05). D2O ingestion resulted in comparable plasma free [2H]-alanine enrichments during immobilization (∼2.5 mole percentage excess) across groups (P > 0.05). Daily MyoPS rates during immobilization were 30 ± 2% (HIGH), 26 ± 3% (LOW), and 27 ± 2% (NO) lower in the immobilized compared with the control leg, with no significant differences between groups (P > 0.05). Conclusions Three days of muscle disuse induces considerable declines in muscle mass and daily MyoPS rates. However, daily protein intake does not modulate any of these muscle deconditioning responses

Aging Is Accompanied by a Blunted Muscle Protein Synthetic Response to Protein Ingestion

<div><p>Purpose</p><p>Progressive loss of skeletal muscle mass with aging (sarcopenia) forms a global health concern. It has been suggested that an impaired capacity to increase muscle protein synthesis rates in response to protein intake is a key contributor to sarcopenia. We assessed whether differences in post-absorptive and/or post-prandial muscle protein synthesis rates exist between large cohorts of healthy young and older men.</p><p>Procedures</p><p>We performed a cross-sectional, retrospective study comparing <i>in vivo</i> post-absorptive muscle protein synthesis rates determined with stable isotope methodologies between 34 healthy young (22±1 y) and 72 older (75±1 y) men, and post-prandial muscle protein synthesis rates between 35 healthy young (22±1 y) and 40 older (74±1 y) men.</p><p>Findings</p><p>Post-absorptive muscle protein synthesis rates did not differ significantly between the young and older group. Post-prandial muscle protein synthesis rates were 16% lower in the older subjects when compared with the young. Muscle protein synthesis rates were >3 fold more responsive to dietary protein ingestion in the young. Irrespective of age, there was a strong negative correlation between post-absorptive muscle protein synthesis rates and the increase in muscle protein synthesis rate following protein ingestion.</p><p>Conclusions</p><p>Aging is associated with the development of muscle anabolic inflexibility which represents a key physiological mechanism underpinning sarcopenia.</p></div

Fractional mixed muscle protein synthesis rates (FSR), calculated using plasma L-[<i>ring</i>-²H₅] phenylalanine enrichments as the precursor pool, in healthy young and elderly men in the post-absorptive state (<i>n</i> = 34 young and <i>n</i> = 72 elderly) and following the ingestion of 20 g protein (post-prandial; <i>n</i> = 35 young and <i>n</i> = 40 elderly.

<p>Delta increases from post-absorptive to post-prandial were analyzed between groups using an unpaired <i>t</i>-test (significantly different; <i>P</i><0.01). Individual responses are reported in the inset figure only in those subjects for whom post-absorptive and post-prandial muscle protein synthesis rates were assessed within the same experiment (<i>n</i> = 55 [22 young and 23 elderly]).</p

Fractional mixed muscle protein synthesis rates (FSR), calculated using plasma L-[<i>ring</i>-²H₅] phenylalanine enrichments as the precursor pool, in healthy young and elderly men in the post-absorptive state (<i>n</i> = 34 young and <i>n</i> = 72 elderly) and following the ingestion of 20 g protein (post-prandial; <i>n</i> = 35 young and <i>n</i> = 40 elderly).

<p>Data were analyzed with multiple unpaired <i>t</i>-tests. Significantly different between corresponding post-absorptive and post-prandial values = ** (<i>P</i><0.01), *** (<i>P</i><0.001). Significantly different compared to corresponding values in the young = †† (P<0.01).</p

Correlation between post-absorptive fractional mixed muscle protein synthesis rates (FSR) and the delta increase in FSR following the ingestion dietary protein (post-prandial) in healthy young (<i>n</i> = 22) and elderly (<i>n</i> = 68) men.

<p>Data were analyzed with 2-tailed tests of significance by using Pearson's correlation coefficients.</p

Graphical representation of the individual values for fractional mixed muscle protein synthesis rates (FSR), calculated using plasma L-[<i>ring</i>-²H₅]phenylalanine enrichments as the precursor pool, in healthy young and elderly men in the post-absorptive state (<i>n</i> = 34 young and <i>n</i> = 72 elderly) and following the ingestion of 20 g protein (post-prandial; <i>n</i> = 35 young and <i>n</i> = 40 elderly).

<p>Graphical representation of the individual values for fractional mixed muscle protein synthesis rates (FSR), calculated using plasma L-[<i>ring</i>-²H₅]phenylalanine enrichments as the precursor pool, in healthy young and elderly men in the post-absorptive state (<i>n</i> = 34 young and <i>n</i> = 72 elderly) and following the ingestion of 20 g protein (post-prandial; <i>n</i> = 35 young and <i>n</i> = 40 elderly).</p

Subjects’ characteristics for comparisons of muscle protein synthesis rates.

<p>Values are means±SEM. Abbreviations: HOMA-IR; Homeostatic Model Assessment of Insulin Resistance [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0140903#pone.0140903.ref057" target="_blank">57</a>].</p><p>Subjects’ characteristics for comparisons of muscle protein synthesis rates.</p