Human sarcopenia reveals an increase in SOCS-3 and myostatin and a reduced efficiency of Akt phosphorylation

Age-related skeletal muscle sarcopenia is linked with increases in falls, fractures, and death and therefore has important socioeconomic consequences. The molecular mechanisms controlling age-related muscle loss in humans are not well understood, but are likely to involve multiple signaling pathways. This study investigated the regulation of several genes and proteins involved in the activation of key signaling pathways promoting muscle hypertrophy, including GH/STAT5, IGF-1/Akt/GSK-3&beta;/4E-BP1, and muscle atrophy, including TNF&alpha;/SOCS-3 and Akt/FKHR/atrogene, in muscle biopsies from 13 young (20 &plusmn; 0.2 years) and 16 older (70 &plusmn; 0.3 years) males. In the older males compared to the young subjects, muscle fiber cross-sectional area was reduced by 40&ndash;45% in the type II muscle fibers. TNF&alpha; and SOCS-3 were increased by 2.8 and 1.5 fold, respectively. Growth hormone receptor protein (GHR) and IGF-1 mRNA were decreased by 45%. Total Akt, but not phosphorylated Akt, was increased by 2.5 fold, which corresponded to a 30% reduction in the efficiency of Akt phosphorylation in the older subjects. Phosphorylated and total GSK-3&beta; were increased by 1.5 and 1.8 fold, respectively, while 4E-BP1 levels were not changed. Nuclear FKHR and FKHRL1 were decreased by 73 and 50%, respectively, with no changes in their atrophy target genes, atrogin-1 and MuRF1. Myostatin mRNA and protein levels were significantly elevated by 2 and 1.4 fold. Human sarcopenia may be linked to a reduction in the activity or sensitivity of anabolic signaling proteins such as GHR, IGF-1, and Akt. TNF&alpha;, SOCS-3, and myostatin are potential candidates influencing this anabolic perturbation.<br /

Bacillus cereus Spores Release Alanine that Synergizes with Inosine to Promote Germination

spores germinate in the presence of a single germinant, inosine, yet with a significant lag period. spores. spores appear to have developed a unique quorum-sensing feedback mechanism to monitor spore density and to coordinate germination

Delayed Recovery of Skeletal Muscle Mass following Hindlimb Immobilization in mTOR Heterozygous Mice

The present study addressed the hypothesis that reducing mTOR, as seen in mTOR heterozygous (+/−) mice, would exaggerate the changes in protein synthesis and degradation observed during hindlimb immobilization as well as impair normal muscle regrowth during the recovery period. Atrophy was produced by unilateral hindlimb immobilization and data compared to the contralateral gastrocnemius. In wild-type (WT) mice, the gradual loss of muscle mass plateaued by day 7. This response was associated with a reduction in basal protein synthesis and development of leucine resistance. Proteasome activity was consistently elevated, but atrogin-1 and MuRF1 mRNAs were only transiently increased returning to basal values by day 7. When assessed 7 days after immobilization, the decreased muscle mass and protein synthesis and increased proteasome activity did not differ between WT and mTOR+/− mice. Moreover, the muscle inflammatory cytokine response did not differ between groups. After 10 days of recovery, WT mice showed no decrement in muscle mass, and this accretion resulted from a sustained increase in protein synthesis and a normalization of proteasome activity. In contrast, mTOR+/− mice failed to fully replete muscle mass at this time, a defect caused by the lack of a compensatory increase in protein synthesis. The delayed muscle regrowth of the previously immobilized muscle in the mTOR+/− mice was associated with a decreased raptor•4EBP1 and increased raptor•Deptor binding. Slowed regrowth was also associated with a sustained inflammatory response (e.g., increased TNFα and CD45 mRNA) during the recovery period and a failure of IGF-I to increase as in WT mice. These data suggest mTOR is relatively more important in regulating the accretion of muscle mass during recovery than the loss of muscle during the atrophy phase, and that protein synthesis is more sensitive than degradation to the reduction in mTOR during muscle regrowth

Effects of whey protein alone or as part of a multi-ingredient formulation on strength, fat-free mass, or lean body mass in resistance-trained individuals: A meta-analysis

BACKGROUND: Even though the positive effects of whey protein-containing supplements for optimizing the anabolic responses and adaptations process in resistance-trained individuals have been supported by several investigations, their use continues to be controversial. Additionally, the administration of different multi-ingredient formulations where whey proteins are combined with carbohydrates, other protein sources, creatine, and amino acids or derivatives, has been extensively proposed as an effective strategy to maximize strength and muscle mass gains in athletes. OBJECTIVE: We aimed to systematically summarize and quantify whether whey protein-containing supplements, administered alone or as a part of a multi-ingredient, could improve the effects of resistance training on fat-free mass or lean body mass, and strength in resistance-trained individuals when compared with other iso-energetic supplements containing carbohydrates or other sources of proteins. METHODS: A structured literature search was conducted on PubMed, Science Direct, Web of Science, Cochrane Libraries, US National Institutes of Health clinicaltrials.gov, SPORTDiscus, and Google Scholar databases. Main inclusion criteria comprised randomized controlled trial study design, adults (aged 18 years and over), resistance-trained individuals, interventions (a resistance training program for a period of 6 weeks or longer, combined with whey protein supplementation administered alone or as a part of a multi-ingredient), and a calorie equivalent contrast supplement from carbohydrates or other non-whey protein sources. Continuous data on fat-free mass and lean body mass, and maximal strength were pooled using a random-effects model. RESULTS: Data from nine randomized controlled trials were included, involving 11 treatments and 192 participants. Overall, with respect to the ingestion of contrast supplements, whey protein supplementation, administered alone or as part of a multi-ingredient, in combination with resistance training, was associated with small extra gains in fat-free mass or lean body mass, resulting in an effect size of g = 0.301, 95% confidence interval (CI) 0.032-0.571. Subgroup analyses showed less clear positive trends resulting in small to moderate effect size g = 0.217 (95% CI -0.113 to 0.547) and g = 0.468 (95% CI 0.003-0.934) in favor of whey and multi-ingredient, respectively. Additionally, a positive overall extra effect was also observed to maximize lower (g = 0.316, 95% CI 0.045-0.588) and upper body maximal strength (g = 0.458, 95% CI 0.161-0.755). Subgroup analyses showed smaller superiority to maximize strength gains with respect to the contrast groups for lower body (whey protein: g = 0.343, 95% CI -0.016 to 0.702, multi-ingredient: g = 0.281, 95% CI -0.135 to 0.697) while in the upper body, multi-ingredient (g = 0.612, 95% CI 0.157-1.068) seemed to produce more clear effects than whey protein alone (g = 0.343, 95% CI -0.048 to 0.735). LIMITATIONS: Studies involving interventions of more than 6 weeks on resistance-training individuals are scarce and account for a small number of participants. Furthermore, no studies with an intervention longer than 12 weeks have been found. The variation regarding the supplementation protocol, namely the different doses criteria or timing of ingestion also add some concerns to the studies comparison. CONCLUSIONS: Whey protein alone or as a part of a multi-ingredient appears to maximize lean body mass or fat-free mass gain, as well as upper and lower body strength improvement with respect to the ingestion of an iso-energetic equivalent carbohydrate or non-whey protein supplement in resistance-training individuals. This enhancement effect seems to be more evident when whey proteins are consumed within a multi-ingredient containing creatine

Blood lactate levels in 31 female dogs with pyometra

<p>Abstract</p> <p>Background</p> <p>Canine pyometra is a life-threatening disease common in countries where spaying of dogs is not routinely performed. The disease is associated with endotoxemia, sepsis, systemic inflammatory response syndrome (SIRS) and a 3–4% mortality rate. Blood lactate analysis is clinically valuable in predicting prognosis and survival, evaluating tissue perfusion and treatment response in human and veterinary critical care settings. The aims of the present study were to investigate 1) the blood lactate levels of female dogs with pyometra by a hand-held analyser and 2) if these levels are related with the clinical status or other biochemical or hematological disorders.</p> <p>Methods</p> <p>In total 31 female dogs with pyometra admitted for surgical ovariohysterectomy and 16 healthy female control dogs were included in the present study. A complete physical examination including SIRS-status determination was performed. Blood samples for lactate concentrations, hematological and biochemical parameters, acid-base and blood gas analysis and other laboratory parameters were collected and subsequently analysed. The diagnosis pyometra was verified with histopathological examination of the uterus and ovaries. Increased hospitalisation length and presence of SIRS were used as indicators of outcome.</p> <p>Results</p> <p>In the pyometra group the median blood lactate level was 1,6 mmol l^-1(range <0.8–2.7 mmol l^-1). In the control group the median lactate level was 1,2 mmol l^-1(range <0.8–2.1 mmol l^-1). Of the 31 bitches 19 (61%) fulfilled 2 or more criteria for SIRS at inclusion, 10 bitches (32%) fulfilled 3 of the SIRS criteria whereas none accomplished more than 3 criteria. Lactate levels did not differ significantly between the pyometra and control group, or between the SIRS positive and SIRS negative dogs with pyometra. Increased lactate concentration (>2.5 mmol l^-1) was demonstrated in one female dog with pyometra (3%), and was not associated with longer hospitalisation or presence of SIRS. Lactate measurement was not indicative of peritonitis. None of the bitches died during or within two months of the hospital stay. The measurements of temperature, heart rate, respiratory rate, percentage bandforms of neutrophilic granulocytes, α₂-globulins, creatinin, pvCO₂, TCO₂and base excess showed significant differences between the SIRS positive and the SIRS negative pyometra cases.</p> <p>Conclusion</p> <p>Increased blood lactate concentrations were demonstrated in 3% (1/31), and SIRS was present in 61% (19/31) of the female dogs with pyometra. Preoperative lactate levels were not related with presence of SIRS or prolonged hospitalisation. Lactate measurement was not indicative of peritonitis. The value of a single and repeated lactate analysis in more severely affected cases remains to be determined.</p

Genome-wide diversity and phylogeography of Mycobacterium avium subsp. paratuberculosis in Canadian dairy cattle

Mycobacterium avium subsp. paratuberculosis (MAP) is the causative bacterium of Johne’s disease (JD) in ruminants. The control of JD in the dairy industry is challenging, but can be improved with a better understanding of the diversity and distribution of MAP subtypes. Previously established molecular typing techniques used to differentiate MAP have not been sufficiently discriminatory and/or reliable to accurately assess the population structure. In this study, the genetic diversity of 182 MAP isolates representing all Canadian provinces was compared to the known global diversity, using single nucleotide polymorphisms identified through whole genome sequencing. MAP isolates from Canada represented a subset of the known global diversity, as there were global isolates intermingled with Canadian isolates, as well as multiple global subtypes that were not found in Canada. One Type III and six “Bison type” isolates were found in Canada as well as one Type II subtype that represented 86% of all Canadian isolates. Rarefaction estimated larger subtype richness in Québec than in other Canadian provinces using a strict definition of MAP subtypes and lower subtype richness in the Atlantic region using a relaxed definition. Significant phylogeographic clustering was observed at the inter-provincial but not at the intra-provincial level, although most major clades were found in all provinces. The large number of shared subtypes among provinces suggests that cattle movement is a major driver of MAP transmission at the herd level, which is further supported by the lack of spatial clustering on an intra-provincial scale

Differences in Muscle Protein Synthesis and Anabolic Signaling in the Postabsorptive State and in Response to Food in 65–80 Year Old Men and Women

Women have less muscle than men but lose it more slowly during aging. To discover potential underlying mechanism(s) for this we evaluated the muscle protein synthesis process in postabsorptive conditions and during feeding in twenty-nine 65–80 year old men (n = 13) and women (n = 16). We discovered that the basal concentration of phosphorylated eEF2Thr56 was ∼40% less (P<0.05) and the basal rate of MPS was ∼30% greater (P = 0.02) in women than in men; the basal concentrations of muscle phosphorylated AktThr308, p70s6kThr389, eIF4ESer209, and eIF4E-BP1Thr37/46 were not different between the sexes. Feeding increased (P<0.05) AktThr308 and p70s6kThr389 phosphorylation to the same extent in men and women but increased (P<0.05) the phosphorylation of eIF4ESer209 and eIF4E-BP1Thr37/46 in men only. Accordingly, feeding increased MPS in men (P<0.01) but not in women. The postabsorptive muscle mRNA concentrations for myoD and myostatin were not different between sexes; feeding doubled myoD mRNA (P<0.05) and halved that of myostatin (P<0.05) in both sexes. Thus, there is sexual dimorphism in MPS and its control in older adults; a greater basal rate of MPS, operating over most of the day may partially explain the slower loss of muscle in older women

Differences in Muscle Protein Synthesis and Anabolic Signaling in the Postabsorptive State and in Response to Food in 65–80 Year Old Men and Women

Women have less muscle than men but lose it more slowly during aging. To discover potential underlying mechanism(s) for this we evaluated the muscle protein synthesis process in postabsorptive conditions and during feeding in twenty-nine 65–80 year old men (n = 13) and women (n = 16). We discovered that the basal concentration of phosphorylated eEF2Thr56 was ∼40% less (P<0.05) and the basal rate of MPS was ∼30% greater (P = 0.02) in women than in men; the basal concentrations of muscle phosphorylated AktThr308, p70s6kThr389, eIF4ESer209, and eIF4E-BP1Thr37/46 were not different between the sexes. Feeding increased (P<0.05) AktThr308 and p70s6kThr389 phosphorylation to the same extent in men and women but increased (P<0.05) the phosphorylation of eIF4ESer209 and eIF4E-BP1Thr37/46 in men only. Accordingly, feeding increased MPS in men (P<0.01) but not in women. The postabsorptive muscle mRNA concentrations for myoD and myostatin were not different between sexes; feeding doubled myoD mRNA (P<0.05) and halved that of myostatin (P<0.05) in both sexes. Thus, there is sexual dimorphism in MPS and its control in older adults; a greater basal rate of MPS, operating over most of the day may partially explain the slower loss of muscle in older women