Muscle quality. II. Effects of strength training in 65-to 75-yr-old men and women

To determine theeffects of strength training (ST) on muscle quality (MQ,strength/muscle volume of the trained muscle group), 12 healthy oldermen (69 ± 3 yr, range 65-75 yr) and 11 healthy older women (68 ± 3 yr, range 65-73 yr) were studied before and after aunilateral leg ST program. After a warm-up set, four sets ofheavy-resistance knee extensor ST exercise were performed 3 days/wk for9 wk on the Keiser K-300 leg extension machine. The men exhibitedgreater absolute increases in the knee extension one-repetition maximum(1-RM) strength test (75 ± 2 and 94 ± 3 kg before andafter training, respectively) and in quadriceps muscle volume measuredby magnetic resonance imaging (1,753 ± 44 and 1,955 ± 43 cm³) than the women (42 ± 2 and 55 ± 3 kg for the 1-RM test and 1,125 ± 53 vs.1,261 ± 65 cm³ forquadriceps muscle volume before and after training, respectively, inwomen; both P < 0.05). However,percent increases were similar for men and women in the 1-RM test (27 and 29% for men and women, respectively), muscle volume (12% forboth), and MQ (14 and 16% for men and women, respectively).Significant increases in MQ were observed in both groups in the trainedleg (both P < 0.05) and in the 1-RMtest for the untrained leg (both P < 0.05), but no significant differences were observed between groups,suggesting neuromuscular adaptations in both gender groups. Thus,although older men appear to have a greater capacity for absolutestrength and muscle mass gains than older women in response to ST, the relative contribution of neuromuscular and hypertrophic factors to theincrease in strength appears to be similar between genders.

     

Development of a fission yeast-based high-throughput screen to identify chemical regulators of cAMP phosphodiesterases

Cyclic nucleotide phosphodiesterases (PDEs) comprise a superfamily of enzymes that serve as drug targets in many human diseases. There is a continuing need to identify high-specificity inhibitors that affect individual PDE families or even subtypes within a single family. The authors describe a fission yeast-based high-throughput screen to detect inhibitors of heterologously expressed adenosine 3',5'-cyclic monophosphate (cAMP) PDEs. The utility of this system is demonstrated by the construction and characterization of strains that express mammalian PDE2A, PDE4A, PDE4B, and PDE8A and respond appropriately to known PDE2A and PDE4 inhibitors. High-throughput screens of 2 bioactive compound libraries for PDE inhibitors using strains expressing PDE2A, PDE4A, PDE4B, and the yeast PDE Cgs2 identified known PDE inhibitors and members of compound classes associated with PDE inhibition. The authors verified that the furanocoumarin imperatorin is a PDE4 inhibitor based on its ability to produce a PDE4-specific elevation of cAMP levels. This platform can be used to identify PDE activators, as well as genes encoding PDE regulators, which could serve as targets for future drug screens.     

miR-126 regulates angiogenic signaling and vascular integrity

Precise regulation of the formation, maintenance, and remodeling of the vasculature is required for normal development, tissue response to injury, and tumor progression. How specific microRNAs intersect with and modulate angiogenic signaling cascades is unknown. Here, we identified microRNAs that were enriched in endothelial cells derived from mouse embryonic stem (ES) cells and in developing mouse embryos. We found that miR-126 regulated the response of endothelial cells to VEGF. Additionally, knockdown of miR-126 in zebrafish resulted in loss of vascular integrity and hemorrhage during embryonic development. miR-126 functioned in part by directly repressing negative regulators of the VEGF pathway, including the Sprouty-related protein SPRED1 and phosphoinositol-3 kinase regulatory subunit 2 (PIK3R2/p85-beta). Increased expression of Spred1 or inhibition of VEGF signaling in zebrafish resulted in defects similar to miR-126 knockdown. These findings illustrate that a single miRNA can regulate vascular integrity and angiogenesis, providing a new target for modulating vascular formation and function.     

Support for the microenvironment hypothesis for adaptive value of gall induction in the California gall wasp, Andricus quercuscalifornicus

Three major hypotheses have been advanced for the adaptive nature of plant galls: nutrition, enemy-avoidance, and microenvironment. Of these, the microenvironment hypothesis has been frequently invoked, but rarely tested directly. We tested this hypothesis in a population of Andricus quercuscalifornicus (Bassett) (Hymenoptera: Cynipidae) wasps inducing galls on Quercus lobata Née (Fagaceae) trees in Northern California, USA. Relative humidity and temperature data gathered from both immature and mature galls in the field indicated that A. quercuscalifornicus larvae modify their microenvironments significantly by raising and stabilizing relative humidity levels inside galls to near saturation. In addition, excised larvae maintained under experimental conditions survived significantly longer under levels of high relative humidity. These data support the hypothesis that through gall induction, A. quercuscalifornicus manipulates its environment adaptively.     

Blood-based detection of radiation exposure in humans based on novel phospho-Smc1 ELISA

The structural maintenance of chromosome 1 (Smc1) protein is a member of the highly conserved cohesin complex and is involved in sister chromatid cohesion. In response to ionizing radiation, Smc1 is phosphorylated at two sites, Ser-957 and Ser-966, and these phosphorylation events are dependent on the ATM protein kinase. In this study, we describe the generation of two novel ELISAs for quantifying phospho-Smc1(Ser-957) and phospho-Smc1(Ser-966). Using these novel assays, we quantify the kinetic and biodosimetric responses of human cells of hematological origin, including immortalized cells, as well as both quiescent and cycling primary human PBMC. Additionally, we demonstrate a robust in vivo response for phospho-Smc1(Ser-957) and phospho-Smc1(Ser-966) in lymphocytes of human patients after therapeutic exposure to ionizing radiation, including total-body irradiation, partial-body irradiation, and internal exposure to (131)I. These assays are useful for quantifying the DNA damage response in experimental systems and potentially for the identification of individuals exposed to radiation after a radiological incident.