Dynamics of muscle fibre growth during postnatal mouse development

Background  

Postnatal growth in mouse is rapid, with total skeletal muscle mass increasing several-fold in the first few weeks. Muscle growth can be achieved by either an increase in muscle fibre number or an increase in the size of individual myofibres, or a combination of both. Where myofibre hypertrophy during growth requires the addition of new myonuclei, these are supplied by muscle satellite cells, the resident stem cells of skeletal muscle.     

Trajectories of participation in organized activities and outcomes in young adulthood

To examine whether trajectories of participation in organized activities during the high school years and beyond (from ages 14 to 20) predicted outcomes at age 21 (externalizing problems, internalizing problems, civic engagement, number of years of education, and perception of physical health), 354 youths (60% girls) were surveyed annually over nine years. Four trajectories were found: (a) “Low and decreasing” (71%), (b) “Moderate and stable” (12%), (c) “High and decreasing after high school” (12%), and (d) “High and increasing after high school” (5%). Results revealed that the predicted outcomes varied according to the different trajectories. Pursuing high levels of activity participation beyond high school was especially beneficial with respect to externalizing problems and educational attainment.     

Reversible inhibition of testicular androgen secretion by 3-, 5- and 6-month controlled-release microsphere formulations of the LH-RH agonist [D-Trp6, des-Gly-NH10(2)] LH-RH ethylamide in the dog

This study examines the effect of treatment with controlled-release poly(DL-lactide-coglycolide) microsphere formulations of the LH-RH agonist [D-Trp6, des-Gly-NH10(2)]-LH-RH ethylamide (LH-RH-A) designed to release about 100 or 200 micrograms of the peptide per day for 3, 5 or 6 months in male dogs. Plasma levels of testosterone and LH-RH-A were measured at 2-day intervals. After the first injection of the 100-micrograms/day formulation, plasma testosterone increased from 1.6 +/- 0.2 to 3.5 +/- 0.6 ng/ml for 5-7 days before decreasing and remaining at 0.05 +/- 0.008 ng/ml for approximately 150 days (5 months). After two months of recovery, microspheres designed to release 100 micrograms for 6 months of LH-RH agonist per day were then injected. Plasma testosterone levels showed an elevation from 1.5 +/- 0.5 to 4.7 +/- 2.0 ng/ml during the first few days before gradually decreasing to castration levels for 200 days (6 months). One month later, plasma testosterone had returned to normal levels. When microspheres designed to deliver an average of 200 micrograms per day of the peptide for 3 months were injected in another series of animals, castration levels of plasma testosterone were maintained for 95 days with a progressive increase to normal values at later time intervals. The animals of the first series of experiments were then sacrificed after 4 months of recovery following maintenance of plasma testosterone at castration levels for a total period of 11 months. The testes, prostate and pituitary gland were kept for histological examination which was completely normal in all tissues. The efficacy and excellent tolerance of the controlled-release form of LH-RH-A as inhibitor of the pituitary-gonadal axis strongly support the use of such long-term controlled-release formulations of LH-RH agonists for the treatment of sex steroid sensitive diseases.     

Amine coupling versus biotin capture for the assessment of sulfonamide as ligands of hCA isoforms

This work was dedicated to the development of a reliable SPR method allowing the simultaneous and quick determination of the affinity and selectivity of designed sulfonamide derivatives for hCAIX and hCAXII versus hCAII, in order to provide an efficient tool to discover drugs for anticancer therapy of solid tumors. We performed for the first time a comparison of two immobilization approaches of hCA isoforms. First one relies on the use of an amine coupling strategy, using a CM7 chip to obtain higher immobilization levels than with a CM5 chip and consequently the affinity with an higher precision (CV% < 10%). The second corresponds to a capture of proteins on a streptavidin chip, named CAP chip, after optimization of biotinylation conditions (amine versus carboxyl coupling, biotin to protein ratio). Thanks to the amine coupling approach, only hCAII and hCAXII isoforms were efficiently biotinylated to reach relevant immobilization (3000 RU and 2700 RU, respectively) to perform affinity studies. For hCAIX, despite a successful biotinylation, capture on the CAP chip was a failure. Finally, concordance between affinities obtained for the three derivatives to CAs isozymes on both chips has allowed to valid the approaches for a further screening of new derivatives.     

Relations floristiques entre les groupements prairiaux du Triseto-Polygonion et les megaphorbiaies (Adenostylion) dans les Alpes occidentales

Résumé L'application de l'analyse factorielle des correspondances à un ensemble de données floristiques relatives aux prairies grasses d'altitude (Triseto-Polygonion) et aux mégaphorbiaies (Adenostylion) permet d'éclaircir la conception phytosociologique de ces groupements dans les Alpes occidentales. Elle conduit à l'éclatement du Trisetetum flavescentis des auteurs suisses en deux associations bien individualisées, Triseto-Meetum localisé aux massifs sud-occidentaux et Triseto-Agrostidetum propre aux chaînes plus septentrionales. Par contre, elle entraîne le rattachement des divers groupements de mégaphorbiaie décrits au seul Adenostylo-Cicerbitetum, association qui se différencie secondairement, selon les secteurs de son aire, en trois sous-unités distinctes. Cette synthèse aboutit, d'autre part, à la mise en évidence d'espèces communes aux deux types de groupements mais qui en fait, sous une apparence morphologique semblable, représentent vraisemblablement des taxons distincts. Dans une seconde phase, l'étude caryologique et l'analyse chimiotaxonomique devraient permenttre de saisir les différences de constitution génotypique existant entre les populations issues des mégaphorbiaies et celles développées dans les groupements du Triseto-Polygonion.     

Noradrenaline reduces the stimulatory effect of interleukin-1α on reactive oxygen species production by oyster immunocytes

Abstract. A growing body of evidence suggests that interleukin-1α (IL-1α) is present in invertebrates. Both invertebrate and human IL-1α can bind to invertebrate receptors and stimulate invertebrate immune functions. The present study shows that IL-1α increases reactive oxygen species (ROS) production by oyster immunocytes. However, physiological doses of noradrenaline (NA) exert a suppressive effect on IL-1α stimulation in vitro . The β-adrenoceptor agonist isoproterenol mimicked the effects of NA and the β-adrenoceptor antagonist propanolol blocked the NA-induced suppression of hemocyte responsiveness to IL-1α. The type IV phosphodiesterase inhibitor rolipram acted in synergy with isoproterenol to reduce hemocyte response to IL-1α and the protein kinase A inhibitor H-89 suppressed the effects of isoproterenol. These results suggest that circulating NA impairs IL-1α-stimulation of oyster hemocyte via a β-adrenoceptor/cyclic AMP/protein kinase-A signaling pathway. Considering that mollusc immunocytes secrete NA, an autocrine regulatory loop may also modulate the ability of these cells to respond to IL-1α.     

A Casein kinase 1/Checkpoint kinase 1 pyrazolo-pyridine protein kinase inhibitor as novel activator of the p53 pathway

Reactivation of the wild-type p53 pathway is one key goal aimed at developing targeted therapeutics in the cancer research field. Although most p53 protein kinases form ‘p53-activating’ signals, there are few kinases whose action can contribute to the inhibition of p53, as Casein kinase 1 (CK1) and Checkpoint kinase 1 (CHK1). Here we report on a pyrazolo-pyridine analogue showing activity against both CK1 and CHK1 kinases that lead to p53 pathway stabilisation, thus having pharmacological similarities to the p53-activator Nutlin-3. These data demonstrate the emerging potential utility of multivalent kinase inhibitors.     

Improving PCR detection of prey in molecular diet studies: importance of group‐specific primer set selection and extraction protocol performances

While the morphological identification of prey remains in predators' faeces is the most commonly used method to study trophic interactions, many studies indicate that this method does not detect all consumed prey. Polymerase chain reaction–based methods are increasingly used to detect prey DNA in the predator food bolus and have proven efficient, delivering highly accurate results. When studying complex diet samples, the extraction of total DNA is a critical step, as polymerase chain reaction (PCR) inhibitors may be co‐extracted. Another critical step involves a careful selection of suitable group‐specific primer sets that should only amplify DNA from the targeted prey taxon. In this study, the food boluses of five Rattus rattus and seven Rattus exulans were analysed using both morphological and molecular methods. We tested a panel of 31 PCR primer pairs targeting bird, invertebrate and plant sequences; four of them were selected to be used as group‐specific primer pairs in PCR protocols. The performances of four DNA extraction protocols (QIAamp^® DNA stool mini kit, DNeasy^® mericon food kit and two of cetyltrimethylammonium bromide‐based methods) were compared using four variables: DNA concentration, A₂₆₀/A₂₈₀ absorbance ratio, food compartment analysed (stomach or faecal contents) and total number of prey‐specific PCR amplification per sample. Our results clearly indicate that the A₂₆₀/A₂₈₀ absorbance ratio, which varies between extraction protocols, is positively correlated to the number of PCR amplifications of each prey taxon. We recommend using the DNeasy^® mericon food kit (QIAGEN), which yielded results very similar to those achieved with the morphological approach.