Regulation of the dystrophin-associated glycoprotein complex composition by the metabolic properties of muscle fibres

The dystrophin-glycoprotein complex (DGC) links the muscle cytoskeleton to the extracellular matrix and is responsible for force transduction and protects the muscle fibres from contraction induced damage. Mutations in components of the DGC are responsible for muscular dystrophies and congenital myopathies. Expression of DGC components have been shown to be altered in many myopathies. In contrast we have very little evidence of whether adaptive changes in muscle impact on DGC expression. In this study we investigated connection between muscle fibre phenotype and the DGC. Our study reveals that the levels of DGC proteins at the sarcolemma differ in highly glycolytic muscle compared to wild-type and that these changes can be normalised by the super-imposition of an oxidative metabolic programme. Importantly we show that the metabolic properties of the muscle do not impact on the total amount of DGC components at the protein level. Our work shows that the metabolic property of a muscle fibre is a key factor in regulating the expression of DGC proteins at the sarcolemma

Responsiveness of pituitary to galanin throughout the reproductive cycle of male European sea bass (Dicentrarchus labrax)

The neuropeptide galanin (Gal) is a putative factor regulating puberty onset and reproduction through its actions on the pituitary. The present study investigated the pituitary responsiveness to galanin and the patterns of galanin receptors (Galrs) expression throughout the reproductive cycle of two years old male European sea bass (Dicentrarchus labrax), an important aquaculture species. Quantitative analysis of pituitary and hypothalamus transcript expression of four galr subtypes revealed differential regulation according to the testicular developmental stage, with an overall decrease in expression from the immature stage to the mid-recrudescence stage. Incubation of pituitary cells with mammalian 1-29 Gal peptide induced significant changes in cAMP concentration, with sensitivities that varied according to the testicular development stages. Furthermore 1-29 Gal was able to stimulate both follicle stimulating hormone (Fsh) and luteinizing hormone (Lh) release from pituitary cell suspensions. The magnitude of the effects and effective concentrations varied according to reproductive stage, with generalized induction of Fsh and Lh release in animals sampled in January (full spermiation). The differential expression of galrs in pituitary and hypothalamus across the reproductive season, together with the differential effects of Gal on gonadotropins release in vitro strongly suggests the involvement of the galaninergic system in the regulation the hypothalamus-pituitary-gonad axis of male sea bass. This is to our knowledge the first clear evidence for the involvement of galanin in the regulation of reproduction in non-mammalian vertebrates. (C) 2017 Elsevier Inc. All rights reserved.European Union Seventh Framework Programme [262336]Spanish Ministry of Science and Innovation (MICINN)Spanish Ministry of the Economy and Competitiveness (MINECO) [AGL2009-11086]Spanish Ministry of the Economy and CompetitivenessRegional Government of Valencia [PROME-TEOH/2014/051]info:eu-repo/semantics/acceptedVersio

Hes5 Expression in the Postnatal and Adult Mouse Inner Ear and the Drug-Damaged Cochlea

The Notch signaling pathway is known to have multiple roles during development of the inner ear. Notch signaling activates transcription of Hes5, a homologue of Drosophila hairy and enhancer of split, which encodes a basic helix-loop-helix transcriptional repressor. Previous studies have shown that Hes5 is expressed in the cochlea during embryonic development, and loss of Hes5 leads to overproduction of auditory and vestibular hair cells. However, due to technical limitations and inconsistency between previous reports, the precise spatial and temporal pattern of Hes5 expression in the postnatal and adult inner ear has remained unclear. In this study, we use Hes5-GFP transgenic mice and in situ hybridization to report the expression pattern of Hes5 in the inner ear. We find that Hes5 is expressed in the developing auditory epithelium of the cochlea beginning at embryonic day 14.5 (E14.5), becomes restricted to a particular subset of cochlear supporting cells, is downregulated in the postnatal cochlea, and is not present in adults. In the vestibular system, we detect Hes5 in developing supporting cells as early as E12.5 and find that Hes5 expression is maintained in some adult vestibular supporting cells. In order to determine the effect of hair cell damage on Notch signaling in the cochlea, we damaged cochlear hair cells of adult Hes5-GFP mice in vivo using injection of kanamycin and furosemide. Although outer hair cells were killed in treated animals and supporting cells were still present after damage, supporting cells did not upregulate Hes5-GFP in the damaged cochlea. Therefore, absence of Notch-Hes5 signaling in the normal and damaged adult cochlea is correlated with lack of regeneration potential, while its presence in the neonatal cochlea and adult vestibular epithelia is associated with greater capacity for plasticity or regeneration in these tissues; which suggests that this pathway may be involved in regulating regenerative potential

Baltimore Holocaust Memorial

General view of the right section of the boxcar monoliths; The Holocaust Memorial in downtown Baltimore was originally built in 1980 and was redesigned in 1997. Today, the centerpiece of the stark gray memorial are two concrete monoliths that represent the boxcars used to transport Jews to the Nazi death camps during World War II. Railroad tracks surround the structure. The redesign, which cost $400,000, required the removal of a grassy hill to give passersby along the Inner Harbor a view of the memorial

Baltimore Holocaust Memorial

Side view of the boxcar monoliths; The Holocaust Memorial in downtown Baltimore was originally built in 1980 and was redesigned in 1997. Today, the centerpiece of the stark gray memorial are two concrete monoliths that represent the boxcars used to transport Jews to the Nazi death camps during World War II. Railroad tracks surround the structure. The redesign, which cost $400,000, required the removal of a grassy hill to give passersby along the Inner Harbor a view of the memorial

Baltimore Holocaust Memorial

Close view of dedication plaque; The Holocaust Memorial in downtown Baltimore was originally built in 1980 and was redesigned in 1997. Today, the centerpiece of the stark gray memorial are two concrete monoliths that represent the boxcars used to transport Jews to the Nazi death camps during World War II. Railroad tracks surround the structure. The redesign, which cost $400,000, required the removal of a grassy hill to give passersby along the Inner Harbor a view of the memorial

Baltimore Holocaust Memorial

General view of the Baltimore Holocaust Memorial; The Holocaust Memorial in downtown Baltimore was originally built in 1980 and was redesigned in 1997. Today, the centerpiece of the stark gray memorial are two concrete monoliths that represent the boxcars used to transport Jews to the Nazi death camps during World War II. Railroad tracks surround the structure. The redesign, which cost $400,000, required the removal of a grassy hill to give passersby along the Inner Harbor a view of the memorial

Baltimore Holocaust Memorial

Close side view of the boxcar monoliths; The Holocaust Memorial in downtown Baltimore was originally built in 1980 and was redesigned in 1997. Today, the centerpiece of the stark gray memorial are two concrete monoliths that represent the boxcars used to transport Jews to the Nazi death camps during World War II. Railroad tracks surround the structure. The redesign, which cost $400,000, required the removal of a grassy hill to give passersby along the Inner Harbor a view of the memorial