Transcriptomic and Epigenetic Regulation of Disuse Atrophy and the Return to Activity in Skeletal Muscle

Physical inactivity and disuse are major contributors to age-related muscle loss. Denervation of skeletal muscle has been previously used as a model with which to investigate muscle atrophy following disuse. Although gene regulatory networks that control skeletal muscle atrophy after denervation have been established, the transcriptome in response to the recovery of muscle after disuse and the associated epigenetic mechanisms that may function to modulate gene expression during skeletal muscle atrophy or recovery have yet to be investigated. We report that silencing the tibialis anterior muscle in rats with tetrodotoxin (TTX)—administered to the common peroneal nerve—resulted in reductions in muscle mass of 7, 29, and 51% with corresponding reductions in muscle fiber cross-sectional area of 18, 42, and 69% after 3, 7, and 14 d of TTX, respectively. Of importance, 7 d of recovery, during which rodents resumed habitual physical activity, restored muscle mass from a reduction of 51% after 14 d TTX to a reduction of only 24% compared with sham control. Returning muscle mass to levels observed at 7 d TTX administration (29% reduction). Transcriptome-wide analysis demonstrated that 3714 genes were differentially expressed across all conditions at a significance of P ≤ 0.001 after disuse-induced atrophy. Of interest, after 7 d of recovery, the expression of genes that were most changed during TTX had returned to that of the sham control. The 20 most differentially expressed genes after microarray analysis were identified across all conditions and were cross-referenced with the most frequently occurring differentially expressed genes between conditions. This gene subset included myogenin (MyoG), Hdac4, Ampd3, Trim63 (MuRF1), and acetylcholine receptor subunit α1 (Chrna1). Transcript expression of these genes and Fboxo32 (MAFbx), because of its previously identified role in disuse atrophy together with Trim63 (MuRF1), were confirmed by real-time quantitative RT-PCR, and DNA methylation of their promoter regions was analyzed by PCR and pyrosequencing. MyoG, Trim63 (MuRF1), Fbxo32 (MAFbx), and Chrna1 demonstrated significantly decreased DNA methylation at key time points after disuse-induced atrophy that corresponded with significantly increased gene expression. Of importance, after TTX cessation and 7 d of recovery, there was a marked increase in the DNA methylation profiles of Trim63 (MuRF1) and Chrna1 back to control levels. This also corresponded with the return of gene expression in the recovery group back to baseline expression observed in sham-operated controls. To our knowledge, this is the first study to demonstrate that skeletal muscle atrophy in response to disuse is accompanied by dynamic epigenetic modifications that are associated with alterations in gene expression, and that these epigenetic modifications and gene expression profiles are reversible after skeletal muscle returns to normal activity

Allium paniculatum L., una specie critica ed erroneamente interpretata della flora europea

Dalle indagini morfologiche e cariologiche condotte \ue8 emerso che Allium paniculatum \ue8 una specie ben differenziata dagli altri taxa della sez. Codonoprasum, con corredo cromosomico poliploide, esaploide o triploide, probabilmente originatosi in seguito all\u2019adattamento ad ambienti sinantropici in territori con bioclima marcatamente mesico, come si desume dalle esigenze ecologiche, dal periodo di fioritura estivo e dalla distribuzione geografica

Calculations of free energy barriers for local mechanisms of hydrogen diffusion in alanates

Brute force histogram calculation and a recently developed method to efficiently reconstruct the free energy profile of complex systems ( the single-sweep method) are combined with ab initio molecular dynamics to study possible local mechanisms for the diffusion of hydrogen in sodium alanates. These compounds may help to understand key properties of solid state hydrogen storage materials. In this work, the identity of a mobile species observed in experiments characterizing the first dissociation reaction of sodium alanates is investigated. The activation barrier of two suggested processes for hydrogen diffusion in Na(3)AlH(6) is evaluated and, by comparing our results with available experimental information, we are able to discriminate among them and to show that one is compatible with the observed signal while the other is not

Calculations of free energy barriers for local mechanisms of hydrogen diffusion in alanates

Brute force histogram calculation and a recently developed method to efficiently reconstruct the free energy profile of complex systems (the single-sweep method) are combined with ab initio molecular dynamics to study possible local mechanisms for the diffusion of hydrogen in sodium alanates. These compounds may help to understand key properties of solid state hydrogen storage materials. In this work, the identity of a mobile species observed in experiments characterizing the first dissociation reaction of sodium alanates is investigated. The activation barrier of two suggested processes for hydrogen diffusion in Na3AlH6 is evaluated and, by comparing our results with available experimental information, we are able to discriminate among them and to show that one is compatible with the observed signal while the other is not