Sirtuin 6 inhibition protects against glucocorticoid-induced skeletal muscle atrophy by regulating IGF/PI3K/AKT signaling

Chronic activation of stress hormones such as glucocorticoids leads to skeletal muscle wasting in mammals. However, the molecular events that mediate glucocorticoid-induced muscle wasting are not well understood. Here, we show that SIRT6, a chromatin-associated deacetylase indirectly regulates glucocorticoid-induced muscle wasting by modulating IGF/PI3K/AKT signaling. Our results show that SIRT6 levels are increased during glucocorticoid-induced reduction of myotube size and during skeletal muscle atrophy in mice. Notably, overexpression of SIRT6 spontaneously decreases the size of primary myotubes in a cell-autonomous manner. On the other hand, SIRT6 depletion increases the diameter of myotubes and protects them against glucocorticoid-induced reduction in myotube size, which is associated with enhanced protein synthesis and repression of atrogenes. In line with this, we find that muscle-specific SIRT6 deficient mice are resistant to glucocorticoid-induced muscle wasting. Mechanistically, we find that SIRT6 deficiency hyperactivates IGF/PI3K/AKT signaling through c-Jun transcription factor-mediated increase in IGF2 expression. The increased activation, in turn, leads to nuclear exclusion and transcriptional repression of the FoxO transcription factor, a key activator of muscle atrophy. Further, we find that pharmacological inhibition of SIRT6 protects against glucocorticoid-induced muscle wasting in mice by regulating IGF/PI3K/AKT signaling implicating the role of SIRT6 in glucocorticoid-induced muscle atrophy.Fil: Mishra, Sneha. No especifíca;Fil: Cosentino, Claudia. Harvard Medical School; Estados UnidosFil: Tamta, Ankit Kumar. No especifíca;Fil: Khan, Danish. No especifíca;Fil: Srinivasan, Shalini. No especifíca;Fil: Ravi, Venkatraman. No especifíca;Fil: Abbotto, Elena. Università degli Studi di Genova; ItaliaFil: Arathi, Bangalore Prabhashankar. No especifíca;Fil: Kumar, Shweta. No especifíca;Fil: Jain, Aditi. No especifíca;Fil: Ramaian, Anand S.. No especifíca;Fil: Kizkekra, Shruti M.. No especifíca;Fil: Rajagopal, Raksha. No especifíca;Fil: Rao, Swathi. No especifíca;Fil: Krishna, Swati. No especifíca;Fil: Asirvatham Jeyaraj, Ninitha. Indian Institute of Technology; IndiaFil: Haggerty, Elizabeth R.. Harvard Medical School; Estados UnidosFil: Silberman, Dafne Magalí. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Kurland, Irwin J.. No especifíca;Fil: Veeranna, Ravindra P.. No especifíca;Fil: Jayavelu, Tamilselvan. No especifíca;Fil: Bruzzone, Santina. Università degli Studi di Genova; ItaliaFil: Mostoslavsky, Raul. Harvard Medical School; Estados UnidosFil: Sundaresan, Nagalingam R.. No especifíca

An ab initio and AIM investigation into the hydration of 2-thioxanthine

<p>Abstract</p> <p>Background</p> <p>Hydration is a universal phenomenon in nature. The interactions between biomolecules and water of hydration play a pivotal role in molecular biology. 2-Thioxanthine (2TX), a thio-modified nucleic acid base, is of significant interest as a DNA inhibitor yet its interactions with hydration water have not been investigated either computationally or experimentally. Here in, we reported an <it>ab initio </it>study of the hydration of 2TX, revealing water can form seven hydrated complexes.</p> <p>Results</p> <p>Hydrogen-bond (H-bond) interactions in 1:1 complexes of 2TX with water are studied at the MP2/6-311G(d, p) and B3LYP/6-311G(d, p) levels. Seven 2TX^...H₂O hydrogen bonded complexes have been theoretically identified and reported for the first time. The proton affinities (PAs) of the O, S, and N atoms and deprotonantion enthalpies (DPEs) of different N-H bonds in 2TX are calculated, factors surrounding why the seven complexes have different hydrogen bond energies are discussed. The theoretical infrared and NMR spectra of hydrated 2TX complexes are reported to probe the characteristics of the proposed H-bonds. An improper blue-shifting H-bond with a shortened C-H bond was found in one case. NBO and AIM analysis were carried out to explain the formation of improper blue-shifting H-bonds, and the H-bonding characteristics are discussed.</p> <p>Conclusion</p> <p>2TX can interact with water by five different H-bonding regimes, N-H^...O, O-H^...N, O-H^...O, O-H^...S and C-H^...O, all of which are medium strength hydrogen bonds. The most stable H-bond complex has a closed structure with two hydrogen bonds (N(7)-H^...O and O-H^...O), whereas the least stable one has an open structure with one H-bond. The interaction energies of the studied complexes are correlated to the PA and DPE involved in H-bond formation. After formation of H-bonds, the calculated IR and NMR spectra of the 2TX-water complexes change greatly, which serves to identify the hydration of 2TX.</p

Studies on <i style="">in vitro</i> propagation of Himalayan cedar (<i style="">Cedrus deodara</i>) using zygotic embryos and stem segments

209-215Adventitious bud formation was examined in zygotic embryos (decoated seeds) of Cedrus deodara, planted in the normal position, using four different media variously supplemented with or without plant growth regulators (PGRs). Following incubation for 7, 14, 21 and 28 days on PGR containing media, the embryos were transferred to respective PGR-free basal media. While embryo swelling was observed in all cases, normal germination was observed only in embryos cultured initially in PGR-free media. Best response, in terms of bud formation (93%), was observed in embryos first cultured on LP medium containing BA and Kinetin (1.0 M each) for 28 days and then transferred to LP medium without any PGR. While the mean number of shoots formed per cultured embryo was also highest (34%) in this combination, these shoots eventually dried when excised and sub-cultured for further multiplication. Success was, however, obtained when the embryos were initially planted in an inverted position on LP medium containing 20.0 M BA for 10 days, and then shifted, again in the inverted position, on the same medium without BA. Although the mean number of shoots formed was low (only 2.5 shoots per embryo), these could be multiplied and elongated. The microshoots (2.0-3.0 cm) thus obtained could be rooted (100%) using ½ strength, PGR-free, LP medium, hardened and established in pots. Besides excised embryos, stem segments were also used as explants. While only a quarter of explants could be established in culture, in contamination-free condition, good sprouting response (3-4 buds per segment) was obtained in certain PGR combinations. The sprouted buds developed into shoots on LP medium containing 5.0 M BA; further subculturing of excised shoots for multiplication, however, resulted in drying up of shoots. Further work is required to overcome this difficulty

Fashion meets science: how advanced breeding approaches could revolutionize the textile industry

Natural fibers have garnered considerable attention owing to their desirable textile properties and advantageous effects on human health. Nevertheless, natural fibers lag behind synthetic fibers in terms of both quality and yield, as these attributes are largely genetically determined. In this article, a comprehensive overview of the natural and synthetic fiber production landscape over the last 10 years is presented, with a particular focus on the role of scientific breeding techniques in improving fiber quality traits in key crops like cotton, hemp, ramie, and flax. Additionally, the article delves into cutting-edge genomics-assisted breeding techniques, including QTL mapping, genome-wide association studies, transgenesis, and genome editing, and their potential role in enhancing fiber quality traits in these crops. A user-friendly compendium of 11226 available QTLs and significant marker-trait associations derived from 136 studies, associated with diverse fiber quality traits in these crops is furnished. Furthermore, the potential applications of transcriptomics in these pivotal crops, elucidating the distinct genes implicated in augmenting fiber quality attributes are investigated. Additionally, information on 11257 candidate/characterized or cloned genes sourced from various studies, emphasizing their key role in the development of high-quality fiber crops is collated. Additionally, the review sheds light on the current progress of marker-assisted selection for fiber quality traits in each crop, providing detailed insights into improved cultivars released for different fiber crops. In conclusion, it is asserted that the application of modern breeding tools holds tremendous potential in catalyzing a transformative shift in the textile industry. Natural fibers possess desirable properties, but they often lag behind synthetic fibers in terms of both quality and quantity. Genomic-assisted breeding has the potential to improve fiber quality traits in cotton, hemp, ramie, and flax. Utilizing available QTLs, marker-trait associations, and candidate genes can contribute to the development of superior fiber crops, underscoring the significance of advanced breeding tools.</p