Mediator complex is a molecular hub integrating signaling, transcription factors, and RNA polymerase II (RNAPII) machinery. Mediator MED23 is involved in adipogenesis and smooth muscle cell differentiation, suggesting its role in energy homeostasis. Here, through the generation and analysis of a liver-specific Med23-knockout mouse, we found that liver Med23 deletion improved glucose and lipid metabolism, as well as insulin responsiveness, and prevented diet-induced obesity. Remarkably, acute hepatic Med23 knockdown in db/db mice significantly improved the lipid profile and glucose tolerance. Mechanistically, MED23 participates in gluconeogenesis and cholesterol synthesis through modulating the transcriptional activity of FOXO1, a key metabolic transcription factor. Indeed, hepatic Med23 deletion impaired the Mediator and RNAPII recruitment and attenuated the expression of FOXO1 target genes. Moreover, this functional interaction between FOXO1 and MED23 is evolutionarily conserved, as the in vivo activities of dFOXO in larval fat body and in adult wing can be partially blocked by Med23 knockdown in Drosophila. Collectively, our data revealed Mediator MED23 as a novel regulator for energy homeostasis, suggesting potential therapeutic strategies against metabolic diseases.
Pythium damping‐off and root rot of soybean [Glycine max (L.) Merr.] causes poor stands and consequently reduces yields. Resistance to seedling diseases caused by Pythium spp. was reported in the soybean cultivar Archer and was described to be associated with the Rps1k gene for resistance to Phytophthora sojae. To characterize the inheritance of Pythium damping‐off resistance in Archer and to determine if this resistance is linked to Rps1k, the cross of Archer × ‘Hutcheson’ (susceptible parent) was made and F2:4 lines generated. Parents and F2:4 lines were screened with Pythium aphanidermatum using a hypocotyl inoculation technique. Five days after inoculation, plant survival was scored. The F2:4 lines and parents were also inoculated with race 7 of P. sojae to assess the association of resistance to Pythium spp. with the Rps1k gene. Data from the F2:4 lines fit the model for a single dominant gene in Archer that confers resistance to P. aphanidermatum. The genetic linkage test showed that resistance to P. aphanidermatum was independent of the Rps1k gene in Archer. To identify the genomic location of the Pythium resistance gene, F2:4 lines were screened with simple sequence repeat (SSR) markers from all the soybean molecular linkage groups (MLGs). Two SSR markers, Satt510 and Satt114 on MLG F, which were polymorphic between the parents and the resistant and susceptible bulks, were shown to be associated with Pythium resistance. The Pythium resistance gene, named Rpa1, was located 10.6 cM from Satt510 and 26.6 cM from Satt114.
Taken together, the alterations described seem to contribute to constituting a state of higher propensity for the development of atherosclerotic cardiovascular disease, which adds to the presence of specific cardiomyopathy.
Development of soybeans [Glycine max (L.) Merr.] with modified phosphorus (P) and sugar composition adds value to soybean meal. The identification and release of the soybean line V99‐5089 with a mutation in the D‐myo‐inositol 3‐phosphate synthase 1 gene (MIPS1) provides a germplasm source that dually enhances both P and sugar composition of soybeans. An evaluation of the recombinant inbred line population from the cross of V99‐5089 × Essex was completed at three environments in 2 yr. Phenotypic selection for modified composition was slightly more effective than marker‐assisted selection with the Satt453 marker, which was 87% efficient. In the mutant lines, a significant genotype × environment interaction was shown for inorganic phosphorus (Pi) concentration but not sugar concentration. Correlations for improving P and sugar composition were favorable, and with the exception of emergence there were no strong correlations with agronomic traits. The correlation of emergence with Pi was significant (r = −0.59), indicating reduced emergence due to the mutation. Reduced emergence is a problem in low phytate germplasm generally and further research is necessary to genetically improve emergence of low phytate lines.
The increase in plasma oxLDL levels, a direct marker of the plaque formation, could constitute a link between atherosclerosis and active acromegaly. LDL oxidation would not be the consequence of diminished antioxidant defences, but of an enhancement in prooxidant factors like ceruloplasmin.
Fusarium head blight (FHB), caused by Fusarium graminearum, is one of the most serious diseases impacting the U.S. barley (Hordeum vulgare) industry. The mycotoxin deoxynivalenol (DON), produced by the pathogen, renders grain unmarketable if concentrations exceed threshold values set for end-use markets. Development of cultivars with improved FHB resistance and reduced DON accumulation is necessary to ensure minimal losses. Elite hulled and hulless genotypes developed by the Virginia Tech winter barley breeding program were screened in inoculated, mist-irrigated FHB nurseries over 2 years at two locations in Virginia to validate resistance levels over years and locations. Results demonstrated that barley genotypes varied significantly for resistance to FHB and DON accumulation. The hulled ‘Nomini’, hulless ‘Eve’, and hulless line VA06H-48 were consistently resistant across locations to both FHB and DON accumulation. Screening the genotypes with molecular markers on chromosomes 2H and 6H for FHB and DON revealed quantitative trait loci regions which may confer resistance in the Virginia Tech germplasm. Ongoing and future work with mapping populations seeks to identify novel regions for resistance to FHB and DON accumulation unique to the Virginia Tech breeding program.
In patients with active acromegaly, GH excess contributes to the development of insulin resistance, and the interaction between both disturbances would be responsible for the appearance of atherogenic pro-oxidative and pro-inflammatory factors. Insulin resistance would be preferably associated with an atherogenic lipoprotein profile and to high CETP activity, while high GH levels would independently predict the increase in LDL-C, ox-LDL and endothelin-1.
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