Rictor is a component of the target of rapamycin complex 2 (TORC2). While TORC2 has been implicated in insulin and other growth factor signaling pathways, the key inputs and outputs of this kinase ...complex remain unknown. We identified mutations in the Caenorhabditis elegans homolog of rictor in a forward genetic screen for increased body fat. Despite high body fat, rictor mutants are developmentally delayed, small in body size, lay an attenuated brood, and are short-lived, indicating that Rictor plays a critical role in appropriately partitioning calories between long-term energy stores and vital organismal processes. Rictor is also necessary to maintain normal feeding on nutrient-rich food sources. In contrast to wild-type animals, which grow more rapidly on nutrient-rich bacterial strains, rictor mutants display even slower growth, a further reduced body size, decreased energy expenditure, and a dramatically extended life span, apparently through inappropriate, decreased consumption of nutrient-rich food. Rictor acts directly in the intestine to regulate fat mass and whole-animal growth. Further, the high-fat phenotype of rictor mutants is genetically dependent on akt-1, akt-2, and serum and glucocorticoid-induced kinase-1 (sgk-1). Alternatively, the life span, growth, and reproductive phenotypes of rictor mutants are mediated predominantly by sgk-1. These data indicate that Rictor/TORC2 is a nutrient-sensitive complex with outputs to AKT and SGK to modulate the assessment of food quality and signal to fat metabolism, growth, feeding behavior, reproduction, and life span.
GH therapy is still controversial, except in severe GH deficiency (SGHD). The objective of this study was to compare the response to growth hormone (GH) therapy in children with partial GH ...insensitivity (PGHIS) and mild GH deficiency (MGHD) with those with SGHD.
Fifteen PGHIS, 11 MGHD, and 19 SGHD subjects, followed up for more than one year in the Brazilian public care service, were evaluated regarding anthropometric and laboratory data at the beginning of treatment, after one year (1st year) on treatment, and at the last assessment (up to ten years in SGHD, up to four years in MGHD, and up to eight years in PGHIS).
Initial height standard deviation score (SDS) in SGHD was lower than in MGHD and PGHIS. Although the increase in 1 st year height SDS in comparison to initial height SDS was not different among the groups, height-SDS after the first year of treatment remained lower in SGHD than in MGHD. There was no difference in height-SDS at the last assessment of the children among the three groups. GH therapy, in the entire period of observation, caused a trend towards lower increase in height SDS in PGHIS than SGHD but similar increases were observed in MGHD and SGHD.
GH therapy increases height in PGHIS and produces similar height effects in MGHD and SGHD.
Sisal fiber–cement composites reinforced with long unidirectional aligned fibers were developed and their physical–mechanical behavior was characterized in the present study. Flat and corrugated ...sheets were cast by a manual lay-out of the fibers in a self-compacted cement matrix and compressed with a pressure of 3
MPa. Direct tensile and bending tests were performed to determine the first crack, post-peak strength and toughness of the composites. Drying shrinkage, capillary water absorption and water tightness tests were performed to characterize the physical properties of the composites. To ensure the composite durability, the ordinary Portland cement matrix was modified by adding metakaolin and calcined waste crushed clay brick to consume the calcium hydroxide generated during Portland cement hydration. The durability of the newly developed composite was determined through accelerated aging conditions using the hot-water immersion test. The developed material presented a multiple cracking behavior under bending, even when subjected to 6
months of hot-water immersion under 60
°C. Scanning Electron Microscopy was used to investigate the micro-structure of the composites before and after aging.
Olefin hydroformylation is a widely used process, both on large scales and in fine chemistry, with catalyst reuse still being one of the main objectives. In recent years, developments in the ...immobilization of catalysts on solid supports that enable their recovery and reuse when applied in catalytic hydroformylations of aromatic and aliphatic olefins have resulted in a boost in the field of heterogeneous catalysis. This review presents the most relevant results reported over the last five years with regard to the development and use of supported catalysts in mesoporous materials, hydrotalcite, carbon materials, and nanoparticles for catalytic hydroformylation of olefins. A critical analysis of the results, especially in the context of reusability and leaching issues, is presented.
The most relevant results relating to the development and use of catalysts supported on mesoporous materials, hydrotalcite, carbon materials, and nanoparticles for metal‐catalyzed hydroformylation of olefins reported over the last five years are reviewed. The results are analyzed with particular regard to reusability and leaching issues.
The effects of subchronic exposure to copper in fat snook (Centropomus parallelus) Oss, Rodrigo Nunes; Edgar Hell KampkeauthorLaboratrio de Ictiologia Aplicada Universidade Vila Velha, Rua Comissrio Jos Dantas de Melo, 21, Vila Velha, ES, Brazil, 29102-770; Adriana Regina Chippari-GomesauthorLaboratrio de Ictiologia Aplicada Universidade Vila Velha, Rua Comissrio Jos Dantas de Melo, 21, Vila Velha, ES, Brazil, 29102-770 ...
2015
Journal Article
Photodynamic therapy, by reducing pain and inflammation and promoting the proliferation of healthy cells, can be used to treat recurrent lesions, such as diabetic foot ulcers. Studies using the ...photosensitizer phthalocyanine, together with the nanostructured copolymeric matrix of Pluronic® and Carbopol® for the treatment of diabetic foot ulcers and leishmaniosis lesions, are showing promising outcomes. Despite their topical or subcutaneous administration, these molecules are absorbed and their systemic effects are unknown. Therefore, we investigated the effect of the subcutaneous administration of the hydroxy-aluminum phthalocyanine hydrogel without illumination on systemic parameters, markers of liver injury, and liver energy metabolism in type 1 diabetic Swiss mice. Both the hydrogel and the different doses of phthalocyanine changed the levels of injury markers and the liver glucose release, sometimes aggravating the alterations caused by the diabetic condition itself. However, the dose of 2.23 µg/mL caused less marked plasmatic and metabolic changes and did not change glucose tolerance or insulin sensitivity of the diabetic mice. These results are indicative that the use of hydroxy-aluminum phthalocyanine hydrogel for the treatment of cutaneous ulcers in diabetic patients is systemically safe.
Cancer stem cells (CSCs) have been hypothesized to represent the driving force behind tumour progression and metastasis, making them attractive cancer targets. However, conclusive experimental ...evidence for their functional relevance is still lacking for most malignancies. Here we show that the leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5) identifies intestinal CSCs in mouse tumours engineered to recapitulate the clinical progression of human colorectal cancer. We demonstrate that selective Lgr5
cell ablation restricts primary tumour growth, but does not result in tumour regression. Instead, tumours are maintained by proliferative Lgr5
cells that continuously attempt to replenish the Lgr5
CSC pool, leading to rapid re-initiation of tumour growth upon treatment cessation. Notably, CSCs are critical for the formation and maintenance of liver metastasis derived from colorectal cancers. Together, our data highlight distinct CSC dependencies for primary versus metastasic tumour growth, and suggest that targeting CSCs may represent a therapeutic opportunity for managing metastatic disease.
Integrase inhibitors (INIs) are an important class of drugs for treating HIV-2 infection, given the limited number of drugs active against this virus. While the clinical efficacy of raltegravir and ...dolutegravir is well established, the clinical efficacy of bictegravir for treating HIV-2 infected patients has not been determined. Little information is available regarding the activity of bictegravir against HIV-2 isolates from patients failing raltegravir-based therapy. In this study, we examined the phenotypic and matched genotypic susceptibility of HIV-2 primary isolates from raltegravir-naïve and raltegravir-failing patients to raltegravir, dolutegravir, and bictegravir, and to the new spiro-β-lactam BSS-730A. The instantaneous inhibitory potential (IIP) was calculated to help predict the clinical activity of bictegravir and BSS-730A. Isolates from raltegravir-naïve patients were highly sensitive to all INIs and BSS-730A. Combined integrase mutations E92A and Q148K conferred high-level resistance to raltegravir, and E92Q and T97A conferred resistance to raltegravir and dolutegravir. The antiviral activity of bictegravir and BSS-730A was not affected by these mutations. BSS-730A displayed strong antiviral synergism with raltegravir. Mean IIP values at Cmax were similar for all INIs and were not significantly affected by resistance mutations. IIP values were significantly higher for BSS-730A than for INIs. The high IIP values of bictegravir and BSS-730A for raltegravir-naïve and raltegravir-resistant HIV-2 isolates highlight their potential value for treating HIV-2 infection. Overall, the results are consistent with the high clinical efficacy of raltegravir and dolutegravir for HIV-2 infection and suggest a promising clinical profile for bictegravir and BSS-730A.
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