mTOR Complex 1 Content and Regulation Is Adapted to Animal Longevity

Decreased content and activity of the mechanistic target of rapamycin (mTOR) signalling pathway, as well as the mTOR complex 1 (mTORC1) itself, are key traits for animal species and human longevity. Since mTORC1 acts as a master regulator of intracellular metabolism, it is responsible, at least in part, for the longevous phenotype. Conversely, increased content and activity of mTOR signalling and mTORC1 are hallmarks of ageing. Additionally, constitutive and aberrant activity of mTORC1 is also found in age-related diseases such as Alzheimer’s disease (AD) and cancer. The downstream processes regulated through this network are diverse, and depend upon nutrient availability. Hence, multiple nutritional strategies capable of regulating mTORC1 activity and, consequently, delaying the ageing process and the development of age-related diseases, are under continuous study. Among these, the restriction of calories is still the most studied and robust intervention capable of downregulating mTOR signalling and feasible for application in the human population.     

Unexpected Reaction of 2,2′‐Bipyridyl‐cycloocta‐1,5‐diene‐nickel(0) with Acetone and Dioxygen

The reaction of (bipy)Ni(cod) ( 1 ) (bipy = 2,2′‐bipyridyl, cod = cycloocta‐1,5‐diene) with dioxygen and acetone at −20°C affords (bipy)Ni(C₉H₁₆O₃) ( 2 ) (C₉H₁₆O₃^2— = 2,4,6,6‐tetramethyl‐tetrahydropyran‐2,4‐diolate), which has been characterized by NMR, MS and an X‐ray crystal structure determination. Acidolysis of compound 2 with two equivalents of acetyl acetone (Hacac) yields (bipy)Ni(acac)₂ and C₉H₁₈O₃ ( 3 ) (2,4,6,6‐tetramethyl‐tetrahydropyran‐2,4‐diol), a cyclic trimer of acetone.     

A novel immersed boundary/Fourier pseudospectral method for flows with thermal effects

ABSTRACT

A novel immersed boundary method (IBM) for flows with thermal effects is proposed, combining high accuracy and low computational cost, provided by the Fourier pseudospectral method (FPSM), for the possibility of handling complex and nonperiodical geometries using the IBM. With focus on incompressible flow problems modeled by Navier-Stokes, mass, and energy equations, the method of manufactured solutions is used for the numerical verification of Dirichlet boundary conditions imposed via the IBM. Then, the proposed method is applied on two different 2-D cases: (1) energy transfer due to natural convection in a square cavity, and (2) an annulus between horizontal concentric cylinders nonuniformly heated. Good agreement with available data in the literature has been achieved.     

Reinvestigation of the synthesis of phenylcalcium iodide and the first structural characterization of a heavy Grignard reagent as [((thf)2CaPhI)3 · (thf)CaO] with a central Ca4 tetrahedron

Phenylcalcium iodide is accessible by direct synthesis from activated calcium and iodobenzene in THF at low temperatures. The use of chloro- or bromobenzene as well as of another solvent such as diethylether lowers the yield significantly. Phenylcalcium iodide cleaves THF already at −20 °C under formation of benzene. From this reaction solution single crystals of the title compound precipitate. The central structural fragment consists of a distorted calcium tetrahedron, centered by an oxygen atom and with Ca atoms being bridged by phenyl groups (average Ca–C 257 pm) and iodide ligands.     

Speech outcome and maxillary growth in patients with unilateral complete cleft lip/palate operated on at 6 versus 12 months of age

A prospective study of speech outcome and maxillofacial growth was carried out in cleft palate patients. Seventy-six cleft palate patients were randomly selected for the study group; 41 patients were operated on at 12 months of age, and 35 patients were operated on at 6 months of age. All patients were followed until they were 4 years of age. All patients underwent a complete speech evaluation, videonasopharyngoscopy, videofluoroscopy, and maxillofacial assessment. The rate of velopharyngeal insufficiency did not differ between the two groups (17 to 19 percent; p > 0.05). However, phonologic development was significantly better (p < 0.05) in the patients operated on at 6 months of age. Furthermore, none of the patients operated on at 6 months of age showed compensatory articulation disorder. In contrast, 62 percent of the patients with postoperative velopharyngeal insufficiency operated on at 12 months of age showed compensatory articulation disorder (p < 0.05). Maxillofacial assessment showed that there were non-significant differences (p > 0.05) in maxillofacial growth in both groups of patients. All patients showed similar degrees of maxillary collapse (p > 0.05). The results of this study suggest that cleft palate repair performed at 6 months of age significantly enhances speech outcome and prevents compensatory articulation disorder.     

Effect of dietary vitamin E levels on fatty acid profiles and nonenzymatic lipid peroxidation in the guinea pig liver

Guinea pigs were fed for five weeks with three diets containing different levels of vitamin E: LOW (but nondeficient, 15 mg of vitamin E/kg diet), MEDIUM (150 mg/kg diet), and HIGH (1,500 mg/kg diet). Dietary vitamin E supplementation did not change oxidative stress indicators in the hydrophilic compartment but increased liver α-tocopherol in a dose-dependent way and strongly decreased sensitivity to nonenzymaticin vitro liver lipid peroxidation. This last effect was already observed in group MEDIUM, and no further decrease inin vitro lipid peroxidation occurred from group MEDIUM to group HIGH. The protective effect of vitamin E againstin vitro lipid peroxidation was observed even though an optimum dietary concentration of vitamin C for this animal model was present in the three different vitamin E diets. Both HIGH and LOW vitamin E decreased percentage fatty acid unsaturation in all phospholipid fractions from membrane origin in relation to group MEDIUM. The results, together with previous information, show that both vitamin E and vitamin C at intermediate concentrations are needed for optimal protection against lipid peroxidation and loss of fatty acid unsaturation even in normal nonstressful conditions. These protective concentrations are higher than those needed to avoid deficiency syndromes.     

Correlation of fatty acid unsaturation of the major liver mitochondrial phospholipid classes in mammals to their maximum life span potential

Free radical damage is considered a determinant factor in the rate of aging. Unsaturated fatty acids are the tissue macromolecules that are most sensitive to oxidative damage. Therefore, the presence of low proportions of fatty acid unsaturation is expected in the tissues of long-lived animals. Accordingly, the fatty acid compositions of the major liver mitochondrial phospholipid classes from eight mammals, ranging in maximum life span potential (MLSP) from 3.5 to 46 yr, show that the total number of double bonds is inversely correlated with MLSP in both phosphatidylcholine (PtdCho) and phosphatidylethanolamine (PtdEtn) (r = 0.757, P < 0.03, and r = 0.862, P < 0.006, respectively), but not in cardiolipin (P = 0.323). This is due not to a low content of unsaturated fatty acids in long-lived animals, but mainly to a redistribution between kinds of fatty acids on PtdCho and PtdEtn, shifting from arachidonic (r = 0.911, P < 0.002, and r = 0.681, P = 0.05, respectively), docosahexaenoic (r = 0.931 and r = 0.965, P < 0.0001, respectively) and palmitic (r = 0.944 and r = 0.974, P < 0.0001, respectively) acids to linoleic acid (r = 0.942, P < 0.0001, for PtdCho; and r = 0.957, P < 0.0001, for PtdEtn). For cardiolipin, only arachidonic acid showed a significantly inverse correlation with MLSP (r = 0.904, P < 0.002). This pattern strongly suggests the presence of a species-specific desaturation pathway and deacylation-reacylation cycle in determining the mitochondrial membrane composition, maintaining a low degree of fatty acid unsaturation in long-lived animals.