Designs for a broad substrate specificity keto acid dehydrogenase

Variations have been made to the structure of the nicotinamide adenine dinucleotide (NAD) dependent L-lactate dehydrogenase from Bacillus stearothermophilus at regions of the enzyme that we believe determine specificity toward different alpha-hydroxy acids (RCHOHCOO-, R = CH3, C2H5, etc.). Two regions of LDH that border the active site (but are not involved in the catalytic reaction) were altered in order to accommodate substrates with hydrophobic side chains larger than that of the naturally preferred substrate, pyruvate (R = CH3). The mutations 102-105GlnLysPro----MetValSer and 236-237AlaAla----GlyGly were made to increase the tolerance for large hydrophobic substrate side chains. The triple and double mutants alone gave little improvement for branched-chain-substituted pyruvates. The five changes together produced a broader substrate specificity alpha-hydroxy acid dehydrogenase, with a 55-fold improved kcat for alpha-ketoisocaproate to a value about 1/14 that of the native enzyme for pyruvate. Rational protein engineering enabled coupled changes in enzyme structure to be obtained with greater probability of success than random mutagenesis.     

Evolutionary algorithms for solving multi-objective travelling salesman problem

This paper studies the application of evolutionary algorithms for bi-objective travelling salesman problem. Two evolutionary algorithms, including estimation of distribution algorithm (EDA) and genetic algorithm (GA), are considered. The solution to this problem is a set of trade-off alternatives. The problem is solved by optimizing the order of the cities so as to simultaneously minimize the two objectives of travelling distance and travelling cost incurred by the travelling salesman. In this paper, binary-representation-based evolutionary algorithms are replaced with an integer-representation. Three existing EDAs are altered to use this integer-representation, namely restricted Boltzmann machine (RBM), univariate marginal distribution algorithm (UMDA), and population-based incremental learning (PBIL). Each city is associated with a representative integer, and the probability of any of this representative integer to be located in any position of the chromosome is constructed through the modeling approach of the EDAs. New sequences of cities are obtained by sampling from the probabilistic model. A refinement operator and a local search operator are proposed in this piece of work. The EDAs are subsequently hybridized with GA in order to complement the limitations of both algorithms. The effect that each of these operators has on the quality of the solutions are investigated. Empirical results show that the hybrid algorithms are capable of finding a set of good trade-off solutions.     

Preoptic BRS3 neurons increase body temperature and heart rate via multiple pathways

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Free transplantation of venous network pattern skin flap

We report a patient treated by transplantation of a venous network pattern skin flap containing two superficial cutaneous veins. Through one of the veins, arterial blood passed into the capillaries, restoring circulation and ensuring survival of the flap.     

Bioaccumulation of selected metals in the gill,liver and muscle tissue of rednose labeo Labeo rosae from two impoundments on the Olifants River,Limpopo river system,South Africa

Metal concentrations in the gill, muscle and liver tissues of Labeo rosae from two impoundments, Loskop and Flag Boshielo dams on the Olifants River, were evaluated in 2011 to detect patterns in metal associations between tissues and impoundments. Elevated concentrations of Ba, Zn, B, Al, Si and Fe, relative to a pristine site in the catchment, were found in the muscle, liver and gill tissues at both impoundments. Molybdenum concentrations were exceptionally high in all tissues at Loskop Dam and in liver at Flag Boshielo Dam. No definite pattern in the ratio metal concentrations within, or between, fish tissues was identified. The expected trend, liver > gills > muscle, was found at both impoundments, but was less prominent at Loskop Dam. Metal concentrations in muscle of Loskop Dam fish were significantly higher than in those at Flag Boshielo Dam. The inverse was true for liver. The long-term impact of elevated metal concentrations on fish health at both impoundments raises concern.     

Aging‐induced Akt activation involves in aging‐related pathologies and Aβ‐induced toxicity

Multicellular signals are altered in the processes of both aging and neurodegenerative diseases, including Alzheimer's disease (AD). Similarities in behavioral and cellular functional changes suggest a common regulator between aging and AD that remains undetermined. Our genetics and behavioral approaches revealed the regulatory role of Akt in both aging and AD pathogenesis. In this study, we found that the activity of Akt is upregulated during aging through epidermal growth factor receptor activation by using the fruit fly as an in vivo model. Downregulation of Akt in neurons improved cell survival, locomotor activity, and starvation challenge in both aged and Aβ42‐expressing flies. Interestingly, increased cAMP levels attenuated both Akt activation‐induced early death and Aβ42‐induced learning deficit in flies. At the molecular level, overexpression of Akt promoted Notch cleavage, suggesting that Akt is an endogenous activity regulator of γ‐secretase. Taken together, this study revealed that Akt is involved in the aging process and Aβ toxicity, and manipulating Akt can restore both neuronal functions and improve behavioral activity during the processes of aging and AD pathogenesis.     

Free and total thyroid hormone levels after parenteral administration of iodine contrast media

An effect of the iodine contrast media used in bronchography and urography on both free and total thyroidal hormones was investigated. Hormones concentrations were assayed prior to and 7 and 30 days following an administration of the contrast. Iodine contrast media have no effect on T3, T4, free T3, and free T4 levels. Therefore, one may conclude that the administration of i.v. contrast media containing iodine does not significantly change the results of thyroid hormones assays does not affect an interpretation of the results.