337 research outputs found

    Biophysical, Biochemical, and Molecular Docking Investigations of Anti-Glycating, Antioxidant, and Protein Structural Stability Potential of Garlic.

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    Garlic has been reported to inhibit protein glycation, a process that underlies several disease processes, including chronic complications of diabetes mellitus. Biophysical, biochemical, and molecular docking investigations were conducted to assess anti-glycating, antioxidant, and protein structural protection activities of garlic. Results from spectral (UV and fluorescence) and circular dichroism (CD) analysis helped ascertain protein conformation and secondary structure protection against glycation to a significant extent. Further, garlic showed heat-induced protein denaturation inhibition activity (52.17%). It also inhibited glycation, advanced glycation end products (AGEs) formation as well as lent human serum albumin (HSA) protein structural stability, as revealed by reduction in browning intensity (65.23%), decrease in protein aggregation index (67.77%), and overall reduction in cross amyloid structure formation (33.26%) compared with positive controls (100%). The significant antioxidant nature of garlic was revealed by FRAP assay (58.23%) and DPPH assay (66.18%). Using molecular docking analysis, some of the important garlic metabolites were investigated for their interactions with the HSA molecule. Molecular docking analysis showed quercetin, a phenolic compound present in garlic, appears to be the most promising inhibitor of glucose interaction with the HSA molecule. Our findings show that garlic can prevent oxidative stress and glycation-induced biomolecular damage and that it can potentially be used in the treatment of several health conditions, including diabetes and other inflammatory diseases

    Deletion of the Ste20-like kinase SLK in skeletal muscle results in a progressive myopathy and muscle weakness

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    Background The Ste20-like kinase, SLK, plays an important role in cell proliferation and cytoskeletal remodeling. In fibroblasts, SLK has been shown to respond to FAK/Src signaling and regulate focal adhesion turnover through Paxillin phosphorylation. Full-length SLK has also been shown to be essential for embryonic development. In myoblasts, the overexpression of a dominant negative SLK is sufficient to block myoblast fusion. Methods In this study, we crossed the Myf5-Cre mouse model with our conditional SLK knockout model to delete SLK in skeletal muscle. A thorough analysis of skeletal muscle tissue was undertaken in order to identify defects in muscle development caused by the lack of SLK. Isometric force analysis was performed on adult knockout mice and compared to age-matched wild-type mice. Furthermore, cardiotoxin injections were performed followed by immunohistochemistry for myogenic markers to assess the efficiency muscle regeneration following SLK deletion. Results We show here that early deletion of SLK from the myogenic lineage does not markedly impair skeletal muscle development but delays the regenerative process. Interestingly, adult mice (~6 months) display an increase in the proportion of central nuclei and increased p38 activation. Furthermore, mice as young as 3 months old present with decreased force generation, suggesting that the loss of SLK impairs myofiber stability and function. Assessment of structural components revealed aberrant localization of focal adhesion proteins, such as FAK and paxillin. Our data show that the loss of SLK results in unstable myofibers resulting in a progressive myopathy. Additionally, the loss of SLK resulted in a delay in muscle regeneration following cardiotoxin injections. Conclusions Our results show that SLK is dispensable for muscle development and regeneration but is required for myofiber stability and optimal force generation

    Metabolomic Response of Calotropis procera Growing in the Desert to Changes in Water Availability

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    Water availability is a major limitation for agricultural productivity. Plants growing in severe arid climates such as deserts provide tools for studying plant growth and performance under extreme drought conditions. The perennial species Calotropis procera used in this study is a shrub growing in many arid areas which has an exceptional ability to adapt and be productive in severe arid conditions. We describe the results of studying the metabolomic response of wild C procera plants growing in the desert to a one time water supply. Leaves of C. procera plants were taken at three time points before and 1 hour, 6 hours and 12 hours after watering and subjected to a metabolomics and lipidomics analysis. Analysis of the data reveals that within one hour after watering C. procera has already responded on the metabolic level to the sudden water availability as evidenced by major changes such as increased levels of most amino acids, a decrease in sucrose, raffinose and maltitol, a decrease in storage lipids (triacylglycerols) and an increase in membrane lipids including photosynthetic membranes. These changes still prevail at the 6 hour time point after watering however 12 hours after watering the metabolomics data are essentially indistinguishable from the prewatering state thus demonstrating not only a rapid response to water availability but also a rapid response to loss of water. Taken together these data suggest that the ability of C. procera to survive under the very harsh drought conditions prevailing in the desert might be associated with its rapid adjustments to water availability and losses

    A simulated annealing based genetic local search algorithm for multi-objective multicast routing problems

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    This paper presents a new hybrid evolutionary algorithm to solve multi-objective multicast routing problems in telecommunication networks. The algorithm combines simulated annealing based strategies and a genetic local search, aiming at a more flexible and effective exploration and exploitation in the search space of the complex problem to find more non-dominated solutions in the Pareto Front. Due to the complex structure of the multicast tree, crossover and mutation operators have been specifically devised concerning the features and constraints in the problem. A new adaptive mutation probability based on simulated annealing is proposed in the hybrid algorithm to adaptively adjust the mutation rate according to the fitness of the new solution against the average quality of the current population during the evolution procedure. Two simulated annealing based search direction tuning strategies are applied to improve the efficiency and effectiveness of the hybrid evolutionary algorithm. Simulations have been carried out on some benchmark multi-objective multicast routing instances and a large amount of random networks with five real world objectives including cost, delay, link utilisations, average delay and delay variation in telecommunication networks. Experimental results demonstrate that both the simulated annealing based strategies and the genetic local search within the proposed multi-objective algorithm, compared with other multi-objective evolutionary algorithms, can efficiently identify high quality non-dominated solution set for multi-objective multicast routing problems and outperform other conventional multi-objective evolutionary algorithms in the literature

    Homo sapiens in Arabia by 85,000 years ago

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    Understanding the timing and character of Homo sapiens expansion out of Africa is critical for inferring the colonisation and admixture processes that underpin global population history. It has been argued that dispersal out of Africa had an early phase, particularly ~130-90 thousand years ago (ka), that only reached the East Mediterranean Levant, and a later phase, ~60-50 ka, that extended across the diverse environments of Eurasia to Sahul. However, recent findings from East Asia and Sahul challenge this model. Here we show that H. sapiens was in the Arabian Peninsula before 85 ka. We describe the Al Wusta-1 (AW-1) intermediate phalanx from the site of Al Wusta in the Nefud Desert, Saudi Arabia. AW-1 is the oldest directly dated fossil of our species outside Africa and the Levant. The palaeoenvironmental context of Al Wusta demonstrates that H. sapiens using Middle Palaeolithic stone tools dispersed into Arabia during a phase of increased precipitation driven by orbital forcing, in association with a primarily African fauna. A Bayesian model incorporating independent chronometric age estimates indicates a chronology for Al Wusta of ~95-86 ka, which we correlate with a humid episode in the later part of Marine Isotope Stage 5 known from various regional records. Al Wusta shows that early dispersals were more spatially and temporally extensive than previously thought. Early H. sapiens dispersals out of Africa were not limited to winter rainfall-fed Levantine Mediterranean woodlands immediately adjacent to Africa, but extended deep into the semi-arid grasslands of Arabia, facilitated by periods of enhanced monsoonal rainfall

    Corrosion behaviour of micro-plasma arc welded stainless steels in H3PO4 under flowing conditions at different temperatures

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    [EN] This paper studies the general corrosion behaviour of the micro-plasma arc welded AISI 316L stainless steel in phosphoric acid at different temperatures (25-60°C) and at a Reynolds number of 1456. Galvanic corrosion has been studied using zero-resistance ammeter (ZRA) measurements and polarization curves (by the mixed potential theory). Results show that the microstructure of the stainless steel is modified due to the micro-plasma arc welding procedure. Coupled current density values obtained from polarization curves increase with temperature. ZRA tests present the highest iG values at 60°C; however, the values are very close to zero for all the temperatures studied. This is in agreement with the low value of the compatibility limit and of the parameter which evaluates the importance of the galvanic phenomenon. Both techniques present the most positive potentials at the highest temperature. This study reveals that micro-plasma arc welded AISI 316L stainless steels are appropriated working in the studied H3PO4 media from a corrosion point of view for all the temperatures analysedThe authors would like to express their gratitude to the Spanish MAEC (PCI Mediterráneo C/8196/07, C/018046/08, D/023608/09) and to Asuncion Jaime for her translation assistance.Sánchez Tovar, R.; Montañés Sanjuan, MT.; García Antón, J.; Guenbour, A.; Ben Bachir, A. (2011). Corrosion behaviour of micro-plasma arc welded stainless steels in H3PO4 under flowing conditions at different temperatures. Corrosion Science. 53(4):1237-1246. https://doi.org/10.1016/j.corsci.2010.12.017S1237124653
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