This study?s primary purpose is to optimize the multistage refrigeration system with statistical methods. Taguchi optimization and ANOVA methods were applied to statistically determine the effects of ...components on system performance. The best operational conditions were defined for the maximum COP and exergy efficiency. Critical parameters have been determined to maximize the system?s performance. The evaporator temperature was defined as the most vital parameter (46.32%), and it is followed by condenser temperature (32.65%) for the maximum COP. The most important two parameters are determined as evaporator temperature with 29.14% and condenser temperature with 20.34% for maximum exergetic performance. As a result of 27 tests, the highest COP of the system was calculated as 2.67 and exergy efficiency as 55.22%. By using the optimum levels determined by Taguchi, it was ensured that the system?s COP was increased to 3.326 and its exergy efficiency to 71.23%. The ANOVA analyses indicate that the results? confidence level is relatively high, to be 99.9%. Another parameter examined in this study is the inter-stage level determination method and its effect on system performance. The method of determining the optimum inter-stage level may vary according to the objective function and system conditions.
Protein structure and function can be regulated via post-translational modifications by numerous enzymatic and nonenzymatic mechanisms. Regulation involving oxidation of sulfur-containing residues ...emerged as a key mechanism of redox control. Unraveling the participants and principles of such regulation is necessary for understanding the biological significance of redox control of cellular processes.
Reversible oxidation of methionine residues by monooxygenases of the Mical family and subsequent reduction of methionine sulfoxides by a selenocysteine-containing methionine sulfoxide reductase B1 (MsrB1) was found to control the assembly and disassembly of actin in mammals, and the Mical/MsrB pair similarly regulates actin in fruit flies. This finding has opened up new avenues for understanding the use of stereospecific methionine oxidation in regulating cellular processes and the roles of MsrB1 and Micals in regulation of actin dynamics.
So far, Micals have been the only known partners of MsrB1, and actin is the only target. It is important to identify additional substrates of Micals and characterize other Mical-like enzymes.
Oxidation of methionine, reviewed here, is an emerging but not well-established mechanism. Studies suggest that methionine oxidation is a form of oxidative damage of proteins, a modification that alters protein structure or function, a tool in redox signaling, and a mechanism that controls protein function. Understanding the functional impact of reversible oxidation of methionine will require identification of targets, substrates, and regulators of Micals and Msrs. Linking the biological processes, in which these proteins participate, might also lead to insights into disease conditions, which involve regulation of actin by Micals and Msrs.
Methionine restriction and life-span control Lee, Byung Cheon; Kaya, Alaattin; Gladyshev , Vadim N.
Annals of the New York Academy of Sciences,
January 2016, Volume:
1363, Issue:
1
Journal Article
Peer reviewed
Open access
Dietary restriction (DR) without malnutrition is associated with longevity in various organisms. However, it has also been shown that reduced calorie intake is often ineffective in extending life ...span. Selecting optimal dietary regimens for DR studies is complicated, as the same regimen may lead to different outcomes depending on genotype and environmental factors. Recent studies suggested that interventions such as moderate protein restriction with or without adequate nutrition (e.g., particular amino acids or carbohydrates) may have additional beneficial effects mediated by certain metabolic and hormonal factors implicated in the biology of aging, regardless of total calorie intake. In particular, it was shown that restriction of a single amino acid, methionine, can mimic the effects of DR and extend life span in various model organisms. We discuss the beneficial effects of a methionine‐restricted diet, the molecular pathways involved, and the use of this regimen in longevity interventions.
Reduced methionine (Met) intake can extend lifespan of rodents; however, whether this regimen represents a general strategy for regulating aging has been controversial. Here we report that Met ...restriction extends lifespan in both fruit flies and yeast, and that this effect requires low amino-acid status. Met restriction in Drosophila mimicks the effect of dietary restriction and is associated with decreased reproduction. However, under conditions of high amino-acid status, Met restriction is ineffective and the trade-off between longevity and reproduction is not observed. Overexpression of InRDN or Tsc2 inhibits lifespan extension by Met restriction, suggesting the role of TOR signalling in the Met control of longevity. Overall, this study defines the specific roles of Met and amino-acid imbalance in aging and suggests that Met restiction is a general strategy for lifespan extension.
Alteration of normal ploidy (aneuploidy) can have a number of opposing effects, such as unbalancing protein abundances and inhibiting cell growth but also accelerating genetic diversification and ...rapid adaptation. The interplay of these detrimental and beneficial effects remains puzzling. Here, to understand how cells develop tolerance to aneuploidy, we subject disomic (i.e. with an extra chromosome copy) strains of yeast to long-term experimental evolution under strong selection, by forcing disomy maintenance and daily population dilution. We characterize mutations, karyotype alterations and gene expression changes, and dissect the associated molecular strategies. Cells with different extra chromosomes accumulated mutations at distinct rates and displayed diverse adaptive events. They tended to evolve towards normal ploidy through chromosomal DNA loss and gene expression changes. We identify genes with recurrent mutations and altered expression in multiple lines, revealing a variant that improves growth under genotoxic stresses. These findings support rapid evolvability of disomic strains that can be used to characterize fitness effects of mutations under different stress conditions.
Cetaceans (whales, dolphins, and porpoises) are a group of mammals adapted to various aquatic habitats, from oceans to freshwater rivers. We report the sequencing, de novo assembly and analysis of a ...finless porpoise genome, and the re-sequencing of an additional 48 finless porpoise individuals. We use these data to reconstruct the demographic history of finless porpoises from their origin to the occupation into the Yangtze River. Analyses of selection between marine and freshwater porpoises identify genes associated with renal water homeostasis and urea cycle, such as urea transporter 2 and angiotensin I-converting enzyme 2, which are likely adaptations associated with the difference in osmotic stress between ocean and rivers. Our results strongly suggest that the critically endangered Yangtze finless porpoises are reproductively isolated from other porpoise populations and harbor unique genetic adaptations, supporting that they should be considered a unique incipient species.
•TOPSIS analysis was applied to decide the refrigerants with enviroeconomic concerns.•Advanced exergy analysis along with Taguchi optimization was considered.•R513a, R134a, and R448a were determined ...as the best refrigerants.•Optimum parameters for high exergetic performance were calculated as A2B3C1D3E3F1.•Compressor efficiency, evaporator were the most effective for avoidable destruction.•Evaporator temperature was the most effective parameter on the performance.
In this study, TOPSIS analysis was applied to decide the optimum refrigerants with cost, safety, environmental and enviroeconomic concerns along with thermophysical properties. A vapor compression refrigeration cycle performance was investigated with the statistical and thermodynamic approaches. COP, exergy efficiency, total, avoidable, and unavoidable exergy destruction rates were calculated for various experimental designs. According to the relative proximity to the ideal solution, the best refrigerants for the system were determined as R513a, R134a, and R448a, respectively. The optimum parameters for the greatest COP and exergetic performance were calculated as A2B3C1D3E3F1. In the optimum case, the best COP and exergy efficiency of 2.65 and 10% and the lowest total exergy destruction of 0.34 kW were achieved for R134a. These are larger than all other 27 experimental patterns. The parameters having an impact on the COP, exergy efficiency, and total exergy destruction rate were found as TEVA > TCON > Refrigerant > ηCOM,H > ηCOM,L > Pin (B > C > A > E > D > F). The evaporator temperature is the most effective parameter on the performance with about 42.8% for the performance. It is followed by that of condenser and refrigerant to be 32.5% and 13.8%. The most effective parameters for the avoidable exergy destruction rate were high- and low-pressure compressors efficiencies, evaporator temperature, and condenser temperature, respectively.
To understand the genetic basis and selective forces acting on longevity, it is useful to examine lifespan variation among closely related species, or ecologically diverse isolates of the same ...species, within a controlled environment. In particular, this approach may lead to understanding mechanisms underlying natural variation in lifespan. Here, we analyzed 76 ecologically diverse wild yeast isolates and discovered a wide diversity of replicative lifespan (RLS). Phylogenetic analyses pointed to genes and environmental factors that strongly interact to modulate the observed aging patterns. We then identified genetic networks causally associated with natural variation in RLS across wild yeast isolates, as well as genes, metabolites, and pathways, many of which have never been associated with yeast lifespan in laboratory settings. In addition, a combined analysis of lifespan-associated metabolic and transcriptomic changes revealed unique adaptations to interconnected amino acid biosynthesis, glutamate metabolism, and mitochondrial function in long-lived strains. Overall, our multiomic and lifespan analyses across diverse isolates of the same species shows how gene-environment interactions shape cellular processes involved in phenotypic variation such as lifespan.
Aerobic respiration is a fundamental energy-generating process; however, there is cost associated with living in an oxygen-rich environment, because partially reduced oxygen species can damage ...cellular components. Organisms evolved enzymes that alleviate this damage and protect the intracellular milieu, most notably thiol peroxidases, which are abundant and conserved enzymes that mediate hydrogen peroxide signaling and act as the first line of defense against oxidants in nearly all living organisms. Deletion of all eight thiol peroxidase genes in yeast (Δ8 strain) is not lethal, but results in slow growth and a high mutation rate. Here we characterized mechanisms that allow yeast cells to survive under conditions of thiol peroxidase deficiency. Two independent Δ8 strains increased mitochondrial content, altered mitochondrial distribution, and became dependent on respiration for growth but they were not hypersensitive to H₂O₂. In addition, both strains independently acquired a second copy of chromosome XI and increased expression of genes encoded by it. Survival of Δ8 cells was dependent on mitochondrial cytochrome-c peroxidase (CCP1) andUTH1, present on chromosome XI. Coexpression of these genes in Δ8 cells led to the elimination of the extra copy of chromosome XI and improved cell growth, whereas deletion of either gene was lethal. Thus, thiol peroxidase deficiency requires dosage compensation ofCCP1andUTH1via chromosome XI aneuploidy, wherein these proteins support hydroperoxide removal with the reducing equivalents generated by the electron transport chain. To our knowledge, this is the first evidence of adaptive aneuploidy counteracting oxidative stress.
Reduction of methionine sulfoxide (MetO) residues in proteins is catalyzed by methionine sulfoxide reductases A (MSRA) and B (MSRB), which act in a stereospecific manner. Catalytic properties of ...these enzymes were previously established mostly using low molecular weight MetO-containing compounds, whereas little is known about the catalysis of MetO reduction in proteins, the physiological substrates of MSRA and MSRB. In this work we exploited an NADPH-dependent thioredoxin system and determined the kinetic parameters of yeast MSRA and MSRB using three different MetO-containing proteins. Both enzymes showed Michaelis-Menten kinetics with the Km lower for protein than for small MetO-containing substrates. MSRA reduced both oxidized proteins and low molecular weight MetO-containing compounds with similar catalytic efficiencies, whereas MSRB was specialized for the reduction of MetO in proteins. Using oxidized glutathione S-transferase as a model substrate, we showed that both MSR types were more efficient in reducing MetO in unfolded than in folded proteins and that their activities increased with the unfolding state. Biochemical quantification and identification of MetO reduced in the substrates by mass spectrometry revealed that the increased activity was due to better access to oxidized MetO in unfolded proteins; it also showed that MSRA was intrinsically more active with unfolded proteins regardless of MetO availability. Moreover, MSRs most efficiently protected cells from oxidative stress that was accompanied by protein unfolding. Overall, this study indicates that MSRs serve a critical function in the folding process by repairing oxidatively damaged nascent polypeptides and unfolded proteins.
Background: Methionine sulfoxide reductases have previously been studied mostly using low molecular weight substrates.
Results: Methionine sulfoxide reductases preferentially reduce unfolded oxidized proteins.
Conclusion: These enzymes serve a critical function in protein folding by repairing oxidized nascent polypeptides and unfolded proteins.
Significance: Understanding precise functions of methionine sulfoxide reductases will help define mechanisms of protein repair and identify their physiological substrates.
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