Lack of Ach1 CoA-Transferase Triggers Apoptosis and Decreases Chronological Lifespan in Yeast

ACH1 encodes a mitochondrial enzyme of Saccharomyces cerevisiae endowed with CoA-transferase activity. It catalyzes the CoASH transfer from succinyl-CoA to acetate generating acetyl-CoA. It is known that ACH1 inactivation results in growth defects on media containing acetate as a sole carbon and energy source which are particularly severe at low pH. Here, we show that chronological aging ach1Δ cells which accumulate a high amount of extracellular acetic acid display a reduced chronological lifespan. The faster drop of cell survival is completely abrogated by alleviating the acid stress either by a calorie restricted regimen that prevents acetic acid production or by transferring chronologically aging mutant cells to water. Moreover, the short-lived phenotype of ach1Δ cells is accompanied by reactive oxygen species accumulation, severe mitochondrial damage, and an early insurgence of apoptosis. A similar pattern of endogenous severe oxidative stress is observed when ach1Δ cells are cultured using acetic acid as a carbon source under acidic conditions. On the whole, our data provide further evidence of the role of acetic acid as cell-extrinsic mediator of cell death during chronological aging and highlight a primary role of Ach1 enzymatic activity in acetic acid detoxification which is important for mitochondrial functionality

HUMYPHEMOL Biocomplex H

Study of effects of one heteropolymer of earthworms humus in complex with phenolic compounds of olive leaves (MOL) Micronized Olive Leaves on Olea Europaea-Ogliarola Salentina affected by Xylella fastidiosa. Vermicomposting differs from conventional composting because the organic material is processed by the digestive systems of worms in the Lumbricidae family. The experiment was designed with randomized ground treatments: (1) T1, Control (without modifying the soil); (2) T2, HM product (VERMICOMPOST WITH ADDED of polyphenols of European olea leaves MOL in variable ratios. In the DPPH test, the MOL has demostred an IC50 value of 0.18 mg / mL. Therefore, the use of the biocomplex H RICH IN BACTERIAL COMMUNITIES POSITIVELY INFLUENCES THE XYLEMATIC VASES, cancels the effect of water stress, consequently oxidative stress and blocking the advance of the xylella. The response is definetly positive. HUMYPHEMOL can act as preventive and as phytoterapeutic innovative method to treat olive trees infected by Xylella

Ethanol and Acetate Acting as Carbon/Energy Sources Negatively Affect Yeast Chronological Aging

In Saccharomyces cerevisiae, the chronological lifespan (CLS) is defined as the length of time that a population of nondividing cells can survive in stationary phase. In this phase, cells remain metabolically active, albeit at reduced levels, and responsive to environmental signals, thus simulating the postmitotic quiescent state of mammalian cells. Many studies on the main nutrient signaling pathways have uncovered the strong influence of growth conditions, including the composition of culture media, on CLS. In this context, two byproducts of yeast glucose fermentation, ethanol and acetic acid, have been proposed as extrinsic proaging factors. Here, we report that ethanol and acetic acid, at physiological levels released in the exhausted medium, both contribute to chronological aging. Moreover, this combined proaging effect is not due to a toxic environment created by their presence but is mainly mediated by the metabolic pathways required for their utilization as carbon/energy sources. In addition, measurements of key enzymatic activities of the glyoxylate cycle and gluconeogenesis, together with respiration assays performed in extreme calorie restriction, point to a long-term quiescent program favoured by glyoxylate/gluconeogenesis flux contrary to a proaging one based on the oxidative metabolism of ethanol/acetate via TCA and mitochondrial respiration

Transcriptional Profiling of ubp10 Null Mutant Reveals Altered Subtelomeric Gene Expression and Insurgence of Oxidative Stress Response

UBP10 codes for a deubiquitinating enzyme of Saccharomyces cerevisiae whose loss of function determines slow growth rate and partial impairment of silencing at telomeres and HM loci. A genome-wide analysis performed on a ubp10 disruptant revealed alterations in expression of subtelomeric genes together with a broad change in the whole transcriptional profile, closely parallel to that induced by oxidative stress. This response was accompanied by intracellular accumulation of reactive oxygen species as well as by DNA fragmentation and phosphatidylserine externalization, two markers of apoptosis. SIR4 inactivation mitigated the wide transcriptome remodeling of the ubp10 null mutant affecting particularly the stress transcriptional profile. Moreover, the ubp10sir4 disruptant did not display apoptotic markers. These results argue in favor of an involvement of deubiquitination in transcriptional control and suggest a linkage between oxidative stress and apoptotic pathway in budding yeast

Altered Expression of Mitochondrial NAD+ Carriers Influences Yeast Chronological Lifespan by Modulating Cytosolic and Mitochondrial Metabolism

Nicotinamide adenine dinucleotide (NAD+) represents an essential cofactor in sustaining cellular bioenergetics and maintaining cellular fitness, and has emerged as a therapeutic target to counteract aging and age-related diseases. Besides NAD+ involvement in multiple redox reactions, it is also required as co-substrate for the activity of Sirtuins, a family of evolutionary conserved NAD+-dependent deacetylases that regulate both metabolism and aging. The founding member of this family is Sir2 of Saccharomyces cerevisiae, a well-established model system for studying aging of post-mitotic mammalian cells. In this context, it refers to chronological aging, in which the chronological lifespan (CLS) is measured. In this paper, we investigated the effects of changes in the cellular content of NAD+ on CLS by altering the expression of mitochondrial NAD+ carriers, namely Ndt1 and Ndt2. We found that the deletion or overexpression of these carriers alters the intracellular levels of NAD+ with opposite outcomes on CLS. In particular, lack of both carriers decreases NAD+ content and extends CLS, whereas NDT1 overexpression increases NAD+ content and reduces CLS. This correlates with opposite cytosolic and mitochondrial metabolic assets shown by the two types of mutants. In the former, an increase in the efficiency of oxidative phosphorylation is observed together with an enhancement of a pro-longevity anabolic metabolism toward gluconeogenesis and trehalose storage. On the contrary, NDT1 overexpression brings about on the one hand, a decrease in the respiratory efficiency generating harmful superoxide anions, and on the other, a decrease in gluconeogenesis and trehalose stores: all this is reflected into a time-dependent loss of mitochondrial functionality during chronological aging

Full-wave EMC Simulations Using Maxwell Garnett Model For Composites With Cylindrical Inclusions

Four different models for effective dielectric properties of biphasic composite containing random or aligned cylindrical inclusions are considered in this paper. These models are based on the Maxwell Garnett (MG) mixing rule. The effects of distribution and orientation of cylindrical inclusions in a composite material is studied. An equivalent averaged material with Debye-like frequency characteristics, suitable for time-domain full-wave numerical electromagnetic simulations is retrieved. This Debye model is derived from the Maxwell Garnett formulation. The numerical model test structure consists of a composite slab inserted in a rectangular waveguide. Simulations are run for the frequency range above the cut-off frequency of the fundamental mode TE10. The differences between the proposed models are quantified using the Feature Selection Validation (FSV) tool. The comparison of the models provides an insight on the effect of inclusion orientation and distribution. © 2011 IEEE

Reconstruction of the Parameters of Debye and Lorentzian Dispersive Media using a Genetic Algorithm

A method for reconstruction of the parameters of the Debye or Lorentzian dispersive media is proposed. In this method, S-parameters of a simple parallel-plate fixture filled with the dispersive medium are measured and modeled using the transmission line equations, provided a single TEM mode propagating in this parallel-plate waveguide. The genetic algorithm is used for searching the parameters of the dispersive medium by means of minimizing the discrepancy between the measured and modeled S-parameters. The results are verified using the full-wave FDTD modeling technique

Extracting R, L, G, C Parameters of Dispersive Planar Transmission Lines from Measured S-Parameters using a Genetic Algorithm

Signal integrity (SI) analysis of printed circuit boards for high-speed digital design requires information on the perunit-length R, L, G, C parameters of the transmission lines. However, these are not always available when the property of the dielectric medium used in the board is unknown. A method to extract R, L, G, and C parameters from parallel-plate and strip transmission line geometries is proposed. It is based on measured scattering parameters and analytical modeling. A genetic algorithm (GA) is used to optimize the extraction by minimizing the frequency domain discrepancy between an objective function, which is the measured scattering matrix parameter, |S21|, and a GA model based on transmission line theory. The extracted R, L, G, and C parameters are then used in a SPICE model for simulation. Good agreement has been achieved in the reported results

Retinoids and cancer: antitumoral effects of ATRA, 9-cis RA and the new retinoid IIF on the HL-60 leukemic cell line.

Objective: To compare the antitumoral effects of all-trans retinoic acid (ATRA) and 9-cis retinoic acid (9-cis RA) with those of 5-OH,11-O-hydrophenanthrene (IIF), a new derivative of retinoic acid. Materials and Methods: The effect of retinoids was tested on cell line HL-60. Cell differentiation and apoptosis were evaluated by morphological and biochemical analysis as bcl-2 protein and by DNA fragmentation assay. The ability to activate retinoic acid receptors (RAR) and/or retinoid X receptors (RXR) and to modulate gene expression was determined by transactivation assay. Results: With cell line HL-60, the antiproliferative effect of IIF was stronger than that of ATRA and 9-cis RA. Following retinoid treatment, cells appeared to differentiate and apoptotic cells were observed. The appearance of DNA laddering and a decrease in the amount of bcl-2 protein confirmed apoptosis. IIF transcriptionally activated RXR-γ more than RAR-α. Conclusion: The findings indicate that IIF transcriptionally activates RXR-γ preferentially, induces apoptosis and has a more antiproliferative activity than ATRA and 9-cis RA on cell line HL-60