Enhanced Longevity by Ibuprofen, Conserved in Multiple Species, Occurs in Yeast through Inhibition of Tryptophan Import

The common non-steroidal anti-inflammatory drug ibuprofen has been associated with a reduced risk of some age-related pathologies. However, a general pro-longevity role for ibuprofen and its mechanistic basis remains unclear. Here we show that ibuprofen increased the lifespan of Saccharomyces cerevisiae, Caenorhabditis elegans and Drosophila melanogaster, indicative of conserved eukaryotic longevity effects. Studies in yeast indicate that ibuprofen destabilizes the Tat2p permease and inhibits tryptophan uptake. Loss of Tat2p increased replicative lifespan (RLS), but ibuprofen did not increase RLS when Tat2p was stabilized or in an already long-lived strain background impaired for aromatic amino acid uptake. Concomitant with lifespan extension, ibuprofen moderately reduced cell size at birth, leading to a delay in the G1 phase of the cell cycle. Similar changes in cell cycle progression were evident in a large dataset of replicatively long-lived yeast deletion strains. These results point to fundamental cell cycle signatures linked with longevity, implicate aromatic amino acid import in aging and identify a largely safe drug that extends lifespan across different kingdoms of life.The open access fee for this work was funded through the Texas A&M University Open Access to Knowledge (OAK) Fund

Repair strategy for housing stock engineering systems to improve energy efficiency

The article discusses problems of current interest concerning the housing and utility sector associated with increasing the level of comfort of living by constantly improving measures for carrying out planned and un-scheduled repairs and surveys. This work provides a methodology for justi-fying the choice of a repair strategy for engineering systems of water sup-ply and sewerage in the process of operating the housing stock, the imple-mentation of which will contribute to the timely and rational repairs and inspections of buildings engineering systems. This will allow systematical-ly eliminating engineering systems malfunctions, predicting and planning the optimal quantity and chronology of repair and restoration activities by maintaining the technical condition of the engineering system elements within the permissible limits during the standard service life.The main goal of the research in the presented material is to substantiate the methodology for choosing a repair strategy for water supply and sewerage systems dur-ing the operation of apartment buildings.The optimal periodicity for the re-pair of engineering systems depends on the failure rate of elements and the costs associated with the execution of all operational activities.Three op-tions considered for organizing repairs of engineering equipment.Applied in actual practice the technique of choosing the repair strategy of engineer-ing systems for selecting the optimal option to organize repairs of engi-neering equipment

Long-term eustatic cyclicity in the Paleogene: a critical assessment

Global sea level has changed cyclically throughout Earth's history due to a variety of mechanisms that operate on a variety of timescales. Here we attempt to place constraints on the “actual” number of sea-level cycles that can be interpreted directly from the eustatic reconstructions. We apply an interpretative algorithm to Paleogene sea level records and identify three orders of eustatic cycles longer than 1 Ma. However, the three-ordered cyclicity might not represent cycles of global eustatic change. First, only cycles of the highest of the established orders (with a timescale of 10 s of Ma) are coherent among different sea-level records. Second, the interpreted cycles are not supported by the compilation of the regional maximum flooding surfaces. Third, climatic history alone cannot explain the eustatic changes. Fourth, the interpreted cyclicity differs significantly from what is known about the tectonic control of eustasy. Fifth, there may be other orders higher than those established. The problem is rooted in (1) the fact that eustatic curves might not necessarily reflect global events (e.g., fluctuations shown on these curves may be artifacts related to regional tectonic activity) and (2) the possible weakness of Paleogene (especially Eocene) eustatic cyclicity and its significant “overprint” by regional tectonic activity. Our attempted analysis claims for significant improvement of the available eustatic reconstructions. Unfortunately, the regional stratigraphical data remain still insufficient to develop any alternative eustatic curve that can be further interpreted to understand the number of “actual” cycle orders

Mining gene expression data for pollutants (dioxin, toluene, formaldehyde) and low dose of gamma-irradiation.

General and specific effects of molecular genetic responses to adverse environmental factors are not well understood. This study examines genome-wide gene expression profiles of Drosophila melanogaster in response to ionizing radiation, formaldehyde, toluene, and 2,3,7,8-tetrachlorodibenzo-p-dioxin. We performed RNA-seq analysis on 25,415 transcripts to measure the change in gene expression in males and females separately. An analysis of the genes unique to each treatment yielded a list of genes as a gene expression signature. In the case of radiation exposure, both sexes exhibited a reproducible increase in their expression of the transcription factors sugarbabe and tramtrack. The influence of dioxin up-regulated metabolic genes, such as anachronism, CG16727, and several genes with unknown function. Toluene activated a gene involved in the response to the toxins, Cyp12d1-p; the transcription factor Fer3's gene; the metabolic genes CG2065, CG30427, and CG34447; and the genes Spn28Da and Spn3, which are responsible for reproduction and immunity. All significantly differentially expressed genes, including those shared among the stressors, can be divided into gene groups using Gene Ontology Biological Process identifiers. These gene groups are related to defense response, biological regulation, the cell cycle, metabolic process, and circadian rhythms. KEGG molecular pathway analysis revealed alteration of the Notch signaling pathway, TGF-beta signaling pathway, proteasome, basal transcription factors, nucleotide excision repair, Jak-STAT signaling pathway, circadian rhythm, Hippo signaling pathway, mTOR signaling pathway, ribosome, mismatch repair, RNA polymerase, mRNA surveillance pathway, Hedgehog signaling pathway, and DNA replication genes. Females and, to a lesser extent, males actively metabolize xenobiotics by the action of cytochrome P450 when under the influence of dioxin and toluene. Finally, in this work we obtained gene expression signatures pollutants (dioxin, toluene), low dose of gamma-irradiation and common molecular pathways for different kind of stressors

The differentially expressed genes in <i>Drosophila melanogaster</i> males and females after the radiation exposure.

<p>A– 5 cGy, B– 10 cGy, C– 20 cGy, D– 40 cGy, 1 –males, 2 –females. Only gene changes with Log₂FC > 1 and p-value < 0.05 during at least one time range are presented.</p

Effect of Low Doses (5-40 cGy) of Gamma-irradiation on Lifespan and Stress-related Genes Expression Profile in <i>Drosophila melanogaster</i>

<div><p>Studying of the effects of low doses of γ-irradiation is a crucial issue in different areas of interest, from environmental safety and industrial monitoring to aerospace and medicine. The goal of this work is to identify changes of lifespan and expression stress-sensitive genes in <i>Drosophila melanogaster</i>, exposed to low doses of γ-irradiation (5 – 40 cGy) on the imaginal stage of development. Although some changes in life extensity in males were identified (the effect of hormesis after the exposure to 5, 10 and 40 cGy) as well as in females (the effect of hormesis after the exposure to 5 and 40 cGy), they were not caused by the organism “physiological” changes. This means that the observed changes in life expectancy are not related to the changes of organism physiological functions after the exposure to low doses of ionizing radiation. The identified changes in gene expression are not dose-dependent, there is not any proportionality between dose and its impact on expression. These results reflect nonlinear effects of low dose radiation and sex-specific radio-resistance of the postmitotic cell state of <i>Drosophila melanogaster </i>imago.</p></div

The genes selected for expression analysis in the samples of <i>Drosophila melanogaster</i> wild-type strain <i>Canton-S</i> 72 hours after radiation exposure in doses from 5 cGy to 40 cGy.

<p>The genes selected for expression analysis in the samples of <i>Drosophila melanogaster</i> wild-type strain <i>Canton-S</i> 72 hours after radiation exposure in doses from 5 cGy to 40 cGy.</p

Influence of low doses of γ-irradiation on the lifespan of <i>Drosophila melanogaster</i>, wild-type line <i>Canton-S</i>.

<p>A–males, B–females, *—p<0.05, **—p<0.01, (Kolmogorov-Smirnov test).</p

Strehler-Mildvan correlation between the parameters of the Gompertz function in <i>Drosophila melanogaster</i> wild-type <i>Canton-S</i> individuals exposed to low doses of ionizing radiation.

<p>Strehler-Mildvan correlation between the parameters of the Gompertz function in <i>Drosophila melanogaster</i> wild-type <i>Canton-S</i> individuals exposed to low doses of ionizing radiation.</p