60 research outputs found

    Regulating retirement savings: An evolutionary psychology approach

    Get PDF
    Individuals make costly systematic investment mistakes in their retirement savings planning, such as investing in the wrong assets and under-diversifying their portfolios. Behavioral economists suggest that people make these mistakes because they rely on heuristics and have certain biases in their thinking. However, they have yet to develop a unifying theory as to why people have these biases and rely on heuristics. In this book, I develop and test the theory that this investment behavior results from traits that evolved to help our distant ancestors survive and reproduce. I describe why it is important to understand the evolutionary history of our brains in order to understand why we may not be very good at solving retirement savings problems. In the first substantive chapter, chapter 2, I apply evolutionary psychology to explain one of the mistakes that individuals have been shown to make in their retirement planning – the mistake of under-diversifying their portfolios. While the chapter is focused on explaining when and why individuals may under-diversify their stock portfolios, the theoretical discussion on evolutionary psychology theories in the chapter can explain why and when individuals will make other seemingly sub-optimal decisions relating to their retirement planning. In chapter 3, I report on an online experiment testing the hypothesis that males for whom mate-seeking is made salient under-diversify their stock portfolios more than other males. The results of the experiment support this hypothesis. Regret is an emotion that evolved to help humans learn from their mistakes, which enhanced their survival and rates of reproduction. I hypothesize in chapter 4 that people make retirement savings decisions in such a way as to minimize regret. I also explain in that chapter why regret may explain why defaults work so well in the retirement savings domain – people follow defaults because it is a regret reducing strategy. Chapter 5 reports on an experiment that tests the hypothesis that regret may explain why defaults and communicating preferences of peers are so effective in changing behavior. The results of the experiment support this hypothesis

    Temporal transcriptomic analysis of the Listeria monocytogenes EGD-e σB regulon

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>The opportunistic food-borne gram-positive pathogen <it>Listeria monocytogenes </it>can exist as a free-living microorganism in the environment and grow in the cytoplasm of vertebrate and invertebrate cells following infection. The general stress response, controlled by the alternative sigma factor, σ<sup>B</sup>, has an important role for bacterial survival both in the environment and during infection. We used quantitative real-time PCR analysis and immuno-blot analysis to examine σ<sup>B </sup>expression during growth of <it>L. monocytogenes </it>EGD-e. Whole genome-based transcriptional profiling was used to identify σ<sup>B</sup>-dependent genes at different growth phases.</p> <p>Results</p> <p>We detected 105 σ<sup>B</sup>-positively regulated genes and 111 genes which appeared to be under negative control of σ<sup>B </sup>and validated 36 σ<sup>B</sup>-positively regulated genes <it>in vivo </it>using a reporter gene fusion system.</p> <p>Conclusion</p> <p>Genes comprising the σ<sup>B </sup>regulon encode solute transporters, novel cell-wall proteins, universal stress proteins, transcriptional regulators and include those involved in osmoregulation, carbon metabolism, ribosome- and envelope-function, as well as virulence and niche-specific survival genes such as those involved in bile resistance and exclusion. Ten of the σ<sup>B</sup>-positively regulated genes of <it>L. monocytogenes </it>are absent in <it>L. innocua</it>. A total of 75 σ<sup>B</sup>-positively regulated listerial genes had homologs in <it>B. subtilis</it>, but only 33 have been previously described as being σ<sup>B</sup>-regulated in <it>B. subtilis </it>even though both species share a highly conserved σ<sup>B</sup>-dependent consensus sequence. A low overlap of genes may reflects adaptation of these bacteria to their respective environmental conditions.</p

    PSORTb 3.0: improved protein subcellular localization prediction with refined localization subcategories and predictive capabilities for all prokaryotes

    Get PDF
    Motivation: PSORTb has remained the most precise bacterial protein subcellular localization (SCL) predictor since it was first made available in 2003. However, the recall needs to be improved and no accurate SCL predictors yet make predictions for archaea, nor differentiate important localization subcategories, such as proteins targeted to a host cell or bacterial hyperstructures/organelles. Such improvements should preferably be encompassed in a freely available web-based predictor that can also be used as a standalone program

    Universal Stress Proteins Are Important for Oxidative and Acid Stress Resistance and Growth of Listeria monocytogenes EGD-e In Vitro and In Vivo

    Get PDF
    Background: Pathogenic bacteria maintain a multifaceted apparatus to resist damage caused by external stimuli. As part of this, the universal stress protein A (UspA) and its homologues, initially discovered in Escherichia coli K-12 were shown to possess an important role in stress resistance and growth in several bacterial species. Methods and Findings: We conducted a study to assess the role of three homologous proteins containing the UspA domain in the facultative intracellular human pathogen Listeria monocytogenes under different stress conditions. The growth properties of three UspA deletion mutants (deltalmo0515, deltalmo1580 and deltalmo2673) were examined either following challenge with a sublethal concentration of hydrogen peroxide or under acidic conditions. We also examined their ability for intracellular survival within murine macrophages. Virulence and growth of usp mutants were further characterized in invertebrate and vertebrate infection models. Tolerance to acidic stress was clearly reduced in &#916;lmo1580 and deltalmo0515, while oxidative stress dramatically diminished growth in all mutants. Survival within macrophages was significantly decreased in deltalmo1580 and deltalmo2673 as compared to the wild-type strain. Viability of infected Galleria mellonella larvae was markedly higher when injected with deltalmo1580 or deltalmo2673 as compared to wild-type strain inoculation, indicating impaired virulence of bacteria lacking these usp genes. Finally, we observed severely restricted growth of all chromosomal deletion mutants in mice livers and spleens as compared to the load of wild-type bacteria following infection. Conclusion: This work provides distinct evidence that universal stress proteins are strongly involved in listerial stress response and survival under both in vitro and in vivo growth conditions

    Pemetrexed pharmacokinetics and pharmacodynamics in a phase I/II study of doublet chemotherapy with vinorelbine: implications for further optimisation of pemetrexed schedules

    Get PDF
    The purpose of this study was to investigate the utility of plasma pharmacokinetic and pharmacodynamic measures including plasma deoxynucleosides, homocysteine and methylmalonic acid concentrations in understanding the time course and extent of the inhibition of thymidylate synthase (TS) by pemetrexed in the context of a phase I/II combination study with vinorelbine. Eighteen patients received supplementation with folic acid and Vitamin B12 1 week before beginning treatment with pemetrexed and vinorelbine administered in a dose-escalating manner on a 21-day cycle. Heparinised blood samples were collected from consenting patients in the first cycle for pharmacokinetic analyses and in the first two cycles for determination of plasma thymidine, deoxyuridine, homocysteine and methylmalonic acid concentrations. These values were correlated with response and toxicity. Plasma deoxyuridine was used as a measure of TS inhibition, and concentrations of deoxyuridine were significantly elevated relative to baseline on days 1 (P<0.01), 2 (P<0.001) and 3 (P<0.05) after treatment at all pemetrexed dose levels (400–700 mg m−2). The magnitude of deoxyuridine elevation correlated with pemetrexed area under the plasma concentration–time curve (AUC) (r2=0.23, P<0.05). However, deoxyuridine concentrations returned to baseline between 8 and 15 days after treatment with pemetrexed, suggesting that inhibition of TS was not durable. Pemetrexed AUC correlated with the percentage decline (relative to baseline) in both platelets (r2=0.58, P<0.001) and leucocytes (r2=0.26, P<0.05) at day 8. Baseline homocysteine was also significantly correlated with these measures of haematological toxicity (r2=0.37, P<0.01 and r2=0.39, P<0.01, respectively). In addition, there was a significant reduction of plasma homocysteine on days 8 (P<0.005) and 15 (P<0.05) in cycle 1 compared to baseline values. The results suggest that the TS inhibitory effects of pemetrexed are short-lived and make the case for a more frequent schedule of administration such as every 2 weeks. The lack of protracted TS inhibition may be due to concomitant vitamin administration, and this may be the mechanism by which vitamins prevent life-threatening toxicity from pemetrexed. Baseline homocysteine concentration remains a predictive marker for haematological toxicity even following folate supplementation

    Low incidence of SARS-CoV-2, risk factors of mortality and the course of illness in the French national cohort of dialysis patients

    Get PDF
    corecore