The Shu complex is a conserved regulator of Rad51 filament formation

The budding yeast Shu complex, a heterotetramer of Shu1, Shu2, Csm2, and Psy3, is important for homologous recombination (HR)-mediated chromosome damage repair and was first characterized a decade ago as promoting Rad51-dependent HR in response to replicative stress, but its mechanistic function and conservation in eukaryotes has remained unknown. Here we provide evidence that the Shu complex is evolutionarily conserved throughout eukaryotes, where it is comprised of a clear Shu2 orthologue physically associating with Rad51 paralogues. The Shu complex itself physically interacts with the rest of the HR machinery during DNA damage repair. Finally, we uncover that the mechanistic function of the Shu complex as a stimulatory co-factor of Rad51 filament formation in vitro, likely explaining the in vivo function of the eukaryotic Shu complex in suppressing error-prone repair. Moving forward, our findings provide a framework for studying the function of the human Shu complex, which will have broad importance in our understanding of DNA damage repair

Species differences in the metabolism of pyrethroid pesticides: potential implications for human health risk assessment

Pyrethroids are a class of synthetic pesticides derived from the pyrethrins, the natural insecticidal ingredients of the pyrethrum extract of Chrysanthemum cinerariaefolium. In an effort to aid species extrapolation of exposure-dose relationships for pyrethroids, this dissertation aimed to develop appropriate data sets and models to address pharmacokinetic uncertainties for this class of chemicals. Based on experimental data in rats and mice it was previously thought that the rate of metabolism of a pyrethroid directly influenced its toxic potency. Preliminary results indicated that the pyrethroid deltamethrin was metabolized nearly twice as rapidly in human liver microsomes (HLM) as it was in rat liver microsomes (RLM). This is in contrast to esfenvalerate, which was metabolized nearly 3 times slower in HLM compared to RLM. Our hypothesis was that hepatic metabolism of pyrethroids drives blood and brain concentrations thus influencing their toxic potency. Research was conducted to understanding species differences in the hepatic metabolism of deltamethrin and esfenvalerate, and to develop a PBPK model of deltamethrin exposure to examine the influence of hepatic metabolism on exposure-dose relationships between rats and humans. Results indicate that initial phase I biotransformation (detoxification) of deltamethrin and esfenvalerate occurs via cytochrome P450 oxidation in RLM. This occurs by the same set of P450s for both compounds. In contrast while esfenvalerate is metabolized primarily by P450 oxidation in HLM, deltamethrin is metabolized primarily via esterase hydrolysis in HLM. Hepatic clearance rates were calculated from microsomal metabolism studies and utilized to parameterize PBPK models of exposure to deltamethrin. A PBPK model of deltamethrin was developed in rats and evaluated based on literature data. The current PBPK model of deltamethrin displays diffusion limited kinetics in all tissue compartments. This has the effect of limiting the influence of species differences in the hepatic clearance of the pyrethroids. Based on these results it is concluded that diffusion of pyrethroids into and out of the liver and brain are more responsible for the pharmacokinetic influence on toxic potency compared to hepatic metabolism in contrast to what has been previously thought

Redistribution in the age of austerity : evidence from Europe 2006 - 2013

We examine the relationship between changes in a country’s public sector fiscal position on inequality at the top and bottom of the income distribution during the age of austerity from 2006 to 2013. We use a parametric Lorenz curve model and Gini-like indices of inequality as our measures to assess distributional changes. Based on Statistics of Income and Living Conditions (EU-SILC) and IMF data for 12 European countries, we find that more severe adjustments to the cyclically adjusted primary balance (i.e., more austerity) are associated with a more unequal distribution of income driven by rising inequality at the top. The data also weakly suggests a decrease in inequality at the bottom. The distributional impact of austerity measures reflects the reliance on regressive policies and likely produces increased incentives for rent-seeking while reducing incentives for workers to increase productivity

Changes in the profile of inequality across Europe since 2005: austerity and redistribution

We present two Gini-like inequality indices that provide a more nuanced picture of how the profile of inequality has changed across European countries since 2005. We use these indices to analyse the distributional changes that can be attributed to the push for austerity. We estimate the JV-indices for 24 European countries over 9 years, and then use this panel to analyse the distributional effects of the fiscal consolidation policies Europe endured after the 2008 crisis. We find that austerity increased income inequality in eurozone countries, but reduced income inequality in countries that do not use the euro as their currency. We uncover a significant new relationship between austerity policies and the tails of the income distribution, further suggesting that in the eurozone these policies on average amount to a redistribution from the bottom to the top

Monetary Policy Transmission in a Macroeconomic Agent-Based Model

In this paper we explore the variety of monetary policy transmission channels in an agent-based macroeconomic model. We identify eight transmission channels and present a model based on [Caiani et al., J. Econ. Dyn. Contr. 69 (2016) 375–480], extended with an interbank market. We then analyze model simulation results of interest rate shocks in terms of GDP and inflation for four of the transmission channels. We find these effects to be small, in line with the view that monetary policy is a weak tool to control inflation

Tungsten nanoparticle and polymer blends as novel coating for radiopaque resorbable inferior vena cava filter

https://openworks.mdanderson.org/sumexp22/1148/thumbnail.jp