Transcription Factor Efg1 Shows a Haploinsufficiency Phenotype in Modulating the Cell Wall Architecture and Immunogenicity of Candida albicans

The Candida albicans transcription factor Efg1 is known to be involved in many different cellular processes, including morphogenesis, general metabolism, and virulence. Here we show that besides its manifold roles, Efg1 also has a prominent effect on cell wall structure and composition, strongly affecting the structural glucan part. Deletion of only one allele of EFG1 already results in severe phenotypes for cell wall biogenesis, comparable to those with deletion of both alleles, indicative of a severe haploinsufficiency for EFG1. The observed defects in structural setup of the cell wall, together with previously reported alterations in expression of cell surface proteins, result in altered immunogenic properties of strains with compromised Efg1 function. This is shown by interaction studies with macrophages and primary dendritic cells. The structural changes in the cell wall carbohydrate meshwork presented here, together with the manifold changes in cell wall protein composition and metabolism reported in other studies, contribute to the altered immune response mounted by innate immune cells and to the altered virulence phenotypes observed for strains lacking EFG1

Traceability for Food Safety and Quality Assurance: Mandatory Systems Miss the Mark

Traceability systems are record-keeping systems that are primarily used to help keep foods with different attributes separate from one another. When information about a particular attribute of a food product is systematically recorded from creation through marketing, traceability for that attribute is established. Recently, policy makers in many countries have begun weighing the usefulness of mandatory traceability for managing such diverse problems as the threat of bio-terrorism, country-of-origin labelling, mad cow disease, and identification of genetically engineered foods. The question before policymakers is, When is mandatory traceability a useful and appropriate policy choice?Agricultural and Food Policy, Food Consumption/Nutrition/Food Safety,

TRACEABILITY IN THE U.S. FOOD SUPPLY: ECONOMIC THEORY AND INDUSTRY STUDIES

This investigation into the traceability baseline in the United States finds that private sector food firms have developed a substantial capacity to trace. Traceability systems are a tool to help firms manage the flow of inputs and products to improve efficiency, product differentiation, food safety, and product quality. Firms balance the private costs and benefits of traceability to determine the efficient level of traceability. In cases of market failure, where the private sector supply of traceability is not socially optimal, the private sector has developed a number of mechanisms to correct the problem, including contracting, third-party safety/quality audits, and industry-maintained standards. The best-targeted government policies for strengthening firms' incentives to invest in traceability are aimed at ensuring that unsafe of falsely advertised foods are quickly removed from the system, while allowing firms the flexibility to determine the manner. Possible policy tools include timed recall standards, increased penalties for distribution of unsafe foods, and increased foodborne-illness surveillance.traceability, tracking, traceback, tracing, recall, supply-side management, food safety, product differentiation, Food Consumption/Nutrition/Food Safety, Industrial Organization,

The Response of Big Sagebrush (\u3ci\u3eArtemisia tridentata\u3c/i\u3e) to Interannual Climate Variation Changes Across Its Range

Understanding how annual climate variation affects population growth rates across a species\u27 range may help us anticipate the effects of climate change on species distribution and abundance. We predict that populations in warmer or wetter parts of a species\u27 range should respond negatively to periods of above average temperature or precipitation, respectively, whereas populations in colder or drier areas should respond positively to periods of above average temperature or precipitation. To test this, we estimated the population sensitivity of a common shrub species, big sagebrush (Artemisia tridentata), to annual climate variation across its range. Our analysis includes 8,175 observations of year‐to‐year change in sagebrush cover or production from 131 monitoring sites in western North America. We coupled these observations with seasonal weather data for each site and analyzed the effects of spring through fall temperatures and fall through spring accumulated precipitation on annual changes in sagebrush abundance. Sensitivity to annual temperature variation supported our hypothesis: years with above average temperatures were beneficial to sagebrush in colder locations and detrimental to sagebrush in hotter locations. In contrast, sensitivity to precipitation did not change significantly across the distribution of sagebrush. This pattern of responses suggests that regional abundance of this species may be more limited by temperature than by precipitation. We also found important differences in how the ecologically distinct subspecies of sagebrush responded to the effects of precipitation and temperature. Our model predicts that a short‐term temperature increase could produce an increase in sagebrush cover at the cold edge of its range and a decrease in cover at the warm edge of its range. This prediction is qualitatively consistent with predictions from species distribution models for sagebrush based on spatial occurrence data, but it provides new mechanistic insight and helps estimate how much and how fast sagebrush cover may change within its range

The Candida albicans Histone Acetyltransferase Hat1 Regulates Stress Resistance and Virulence via Distinct Chromatin Assembly Pathways

Human fungal pathogens like Candida albicans respond to host immune surveillance by rapidly adapting their transcriptional programs. Chromatin assembly factors are involved in the regulation of stress genes by modulating the histone density at these loci. Here, we report a novel role for the chromatin assembly-associated histone acetyltransferase complex NuB4 in regulating oxidative stress resistance, antifungal drug tolerance and virulence in C. albicans. Strikingly, depletion of the NuB4 catalytic subunit, the histone acetyltransferase Hat1, markedly increases resistance to oxidative stress and tolerance to azole antifungals. Hydrogen peroxide resistance in cells lacking Hat1 results from higher induction rates of oxidative stress gene expression, accompanied by reduced histone density as well as subsequent increased RNA polymerase recruitment. Furthermore, hat1Delta/Delta cells, despite showing growth defects in vitro, display reduced susceptibility to reactive oxygen-mediated killing by innate immune cells. Thus, clearance from infected mice is delayed although cells lacking Hat1 are severely compromised in killing the host. Interestingly, increased oxidative stress resistance and azole tolerance are phenocopied by the loss of histone chaperone complexes CAF-1 and HIR, respectively, suggesting a central role for NuB4 in the delivery of histones destined for chromatin assembly via distinct pathways. Remarkably, the oxidative stress phenotype of hat1Delta/Delta cells is a species-specific trait only found in C. albicans and members of the CTG clade. The reduced azole susceptibility appears to be conserved in a wider range of fungi. Thus, our work demonstrates how highly conserved chromatin assembly pathways can acquire new functions in pathogenic fungi during coevolution with the host