Transcriptional repression by ApiAP2 factors is central to chronic toxoplasmosis

Tachyzoite to bradyzoite development in Toxoplasma is marked by major changes in gene expression resulting in a parasite that expresses a new repertoire of surface antigens hidden inside a modified parasitophorous vacuole called the tissue cyst. The factors that control this important life cycle transition are not well understood. Here we describe an important transcriptional repressor mechanism controlling bradyzoite differentiation that operates in the tachyzoite stage. The ApiAP2 factor, AP2IV-4, is a nuclear factor dynamically expressed in late S phase through mitosis/cytokinesis of the tachyzoite cell cycle. Remarkably, deletion of the AP2IV-4 locus resulted in the expression of a subset of bradyzoite-specific proteins in replicating tachyzoites that included tissue cyst wall components BPK1, MCP4, CST1 and the surface antigen SRS9. In the murine animal model, the mis-timing of bradyzoite antigens in tachyzoites lacking AP2IV-4 caused a potent inflammatory monocyte immune response that effectively eliminated this parasite and prevented tissue cyst formation in mouse brain tissue. Altogether, these results indicate that suppression of bradyzoite antigens by AP2IV-4 during acute infection is required for Toxoplasma to successfully establish a chronic infection in the immune-competent host

The transcriptome of Toxoplasma gondii

BACKGROUND: Toxoplasma gondii gives rise to toxoplasmosis, among the most prevalent parasitic diseases of animals and man. Transformation of the tachzyoite stage into the latent bradyzoite-cyst form underlies chronic disease and leads to a lifetime risk of recrudescence in individuals whose immune system becomes compromised. Given the importance of tissue cyst formation, there has been intensive focus on the development of methods to study bradyzoite differentiation, although the molecular basis for the developmental switch is still largely unknown. RESULTS: We have used serial analysis of gene expression (SAGE) to define the Toxoplasma gondii transcriptome of the intermediate-host life cycle that leads to the formation of the bradyzoite/tissue cyst. A broad view of gene expression is provided by >4-fold coverage from nine distinct libraries (~300,000 SAGE tags) representing key developmental transitions in primary parasite populations and in laboratory strains representing the three canonical genotypes. SAGE tags, and their corresponding mRNAs, were analyzed with respect to abundance, uniqueness, and antisense/sense polarity and chromosome distribution and developmental specificity. CONCLUSION: This study demonstrates that phenotypic transitions during parasite development were marked by unique stage-specific mRNAs that accounted for 18% of the total SAGE tags and varied from 1–5% of the tags in each developmental stage. We have also found that Toxoplasma mRNA pools have a unique parasite-specific composition with 1 in 5 transcripts encoding Apicomplexa-specific genes functioning in parasite invasion and transmission. Developmentally co-regulated genes were dispersed across all Toxoplasma chromosomes, as were tags representing each abundance class, and a variety of biochemical pathways indicating that trans-acting mechanisms likely control gene expression in this parasite. We observed distinct similarities in the specificity and expression levels of mRNAs in primary populations (Day-6 post-sporozoite infection) that occur prior to the onset of bradyzoite development that were uniquely shared with the virulent Type I-RH laboratory strain suggesting that development of RH may be arrested. By contrast, strains from Type II-Me49B7 and Type III-VEGmsj contain SAGE tags corresponding to bradyzoite genes, which suggests that priming of developmental expression likely plays a role in the greater capacity of these strains to complete bradyzoite development

Frozen Soils: A Perspective On Past And Future Research For Promoting Sustainable Agricultural Systems

Frozen soils impact many industries which rely· on soil, water, and .air resources in developing and manufacturing products. Most noteworthy is the agricultural industry in the northern United States where soils, which sustain food and fiber production, are subjected to frequent freezing and thawing. Soil freezing and thawing influences soil erodibility, surface and ground water quality, air quality, and biological activity. Many strides toward understanding frozen soil processes and managing lands to minimize the adverse effects of freezing and thawing have been made over the last two decades. Yet, further efforts to identify frozen soil processes which influence wind and water erosion, soil faunal adaptation, soil quality, movement of agricultural chemicals,· and rural and urban water supplies will aid industry and society in meeting future needs for food and water

The main features of issue and circulation of exchange bonds in the Russian Federation

The main features of stock exchange bonds were considered in the article, as well as the difference between stock exchange bonds and classical bonds. Two new types which appeared in the Russian federation in 2015-2016, such as single-day stock exchange bonds, and bonds issued within programs of exchange bonds. As the result, a conclusion was drawn on the future development of stock exchange bonds in Russian financial markets

Onset of Mobilization and the Fraction of Trapped Foam in Porous Media

The dynamic behavior of foam trapped in porous media is modeled here with a pore network simulator. We predict the magnitude of the pressure drop leading to the onset of flow of foam lamellae in the region containing trapped foam. This mobilization pressure drop depends only on the number of lamellae in the flow path and on the geometry of the pores that make up this path. The principles learned in this study allow us to predict the fraction of foam that is trapped in a porous medium under given flow conditions. We present here the first analytic expression for the trapped foam fraction as a function of the pressure gradient, and of the mean and standard deviation of the pore size distribution. This expression provides a missing piece for the continuum foam flow models based on the moments of the volume-averaged population balance of foam bubbles