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

Intelligent Geographical Information Retrieval using Ontology

With Web 3.0 gaining popularity, efficiently retrieving geographical information from ever growing geospatial data is an important task. We address two issues in this work.Firstly, consider the query “Find all restaurants towards the east of Singhania school within a distance of 50km”. In current systems to get the required result, first all the objects of type restaurant are extracted, then those within a required distance range are filtered and finally the approximate direction is determined by comparing co-ordinates. This processing is done at run-time i.e. dynamically when the query is executed. In this paper, we suggest a technique to avoid this computational overhead by constructing triples after pre-processing data from the existing ontologies to make implicit information explicitly available.Secondly, to address queries like “Find all schools in Mumbai”, the current systems manually construct a polygon which encloses Mumbai and then the required schools are filtered out. The task of determining a polygon which encircles the required locality is laborious if done manually and inaccurate with APIs like Google Maps. We propose an accurate technique which automatically forms the enclosing polygon for a region under consideration

Acurateţea clinicianului în interpretarea subiectivă a marcajelor hîrtiei de articulaţie

Obiective: Scopul acestui studiu a fost de a determina dacă interpretarea subiectivă a marcajelor de hârtie este o metodă de încredere pentru identificarea relativă a forţelor (contactelor dentare) ocluzale. Metodologie: 295 de medici au ales „cele mai puternice“ și “ cele mai puţin puternice (slabe)“ contacte ocluzale analizînd fotografii ocluzale ale marcajelor hîrtiei de articulaţie care au fost ulterior comparate cu analiza ocluzală computerizată ce a măsurat forţele ocluzale ale acelorași contacte dentare. Deviaţiile standard au fost calculate prin ani de practica clinică și prin numărul de cursuri frecventate pe tema ocluziei. De asemenea, a fost efectuată o analiză „Chi–square“ (Chi–pătrat). Rezultate: Valoarea medie corectă pentru 295 de medici stomatologi participanţi a fost de 1,53 (± 1.234). Nu au existat diferenţe semnificative legate de anii în practică (P> 0,16) sau numărul de cursuri luate pe tema ocluziei (P> 0,75). Analiza Chi–pătrat a arătat o sensibilitate de 12,6%, o specificitate de 12,4%, o valoare predictivă pozitivă de 12,58% și o valoare predictivă negativă de 12,42%. Șansa a fost apreciată corect la 12,5%. Concluzii: Interpretarea subiectivă este o metodă clinică ineficientă pentru determinarea relativă a forţei contactelor dentare ocluzale. Scorurile mici obţinute de la un grup mare de medici stomatologi participanţi sugerează că medicii nu sunt în măsură să diferenţieze în mod fiabil forţele mari și mici de ocluzie analizînd marcajele hîrtiei de articulaţie. Această metodă mult timp utilizată, de a identifica vizual marcajele hârtiei de articulaţie ce evidenţiază „forţa“ contactelor ocluzale, ar trebui să fie înlocuită cu o metodă obiectivă bazată pe măsurare.Summary. Aims: The aim of this study was to determine whether Subjective Interpretation of paper markings is a reliable method for identifying the relative occlusal force content of tooth contacts. Methodology: 295 clinicians selected the „Most Forceful“ and „Least Forceful“ occlusal contacts in six occlusal–view photographs of articulating paper marks that were later compar,ed against computerized occlusal analysis relative occlusal force measurements of the same tooth contacts . Means and standart deviations were calculated by years in clinical practice and by number of occlusion courses taken . A Chi–square analysis was also performed. Results: The mean correct for 295 participant dentists was 1.53 ( ±: 1.234). There were no significant differences found for years in pracice (P>0.16) or number of occlusion courses taken (P>0.75). The Chi square analysis showed a sensitivity of 12.6%, a specificity of 12.4%, a positive predictive value of 12.58% , and a negative predictive value of 12.42%. Chance was calculated at 12.5% correct. Conclusions: Subjective Interpretation is an ineffective clinical method for determining the relative occlusal force content of tooth contacts . The reported low scores obtained from a large group of participant dentists suggest clinicians are unable to reliably differentiate high and low occlusal force from looking at articulating paper marks. This longstanding method of visually observing articulating paper marks for occlusal contact force content should be replaced with a measurement –based, objective method

Geophysical anomalies and quartz deformation of the Warburton West structure, central Australia

This paper reports geophysical anomalies and intra-crystalline quartz lamellae in drill cores from the Warburton West Basin overlapping the border of South Australia and the Northern Territory. The pre-Upper Carboniferous ~450×300km-large Warburton Basin, north-eastern South Australia, is marked by distinct eastern and western magnetic, gravity and low-velocity seismic tomography anomalies. Quartz grains from arenite core samples contain intra-crystalline lamellae in carbonate-quartz veins and in clastic grains, similar to those reported earlier from arenites, volcanic rocks and granites from the Warburton East Basin. Universal Stage measurements of quartz lamellae in both sub-basins define Miller-Bravais indices of {10-12} and {10-13}. In-situ quartz lamellae occur only in pre-Late Carboniferous rocks whereas lamellae-bearing clastic quartz grains occur in both pre-Late Carboniferous and post-Late Carboniferous rocks - the latter likely redeposited from the pre-Late Carboniferous basement. Quartz lamellae in clastic quartz grains are mostly curved and bent either due to tectonic deformation or to re-deformation of impact-generated planar features during crustal rebound or/and post-impact tectonic deformation. Seismic tomography low-velocity anomalies in both Warburton West Basin and Warburton East Basin suggest fracturing of the crust to depths of more than 20km. Geophysical modelling of the Cooper Basin, which overlies the eastern Warburton East Basin, suggests existence of a body of high-density (~2.9-3.0gr/cm) and high magnetic susceptibility (SI~0.012-0.037) at a depth of ~6-10km at the centre of the anomalies. In the Warburton West Basin a large magnetic body of SI=0.030 is modelled below ~10km, with a large positive gravity anomaly offset to the north of the magnetic anomaly. In both the Warburton East and Warburton West the deep crustal fracturing suggested by the low velocity seismic tomography complicates interpretations of the gravity data. Universal Stage measurements of quartz lamellae suggest presence of both planar deformation features of shock metamorphic derivation and deformed planar lamella. The latter may be attributed either to re-deformation of impact-generated lamella, impact rebound deformation or/and post impact tectonic deformation. The magnetic anomalies in the Warburton East and West sub-basins are interpreted in terms of (1) presence of deep seated central mafic bodies; (2) deep crustal fracturing and (3) removal of Devonian and Carboniferous strata associated with rebound of a central uplift consequent on large asteroid impact. Further tests of the Warburton structures require deep crustal seismic transects

Susceptibility of Toxoplasma gondii to autophagy in human cells relies on multiple interacting parasite loci

Autophagy is a process used by cells to recycle organelles and macromolecules and to eliminate intracellular pathogens. Previous studies have shown that some stains o

Learned cardinalities: Estimating correlated joins with deep learning

We describe a new deep learning approach to cardinality estimation. MSCN is a multi-set convolutional network, tailored to representing relational query plans, that employs set semantics to capture query features and true cardinalities. MSCN builds on sampling-based estimation, addressing its weaknesses when no sampled tuples qualify a predicate, and in capturing join-crossing correlations. Our evaluation of MSCN using a real-world dataset shows that deep learning signiicantly enhances the quality of cardinality estimation, which is the core problem in query optimization