Genetic Variations in the Purinergic P2X7 Receptor Are Associated with the Immune Response to Ocular Toxoplasmosis in Colombia.

Ocular toxoplasmosis (OT) is characterized by inflammation within the eye and is the most recognized clinical manifestation of toxoplasmosis. The objective of this study was to identify new single-nucleotide polymorphisms (SNPs) in the P2RX7 gene that may have significance in the immune response to OT in Colombian patients. A case-control study was conducted to investigate the associations between SNPs (rs1718119 and rs2230912) in the P2RX7 gene and OT in 64 Colombian patients with OT and 64 controls. Capillary electrophoresis was used to analyze the amplification products, and in silico algorithms were employed to predict deleterious SNPs. Stability analysis of amino acid changes indicated that both mutations could lead to decreased protein structure stability. A nonsynonymous SNP, Gln460Arg, located in the long cytoplasmic tail of the receptor, showed a significant association with OT (Bonferroni correction (BONF) = 0.029; odds ratio OR = 3.46; confidence interval CI: 1.05 to 11.39), while no significant association between rs1718119 and OT risk was observed. Based on the 3D structure analysis of the P2RX7 protein trimer, it is hypothesized that an increase in the flexibility of the cytoplasmic domain of this receptor could alter its function. This SNP could potentially serve as a biomarker for identifying Colombian patients at risk of OT.

Perfil cognitivo y social en niños y niñas con Trastorno del Espectro Autista / Cognitive and social profile in children with autism spectrum disorder

El Trastorno del Espectro Autista (TEA) es una condición que se caracteriza por presentar fallas en la conducta social y comportamientos repetitivos. Su perfil neuropsicológico muestra hallaz-gos heterogéneos que dependen de la severidad del trastorno. El objetivo del presente trabajo es describir el funcionamiento neuropsicológico de una muestra de niños y niñas con TEA que asisten al Instituto para el Desarrollo Integral del Niño en condición de Autismo (DINA). La muestra estuvo conformada por 78 participantes, 15.4% de género femenino y 84.6% de géne-ro masculino, con edades entre los 6 y los 16 años. Los instrumentos utilizados fueron protocolo neuropsicológico adaptado de la ENI, prorrateo de inteligencia del WISC-IV, Test de Sally y Ann, Test de Expresiones faciales adaptadopor Paul Ekman y el Test de la Mirada para niños, El Test de Metidas de Pata, e Historias Extrañas de Happé. Los resultados se discuten a la luz de la li-teratura científica sobre el tema.

Autism Spectrum Disorder (ASD) is a condition that is characterized by failures in social behav-ior and repetitive behaviors. The neuropsychological profile shows heterogeneous findings that depends on the severity of the disorder. The objective of this paper is to describe the neuropsychological functioning of a sample of children with ASD who attend the Institute for the Integral Development of Children with Autism (DINA). The sample consisted of 78 partici-pants, 15.4% female and 84.6% male, aged between6 and 16 years. The instruments used were the neuropsychological protocol adapted from the ENI, intelligence apportionment from the WISC-IV, Sally and Ann Test, Facial Expressions Test adapted by Paul Ekman and Reading the Mind in the Eye for children, Faux Pas Test, and The Happé’s Strange Stories test. The re-sults are discussed considering the scientific literature on the subject. (AU)

Toxoplasma gondii infection and peripheral-blood gene expression profiling of older people reveals dysregulation of cytokines and identifies hub genes as potential therapeutic targets.

Infections of humans with the protozoan parasite Toxoplasma gondii (T. gondii) can lead to the disease's development, even in an asymptomatic status. However, the mechanisms that result in these clinical outcomes after infection are poorly understood. This study aimed to explore the molecular pathogenesis of toxoplasmosis-related inflammation through next-generation sequencing, to assess RNA expression profiles in peripheral blood from 5 female patients with chronic toxoplasmosis and 5 healthy female controls. All plasma samples were analyzed for anti-Toxoplasma IgG and IgM antibody titers by using electrochemiluminescence. Detection of acute and chronic toxoplasmosis was carried out using the ELISA IgG avidity. We evaluated the levels of INF-γ, IL-2, IL-12, TNF-α, IL-10, and IL-1ß in culture supernatants of Peripheral Blood Mononuclear Cells infected with Toxoplasma lysate antigen (TLA) prepared with tachyzoites of strain T. gondii RH. Differential expression analysis was performed using DESeq2, pathway and enrichment analysis of DEGs was done on WEB-based Gene SeT AnaLysis Toolkit (WebGestalt) and Protein-protein interaction was carried out using NetworkAnalyst with STRING. In older people with chronic asymptomatic infection, a significant difference in the levels of inflammatory cytokines INF-γ and IL-2 was observed compared to seronegative individuals. Our results revealed differences in the regulation of critical biological processes involved in host responses to chronic T. gondii infection. Gene ontology analysis revealed several biologically relevant inflammatory and immune-related pathways.

Inflammatory gene expression profiling in peripheral blood from patients with Alzheimer's disease reveals key pathways and hub genes with potential diagnostic utility: a preliminary study.

BACKGROUND: Alzheimer's disease (AD) is an age-related neurodegenerative disease caused by central nervous system disorders. Late-onset Alzheimer disease (LOAD) is the most common neurodegenerative disorder worldwide. Differences at the expression level of certain genes, resulting from either genetic variations or environmental interactions, might be one of the mechanisms underlying differential risks for developing AD. Peripheral blood genome transcriptional profiling may provide a powerful and minimally invasive tool for the identification of novel targets beyond Aß and tau for AD research. METHODS: This preliminary study explores molecular pathogenesis of LOAD-related inflammation through next generation sequencing, to assess RNA expression profiles in peripheral blood from five patients with LOAD and 10 healthy controls. RESULTS: The analysis of RNA expression profiles revealed 94 genes up-regulated and 147 down-regulated. Gene function analysis, including Gene Ontology (GO) and KOBAS-Kyoto Encyclopedia of DEGs and Genomes (KEGG) pathways indicated upregulation of interferon family (INF) signaling, while the down-regulated genes were mainly associated with the cell cycle process. KEGG metabolic pathways mapping showed gene expression alterations in the signaling pathways of JAK/STAT, chemokines, MAP kinases and Alzheimer disease. The results of this preliminary study provided not only a comprehensive picture of gene expression, but also the key processes associated with pathology for the regulation of neuroinflammation, to improve the current mechanisms to treat LOAD.

Publisher Correction: Toxoplasma Modulates Signature Pathways of Human Epilepsy, Neurodegeneration & Cancer.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Toxoplasma Modulates Signature Pathways of Human Epilepsy, Neurodegeneration & Cancer.

One third of humans are infected lifelong with the brain-dwelling, protozoan parasite, Toxoplasma gondii. Approximately fifteen million of these have congenital toxoplasmosis. Although neurobehavioral disease is associated with seropositivity, causality is unproven. To better understand what this parasite does to human brains, we performed a comprehensive systems analysis of the infected brain: We identified susceptibility genes for congenital toxoplasmosis in our cohort of infected humans and found these genes are expressed in human brain. Transcriptomic and quantitative proteomic analyses of infected human, primary, neuronal stem and monocytic cells revealed effects on neurodevelopment and plasticity in neural, immune, and endocrine networks. These findings were supported by identification of protein and miRNA biomarkers in sera of ill children reflecting brain damage and T. gondii infection. These data were deconvoluted using three systems biology approaches: "Orbital-deconvolution" elucidated upstream, regulatory pathways interconnecting human susceptibility genes, biomarkers, proteomes, and transcriptomes. "Cluster-deconvolution" revealed visual protein-protein interaction clusters involved in processes affecting brain functions and circuitry, including lipid metabolism, leukocyte migration and olfaction. Finally, "disease-deconvolution" identified associations between the parasite-brain interactions and epilepsy, movement disorders, Alzheimer's disease, and cancer. This "reconstruction-deconvolution" logic provides templates of progenitor cells' potentiating effects, and components affecting human brain parasitism and diseases.

Toxoplasmosis as a travel risk.

Toxoplasma gondii is a protozoan parasite with worldwide distribution that infects more than one third of the global population. Primary infection in immunocompetent individuals is usually asymptomatic; however, different organs can be affected in immunocompromised individuals leading to the development of encephalitis, myocarditis or pneumonitis. The prevalence of infection with Toxoplasma as well as its genetic structure varies geographically and for that reason travel may be considered as a risk factor to acquire the infection. As toxoplasmosis is a foodborne disease, health care providers should give health education on prevention measures to all prospective travelers in order to decrease the risk of infection in endemic areas. This review presents an overview of the infection with T. gondii with some considerations for travelers to and from endemic zones.