Total synthesis of the cyanobacterial metabolite nostodione A: discovery of its antiparasitic activity against Toxoplasma gondii.

A total synthesis of the cyanobacterial natural product nostodione A is reported involving a convergent, diversity-oriented route. A small assemblage of structural analogues were prepared and their cytotoxicity and anti-invasion activity against the protozoal parasite Toxoplasma gondii is reported for the first time.

Genome-wide genetic and transcriptomic investigation of variation in antibody response to dietary antigens.

Increased immunoglobulin G (IgG) response to dietary antigens can be associated with gastrointestinal dysfunction and autoimmunity. The underlying processes contributing to these adverse reactions remain largely unknown, and it is likely that genetic factors play a role. Here, we estimate heritability and attempt to localize genetic factors influencing IgG antibody levels against food-derived antigens using an integrative genomics approach.

Association between cytomegalovirus antibody levels and cognitive functioning in non-elderly adults.

Background: Elevated levels of antibodies to Cytomegalovirus (CMV) have been associated with cognitive impairment, but the quantitative relationship between CMV antibody levels and domains of cognitive functioning in younger adults has not been established.

Methods: We measured IgG class antibodies to Cytomegalovirus in 521 individuals, mean age 32.8 years.

A longitudinal study of cognitive functioning in schizophrenia: clinical and biological predictors.

Background: Cognitive deficits are a central feature of schizophrenia but it is not certain how cognitive functioning changes over time. The purpose of this prospective longitudinal study was to determine the temporal change of cognitive functioning and the predictors of cognitive performance from among demographic, clinical, and biological variables.

Methods: Participants were individuals with schizophrenia or schizoaffective disorder whose cognitive functioning was assessed at multiple time points with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).

Inflammatory molecular signature associated with infectious agents in psychosis.

Schizophrenia (SZ) is a devastating mental condition with onset in young adulthood. The identification of molecular biomarkers that reflect illness pathology is crucial. Recent evidence suggested immune and inflammatory cascades in conjunction with infection may play a role in the pathology.

MicroRNA-132 dysregulation in Toxoplasma gondii infection has implications for dopamine signaling pathway.

Congenital toxoplasmosis and toxoplasmic encephalitis can be associated with severe neuropsychiatric symptoms. However, which host cell processes are regulated and how Toxoplasma gondii affects these changes remain unclear. MicroRNAs (miRNAs) are small noncoding RNA sequences critical to neurodevelopment and adult neuronal processes by coordinating the activity of multiple genes within biological networks.

Persistent infection by HSV-1 is associated with changes in functional architecture of iPSC-derived neurons and brain activation patterns underlying working memory performance.

Background: Herpes simplex virus, type 1 (HSV-1) commonly produces lytic mucosal lesions. It invariably initiates latent infection in sensory ganglia enabling persistent, lifelong infection. Acute HSV-1 encephalitis is rare and definitive evidence of latent infection in the brain is lacking.

A thiazole derivative of artemisinin moderately reduces Toxoplasma gondii cyst burden in infected mice.

Toxoplasmosis continues to be a public health problem, causing significant morbidity worldwide. Currently available medications, effective for acute toxoplasmosis, are nonetheless problematic due to adverse side effects in many patients. In addition, no medication is able to completely eradicate the parasite cysts, rendering infected individuals at risk for reactivation upon becoming immunocompromised.

Transcriptional derepression of the ERVWE1 locus following influenza A virus infection.

Unlabelled: Syncytin-1, a fusogenic protein encoded by a human endogenous retrovirus of the W family (HERV-W) element (ERVWE1), is expressed in the syncytiotrophoblast layer of the placenta. This locus is transcriptionally repressed in adult tissues through promoter CpG methylation and suppressive histone modifications. Whereas syncytin-1 appears to be crucial for the development and functioning of the human placenta, its ectopic expression has been associated with pathological conditions, such as multiple sclerosis and schizophrenia.

Multiplex immunoassay analysis of plasma shows prominent upregulation of growth factor activity pathways linked to GSK3β signaling in bipolar patients.

Background: Our understanding of bipolar disorder (BD) aetiology has advanced in recent years but our ability to translate this to improve patient care in the clinic is still limited.

Methods: In this study, we have measured the concentrations of 190 different molecules using sensitive multiplex immunoassays in plasma of 17 BD patients compared to 46 matched control subjects.

Results: The analyses led to the identification of 26 dysregulated proteins in BD patients compared to controls.

Seroreactive marker for inflammatory bowel disease and associations with antibodies to dietary proteins in bipolar disorder.

Objectives: Immune sensitivity to wheat glutens and bovine milk caseins may affect a subset of individuals with bipolar disorder. Digested byproducts of these foods are exorphins that have the potential to impact brain physiology through action at opioid receptors. Inflammation in the gastrointestinal (GI) tract might accelerate exposure of food antigens to systemic circulation and help explain elevated gluten and casein antibody levels in individuals with bipolar disorder.

Synthesis and anti-toxoplasmosis activity of 4-arylquinoline-2-carboxylate derivatives.

A one-step synthesis of 4-arylquinoline-2-carboxylates along with their antiprotozoal activity against the pathogenic parasite Toxoplasma gondii is reported. Mechanistic insights into the role of Lewis acid (silver triflate) versus Bronsted acid (triflic acid) catalysis are revealed clarifying aspects of the mechanism of the quinoline synthesis.

HLA associations in schizophrenia: are we re-discovering the wheel?

Associations between human leukocyte antigen (HLA) polymorphisms on chromosome 6p and schizophrenia (SZ) risk have been evaluated for over five decades. Numerous case-control studies from the candidate gene era analyzed moderately sized samples and reported nominally significant associations with several loci in the HLA region (sample sizes, n = 100-400). The risk conferred by individual alleles was modest (odds ratios < 2.

Association between antibodies to multiple infectious and food antigens and new onset schizophrenia among US military personnel.

Introduction: Multiple studies have documented immune activation in many individuals with schizophrenia suggesting that antigens capable of generating a prolonged immune response may be important environmental factors in many cases of this disorder. While existing studies have found single-agent associations of antibodies to food and neurotropic infectious agents with schizophrenia, a simultaneous examination of multiple agents may shed light on agent interactions or possible etiopathogenic pathways.

Methods: We used traditional regression and novel statistical techniques to examine associations of single and combined infectious and food antigens with schizophrenia.

Antibodies to Toxoplasma gondii in individuals with mania.

Objectives: Increased rates of infection with Toxoplasma gondii have been found in individuals with schizophrenia as compared to control groups but this issue has not been studied in mania.

Methods: We measured immunoglobulin G (IgG) and IgM class antibodies to T. gondii in 57 individuals with mania who were assessed at up to three time-points.

Cytomegalovirus seropositivity and serointensity are associated with hippocampal volume and verbal memory in schizophrenia and bipolar disorder.

Introduction: Cytomegalovirus (CMV) is a member of the herpesviridae family that has a limbic and temporal gray matter tropism. It is usually latent in humans but has been associated with schizophrenia, bipolar disorder and cognitive deficits in some populations. Hippocampal decreased volume and dysfunction play a critical role in these cognitive deficits.

A combined marker of inflammation in individuals with mania.

Background: Markers of immune activation have been associated with mania but have not been examined in combination. We studied the association between mania and an inflammation score based on four immune markers.

Methods: A total of 57 individuals with mania were assessed at up to three time points: the day of hospital admission, evaluation several days later, and six-month follow-up.

Mortality in schizophrenia: clinical and serological predictors.

Persons with schizophrenia have a reduced life expectancy largely due to death from natural causes. Factors that have been previously associated with excess mortality include cigarette smoking and antipsychotic medication. The role of other environmental factors such as exposure to infectious agents has been the subject of only limited investigation.

Exposure to herpes simplex virus, type 1 and reduced cognitive function.

Herpes simplex virus, type 1 (HSV-1) causes cold sores, keratitis and rarely, fatal encephalitis. The infection is lifelong, with sensory ganglia serving as reservoirs of latent infection. Recently, exposure to HSV-1 has also been repeatedly associated with reduced cognitive function among healthy individuals without prior encephalitis.

Toxoplasma oocysts as a public health problem.

Waterborne outbreaks of Toxoplasma gondii have focused attention on the importance of oocysts shed in the feces of infected cats. Cat feces deposited annually into the environment in the United States total approximately 1.2 million metric tons.

Abnormalities of neurotransmitter and neuropeptide systems in human neuroepithelioma cells infected by three Toxoplasma strains.

Since Toxoplasma gondii can establish a persistent infection in the central nervous system in humans, we studied its effects on a host's neurotransmitter and neuropeptide systems (NNS). Using microarray technology, we have screened the expression of genes coding for NNS in human neuroepithelioma cells in response to representative strains of Toxoplasma to identify potential target genes. Transcripts that displayed expression levels distinct from uninfected controls were examined by RT-PCR and Western blot.

Discordant patterns of bacterial translocation markers and implications for innate immune imbalances in schizophrenia.

The origin of inflammation in psychiatric disorders is not well understood. The translocation of commensal microbiota across the gastrointestinal barrier can result in a persistent state of low-grade immune activation and/or inflammation. We measured serological surrogate markers of bacterial translocation (soluble CD14 (sCD14) and lipopolysaccharide binding protein (LBP)) in two psychiatric cohorts and compared these levels to C-reactive protein (CRP), body mass index (BMI), and food-related and autoimmune antibodies.

Elevated C-reactive protein and cognitive deficits in individuals with bipolar disorder.

Background: Some individuals with bipolar disorder have cognitive deficits even when euthymic. In previous studies, we found an association between elevated levels of C-reactive protein (CRP), a marker of inflammation, and reduced cognitive functioning in schizophrenia. This issue has not been examined in bipolar disorder.

Application of meta-analysis methods for identifying proteomic expression level differences.

We present new statistical approaches for identification of proteins with expression levels that are significantly changed when applying meta-analysis to two or more independent experiments. We showed that the Euclidean distance measure has reduced risk of false positives compared to the rank product method. Our Ψ-ranking method has advantages over the traditional fold-change approach by incorporating both the fold-change direction as well as the p-value.