Host response profile of human brain proteome in toxoplasma encephalitis co-infected with HIV

Background

Toxoplasma encephalitis is caused by the opportunistic protozoan parasite Toxoplasma gondii. Primary infection with T. gondii in immunocompetent individuals remains largely asymptomatic. In contrast, in immunocompromised individuals, reactivation of the parasite results in severe complications and mortality. Molecular changes at the protein level in the host central nervous system and proteins associated with pathogenesis of toxoplasma encephalitis are largely unexplored. We used a global quantitative proteomic strategy to identify differentially regulated proteins and affected molecular networks in the human host during T. gondii infection with HIV co-infection.

Results

We identified 3,496 proteins out of which 607 proteins were differentially expressed (≥1.5-fold) when frontal lobe of the brain from patients diagnosed with toxoplasma encephalitis was compared to control brain tissues. We validated differential expression of 3 proteins through immunohistochemistry, which was confirmed to be consistent with mass spectrometry analysis. Pathway analysis of differentially expressed proteins indicated deregulation of several pathways involved in antigen processing, immune response, neuronal growth, neurotransmitter transport and energy metabolism.

Conclusions

Global quantitative proteomic approach adopted in this study generated a comparative proteome profile of brain tissues from toxoplasma encephalitis patients co-infected with HIV. Differentially expressed proteins include previously reported and several new proteins in the context of T. gondii and HIV infection, which can be further investigated. Molecular pathways identified to be associated with the disease should enhance our understanding of pathogenesis in toxoplasma encephalitis.

Electronic supplementary material

The online version of this article (doi:10.1186/1559-0275-11-39) contains supplementary material, which is available to authorized users.     

Prey selection and food habits of three sympatric large carnivores in a tropical lowland forest of the Eastern Himalayan Biodiversity Hotspot

Prey selection and the feeding habits of tiger Panthera tigris, leopard Panthera pardus and Asiatic wild dog Cuon alpinus were investigated from June 2009 to December 2011 in Pakke Tiger Reserve, Arunachal Pradesh. A total of 422 scats were analyzed of which, 109 scats were of tigers, 150 were of leopard and 163 scats were of dholes. Multinomial Likelihood ratio test was used to estimate the prey selectivity of predators and Ivlev index, Pianka index were used to estimate prey preference and overlap respectively. Biomass consumption for three sympatric predators varied from 254.3 kg for dholes to 599.1 kg for tigers. Sambar, barking deer, wild pig were preyed more than their availability by all the predators. Ivlev index shows barking deer and sambar were preferred more than available prey for tiger where as leopard preferred sambar more than available and avoided barking deer. Dhole preferred more than available wild pig and barking deer. There was a high overlap between tiger–leopard (85.3%) and tiger–dhole (77.5%). To the best of our understanding, this study provides the first reliable information on prey selection and food habits of sympatric large carnivores in a protected area of Eastern Himalayan tropical rainforest.     

Immunogenic gangliosides in human ovarian carcinoma

Ganglioside signatures of four poorly and three moderately differentiated ovarian epithelial cancer (OEC) cell lines reveal the presence of GM3, GM2, GD2, O-AcGD2, GD1a and GM1b. The expression of GM3, presence of GD1a and GM1b in the ascitic fluid and plasma, together with a positive correlation in the total-gangliosides levels between ascitic fluid and plasma of OEC patients support the earlier contention that the tumor-gangliosides may be released (or shed) into the tumor-microenvironment. The immunogenicity of OEC-gangliosides is determined by comparing anti-ganglioside-IgM titers in ascitic fluid (n = 14) and plasma (n = 23) of OEC-patients and age-matched healthy (n = 14). The titers were measured by ELISA. Strikingly, the level of anti-GD1a-IgM is significantly higher in ascitic fluid and plasma of patients than in the plasma of healthy volunteers. Paired sample analysis of ascitic fluid and plasma from the same patients confirmed the significant expression of anti-GD1a IgM in OEC patients, while no such difference was observed with other anti-ganglioside IgMs among different groups. The significance of the endogenous IgM response to GD1a may be to eliminate this immunosuppressive-ganglioside from the tumor-microenvironment.     

Investigation of DNA binding mechanism, photoinduced cleavage activity, electrochemical properties and biological functions of mixed ligand copper(II) complexes with benzimidazole derivatives: synthesis and spectral characterization

The benzimidazole derivative Schiff bases and their copper(II) (Cu(II)) mixed-polypyridyl complexes (1-4) have been synthesized and characterized by the spectral and analytical techniques. DNA binding/cleavage studies indicate a stronger binding capability for the complex 4 which is confirmed by the absorbance, viscometric and gel-electrophoresis studies. The photocleavage of plasmid pBR322 DNA reveals that hydroxyl radical (OH(?)) and singlet oxygen ((1)O(2)) are likely to be the reactive species. Analysis of the growth activity shows that the antimicrobial effect of these Schiff bases on Gram-negative bacteria is higher than that on Gram-positive. Furthermore, the complexes having nitro group show an increased antimicrobial effect.     

Association of 25-Hydroxyvitamin D status and genetic variation in the vitamin D metabolic pathway with FEV1 in the Framingham Heart Study

Background

Vitamin D is associated with lung function in cross-sectional studies, and vitamin D inadequacy is hypothesized to play a role in the pathogenesis of chronic obstructive pulmonary disease. Further data are needed to clarify the relation between vitamin D status, genetic variation in vitamin D metabolic genes, and cross-sectional and longitudinal changes in lung function in healthy adults.

Methods

We estimated the association between serum 25-hydroxyvitamin D [25(OH)D] and cross-sectional forced expiratory volume in the first second (FEV₁) in Framingham Heart Study (FHS) Offspring and Third Generation participants and the association between serum 25(OH)D and longitudinal change in FEV₁ in Third Generation participants using linear mixed-effects models. Using a gene-based approach, we investigated the association between 241 SNPs in 6 select vitamin D metabolic genes in relation to longitudinal change in FEV₁ in Offspring participants and pursued replication of these findings in a meta-analyzed set of 4 independent cohorts.

Results

We found a positive cross-sectional association between 25(OH)D and FEV₁ in FHS Offspring and Third Generation participants (P = 0.004). There was little or no association between 25(OH)D and longitudinal change in FEV₁ in Third Generation participants (P = 0.97). In Offspring participants, the CYP2R1 gene, hypothesized to influence usual serum 25(OH)D status, was associated with longitudinal change in FEV₁ (gene-based P < 0.05). The most significantly associated SNP from CYP2R1 had a consistent direction of association with FEV₁ in the meta-analyzed set of replication cohorts, but the association did not reach statistical significance thresholds (P = 0.09).

Conclusions

Serum 25(OH)D status was associated with cross-sectional FEV₁, but not longitudinal change in FEV₁. The inconsistent associations may be driven by differences in the groups studied. CYP2R1 demonstrated a gene-based association with longitudinal change in FEV₁ and is a promising candidate gene for further studies.

Electronic supplementary material

The online version of this article (doi:10.1186/s12931-015-0238-y) contains supplementary material, which is available to authorized users.     

Optimisation of a quantitative polymerase chain reaction-based strategy for the detection and quantification of human herpesvirus 6 DNA in patients undergoing allogeneic haematopoietic stem cell transplantation

Human herpesvirus 6 (HHV-6) may cause severe complications after haematopoietic stem cell transplantation (HSCT). Monitoring this virus and providing precise, rapid and early diagnosis of related clinical diseases, constitute essential measures to improve outcomes. A prospective survey on the incidence and clinical features of HHV-6 infections after HSCT has not yet been conducted in Brazilian patients and the impact of this infection on HSCT outcome remains unclear. A rapid test based on real-time quantitative polymerase chain reaction (qPCR) has been optimised to screen and quantify clinical samples for HHV-6. The detection step was based on reaction with TaqMan^® hydrolysis probes. A set of previously described primers and probes have been tested to evaluate efficiency, sensitivity and reproducibility. The target efficiency range was 91.4% with linearity ranging from 10-10⁶ copies/reaction and a limit of detection of five copies/reaction or 250 copies/mL of plasma. The qPCR assay developed in the present study was simple, rapid and sensitive, allowing the detection of a wide range of HHV-6 loads. In conclusion, this test may be useful as a practical tool to help elucidate the clinical relevance of HHV-6 infection and reactivation in different scenarios and to determine the need for surveillance.     

Effect of neurotensin on pancreatic function in man

The effect of neurotensin on submaximally-stimulated hepatobiliary and pancreatic secretion was studied in 6 healthy subjects. An intravenous infusion of neurotensin 1.4 ± 0.3 pmol/kg/min, designed to reproduce plasma neurotensin immunoreactivity levels within the physiological range, produced a significant increase in pancreatic bicarbonate output. Plasma concentrations of pancreatic polypeptide rose by 83 ± 16 pmol/l and were associated with a small reduction in trypsin, but no significant change in bilirubin outputs.