IL4, IL13, GSTM1 and T1 variants and susceptibility to Schistosomiasis and associated bladder pathologies in Eggua, Nigeria

Failure of the human host to elicit adequate immune responses to the adult Schistosoma haematobium worm and continuous strong inflammatory responses to the eggs have been the main causes of bladder pathology in chronic Schistosomiasis. Identification of susceptibility biomarkers for schistosomiasis- associated bladder pathology is necessary in order to detect genetic factors responsible for the infection and spread of the disease. The aim of this study was to identify candidate-biomarkers for susceptibility to schistosomiasis and its associated pathologies. A total of 371 adult participants, comprising 130 males and 241 females from Eggua community, Ogun State, Nigeria, were randomly recruited into a cross sectional study from August 2012 to May 2014. They were screened for S. haematobium ova and bladder pathologies by microscopy and ultrasonography, respectively. Human host susceptibility to schistosomiasis and its associated bladder pathologies were determined by PCR genotyping of Interleukin (IL4 and IL13) genes, and glutathione-S-transferase (GSTT1 and GSTM1) genes. The overall prevalence of S. haematobium in the population was 29.3% (108/369). Bladder pathologies were observed in 32.3% (117/362) of the population. Polymorphisms in IL 4-590 and IL 13-1055 were observed in 24.1% and 9.3% schistosomiasis cases, respectively. The IL 13-1055 polymorphism did not indicate susceptibility to schistosomiasis in males (OR 0.7, 95% CI 0.3-2.1) but a slight risk was found in females (OR 1.1, 95% CI 0.7-1.7). Participants with GSTM1 and GSTT1 polymorphisms expressed elevated risks of bladder pathologies (OR = 4.3, 95% CI 2.0 - 9.2 and OR = 4.2, 95% CI 1.5 – 12.0, respectively), with the pathology and schistosomiasis group having more GST polymorphisms than bladder pathologies. Keywords: Polymorphisms, Cytokines, GST, schistosomiasis and pathologie

X chromosome inactivation does not necessarily determine the severity of the phenotype in Rett syndrome patients

Rett syndrome (RTT) is a severe neurological disorder usually caused by mutations in the MECP2 gene. Since the MECP2 gene is located on the X chromosome, X chromosome inactivation (XCI) could play a role in the wide range of phenotypic variation of RTT patients; however, classical methylation-based protocols to evaluate XCI could not determine whether the preferentially inactivated X chromosome carried the mutant or the wild-type allele. Therefore, we developed an allele-specific methylation-based assay to evaluate methylation at the loci of several recurrent MECP2 mutations. We analyzed the XCI patterns in the blood of 174 RTT patients, but we did not find a clear correlation between XCI and the clinical presentation. We also compared XCI in blood and brain cortex samples of two patients and found differences between XCI patterns in these tissues. However, RTT mainly being a neurological disease complicates the establishment of a correlation between the XCI in blood and the clinical presentation of the patients. Furthermore, we analyzed MECP2 transcript levels and found differences from the expected levels according to XCI. Many factors other than XCI could affect the RTT phenotype, which in combination could influence the clinical presentation of RTT patients to a greater extent than slight variations in the XCI pattern

Heme Enzyme Structure and Function

The review focuses on those enzymes that catalyze oxidation reactions and those for which crystal structures are available. There are two broad classes of heme enzyme oxidants: oxygenases that use O2 to oxidize, oxygenate, substrates and peroxidases that use 2O2 to oxidize. The review demonstrates that out of the oxidants molecular oxygen is the most unusual, as O2 is not a reactive molecule despite the oxidation of nearly all biological molecules by O2 being a thermodynamically favorable process. The reason is that there is a large kinetic barrier to these reactions owing to O2 being a paramagnetic molecule so that the reaction between a majority of biological molecules that have paired spins is a spin forbidden process