Analysis of expression profiling data suggests explanation for difficulties in finding biomarkers for nasal polyps.

BACKGROUND: Identification of clinically useful biomarkers for Nasal Polyposis in chronic rhinosinusitis (CRSwNP) has proven dif-ficult. We analyzed gene expression profiling data to find explanations for this. METHODS: We analyzed mRNA expression profiling data, GSE36830, of six uncinate tissues from healthy controls and six NP from CRSwNP patients. We performed Ingenuity Pathway Analysis (IPA) of differentially expressed genes to identify pathways and predicted upstream regulators. RESULTS: We identified 1,608 differentially expressed genes and 177 significant pathways, of which Th1 and Th2 activation pathway and leukocyte extravasation signaling were most significant. We identified 75 upstream regulators whose activity was predicted to be upregulated. These included regulators of known pathogenic and therapeutic relevance, like IL-4. However, only seven of the 75 regulators were actually differentially expressed in NP, namely CSF1, TYROBP, CCL2, CCL11, SELP, ADORA3, ICAM1. Interes-tingly, these did not include IL-4, and four of the seven were receptors. This suggested a potential explanation for the discrepancy between the predicted and observed expression levels of the regulators, namely that the receptors, and not their ligands, were upregulated. Indeed, we found that 10 receptors of key predicted upstream regulators were upregulated, including IL4R. CONCLUSION: Our findings indicate that the difficulties in finding specific biomarkers for CRSwNP depend on the complex underly-ing mechanisms, which include multiple pathways and regulators, each of which may be subdivided into multiple components such as ligands, soluble and membrane-bound receptors. This suggests that combinations of biomarkers may be needed for CRSwNP diagnostics.

Predicting poverty. Data mining approaches to the health and demographic surveillance system in Cuatro Santos, Nicaragua.

BACKGROUND: In order to further identify the needed interventions for continued poverty reduction in our study area Cuatro Santos, northern Nicaragua, we aimed to elucidate what predicts poverty, measured by the Unsatisfied Basic Need index. This analysis was done by using decision tree methodology applied to the Cuatro Santos health and demographic surveillance databases. METHODS: Using variables derived from the health and demographic surveillance update 2014, transferring individual data to the household level we used the decision tree framework Conditional Inference trees to predict the outcome "poverty" defined as two to four unsatisfied basic needs using the Unsatisfied Basic Need Index. We further validated the trees by applying Conditional random forest analyses in order to assess and rank the importance of predictors about their ability to explain the variation of the outcome "poverty." The majority of the Cuatro Santos households provided information and the included variables measured housing conditions, assets, and demographic experiences since the last update (5 yrs), earlier participation in interventions and food security during the last 4 weeks. RESULTS: Poverty was rare in households that have some assets and someone in the household that has a higher education than primary school. For these households participating in the intervention that installed piped water with water meter was most important, but also when excluding this variable, the resulting tree showed the same results. When assets were not taken into consideration, the importance of education was pronounced as a predictor for welfare. The results were further strengthened by the validation using Conditional random forest modeling showing the same variables being important as predicting the outcome in the CI tree analysis. As assets can be a result, rather than a predictor of more affluence our results in summary point specifically to the importance of education and participation in the water installation intervention as predictors for more affluence. CONCLUSION: Predictors of poverty are useful for directing interventions and in the Cuatro Santos area education seems most important to prioritize. Hopefully, the lessons learned can continue to develop the Cuatro Santos communities as well as development in similar poor rural settings around the world.

[Affinity modification of EcoRII restriction endonuclease by a DNA-duplex containing a monosubstituted pyrophosphate internucleotide bond]. / Affinnaia modifikatsiia éndonukleazy restriktsii EcoRII DNA-dupleksom, soderzhashchim monozameshchennuiu pirofosfatnuiu mezhnukleotidnuiu sviaz'.

Oligonucleotide duplex with an active monosubstituted pyrophosphate bond within the recognition site of the EcoRII restriction endonuclease was cross-linked to this enzyme with a yield of 10-15%. The cross-linking specificity was proved by the absence of the cross-linking to a DNA duplex with the same modification but without the EcoRII recognition site as well as by unmodified EcoRII substrate's inhibition of the cross-linking.

[A method for S-adenosylmethionine determination in extracts of microbial cells]. / Metod opredeleniia S-adenozilmetionina v ékstraktakh kletok mikroorganizmov.

A technique for quantification of S-adenosylmethionine in microbial cell-free extracts is proposed that involves dilution of S-adenosyl-L-(methyl-3H)methionine with non-labelled S-adenosylmethionine followed by DNA-cytosine-methyltransferase reaction. The content of S-adenosylmethionine and the activity of S-adenosylmethionine synthetase in yeasts and E. coli MRE-600 are in good agreement with the results obtained with labelled L-methionine and consistent with literature data. The sensitivity of the technique is about 0.1 nmol/0.1 ml of the reaction mixture (10(-6) M). The error was about 5% in every series of experiments. However, the combined use of different DNA-methyltransferase preparations resulted in a higher experimental error (up to 15%), which should be taken into consideration.