Gene expression in large pedigrees: analytic approaches.

BackgroundWe currently have the ability to quantify transcript abundance of messenger RNA (mRNA), genome-wide, using microarray technologies. Analyzing genotype, phenotype and expression data from 20 pedigrees, the members of our Genetic Analysis Workshop (GAW) 19 gene expression group published 9 papers, tackling some timely and important problems and questions. To study the complexity and interrelationships of genetics and gene expression, we used established statistical tools, developed newer statistical tools, and developed and applied extensions to these tools.MethodsTo study gene expression correlations in the pedigree members (without incorporating genotype or trait data into the analysis), 2 papers used principal components analysis, weighted gene coexpression network analysis, meta-analyses, gene enrichment analyses, and linear mixed models. To explore the relationship between genetics and gene expression, 2 papers studied expression quantitative trait locus allelic heterogeneity through conditional association analyses, and epistasis through interaction analyses. A third paper assessed the feasibility of applying allele-specific binding to filter potential regulatory single-nucleotide polymorphisms (SNPs). Analytic approaches included linear mixed models based on measured genotypes in pedigrees, permutation tests, and covariance kernels. To incorporate both genotype and phenotype data with gene expression, 4 groups employed linear mixed models, nonparametric weighted U statistics, structural equation modeling, Bayesian unified frameworks, and multiple regression.Results and discussionRegarding the analysis of pedigree data, we found that gene expression is familial, indicating that at least 1 factor for pedigree membership or multiple factors for the degree of relationship should be included in analyses, and we developed a method to adjust for familiality prior to conducting weighted co-expression gene network analysis. For SNP association and conditional analyses, we found FaST-LMM (Factored Spectrally Transformed Linear Mixed Model) and SOLAR-MGA (Sequential Oligogenic Linkage Analysis Routines -Major Gene Analysis) have similar type 1 and type 2 errors and can be used almost interchangeably. To improve the power and precision of association tests, prior knowledge of DNase-I hypersensitivity sites or other relevant biological annotations can be incorporated into the analyses. On a biological level, eQTL (expression quantitative trait loci) are genetically complex, exhibiting both allelic heterogeneity and epistasis. Including both genotype and phenotype data together with measurements of gene expression was found to be generally advantageous in terms of generating improved levels of significance and in providing more interpretable biological models.ConclusionsPedigrees can be used to conduct analyses of and enhance gene expression studies

A study to determine similarities and variances among medical-surgical nursing instructors in rating selected science principles underlying the nursing care of a patient with an ileostomy

Thesis (M.S.)--Boston Universit

Sustainable Agricultural Bioindustry Development: Integration of Cassava Cultivation with Beef Cattle Husbandry in North Sulawesi Province

This paper reviews the potential sustainable agricultural bioindustry development based on animal feed and organic fertilizer through an integration between crops cultivation with livestock production. This bio-industrial development could be carried out successfully in Indonesia, including in the region of North Sulawesi Province. Cattle feed bioindustry could be developed from biomass of cassava plantation, such as the cassava leaves, tubers and cassava peelers. Whereas, the solid and liquid organic fertilizers bioindustry could be developed from cattle feces and urine. Agricultural bioindustry can be carried out in all areas of North Sulawesi Province, because almost in every district has beef cattle and cassava plants. The largest cassava production in North Sulawesi Province are in the regencies of Bolaang Mongondow, Sangihe Island and Talaud Island. Whereas the highest population of beef cattle are in the regencies of Bolaang Mongondow, North Bolaang Mongondow, Minahasa, North Minahasa and South Minahasa. Therefore, this type of bioindustry will be well implemented in the three regencies of Bolaang Mongondow, Minahasa and North Minahasa, as there are large cassava plants and with a high livestock population in these three areas. Although numbers of beef cattle population are also higher in some other regencies, but the production of cassava in those areas are still very small

Impact of glucuronide interferences on therapeutic drug monitoring of posaconazole by tandem mass spectrometry

Background: Posaconazole is a novel antifungal drug for oral application intended especially for therapy of invasive mycoses. Due to variable gastrointestinal absorption, adverse side effects, and suspected drug-drug interactions, therapeutic drug monitoring (TDM) of posaconazole is recommended. Method: A fast ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for quantification of posaconazole with a run-time <3 min was developed and compared to a LC-MS/MS method and HPLC method with fluorescence detection. Results: During evaluation of UPLC-MS/MS, two earlier eluting peaks were observed in the MRM trace of posaconazole. This was only seen in patient samples, but not in spiked calibrator samples. Comparison with LC-MS/MS disclosed a significant bias with higher concentrations measured by LC-MS/MS, while UPLC-MS/MS showed excellent agreement with the commercially available HPLC method. In the LC-MS/MS procedure, comparably wide and left side shifted peaks were noticed. This could be ascribed to in-source fragmentation of conjugate metabolites during electrospray ionisation. Precursor and product ion scans confirmed the assumption that the additional compounds are posaconazole glucuronides. Reducing the cone voltage led to disappearance of the glucuronide peaks. Slight modification of the LC-MS/MS method enabled separation of the main interference, leading to significantly reduced deviation. Conclusions: These results highlight the necessity to reliably eliminate interference from labile drug metabolites for correct TDM results, either by sufficient separation or selective MS conditions. The presented UPLC-MS/MS method provides a reliable and fast assay for TDM of posaconazole. Clin Chem Lab Med 2010; 48:1723-31

Introducing of plant species through the sowing of crops in the Balearic Islands

S'han analitzat mostres de lots de llavors de cinc espècies de plantes cultivades per a conèixer el problema de la presència de llavors d'espècies no desitjades. S'han identificat llavors de 50 espècies diferents entre les quals destaquen Abutilon theophrasti, Amaranthus spp., Datura stramonium i Cichorium endivia ssp. divaricatum. També s'ha identificat Echinaria capitata, una espècie mediterrània però que no s'ha citat mai a les Illes Balears. Les mostres que pertanyen a lots de llavors no certificats mostren una presència notablement superior de llavors contaminants que els lots certificats, doncs hem trobat fins a un 5,8% de llavors no desitjades i fins a 37 tipus diferents de llavors contaminants en una sola mostra. Però aquest treball demostra que la regulació de certificació de llavors no elimina el problema de la introducció de noves espècies a les Illes. Per això es recomana endurir aquesta regulació tant quantitativament com qualitativa.Lots of commercial seeds of five plant species were analysed to get a better understanding of the problem of the presence of seeds of non desirable species. Fifty different species were identified, amongst them standout: Abutilon theophrasti, Amaranthus spp., Datura stramonium and Cichorium endivia ssp. divaricatum. Also identified was Echinaria capitata, a Mediterranean species that has never been cited in the Balearic Islands. The samples that pertained to non-certified seeds showed a notable higher presence of contaminated seeds than those from the certified lots: the former lots had up to 5.8% of undesirable seeds and up to 37 different types of contaminating seeds in a single sample. However, this communication shows that the regulation of contaminated seeds does not eliminate the introduction of new species to the Islands. For this reason, it is recommended that the regulations should be stiffened both quantitatively as well as qualitatively

Testing Intra-Industry Trade Between Portugal and Spain [1990-1996]

This paper shows how, in the period 1990-1996, economic integration between the two Iberian economies has deepened through intra-industry trade. The enquiry was led at the level of the main forty traded products. In this context, several tests have been made. Our analysis combines first the application of the Grubel and Lloyd index of the main forty products and the marginal intra-industry trade of Brulhart, and Brulhart and Elliot. On the basis of these indexes we defined our criterion for the selection of the competitive cluster of Portugal throughout the period. We have also considered the global intra-industry trade, in nominal and real terms, according to the method of Greenaway et al. In econometric terms we have tried to know which is the relation between the intra-industry trade index and the marginal intra-industry trade at the level of the main forty products, the results however were not unequivocal. The same is true as far as concerns the relation between the intra-industry trade index and the net export position at the level of the same products. Despite the fact that some attempts have been inconclusive, knowledge about Iberian trade has developed in a field essential to its upgrading, and the way is open for further research.intra-industry trade; marginal intra-industry trade; competitive cluster; net export position.

Sensory substitution for space gloves and for space robots

Sensory substitution systems for space applications are described. Physical sensors replace missing human receptors and feed information to the interpretive centers of a different sense. The brain is plastic enough so that, with training, the subject localizes the input as if it were received through the missing receptors. Astronauts have difficulty feeling objects through space suit gloves because of their thickness and because of the 4.3 psi pressure difference. Miniature force sensors on the glove palm drive an electrotactile belt around the waist, thus augmenting the missing tactile sensation. A proposed teleoperator system with telepresence for a space robot would incorporate teleproprioception and a force sensor/electrotactile belt sensory substitution system for teletouch