RET mutational spectrum in Hirschsprung disease: evaluation of 601 Chinese patients

Rare (RVs) and common variants of the RET gene contribute to Hirschsprung disease (HSCR; congenital aganglionosis). While RET common variants are strongly associated with the commonest manifestation of the disease (males; short-segment aganglionosis; sporadic), rare coding sequence (CDS) variants are more frequently found in the lesser common and more severe forms of the disease (females; long/total colonic aganglionosis; familial).Here we present the screening for RVs in the RET CDS and intron/exon boundaries of 601 Chinese HSCR patients, the largest number of patients ever reported. We identified 61 different heterozygous RVs (50 novel) distributed among 100 patients (16.64%). Those include 14 silent, 29 missense, 5 nonsense, 4 frame-shifts, and one in-frame amino-acid deletion in the CDS, two splice-site deletions, 4 nucleotide substitutions and a 22-bp deletion in the intron/exon boundaries and 1 single-nucleotide substitution in the 5' untranslated region. Exonic variants were mainly clustered in RET the extracellular domain. RET RVs were more frequent among patients with the most severe phenotype (24% vs. 15% in short-HSCR). Phasing RVs with the RET HSCR-associated haplotype suggests that RVs do not underlie the undisputable association of RET common variants with HSCR. None of the variants were found in 250 Chinese controls.     

Evaluation of Beauveria bassiana (Hyphomycetes) isolates as potential agents for control of Dendroctonus valens

Abstract The red turpentine beetle (RTB), Dendroctonus valens LeConte, as a destructive invasive pest, has become one of the most economically important forest pest in China. Effective control measures are desperately needed. Entomopathogenic fungi, such as Beauveria bassiana, have shown great potential for the management of some bark beetle species. In this study, 12 isolates of B. bassiana from bark beetle were examined for biological characteristics and virulence, to assess their potential as biocontrol agents for RTB. There were significant differences (at P= 0.05) in colony growth rate, conidial yield, conidial germination, tolerance to UV light and extracellular proteases activity among the tested B. bassiana isolates. Isolates, including Bb1801, Bb1906, Bb789 and Bb773, exhibited the best characteristics, because they have faster hyphal growth rate, higher spore production and faster spore germination, higher UV tolerance and protease (Pr1) production. The results of a pathogenicity test of B. bassiana on RTB larvae showed that most isolates of B. bassiana have demonstrated high efficacy and the highest virulent isolate was Bb1801, which killed 100% of the treated insects and had a median lethal time (LT₅₀) of 4.60 days at a concentration of 1×10⁷ conidia/mL. Therefore, isolate Bb1801 has a great potential for sustainable control of RTB in the forest. The correlation between biological characteristics and virulence of the fungal isolates is discussed and the possibility of combination of entomopathogenic fungi with semiochemicals, as one of the promising strategy for RTB control, is considered.     

csd alleles in the red dwarf honey bee (Apis florea,Hymenoptera: Apidae) show exceptionally high nucleotide diversity

Abstract The single locus complementary sex determination (sl‐csd) gene is the primary gene determining the gender of honey bees (Apis spp.). While the csd gene has been well studied in the Western honey bee (Apis mellifera), and comparable data exist in both the Eastern honey bee (Apis cerana) and the giant honey bee (Apis dorsata), no studies have been conducted in the red dwarf honey bee, Apis florea. In this study we cloned the genomic region 3 of the A. florea csd gene from 60 workers, and identified 12 csd alleles. Analysis showed that similar to A. mellifera, region 3 of the csd gene contains a RS domain at the N terminal, a proline‐rich domain at the C terminal, and a hypervariable region in the middle. However, the A. florea csd gene possessed a much higher level of nucleotide diversity, compared to A. mellifera, A. cerana and Apis dorsata. We also show that similar to the other three Apis species, in A. florea, nonsynonymous mutations in the csd gene are selectively favored in young alleles.     

Comparative study of SVM methods combined with voxel selection for object category classification on fMRI data

Background

Support vector machine (SVM) has been widely used as accurate and reliable method to decipher brain patterns from functional MRI (fMRI) data. Previous studies have not found a clear benefit for non-linear (polynomial kernel) SVM versus linear one. Here, a more effective non-linear SVM using radial basis function (RBF) kernel is compared with linear SVM. Different from traditional studies which focused either merely on the evaluation of different types of SVM or the voxel selection methods, we aimed to investigate the overall performance of linear and RBF SVM for fMRI classification together with voxel selection schemes on classification accuracy and time-consuming.

Methodology/Principal Findings

Six different voxel selection methods were employed to decide which voxels of fMRI data would be included in SVM classifiers with linear and RBF kernels in classifying 4-category objects. Then the overall performances of voxel selection and classification methods were compared. Results showed that: (1) Voxel selection had an important impact on the classification accuracy of the classifiers: in a relative low dimensional feature space, RBF SVM outperformed linear SVM significantly; in a relative high dimensional space, linear SVM performed better than its counterpart; (2) Considering the classification accuracy and time-consuming holistically, linear SVM with relative more voxels as features and RBF SVM with small set of voxels (after PCA) could achieve the better accuracy and cost shorter time.

Conclusions/Significance

The present work provides the first empirical result of linear and RBF SVM in classification of fMRI data, combined with voxel selection methods. Based on the findings, if only classification accuracy was concerned, RBF SVM with appropriate small voxels and linear SVM with relative more voxels were two suggested solutions; if users concerned more about the computational time, RBF SVM with relative small set of voxels when part of the principal components were kept as features was a better choice.     

Effects of substituted phenylethylamines on blowfly feeding behavior

The pharmacology of adult Phormia regina (Meigen) feeding behavior was explored by injecting candidate drugs into starved blowflies and then determining their responsiveness to aqueous sucrose, via the proboscis extension reflex. d-Amphetamine caused responsiveness to fall dramatically, while related drugs and biogenic amines had varying effects. When d-amphetamine-treated flies were fed 1 M sucrose, they consumed significantly more than control flies. Electrophysiological studies demonstrated that the responses of tarsal sugar receptor neurons to aqueous sucrose were not significantly altered by d-amphetamine. These observations are compatible with our hypothesis that octopamine positively modulates blowfly feeding behavior and suggest that other aromatic biogenic amines affect feeding behavior in this insect.     

DNA sequence evidence for polymorphic forms of human serum amyloid A (SAA)

Serum amyloid A (SAA) is an acute-phase reactant and precursor to amyloid A protein, the major constituent of the fibril deposits of reactive amyloidosis. The factors determining whether the 104-amino acid SAA molecule is converted into the 76-amino acid amyloid A protein and deposited as fibrils are not known. As an initial step toward investigating the possibility that a particular primary structure of SAA is involved in amyloid formation, we have cloned and determined the nucleotide sequence of human SAA-specific cDNAs. The first clone, selected using an oligonucleotide probe, was shown to encode the signal peptide and amino-terminal region of SAA. The cDNA of this clone served as probe in the selection of two distinct, full-length SAA cDNAs, initially differentiated by the presence (pSAA21) or absence (pSAA82) of a PstI site in the coding sequence. The complete nucleotide sequence of pSAA82 cDNA was determined. Since there appear to be multiple human SAA alleles, it is conceivable that their differential expression is important to amyloid formation.