Steroid sulfatase is a potential modifier of cognition in attention deficit hyperactivity disorder

Deletions encompassing the X-linked STS gene (encoding steroid sulfatase) have been observed in subjects with neurodevelopmental disorders, including attention deficit hyperactivity disorder (ADHD). Recently, two single nucleotide polymorphisms (SNPs) within STS (rs12861247 and rs17268988) have been reported to be associated with ADHD risk and inattentive symptoms in ADHD, respectively. Using a UK sample of ADHD subjects (aged 5-18 years), we tested the hypothesis that rs12861247 is associated with ADHD risk using a case-control approach (comparing 327 ADHD cases with 358 male controls from the Wellcome Trust Case Control Consortium). Using a subset of males from the ADHD sample, we also examined whether variation within STS is associated with symptomatology/cognitive function in ADHD. We then tested whether SNPs associated with cognitive function in ADHD were also associated with cognitive function in healthy male subjects using a German sample (n = 143, aged 18-30 years), and whether STS was expressed in brain regions pertinent to ADHD pathology during development. We did not replicate the previously identified association with rs12861247. However, in ADHD males, variation at rs17268988 was associated with inattentive symptoms, while variation within STS was significantly associated with performance on three cognitive measures. Three SNPs associated with cognitive function in ADHD males were not associated with cognitive function in healthy males. STS was highly expressed in the developing cerebellar neuroepithelium, basal ganglia, thalamus, pituitary gland, hypothalamus and choroid plexus. These data suggest that genetic variants affecting STS expression and/or activity could influence the function of brain regions perturbed in ADHD.     

A subset of small nuclear ribonucleoprotein particle antigens is a component of the nuclear matrix

We have assessed whether antigenic proteins associated with small nuclear ribonucleoprotein particles (snRNP) are associated with the nuclear matrix. Immunofluorescence studies showed that a subset of these particles (those reactive with anti-Sm antisera) were associated with the nuclear matrix, while a different set of particles (those reactive with anti-La antisera) were not associated with the nuclear matrix. Immunoprecipitation experiments showed that three specific polypeptide components of the snRNP reactive with the anti-Sm antisera were significantly enriched in nuclear matrix proteins.     

Association between lncRNA-H19 polymorphisms and hepatoblastoma risk in an ethic Chinese population

H19 polymorphisms are associated with increased susceptibility to several cancers; however, their role in hepatoblastoma remains unclear. In this study, we investigated the association between three H19 polymorphisms (rs2839698 G>A, rs3024270 C>G, rs217727 G>A) and hepatoblastoma susceptibility in 213 hepatoblastoma patients. The rs2839698 and rs3024270 polymorphisms were associated with significantly increased hepatoblastoma risk, with the GG genotype associated with a higher risk of hepatoblastoma than the CC genotype at the rs3024270 locus. The rs217727 polymorphism was associated with significantly decreased hepatoblastoma risk, with the AG genotype associated with a lower risk of hepatoblastoma than the GG genotype. These findings were confirmed by combined analysis, and stratification analysis revealed that age, gender and clinical stage were associated with increased hepatoblastoma susceptibility. The GGG and AGG haplotypes were significantly associated with increased hepatoblastoma risk compared with the GCA reference (rs2839698, rs3024270, rs217727). The rs2839698 and rs3024270 polymorphisms correlated with decreased MRPL23-AS1 expression, whereas the rs217727 polymorphism was associated with increased MRPL23-AS1 expression. Overall, the H19 rs2839698, rs3024270 and rs217727 polymorphisms were associated with hepatoblastoma susceptibility in a Chinese Han population.     

The relationship between psychosocial stress, age, BMI, CRP, lifestyle, and the metabolic syndrome in apparently healthy subjects

The aim of this cross-sectional study was to examine the factors which may be associated with the metabolic syndrome by exploring the relationship between psychosocial stress, age, body mass index (BMI), C-reactive protein (CRP), lifestyle factors, and the components of the metabolic syndrome, such as glycated hemoglobin (HbA1c), fasting blood sugar (FBS), body fat percentage, and triglyceride concentration, among apparently healthy subjects. Psychosocial stress was measured by the use of the inventory to measure psychosocial stress (IMPS). One thousand four hundred and ninety-nine people out of 1,941 public school workers admitted to a hospital for a medical check-up responded to the IMPS, yielding a response rate of 77.2%. A total of 1,201 workers excluding 298 who were taking medication for various diseases were analyzed with the use of hierarchical multiple regression models. It was found that IMPS-measured stress score, age, BMI, and smoking habit were associated with an increase in glycated hemoglobin among men, while alcohol consumption was associated with a decrease in glycated hemoglobin. Stress score, age, BMI, and alcohol consumption were found to be associated with an increase in FBS among men, while smoking and exercise habits were associated with a decrease in FBS. CRP was found to be associated with an increase in body fat percentage among men, though stress score was not associated with an increase in body fat percentage. Stress score, age, and BMI were associated with an increase in triglyceride concentration among women. The findings of the present study seem to be in line with the hypothesis that psychosocial stress plays an important role in developing the metabolic syndrome, which may be associated with inflammatory processes in the vascular wall, resulting in atherosclerosis and cardiovascular disease.     

Auditory imagery associated with Japanese onomatopoeic representation

When we want to express the subjective impression of sound, we usually use onomatopoeias. We investigated the relationship between the impression of auditory imagery associated with Japanese onomatopoeic representation and onomatopoeic features. Subjects rated the impressions of auditory imageries associated with 40 onomatopoeias on semantic differential scales. Principal component analysis was applied to the rating data and the scales were integrated to the components of beauty, potency and sharpness. We determined the relationship between phonetic features of onomatopoeias and tonal features of the auditory imageries on the obtained principal components. Onomatopoeic representations that included voiced consonants were associated with a "dirty" impression. Onomatopoeic representations that contained approximant sounds were associated with a "powerful" impression. The vowel /i/ was associated with a "sharp" impression and vowels /u/ and /o/ were associated with a "dull" impression. The obtained tendencies confirmed that some onomatopoeic features reflected particular impressions of auditory imagery.     

Three-dimensional reconstruction of tubulin in zinc-induced sheets: II. Consequences of removal of microtubule associated proteins

The three-dimensional structure of zinc-induced tubulin sheets freed of microtubule associated proteins has been determined to 20 Å resolution by electron microscopy and image reconstruction. The determination was carried out with porcine brain tubulin separated from microtubule associated proteins by phosphocellulose chromatography. Negatively stained samples were tilted using the goniometer stage of the electron microscope to provide images of the tubulin sheets ranging in tilt from ?60 ° to +60 °. The micrographs were digitized and subjected to a cross-correlation analysis to compensate for smooth curvature of the lattice in the sheets. For each angle of tilt, an average unit cell was obtained from the cross-correlation analysis and subsequently a Fourier transform was computed for inclusion in the three-dimensional Fourier data set. The transforms of 47 tilted images plus the average of five untilted sheets were combined and an inverse Fourier transform was applied to give a threedimensional reconstruction of the microtubule associated protein-free tubulin sheets. Comparison of the protofilament structure in these sheets with the previously published protofilament structure of zinc-induced tubulin sheets containing microtubule associated proteins reveals a number of consequences of the removal of microtubule associated proteins. (1) The extensive internal contact along the protofilament observed in microtubule associated protein-containing tubulin sheets is maintained in microtubule associated protein-free tubulin sheets. (2) In projection, the protofilaments in microtubule associated protein-free tubulin sheets are 2.2 Å closer together than in microtubule associated protein-tubulin sheets. (3) The deviations of adjacent protofilaments from the plane of the sheets when viewed end-on are more pronounced in the absence of microtubule associated proteins. Differences are also observed at the level of individual tubulin subunits. In particular, the distinct cleft which was found in one class of subunits in tubulin sheets with microtubule associated proteins is absent in the microtubule associated protein-free tubulin sheets. The loss of this cleft and some changes in the shape of the tubulin subunits upon removal of microtubule associated proteins suggest a possible site for the interaction of tubulin with microtubule associated proteins.     

p68 Sam is a substrate of the insulin receptor and associates with the SH2 domains of p85 PI3K.

The 68 kDa Src substrate associated during mitosis is an RNA binding protein with Src homology 2 and 3 domain binding sites. A role for Src associated in mitosis 68 as an adaptor protein in signaling transduction has been proposed in different systems such as T-cell receptors. In the present work, we have sought to assess the possible role of Src associated in mitosis 68 in insulin receptor signaling. We performed in vivo studies in HTC-IR cells and in vitro studies using recombinant Src associated in mitosis 68, purified insulin receptor and fusion proteins containing either the N-terminal or the C-terminal Src homology 2 domain of p85 phosphatidylinositol-3-kinase. We have found that Src associated in mitosis 68 is a substrate of the insulin receptor both in vivo and in vitro. Moreover, tyrosine-phosphorylated Src associated in mitosis 68 was found to associate with p85 phosphatidylinositol-3-kinase in response to insulin, as assessed by co-immunoprecipitation studies. Therefore, Src associated in mitosis 68 may be part of the signaling complexes of insulin receptor along with p85. In vitro studies demonstrate that Src associated in mitosis 68 associates with the Src homology 2 domains of p85 after tyrosine phosphorylation by the activated insulin receptor. Moreover, tyr-phosphorylated Src associated in mitosis 68 binds with a higher affinity to the N-terminal Src homology 2 domain of p85 compared to the C-terminal Src homology 2 domain of p85, suggesting a preferential association of Src associated in mitosis 68 with the N-terminal Src homology 2 domain of p85. This association may be important for the link of the signaling with RNA metabolism.     

The function of proteins that interact with mRNA

Specific proteins are associated with mRNA in the cytoplasm of eukaryotic cells. The complement of associated proteins depends upon whether the mRNA is an integral component of the polysomal complex being translated, or, alternatively, whether it is part of the non-translated free mRNP fraction. By subjecting cells to ultraviolet irradiation in vivo to cross-link proteins to mRNA, mRNP proteins have been shown to be associated with specific regions of the mRNA molecule. Examination of mRNP complexes containing a unique mRNA has suggested that not all mRNA contain the same family of associated RNA binding proteins. The function of mRNA associated proteins may include a role in providing stability for mRNA, and/or in modulating translation. With the recent demonstrations that both free and polysomal mRNPs are associated with the cytoskeletal framework, specific mRNP proteins may play a role in determining the subcellular localization of specific mRNPs.     

Pyoderma gangrenosum associated with primary thrombocythaemia.

Pyoderma gangrenosum is most commonly associated with inflammatory bowel disease and rheumatoid arthritis, but it has been associated with various haematological malignancies. A 54-year-old man with no history of bowel disease or arthritis presented with a leg ulcer, which healed after treatment. Results of bone marrow aspiration were compatible with primary thrombocythaemia. Seven weeks later there were pronounced recurrence of the ulceration and pyoderma gangrenosum was diagnosed. The appearance of pyoderma gangrenosum associated with blood disorders may differ from that associated with bowel and joint disease.     

Microbial communities associated with skeletal tumors on Porites compressa

Coral tumors are atypical skeletal forms found on coral reefs worldwide. Here we present an analysis of the microbial communities associated with skeletal tumors on the coral Porites compressa. Microbial growth rates on both healthy and tumorous P. compressa were decoupled from the surrounding water column. Microbial communities associated with tumorous colonies had a significantly faster growth rate than those associated with healthy P. compressa. The microbial community associated with the tumors contained more culturable Vibrio spp. and could utilize more carbon sources than the microbes associated with healthy colonies. Presence of tumors affected the composition and dynamics of the microbial population associated with the entire colony.     

Genetic Variation of the Human Urinary Tract Innate Immune Response and Asymptomatic Bacteriuria in Women

Background

Although several studies suggest that genetic factors are associated with human UTI susceptibility, the role of DNA variation in regulating early in vivo urine inflammatory responses has not been fully examined. We examined whether candidate gene polymorphisms were associated with altered urine inflammatory profiles in asymptomatic women with or without bacteriuria.

Methodology

We conducted a cross-sectional analysis of asymptomatic bacteriuria (ASB) in 1,261 asymptomatic women ages 18-49 years originally enrolled as participants in a population-based case-control study of recurrent UTI and pyelonephritis. We genotyped polymorphisms in CXCR1, CXCR2, TLR1, TLR2, TLR4, TLR5, and TIRAP in women with and without ASB. We collected urine samples and measured levels of uropathogenic bacteria, neutrophils, and chemokines.

Principal Findings

Polymorphism TLR2_G2258A, a variant associated with decreased lipopeptide-induced signaling, was associated with increased ASB risk (odds ratio 3.44, 95%CI; 1.65–7.17). Three CXCR1 polymorphisms were associated with ASB caused by gram-positive organisms. ASB was associated with urinary CXCL-8 levels, but not CXCL-5, CXCL-6, or sICAM-1 (P≤0.0001). Urinary levels of CXCL-8 and CXCL-6, but not ICAM-1, were associated with higher neutrophil levels (P≤0.0001). In addition, polymorphism CXCR1_G827C was associated with increased CXCL-8 levels in women with ASB (P = 0.004).

Conclusions

TLR2 and CXCR1 polymorphisms were associated with ASB and a CXCR1 variant was associated with urine CXCL-8 levels. These results suggest that genetic factors are associated with early in vivo human bladder immune responses prior to the development of symptomatic UTIs.     

Glycosylation and rheumatic disease

Rheumatoid arthritis (RA) and other rheumatic diseases are associated with a significant defect in the galactosyltransferase enzyme that results in a profound change in the galactosylation of immunoglobulin G. This change has been demonstrated to be integrally associated with pathogenic mechanisms associated with inflammation in RA. It is not thought that these changes are unique to RA, but it is thought that there may be subtle changes in the disruption of glycosylation homeostasis causing a unique sugar change to be associated with a number of other rheumatic diseases. This is referred to as 'sugar printing the rheumatic diseases' and may be a concept useful both diagnostically and therapeutically.     

Locating QTL for osmotic adjustment and dehydration tolerance in rice

Research was conducted to identify and map quantitative traitloci (QTL) associated with dehydration tolerance and osmoticadjustment of rice. Osmotic adjustment capacity and lethal osmoticpotential were determined for 52 recombinant inbred lines grownin a controlled environment under conditions of a slowly developedstress. The lines were from a cross between an Indica cultivar,Co39, of lowland adaptation and a Japonica cultivar, Moroberekan,a traditional upland cultivar. The QTL analysis was conductedusing single marker analysis (ANOVA) and interval analysis (Mapmaker/QTL).The measurements obtained and the QTL identified were comparedto root traits and leaf rolling scores measured on the samelines. One major locus was associated with osmotic adjustment. Theputative locus for osmotic adjustment may be homoeologous witha single recessive gene previously identified for the same traitin wheat. The putative osmotic adjustment locus and two of thefive QTL associated with dehydration tolerance were close tochromosomal regions associated with root morphology. In thispopulation, osmotic adjustment and dehydration tolerance werenegatively associated with root morphological characters associatedwith drought avoidance. High osmotic adjustment and dehydrationtolerance were associated with Co39 alleles and extensive rootsystems were associated with Moroberekan alleles. To combinehigh osmotic adjustment with extensive root systems, the linkagebetween these traits will need to be broken. Alternatively,if the target environment is a lowland environment with onlybrief water deficit periods, selection for drought tolerancecharacteristics without consideration of the root system maybe most appropriate. Key words: Drought, rice, osmotic adjustment, dehydration tolerance, molecular markers, QTL, breeding     

An independent validation study of loci associated with nematode resistance in sheep

Gastrointestinal nematode infection is a constraint on sheep production worldwide. Selective breeding programmes to enhance resistance to nematode infection are currently being implemented in a number of countries. Identification of loci associated with resistance to infection or causative mutations for resistance would enable more effective selection. Loci associated with indicator traits for nematode resistance has been identified in previous studies. In this study, Scottish Blackface, Texel and Suffolk lambs were used to validate the effects at eight genomic regions previously associated with nematode resistance (OAR3, 4, 5, 7, 12, 13, 14, 21). No SNP was significantly associated with nematode resistance at the region‐wide level but seven SNPs in three of the regions (OAR4, 12, 14) were nominally associated with trichostrongyle egg count in this study and six of these were also significant when fitted as single SNP effects. Nematodirus egg count was nominally associated with SNPs on OAR3, 4, 7 and 12.     

Factors associated with a purine-rich exonic splicing enhancer sequence in Xenopus oocyte nucleus

Purine-rich exonic splicing enhancers (ESEs) stimulate splicing of the adjacent introns with suboptimal splice sites. To elucidate the mechanism regarding ESEs, factors specifically associated with ESEs in HeLa cell nuclear extracts were previously investigated, and shown to include SR (serine/arginine-rich) proteins. However, factors associated with ESEs in vivo have not yet been explored. Here we show that a GAA repeat RNA sequence, a typical ESE, is associated in Xenopus oocyte nuclei with at least one SR protein, SF2/ASF, as was expected. Moreover, components of SF3a/b complexes, U2 snRNA, and U2AF(65) were also found to be associated with the ESE in the nucleus. Since SF3a/b complexes are the constituents of the 17S U2 snRNP, these results suggest that the 17S U2 snRNP is associated with the ESE in the nucleus, probably through bridging interactions of U2AF and SR proteins. The identified factors may represent a functional splicing enhancer complex in vivo.     

Prevalence of psammoma bodies in Papanicolaou-stained cervicovaginal smears

Reports from sequential series of 234,318 cervicovaginal smears from a period of three years were reviewed to ascertain the prevalence and significance of psammoma bodies. Seven smears contained psammoma bodies. Three of the seven were associated with benign conditions and four were associated with a cancer (two serous papillary endometrial adenocarcinomas, one ovarian serous cystadenocarcinoma and one serous papillary carcinoma of the peritoneum). The prevalence of psammoma bodies in benign cases was much higher than reported in previous studies, in which most findings of psammoma bodies were associated with malignancy, particularly ovarian carcinoma. A consistent and useful feature in distinguishing psammoma bodies associated with benign or malignant disease was the presence of a few adherent small bland-appearing glandular cells in benign disorders and adherent malignant glandular cells in cases of carcinoma. A more conservative work-up may be merited in young women with clearly benign cells associated with psamoma bodies in a cervicovaginal smear and an otherwise negative physical examination and noncontributory endometrial sampling.     

Structural plasticity associated with the beta-propeller architecture

The beta-propeller architecture observed in protein tertiary structure and classified into the five different types according to number of 'blades' (or beta-sheets) and a sixth type classified according to the secondary structure composition of the blades (the beta beta alpha beta-molecular unit) is characterized by variations (or plasticity) in the structure. These correspond to the number of beta-strands associated with the blade, the number of amino acid residues associated with equivalent beta-strands in the different blades and the presence of alpha-helices and twisted beta-strands. We have generated a beta-sheet associated beta-strand pattern that may be important for protein structure prediction and modeling. Analysis of the beta-propellers extracted primarily from the SCOP database revealed there are 179 beta-propellers. The examination of the secondary structure corresponding to the beta-propeller using PDBsum that was useful to define the beta-sheet associated beta-strand pattern, combined with visualization on graphics display revealed structural plasticity associated with the beta-propeller architecture. Particularly, the type 6- and 7-bladed beta-propellers known to be associated with sequence and functional diversity are more common and associated with relatively more structural variations compared to the other beta-propeller types.