The dominant 55kDa allergen of the subtropical Bahia grass (Paspalum notatum) pollen is a group 13 pollen allergen, Pas n 13

Bahia grass, Paspalum notatum, is an important pollen allergen source with a long season of pollination and wide distribution in subtropical and temperate regions. We aimed to characterize the 55. kDa allergen of Bahia grass pollen (BaGP) and ascertain its clinical importance. BaGP extract was separated by 2D-PAGE and immunoblotted with serum IgE of a grass pollen-allergic patient. The amino-terminal protein sequence of the predominant allergen isoform at 55. kDa had similarity with the group 13 allergens of Timothy grass and maize pollen, Phl p 13 and Zea m 13. Four sequences obtained by rapid amplification of the allergen cDNA ends represented multiple isoforms of Pas n 13. The predicted full length cDNA for Pas n 13 encoded a 423 amino acid glycoprotein including a signal peptide of 28 residues and with a predicted pI of 7.0. Tandem mass spectrometry of tryptic peptides of 2D gel spots identified peptides specific to the deduced amino acid sequence for each of the four Pas n 13 cDNA, representing 47% of the predicted mature protein sequence of Pas n 13. There was 80.6% and 72.6% amino acid identity with Zea m 13 and Phl p 13, respectively. Reactivity with a Phl p 13-specific monoclonal antibody AF6 supported designation of this allergen as Pas n 13. The allergen was purified from BaGP extract by ammonium sulphate precipitation, hydrophobic interaction and size exclusion chromatography. Purified Pas n 13 reacted with serum IgE of 34 of 71 (48%) grass pollen-allergic patients and specifically inhibited IgE reactivity with the 55. kDa band of BaGP for two grass pollen-allergic donors. Four isoforms of Pas n 13 from pI 6.3-7.8 had IgE-reactivity with grass pollen allergic sera. The allergenic activity of purified Pas n 13 was demonstrated by activation of basophils from whole blood of three grass pollen-allergic donors tested but not control donors. Pas n 13 is thus a clinically relevant pollen allergen of the subtropical Bahia grass likely to be important in eliciting seasonal allergic rhinitis and asthma in grass pollen-allergic patients.

PTHR1 polymorphisms influence BMD variation through effects on the growing skeleton

We investigated whether polymorphisms in PTHR1 are associated with bone mineral density (BMD), to determine whether the association of this gene with BMD was due to effects on attainment of peak bone mass or effects on subsequent bone loss. The PTHR1 gene, including its 14 exons, their exon-intron boundaries, and 1,500 bp of its promoter region, was screened for polymorphisms by denaturing high-performance liquid chromatography (dHPLC) and sequencing in 36 osteoporotic cases. Eleven single-nucleotide polymorphisms (SNPs), one tetranucleotide repeat, and one tetranucleotide deletion were identified. A cohort of 634 families, including 1,236 men (39%) and 1,926 women (61%) ascertained with probands with low BMD (Z< -2.0) and the Children in Focus subset of the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort (785 unrelated individuals, mean age 118 months), were genotyped for the five most informative SNPs (minor allele frequency >5%) and the tetranucleotide repeat. In our osteoporosis families, association was noted between lumbar spine BMD and alleles of a known functional tetranucleotide repeat (U4) in the PTHR1 promoter region (P = 0.042) and between two and three marker haplotypes of PTHR1 polymorphisms with lumbar spine, femoral neck, and total hip BMD (P = 0.021-0.047). This association was restricted to the youngest tertile of the population (age 16-39 years, P = 0.013-0.048). A similar association was found for the ALSPAC cohort: two marker haplotypes of SNPs A48609T and C52813T were associated with height (P = 0.006) and total body less head BMD (P = 0.02), corrected for age and gender, confirming the family findings. These findings suggest a role for PTHR1 variation in determining peak BMD.

Synthesis and luminescent properties of star-burst D-Pi-A compounds based on 1,3,5-triazine core and carbazole end-capped phenylene ethynylene arms

Two new star-burst compounds based on 1,3,5-triazine core and carbazole end-capped phenylene ethynylene arms (1a and 1b) were synthesized and characterized. Their photophysical properties were investigated systematically via spectroscopic and theoretical methods. Both compounds exhibit strong 1π–π⁎ transitions in the UV region and intense 1π–π⁎/intramolecular charge transfer (1ICT) absorption bands in the UV–vis region. Introducing the carbazole end-capped phenylene ethynylene arm on the 1,3,5-triazine core causes a slight bathochromic shift and enhanced molar extinction coefficient of the 1π–π⁎/1ICT transition band. Both compounds are emissive in solution at room temperature and 77 K, which exhibit pronounced positive solvatochromic effect. The emitting state could be ascribed to 1ICT state in more polar solvent, and 1π–π⁎ state in low-polarity solvent. The high emission quantum yields (Φem=0.90~1.0) of 1a and 1b (in hexane and toluene) make them potential candidates as efficient light-emitting materials. The spectroscopic studies and theoretical calculations indicate that the photophysical properties of these compounds can be tuned by the carbazole end-capped phenylene ethynylene arm, which would also be useful for rational design of photofunctional materials.

Automated categorisation of patent claims that reference human genome sequences

Debates on gene patents have necessitated the analysis of patents that disclose and reference human sequences. In this study, we built an automated classifier that assigns sequences to one of nine predefined categories according to their functional roles in patent claims by applying natural language processing and supervised learning techniques. To improve its correctness, we experimented with various feature mappings, resulting in the maximal accuracy of 79%.

Vitamin D deficiency in patients with malignancy in Brisbane

PURPOSE: This study aims to investigate the prevalence and factors predictive of vitamin D deficiency in patients with malignancy in Brisbane, Australia (latitude 27° S). METHODS: This is a prospective cross-sectional study measuring serum levels of 25-hydroxyvitamin D (25-OHD) in 100 subjects with non-haematological cancer at least 18 years of age not taking vitamin D supplements attending a day oncology unit and oncology/palliative care inpatient ward in Brisbane, Australia. RESULTS: Thirty-seven per cent of outpatient and 49 % of inpatient subjects respectively were vitamin D deficient. Functional status was predictive of low vitamin D levels. CONCLUSION: There was a high prevalence of vitamin D deficiency in patients with cancer in Brisbane, Australia.

Serum vitamin D levels are lower in Australian children and adolescents with type 1 diabetes than in children without diabetes

Vitamin D is synthesised in the skin through the action of UVB radiation (sunlight), and 25-hydroxy vitamin D (25OHD) measured in serum as a marker of vitamin D status. Several studies, mostly conducted in high latitudes, have shown an association between type 1 diabetes mellitus (T1DM) and low serum 25OHD. We conducted a case-control study to determine whether, in a sub-tropical environment with abundant sunlight (latitude 27.5°S), children with T1DM have lower serum vitamin D than children without diabetes. Fifty-six children with T1DM (14 newly diagnosed) and 46 unrelated control children participated in the study. Serum 25OHD, 1,25-dihydroxy vitamin D (1,25(OH)2D) and selected biochemical indices were measured. Vitamin D receptor (VDR) polymorphisms Taq1, Fok1, and Apa1 were genotyped. Fitzpatrick skin classification, self-reported daily hours of outdoor exposure, and mean UV index over the 35d prior to blood collection were recorded. Serum 25OHD was lower in children with T1DM (n=56) than in controls (n=46) [mean (95%CI)=78.7 (71.8-85.6) nmol/L vs. 91.4 (83.5-98.7) nmol/L, p=0.02]. T1DM children had lower self-reported outdoor exposure and mean UV exposure, but no significant difference in distribution of VDR polymorphisms. 25OHD remained lower in children with T1DM after covariate adjustment. Children newly diagnosed with T1DM had lower 1,25(OH)2D [median (IQR)=89 (68-122) pmol/L] than controls [121 (108-159) pmol/L, p=0.03], or children with established diabetes [137 (113-153) pmol/L, p=0.01]. Children with T1DM have lower 25OHD than controls, even in an environment of abundant sunlight. Whether low vitamin D is a risk factor or consequence of T1DM is unknown. © 2012 John Wiley & Sons A/S.

Investigating the genetic association between ERAP1 and ankylosing spondylitis

A strong association between ERAP1 and ankylosing spondylitis (AS) was recently identified by the Wellcome Trust Case Control Consortium and the Australo-Anglo-American Spondylitis Consortium (WTCCC-TASC) study. ERAP1 is highly polymorphic with strong linkage disequilibrium evident across the gene. We therefore conducted a series of experiments to try to identify the primary genetic association(s) with ERAP1. We replicated the original associations in an independent set of 730 patients and 1021 controls, resequenced ERAP1 to define the full extent of coding polymorphisms and tested all variants in additional association studies. The genetic association with ERAP1 was independently confirmed; the strongest association was with rs30187 in the replication set (P = 3.4 × 103). When the data were combined with the original WTCCC-TASC study the strongest association was with rs27044 (P = 1.1 × 10-9). We identified 33 sequence polymorphisms in ERAP1, including three novel and eight known non-synonymous polymorphisms. We report several new associations between AS and polymorphisms distributed across ERAP1 from the extended case-control study, the most significant of which was with rs27434 (P = 4.7 × 10-7). Regression analysis failed to identify a primary association clearly; we therefore used data from HapMap to impute genotypes for an additional 205 non-coding SNPs located within and adjacent to ERAP1. A number of highly significant associations (P < 5 × 10-9) were identified in regulatory sequences which are good candidates for causing susceptibility to AS, possibly by regulating ERAP1 expression. © 2009 The Author(s).

Draft genome and plasmid sequences of Chlamydia pneumoniae strain B21 from an Australian endangered marsupial, the western barred bandicoot

Chlamydia pneumoniae is a ubiquitous intracellular pathogen, first associated with human respiratory disease and subsequently detected in a range of mammals, amphibians, and reptiles. Here we report the draft genome sequence for strain B21 of C. pneumoniae, isolated from the endangered Australian marsupial the western barred bandicoot.

Genetic control of bone density and turnover: Role of the collagen 1α1, estrogen receptor, and vitamin D receptor genes

Genetic factors are known to influence both the peak bone mass and probably the rate of change in bone density. A range of regulatory and structural genes has been proposed to be involved including collagen 1α1 (COL1A1), the estrogen receptor (ER), and the vitamin D receptor (VDR), but the actual genes involved are uncertain. We therefore studied the role of the COL1A1 and VDR loci in control of bone density by linkage in 45 dizygotic twin pairs and 29 nuclear families comprising 120 individuals. The influences on bone density of polymorphisms of COL1A1, VDR, and ER were studied by association both cross-sectionally and longitudinally in 193 elderly postmenopausal women (average age, 69 years) over a mean follow-up time of 6.3 years. Weak linkage of the COL1A1 locus with bone density was observed in both twins and families (p = 0.02 in both data sets), confirming previous observations of linkage of this locus with bone density. Association between the MscI polymorphism of COL1A1 and rate of lumbar spine bone loss was observed with significant gene-environment interaction related to dietary calcium intake (p = 0.0006). In the lowest tertile of dietary calcium intake, carriers of "s" alleles lost more bone than "SS" homozygotes (p = 0.01), whereas the opposite was observed in the highest dietary calcium intake (p = 0.003). Association also was observed between rate of bone loss at both the femoral neck and the lumbar spine and the TaqI VDR polymorphism (p = 0.03). This association was strongest in those in the lowest tertile of calcium intake, also suggesting the presence of gene-environment interaction involving dietary calcium and VDR, influencing bone turnover. No significant association was observed between the PvuII ER polymorphism alone or in combination with VDR or COL1A1 genotypes, with either bone density or its rate of change. These data support the involvement of COL1A1 in determination of bone density and the interaction of both COL1A1 and VDR with calcium intake in regulation of change of bone density over time.

Public disclosure of biological sequences in global patent practice

Biological sequences are an important part of global patenting, with unique challenges for their effective and equitable use in practice and in policy. Because their function can only be determined with computer-aided technology, the form in which sequences are disclosed matters greatly. Similarly, the scope of patent rights sought and granted requires computer readable data and tools for comparison. Critically, the primary data provided to the national patent offices and thence to the public, must be comprehensive, standardized, timely and meaningful. It is not yet. The proposed global Patent Sequence (PatSeq) Data platform can enable national and regional jurisdictions meet the desired standards.

Structures of three different neutral polysaccharides of Acinetobacter baumannii, NIPH190, NIPH201, and NIPH615, assigned to K30, K45, and K48 capsule types, respectively, based on capsule biosynthesis gene clusters

Neutral capsular polysaccharides (CPSs) were isolated from Acinetobacter baumannii NIPH190, NIPH201, and NIPH615. The CPSs were found to contain common monosaccharides only and to be branched with a side-chain 1→3-linked β-d-glucopyranose residue. Structures of the oligosaccharide repeat units (K units) of the CPSs were elucidated by 1D and 2D 1H and 13C NMR spectroscopy. Novel CPS biosynthesis gene clusters, designated KL30, KL45, and KL48, were found at the K locus in the genome sequences of NIPH190, NIPH201, and NIPH615, respectively. The genetic content of each gene cluster correlated with the structure of the CPS unit established, and therefore, the capsular types of the strains studied were designated as K30, K45, and K48, respectively. The initiating sugar of each K unit was predicted, and glycosyltransferases encoded by each gene cluster were assigned to the formation of the linkages between sugars in the corresponding K unit.

Inverse Correlation between Vitamin D and C-Reactive Protein in Newborns

Some studies suggested that adequate vitamin D might reduce inflammation in adults. However, little is known about this association in early life. We aimed to determine the relationship between cord blood 25-hydroxyvitamin D (25(OH)D) and C-reactive protein (CRP) in neonates. Cord blood levels of 25(OH)D and CRP were measured in 1491 neonates in Hefei, China. Potential confounders including maternal sociodemographic characteristics, perinatal health status, lifestyle, and birth outcomes were prospectively collected. The average values of cord blood 25(OH)D and CRP were 39.43 nmol/L (SD = 20.35) and 6.71 mg/L (SD = 3.07), respectively. Stratified by 25(OH)D levels, per 10 nmol/L increase in 25(OH)D, CRP decreased by 1.42 mg/L (95% CI: 0.90, 1.95) among neonates with 25(OH)D <25.0 nmol/L, and decreased by 0.49 mg/L (95% CI: 0.17, 0.80) among neonates with 25(OH)D between 25.0 nmol/L and 49.9 nmol/L, after adjusting for potential confounders. However, no significant association between 25(OH)D and CRP was observed among neonates with 25(OH)D ≥50 nmol/L. Cord blood 25(OH)D and CRP levels showed a significant seasonal trend with lower 25(OH)D and higher CRP during winter-spring than summer-autumn. Stratified by season, a significant linear association of 25(OH)D with CRP was observed in neonates born in winter-spring (adjusted β = −0.11, 95% CI: −0.13, −0.10), but not summer-autumn. Among neonates born in winter-spring, neonates with 25(OH)D <25 nmol/L had higher risk of CRP ≥10 mg/L (adjusted OR = 3.06, 95% CI: 2.00, 4.69), compared to neonates with 25(OH)D ≥25 nmol/L. Neonates with vitamin D deficiency had higher risk of exposure to elevated inflammation at birth.

On the probability of dizygotic twins being concordant for two alleles at multiple polymorphic loci

Accurate determination of same-sex twin zygosity is important for medical, scientific and personal reasons. Determination may be based upon questionnaire data, blood group, enzyme isoforms and fetal membrane examination, but assignment of zygosity must ultimately be confirmed by genotypic data. Here methods are reviewed for calculating average probabilities of correctly concluding a twin pair is monozygotic, given they share the same genotypes across all loci for commonly utilized multiplex short tandem repeat (STR) kits.

Cross-sectional study of a microsatellite marker in the low density lipoprotein receptor gene in obese normotensives

1. The low density lipoprotein receptor is an important regulator of serum cholesterol which may have implications for the development of both hypertension and obesity. In this study, genotypes for a low density lipoprotein receptor gene (LDLR) dinucleotide polymorphism were determined in both lean and obese normotensive populations. 2. In previous cross-sectional association studies an ApaLI and a HincII polymorphism for LDLR were shown to be associated with obesity in essential hypertensives. However, these polymorphisms did not show an association with obesity in normotensives. 3. In contrast, this study reports that preliminary results for an LDLR microsatellite marker, located more towards the 3' end of the gene, show a significant association with obesity in the normotensive population studied. These results indicate that LDLR could play an important role in the development of obesity, which might be independent of hypertension.

Cord blood 25-hydroxyvitamin D and fetal growth in the China-Anhui birth cohort study

We determined the association of cord blood 25-hydroxyvitamin D [25(OH)D] with birth weight and the risk of small for gestational age (SGA). As part of the China-Anhui Birth Cohort (C-ABC) study, we measured cord blood levels of 25(OH)D in 1491 neonates in Hefei, China. The data on maternal sociodemographic characteristics, health status, lifestyle, birth outcomes were prospectively collected. Multiple regression models were used to estimate the association of 25(OH)D levels with birth weight and the risk of SGA. Compared with neonates in the lowest decile of cord blood 25(OH)D levels, neonates in four deciles (the fourth, fifth, sixth and seventh deciles) had significantly increased birth weight and decreased risk of SGA. Multiple linear regression models showed that per 10 nmol/L increase in cord blood 25(OH)D, birth weight increased by 61.0 g (95% CI: 31.9, 89.9) at concentrations less than 40 nmol/L, and then decreased by 68.5 g (95% CI: −110.5, −26.6) at concentrations from 40 to 70 nmol/L. This study provides the first epidemiological evidence that there was an inverted U shaped relationship between neonatal vitamin D status and fetal growth, and the risk of SGA reduced at moderate concentration.