Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture

Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 × 10−8). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 × 10−4, Bonferroni corrected), of which six reached P < 5 × 10−8, including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.

Airway cellularity, lipid laden macrophages and microbiology of gastric juice and airways in children with reflux oesophagitis

Background: Gastroesophageal reflux disease (GORD) can cause respiratory disease in children from recurrent aspiration of gastric contents. GORD can be defined in several ways and one of the most common method is presence of reflux oesophagitis. In children with GORD and respiratory disease, airway neutrophilia has been described. However, there are no prospective studies that have examined airway cellularity in children with GORD but without respiratory disease. The aims of the study were to compare (1) BAL cellularity and lipid laden macrophage index (LLMI) and, (2) microbiology of BAL and gastric juices of children with GORD (G+) to those without (G-). Methods: In 150 children aged <14-years, gastric aspirates and bronchoscopic airway lavage (BAL) were obtained during elective flexible upper endoscopy. GORD was defined as presence of reflux oesophagitis on distal oesophageal biopsies. Results: BAL neutrophil% in G- group (n = 63) was marginally but significantly higher than that in the G+ group (n = 77), (median of 7.5 and 5 respectively, p = 0.002). Lipid laden macrophage index (LLMI), BAL percentages of lymphocyte, eosinophil and macrophage were similar between groups. Viral studies were negative in all, bacterial cultures positive in 20.7% of BALs and in 5.3% of gastric aspirates. BAL cultures did not reflect gastric aspirate cultures in all but one child. Conclusion: In children without respiratory disease, GORD defined by presence of reflux oesophagitis, is not associated with BAL cellular profile or LLMI abnormality. Abnormal microbiology of the airways, when present, is not related to reflux oesophagitis and does not reflect that of gastric juices. © 2005 Chang et al; licensee BioMed Central Ltd.

Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants

We have genotyped 14,436 nonsynonymous SNPs (nsSNPs) and 897 major histocompatibility complex (MHC) tag SNPs from 1,000 independent cases of ankylosing spondylitis (AS), autoimmune thyroid disease (AITD), multiple sclerosis (MS) and breast cancer (BC). Comparing these data against a common control dataset derived from 1,500 randomly selected healthy British individuals, we report initial association and independent replication in a North American sample of two new loci related to ankylosing spondylitis, ARTS1 and IL23R, and confirmation of the previously reported association of AITD with TSHR and FCRL3. These findings, enabled in part by increased statistical power resulting from the expansion of the control reference group to include individuals from the other disease groups, highlight notable new possibilities for autoimmune regulation and suggest that IL23R may be a common susceptibility factor for the major 'seronegative' diseases.

Tip-induced C--H activation and oligomerization of thienoanthracenes

The tip of a scanning tunneling microscope (STM) can be used to dehydrogenate freely-diffusing tetrathienoanthracene (TTA) molecules on Cu(111), trapping the molecules into metal-coordinated oligomeric structures. The process proceeds at bias voltages above ∼3 V and produces organometallic structures identical to those resulting from the thermally-activated cross-coupling of a halogenated analogue. The process appears to be substrate dependent: no oligomerization was observed on Ag(111) or HOPG. This approach demonstrates the possibility of controlled synthesis and nanoscale patterning of 2D oligomer structures on selected surfaces.

Traffic and nucleation events as main sources of ultrafine particles in high-insolation developed world cities

Road traffic emissions are often considered the main source of ultrafine particles (UFP, diameter smaller than 100 nm) in urban environments. However, recent studies worldwide have shown that - in high-insolation urban regions at least - new particle formation events can also contribute to UFP. In order to quantify such events we systematically studied three cities located in predominantly sunny environments: Barcelona (Spain), Madrid (Spain) and Brisbane (Australia). Three long term datasets (1-2 years) of fine and ultrafine particle number size distributions (measured by SMPS, Scanning Mobility Particle Sizer) were analysed. Compared to total particle number concentrations, aerosol size distributions offer far more information on the type, origin and atmospheric evolution of the particles. By applying k-Means clustering analysis, we categorized the collected aerosol size distributions in three main categories: “Traffic” (prevailing 44-63% of the time), “Nucleation” (14-19%) and “Background pollution and Specific cases” (7-22%). Measurements from Rome (Italy) and Los Angeles (California) were also included to complement the study. The daily variation of the average UFP concentrations for a typical nucleation day at each site revealed a similar pattern for all cities, with three distinct particle bursts. A morning and an evening spike reflected traffic rush hours, whereas a third one at midday showed nucleation events. The photochemically nucleated particles burst lasted 1-4 hours, reaching sizes of 30-40 nm. On average, the occurrence of particle size spectra dominated by nucleation events was 16% of the time, showing the importance of this process as a source of UFP in urban environments exposed to high solar radiation. On average, nucleation events lasting for 2 hours or more occurred on 55% of the days, this extending to >4hrs in 28% of the days, demonstrating that atmospheric conditions in urban environments are not favourable to the growth of photochemically nucleated particles. In summary, although traffic remains the main source of UFP in urban areas, in developed countries with high insolation urban nucleation events are also a main source of UFP. If traffic-related particle concentrations are reduced in the future, nucleation events will likely increase in urban areas, due to the reduced urban condensation sinks.

Wetting, solubility and chemical characteristics of plasma-polymerized 1-isopropyl-4-methyl-1,4-cyclohexadiene thin films

Investigations on the wetting, solubility and chemical composition of plasma polymer thin films provide an insight into the feasibility of implementing these polymeric materials in organic electronics, particularly where wet solution processing is involved. In this study, thin films were prepared from 1-isopropyl-4-methyl-1,4-cyclohexadiene (γ-Terpinene) using radio frequency (RF) plasma polymerization. FTIR showed the polymers to be structurally dissimilar to the original monomer and highly cross-linked, where the loss of original functional groups and the degree of cross-linking increased with deposition power. The polymer surfaces were hydrocarbon-rich, with oxygen present in the form of O–H and C=O functional groups. The oxygen content decreased with deposition power, with films becoming more hydrophobic and, thus, less wettable. The advancing and receding contact angles were investigated, and the water advancing contact angle was found to increase from 63.14° to 73.53° for thin films prepared with an RF power of 10 W to 75 W. The wetting envelopes for the surfaces were constructed to enable the prediction of the surfaces’ wettability for other solvents. The effect of roughness on the wetting behaviour of the films was insignificant. The polymers were determined to resist solubilization in solvents commonly used in the deposition of organic semiconducting layers, including chloroform and chlorobenzene, with higher stability observed in films fabricated at higher RF power.