Multiple alleles of ACAN associated with chondrodysplastic dwarfism in Miniature horses.

Chondrodysplastic dwarfism in Miniature horses appeared to be a recessive genetic trait based on the occurrence of affected offspring by normal parents. Dwarf phenotypes vary and range from abnormal abortuses to viable offspring with evidence of skeletal dysplasia. A genome-wide association study implicated a region of ECA1 with dwarfism in Miniature horses. Aggrecan (ACAN) was a candidate gene in that region, and exons were sequenced to compare DNA sequences for dwarf and non-dwarf horses. Sequencing led to the discovery of variants in exons 2, 6, 7 and 15 associated with dwarfism. The four variants are identified with reference to Ecab 3.0 (GCF_002863925.1) as g.95291270del (rs1095048841), g.95284530C>T (ERP107353), g.95282140C>G (rs1095048823) and g.95257480_95257500del (rs1095048839) and designated here as D1, D2, D3* and D4 respectively. A previous study at another laboratory reported dwarfism associated with homozygosity for D3*. Homozygotes for those variants and compound heterozygotes for any combination of those variants always expressed a dwarfism phenotype. However, eight additional horses with dwarfism were found, seven of which were heterozygotes for D2, D3* or D4, suggesting the existence of additional ACAN alleles causing dwarfism. Among Miniature horses, the combined frequency of D1, D2, D3* and D4 was 0.163, suggesting a carrier rate of 26.2% for alleles causing chondrodysplastic dwarfism.

Generation of an equine biobank to be used for Functional Annotation of Animal Genomes project.

The Functional Annotation of Animal Genomes (FAANG) project aims to identify genomic regulatory elements in both sexes across multiple stages of development in domesticated animals. This study represents the first stage of the FAANG project for the horse, Equus caballus. A biobank of 80 tissue samples, two cell lines and six body fluids was created from two adult Thoroughbred mares. Ante-mortem assessments included full physical examinations, lameness, ophthalmologic and neurologic evaluations. Complete blood counts and serum biochemistries were also performed. At necropsy, in addition to tissue samples, aliquots of serum, ethylenediaminetetraacetic acid (EDTA) plasma, heparinized plasma, cerebrospinal fluid, synovial fluid, urine and microbiome samples from all regions of the gastrointestinal and urogenital tracts were collected. Epidermal keratinocytes and dermal fibroblasts were cultured from skin samples. All tissues were grossly and histologically evaluated by a board-certified veterinary pathologist. The results of the clinical and pathological evaluations identified subclinical eosinophilic and lymphocytic infiltration throughout the length of the gastrointestinal tract as well as a mild clinical lameness in both animals. Each sample was cryo-preserved in multiple ways, and nuclei were extracted from selected tissues. These samples represent the first published systemically healthy equine-specific biobank with extensive clinical phenotyping ante- and post-mortem. The tissues in the biobank are intended for community-wide use in the functional annotation of the equine genome. The use of the biobank will improve the quality of the reference annotation and allow all equine researchers to elucidate unknown genomic and epigenomic causes of disease.

Multiple imputation using linked proxy outcome data resulted in important bias reduction and efficiency gains: a simulation study.

BACKGROUND: When an outcome variable is missing not at random (MNAR: probability of missingness depends on outcome values), estimates of the effect of an exposure on this outcome are often biased. We investigated the extent of this bias and examined whether the bias can be reduced through incorporating proxy outcomes obtained through linkage to administrative data as auxiliary variables in multiple imputation (MI). METHODS: Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC) we estimated the association between breastfeeding and IQ (continuous outcome), incorporating linked attainment data (proxies for IQ) as auxiliary variables in MI models. Simulation studies explored the impact of varying the proportion of missing data (from 20 to 80%), the correlation between the outcome and its proxy (0.1-0.9), the strength of the missing data mechanism, and having a proxy variable that was incomplete. RESULTS: Incorporating a linked proxy for the missing outcome as an auxiliary variable reduced bias and increased efficiency in all scenarios, even when 80% of the outcome was missing. Using an incomplete proxy was similarly beneficial. High correlations (> 0.5) between the outcome and its proxy substantially reduced the missing information. Consistent with this, ALSPAC analysis showed inclusion of a proxy reduced bias and improved efficiency. Gains with additional proxies were modest. CONCLUSIONS: In longitudinal studies with loss to follow-up, incorporating proxies for this study outcome obtained via linkage to external sources of data as auxiliary variables in MI models can give practically important bias reduction and efficiency gains when the study outcome is MNAR.

Transfer of CVD-grown graphene for room temperature gas sensors.

An easy transfer procedure to obtain graphene-based gas sensing devices operating at room temperature (RT) is presented. Starting from chemical vapor deposition-grown graphene on copper foil, we obtained single layer graphene which could be transferred onto arbitrary substrates. In particular, we placed single layer graphene on top of a SiO2/Si substrate with pre-patterned Pt electrodes to realize a chemiresistor gas sensor able to operate at RT. The responses to ammonia (10, 20, 30 ppm) and nitrogen dioxide (1, 2, 3 ppm) are shown at different values of relative humidity, in dark and under 254 nm UV light. In order to check the sensor selectivity, gas response has also been tested towards hydrogen, ethanol, acetone and carbon oxide. Finally, a model based on linear dispersion relation characteristic of graphene, which take into account humidity and UV light effects, has been proposed.

2D Supramolecular networks of dibenzonitrilediacetylene on Ag(111) stabilized by intermolecular hydrogen bonding.

The two-dimensional (2D) surface-directed self-assembly of dibenzonitrile diacetylene (DBDA) on Ag(111) under ultrahigh vacuum (UHV) conditions was investigated by combining scanning tunneling microscopy (STM), X-ray photoelectron spectroscopy (XPS) and theoretical simulations based on density functional theory (DFT) calculations. The molecule consists of two benzonitrile groups (-C6H4-C[triple bond, length as m-dash]N) on each side of a diacetylene (-C[triple bond, length as m-dash]C-C[triple bond, length as m-dash]C-) backbone. The terminating nitrile (-C[triple bond, length as m-dash]N) groups at the meta position of the phenyl rings lead to cis and trans stereoisomers. The trans isomer is prochiral and can adsorb in the R or S configuration, leading to the formation of enantiomeric self-assembled networks on the surface. We identify two simultaneously present supramolecular networks, termed parallel and chevron phases, as well as a less frequently observed butterfly phase. These networks are formed from pure R (or S) domains, racemic mixtures (RS), and cis isomers, respectively. Our complementary data illustrates that the formation of the 2D supramolecular networks is driven by intermolecular hydrogen bonding between nitrile and phenyl groups (-C[triple bond, length as m-dash]NH-C6H3). This study illustrates that the molecular arrangement of each network depends on the geometry of the isomers. The orientation of the nitrile group controls the formation of the most energetically stable network via intermolecular hydrogen bonding.

A novel strategy to reduce very late HIV diagnosis in high-prevalence areas in South-West England: serious incident audit.

Background: Very late diagnosis of HIV is a serious public health issue. We used serious incident reporting (SIR) to identify and address reasons for late diagnoses across the patient pathway. Methods: Cases of very late HIV diagnosis were reported via SIR in two 6-month batches between 2011 and 2012 in Bournemouth, Poole and Bristol. Case notes were reviewed for missed opportunities for earlier diagnosis using a root-cause analysis tool. Results: A total of 33 patients (aged 30-67 years, 66% male) were diagnosed very late. Although the majority were white British (n = 17), Black African (n = 9) and Eastern European (n = 4) ethnicities were over-represented. Twenty-four (73%) patients had clinical indicator conditions for HIV, 30 (91%) had a risk factor for HIV acquisition, with 13 (39%) having 2 or more (men-who-have-sex-with-men (n = 11), partner HIV positive (n = 11), from high-prevalence area (n = 12)). Actions resulting from SIR included increasing awareness of indicator conditions, HIV education days within primary care, and initiatives to increase testing within hospital specialities. Conclusions: SIR allowed identification of reasons for very late HIV diagnosis and provided an impetus for initiatives to address them. SIR may be part of an effective strategy to prevent late diagnosis of HIV which would have important benefits for individual and population health.

'When you are homeless, you are not thinking about your medication, but your food, shelter or heat for the night': behavioural determinants of homeless patients' adherence to prescribed medicines.

OBJECTIVES: This study aimed to explore behavioural determinants of homeless patients' adherence to prescribed medicines using Theoretical Domains Framework (TDF). STUDY DESIGN: A qualitative study using semi-structured, face-to-face interviews. METHODS: Participants were recruited from a homelessness primary healthcare centre in Aberdeen, United Kingdom (UK). Face-to-face interviews were audio-recorded and transcribed verbatim. Thematic analysis of the interview data was conducted using the Framework Approach based on the Theoretical Domains Framework. National Health Service ethical and Research and Development (R&D) approval was obtained. RESULTS: Twenty-five patients were interviewed, at which point data saturation was achieved. A total of 13 out of 14 Theoretical Domains Framework domains were identified that explained the determinants of adherence or non-adherence to prescribed medicines. These included: 'beliefs about consequences' (e.g. non-adherence leading to poor health); 'goals' of therapy (e.g. being a 'normal' person with particular reference to methadone adherence); and 'environmental context and resources' (e.g. stolen medicines and the lack of secure storage). Obtaining food and shelter was higher priority than access and adherence to prescribed medicines while being homeless. CONCLUSIONS: Behavioural determinants of non-adherence identified in this study were mostly related to participants' homelessness and associated lifestyle. Results are relevant to developing behaviour change interventions targeting non-adherent homeless patients and to the education of healthcare professionals serving this vulnerable population.

Substrate Effects in the Supramolecular Assembly of 1,3,5-Benzene Tricarboxylic Acid on Graphite and Graphene.

The behavior of small molecules on a surface depends critically on both molecule-substrate and intermolecular interactions. We present here a detailed comparative investigation of 1,3,5-benzene tricarboxylic acid (trimesic acid, TMA) on two different surfaces: highly oriented pyrolytic graphite (HOPG) and single-layer graphene (SLG) grown on a polycrystalline Cu foil. On the basis of high-resolution scanning tunnelling microscopy (STM) images, we show that the epitaxy matrix for the hexagonal TMA chicken wire phase is identical on these two surfaces, and, using density functional theory (DFT) with a non-local van der Waals correlation contribution, we identify the most energetically favorable adsorption geometries. Simulated STM images based on these calculations suggest that the TMA lattice can stably adsorb on sites other than those identified to maximize binding interactions with the substrate. This is consistent with our net energy calculations that suggest that intermolecular interactions (TMA-TMA dimer bonding) are dominant over TMA-substrate interactions in stabilizing the system. STM images demonstrate the robustness of the TMA films on SLG, where the molecular network extends across the variable topography of the SLG substrates and remains intact after rinsing and drying the films. These results help to elucidate molecular behavior on SLG and suggest significant similarities between adsorption on HOPG and SLG.

Cervical Vertebral Lesions in Equine Stenotic Myelopathy.

Skeletal lesions in the articular processes of cervical vertebrae C2 to C7 were compared between Thoroughbred horses with cervical stenotic myelopathy (17 males, 2 females; age, 6-50 months) and controls (6 males, 3 females; age, 9-67 months). Lesions identified by magnetic resonance imaging occurred with an increased frequency and severity in diseased horses and were not limited to sites of spinal cord compression. Lesions involved both the articular cartilage and trabecular bone and were further characterized using micro-computed tomography and histopathology. The most common histologic lesions included osteochondrosis, osseous cyst-like structures, fibrous tissue replacement of trabecular bone, retained cartilage matrix spicules, and osteosclerosis. Osseous cyst-like structures were interpreted to be true bone cysts given they were a closed cavity with a cellular lining that separated the cyst from surrounding bone. This is the first report of bone cysts in the cervical articular processes of horses with cervical stenotic myelopathy. The morphology and distribution of the lesions provide additional support for the previously proposed pathogenesis that developmental abnormalities with likely secondary biomechanical influences on the cervical spine contribute to equine cervical stenotic myelopathy.

Molecular self-assembly on graphene.

The formation of ordered arrays of molecules via self-assembly is a rapid, scalable route towards the realization of nanoscale architectures with tailored properties. In recent years, graphene has emerged as an appealing substrate for molecular self-assembly in two dimensions. Here, the first five years of progress in supramolecular organization on graphene are reviewed. The self-assembly process can vary depending on the type of graphene employed: epitaxial graphene, grown in situ on a metal surface, and non-epitaxial graphene, transferred onto an arbitrary substrate, can have different effects on the final structure. On epitaxial graphene, the process is sensitive to the interaction between the graphene and the substrate on which it is grown. In the case of graphene that strongly interacts with its substrate, such as graphene/Ru(0001), the inhomogeneous adsorption landscape of the graphene moiré superlattice provides a unique opportunity for guiding molecular organization, since molecules experience spatially constrained diffusion and adsorption. On weaker-interacting epitaxial graphene films, and on non-epitaxial graphene transferred onto a host substrate, self-assembly leads to films similar to those obtained on graphite surfaces. The efficacy of a graphene layer for facilitating planar adsorption of aromatic molecules has been repeatedly demonstrated, indicating that it can be used to direct molecular adsorption, and therefore carrier transport, in a certain orientation, and suggesting that the use of transferred graphene may allow for predictible molecular self-assembly on a wide range of surfaces.

Associations of cannabis and cigarette use with psychotic experiences at age 18: findings from the Avon Longitudinal Study of Parents and Children.

BACKGROUND: A clearer understanding of the basis for the association between cannabis use and psychotic experiences (PEs) is required. Our aim was to examine the extent to which associations between cannabis and cigarette use and PEs are due to confounding. METHOD: A cohort study of 1756 adolescents with data on cannabis use, cigarette use and PEs. RESULTS: Cannabis use and cigarette use at age 16 were both associated, to a similar degree, with PEs at age 18 [odds ratio (OR) 1.48, 95% confidence interval (CI) 1.18-1.86 for cannabis and OR 1.61, 95% CI 1.31-1.98 for cigarettes]. Adjustment for cigarette smoking frequency (OR 1.27, 95% CI 0.91-1.76) or other illicit drug use (OR 1.25, 95% CI 0.91-1.73) substantially attenuated the relationship between cannabis and PEs. The attenuation was to a lesser degree when cannabis use was adjusted for in the cigarette PE association (OR 1.42, 95% CI 1.05-1.92). However, almost all of the participants used cannabis with tobacco, including those who classed themselves as non-cigarette smokers. CONCLUSIONS: Teasing out the effects of cannabis from tobacco is highly complex and may not have been dealt with adequately in studies to date, including this one. Complementary methods are required to robustly examine the independent effects of cannabis, tobacco and other illicit drugs on PEs.

Incidence of Chlamydia trachomatis infection in women in England: two methods of estimation.

Information on the incidence of Chlamydia trachomatis (CT) is essential for models of the effectiveness and cost-effectiveness of screening programmes. We developed two independent estimates of CT incidence in women in England: one based on an incidence study, with estimates 'recalibrated' to the general population using data on setting-specific relative risks, and allowing for clearance and re-infection during follow-up; the second based on UK prevalence data, and information on the duration of CT infection. The consistency of independent sources of data on incidence, prevalence and duration, validates estimates of these parameters. Pooled estimates of the annual incidence rate in women aged 16-24 and 16-44 years for 2001-2005 using all these data were 0·05 [95% credible interval (CrI) 0·035-0·071] and 0·021 (95% CrI 0·015-0·028), respectively. Although, the estimates apply to England, similar methods could be used in other countries. The methods could be extended to dynamic models to synthesize, and assess the consistency of data on contact and transmission rates.

Thermal evolution of the submonolayer near-surface alloy of ZnPd on Pd(111).

We have performed a high-resolution synchrotron radiation photoelectron spectroscopy study of the initial growth stages of the ZnPd near-surface alloy on Pd(111), complemented by scanning tunnelling microscopy data. We show that the chemical environment for surfaces containing less than half of one monolayer of Zn is chemically distinct from subsequent layers. Surfaces where the deposition is performed at room temperature contain ZnPd islands surrounded by a substrate with dilute Zn substitutions. Annealing these surfaces drives the Zn towards the substrate top-layer, and favours the completion of the first 1 : 1 monolayer before the onset of growth in the next layer.

Surface structure of Pd(111) with less than half a monolayer of Zn.

We have characterized the structural properties of submonolayer amounts of Zn on Pd(111) using scanning tunneling microscopy (STM) and spot-profile analysis low energy electron diffraction (SPA-LEED). Following room temperature deposition of ≈0.06 monolayers (ML) Zn onto Pd(111), we observe the substitution of Zn for Pd in the surface layer. At ≈0.20 ML of deposited Zn, STM reveals a locally ordered phase with a (2/√3 × 2/√3)R30° unit cell located near Zn substitutions; SPA-LEED patterns reveal the same periodicity. We attribute this phase to the metastable bonding of atoms or clusters predominantly in hollow sites surrounding Zn substitutions in the surface layer. At ≈0.4 ML, STM images reveal local (√3 × âˆš3)R30° and (2 × 1) ordering on surfaces annealed to 350 K. At coverages near 0.5 ML, both STM and SPA-LEED show the onset of the formation of the (2 × 1) ordering associated with the Zn : Pd 1 : 1 alloy phase. At all coverages, the surface is dominated by island growth; the islands' size and density is shown to depend critically on annealing at temperatures as low as 350 K. These results provide insight into the structural features of a Zn/Pd(111) coverage regime that has been much debated in recent years.

Structural and functional analysis of intra-articular interzone tissue in axolotl salamanders.

OBJECTIVE: Knowledge of mechanisms directing diarthrodial joint development may be useful in understanding joint pathologies and identifying new therapies. We have previously established that axolotl salamanders can fully repair large articular cartilage lesions, which may be due to the presence of an interzone-like tissue in the intra-articular space. Study objectives were to further characterize axolotl diarthrodial joint structure and determine the differentiation potential of interzone-like tissue in a skeletal microenvironment. DESIGN: Diarthrodial joint morphology and expression of aggrecan, brother of CDO (BOC), type I collagen, type II collagen, and growth/differentiation factor 5 (GDF5) were examined in femorotibial joints of sexually mature (>12 months) axolotls. Joint tissue cellularity was evaluated in individuals from 2 to 24 months of age. Chondrogenic potential of the interzone was evaluated by placing interzone-like tissue into 4 mm tibial defects. RESULTS: Cavitation reached completion in the femoroacetabular and humeroradial joints, but an interzone-like tissue was retained in the intra-articular space of distal limb joints. Joint tissue cellularity decreased to 7 months of age and then remained stable. Gene expression patterns of joint markers are broadly similar in developing mammals and mature axolotls. When interzone-like tissue was transplanted into critical size skeletal defects, an accessory joint developed within the defect site. CONCLUSIONS: These experiments indicate that mature axolotl diarthrodial joints are phenotypically similar to developing synovial joints in mammals. Generation of an accessory joint by interzone-like tissue suggests multipotent cellular differentiation potential similar to that of interzone cells in the mammalian fetus. The data support the axolotl as a novel vertebrate model for joint development and repair.

Modified Stranski-Krastanov growth in Ge/Si heterostructures via nanostenciled pulsed laser deposition.

The combination of nanostenciling with pulsed laser deposition (PLD) provides a flexible, fast approach for patterning the growth of Ge on Si. Within each stencilled site, the morphological evolution of the Ge structures with deposition follows a modified Stranski-Krastanov (SK) growth mode. By systematically varying the PLD parameters (laser repetition rate and number of pulses) on two different substrate orientations (111 and 100), we have observed corresponding changes in growth morphology, strain and elemental composition using scanning electron microscopy, atomic force microscopy and µ-Raman spectroscopy. The growth behaviour is well predicted within a classical SK scheme, although the Si(100) growth exhibits significant relaxation and ripening with increasing coverage. Other novel aspects of the growth include the increased thickness of the wetting layer and the kinetic control of Si/Ge intermixing via the PLD repetition rate.

Patterns of alcohol use and multiple risk behaviour by gender during early and late adolescence: the ALSPAC cohort.

BACKGROUND: Adolescent risk behaviours such as smoking, alcohol use and antisocial behaviour are associated with increased risk of morbidity and mortality. Patterns of risk behaviour may vary between genders during adolescence. METHODS: Analysis of data from a longitudinal birth cohort to assess the prevalence and distribution of multiple risk behaviours by gender at age 15-16 years with a focus on alcohol use at age 10, 13 and 15 years. RESULTS: By age 15 years, over half of boys and girls had consumed alcohol and one-fifth had engaged in binge drinking with no clear difference by gender. At age 15-16 years, the most prevalent risk behaviours were physical inactivity (74%), antisocial and criminal behaviour (42%) and hazardous drinking (34%). Boys and girls engaged in a similar number of behaviours but antisocial and criminal behaviours, cannabis use and vehicle-related risk behaviours were more prevalent among boys, whilst tobacco smoking, self-harm and physical inactivity were more prevalent among girls. CONCLUSION: Multiple risk behaviour is prevalent in both genders during adolescence but the pattern of individual risk behaviour varies between boys and girls. Effective interventions at the individual, family, school, community or population level are needed to address gender-specific patterns of risk behaviour during adolescence.

Premature mortality in Scottish injecting drug users: a life-history approach.

In Scotland, deaths in drug users are known to be higher than in the rest of the UK and most of Europe. Reducing drug-related deaths is currently a national priority for the Scottish Government.  This study aimed to present a description of the life histories of a group of injecting drug users who have recently died, with a view to highlighting areas for further research. The Edinburgh Addiction Cohort study recently carried out 432 follow-up interviews between the years 2005 and 2007. Thirty-three cases who completed this extensive interview detailing early life, education, employment, drug use, opiate substitution treatment, criminal history, mental health problems and overdose have subsequently died, leaving this source of rich information about their lives. The design of the interview used the life grid approach. Information was also compiled from full primary care records and General Register Office death certificates. Early life adversity was apparent for many cases, with a steady progression into early criminal behaviour and drug misuse. Poor adult life outcomes illustrated the lifelong damaging effects of drug injecting. Death occurred significantly earlier than in the general population or those living in deprived communities who did not use drugs. In conclusion, a clearer understanding of the life histories of problem drug users would be advantageous for health-care professionals and policy-makers. More qualitative research studies are needed to highlight areas which might require early intervention and also complement the existing secondary data studies.

Intrinsic repair of full-thickness articular cartilage defects in the axolotl salamander.

OBJECTIVE: The ability to fully regenerate lost limbs has made the axolotl salamander (Ambystoma mexicanum) a valuable model for studies of tissue regeneration. The current experiments investigate the ability of these vertebrates to repair large articular cartilage defects and restore normal hyaline cartilage and joint structure independent of limb amputation. METHODS: Full-thickness articular cartilage defects were made by resection of the medial femoral condyle to the level of the metaphysis. At 0, 2 days, 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 weeks post-surgery, the repair process was analyzed on H&E and Safranin-O stained 7 µm tissue sections. Symmetric Kullback-Leibler (SKL) divergences were used to assess proteoglycan staining intensities. Immunohistochemistry was performed for collagen types I and II. RESULTS: A fibrous "interzone-like" tissue occupies the intraarticular space of the axolotl femorotibial joint and no evidence of joint cavitation was observed. By 4 weeks post-surgery, cells within the defect site exhibited morphological similarities to those of the interzone-like tissue. At 24 weeks, joint structure and cartilaginous tissue repair were confirmed by immunohistochemistry for collagen types I and II. Quantitation of Safranin-O staining indicated restoration of proteoglycan content by 18 weeks. CONCLUSIONS: The axolotl femorotibial joint has morphological similarities to the developing mammalian diarthrodial joint. Cells in the intraarticular space may be homologous to the interzone tissue and contribute to intrinsic repair of full-thickness articular cartilage defects. Taken together, these results suggest that the axolotl may serve as a valuable model for the investigation of cellular and molecular mechanisms that achieve full articular cartilage repair.

Brother of CDO (BOC) expression in equine articular cartilage.

Brother of CDO (BOC) is a cell surface receptor that derives its name from the structurally related protein, cell adhesion molecule-related/down-regulated by oncogenes (CDO, sometimes CDON). High levels of BOC mRNA and protein expression have been described in embryonic tissues with active cell proliferation and ongoing cellular differentiation(1,2). A microarray-based screen of RNA isolated from 11 different adult equine tissues unexpectedly identified BOC as having an expression pattern restricted to articular cartilage. The objective of this study was to further investigate BOC expression in adult articular cartilage relative to other tissues. Both RT-qPCR and mRNA sequencing confirmed the microarray data. Steady state BOC mRNA levels in articular cartilage were substantially higher than in the other adult tissues tested, neonatal tendon, placenta, and whole embryo. The expression of BOC displayed a pattern of tissue specificity comparable to well established cartilage matrix protein biomarkers. BOC mRNA levels in articular cartilage increased with age, but were rapidly down-regulated when chondrocytes were enzymatically isolated from the cartilage matrix and expanded in monolayer culture. Relative expression patterns of CDO were broadly similar, but displayed lower fold change differences. A functional role in articular cartilage that involves Hedgehog signaling is suggested by the known binding affinity of BOC for all three Hedgehog ligands. These data also extend BOC and CDO biology to a post-mitotic and highly differentiated cell type within a mature tissue.