The genetic epidemiology of joint shape and the development of osteoarthritis

Congruent, low-friction relative movement between the articulating elements of a synovial joint is an essential pre-requisite for sustained, efficient, function. Where disorders of joint formation or maintenance exist, mechanical overloading and osteoarthritis (OA) follow. The heritable component of OA accounts for ~ 50% of susceptible risk. Although almost 100 genetic risk loci for OA have now been identified, and the epidemiological relationship between joint development, joint shape and osteoarthritis is well established, we still have only a limited understanding of the contribution that genetic variation makes to joint shape and how this modulates OA risk. In this article, a brief overview of synovial joint development and its genetic regulation is followed by a review of current knowledge on the genetic epidemiology of established joint shape disorders and common shape variation. A summary of current genetic epidemiology of OA is also given, together with current evidence on the genetic overlap between shape variation and OA. Finally, the established genetic risk loci for both joint shape and osteoarthritis are discussed

Whole-genome sequencing identifies rare genotypes in COMP and CHADL associated with high risk of hip osteoarthritis.

To access publisher's full text version of this article click on the hyperlink belowWe performed a genome-wide association study of total hip replacements, based on variants identified through whole-genome sequencing, which included 4,657 Icelandic patients and 207,514 population controls. We discovered two rare signals that strongly associate with osteoarthritis total hip replacement: a missense variant, c.1141G>C (p.Asp369His), in the COMP gene (allelic frequency = 0.026%, P = 4.0 × 10(-12), odds ratio (OR) = 16.7) and a frameshift mutation, rs532464664 (p.Val330Glyfs*106), in the CHADL gene that associates through a recessive mode of inheritance (homozygote frequency = 0.15%, P = 4.5 × 10(-18), OR = 7.71). On average, c.1141G>C heterozygotes and individuals homozygous for rs532464664 had their hip replacement operation 13.5 years and 4.9 years earlier than others (P = 0.0020 and P = 0.0026), respectively. We show that the full-length CHADL transcript is expressed in cartilage. Furthermore, the premature stop codon introduced by the CHADL frameshift mutation results in nonsense-mediated decay of the mutant transcripts

Biosensors Based on Nanomaterials: Transducers and Modified Surfaces for Diagnostics

The use of nanoparticles has opened a new era in the development of nanobiosensors capable of achieving analytical responses that compete with the most powerful instrumental techniques. Nanobiosensors are devices that allow analytical determinations through a specific action event between an analyte ofinterest and a bio-recognition molecule. These recognition molecules as enzymes,antibodies, nucleic acids, and aptamers are studied in detail in this chapter. The role of nanomaterials in biosensors is described in a separate section since they play a central role, allowing the understanding of their physicochemical properties such as quantum confinement, surface plasmon resonance, magnetic properties, and the effect of area increase. In addition, a brief review is provided about some basic concepts for the integration of the sensor components and their function in sensing systems found in the literature. Subsequently, a classification is proposed to summarize its fundamental characteristics, mechanism of operation, analytical characteristics, advantages, and disadvantages. Then, the main nanobiosensor types found in the literature are detailed, and specific explanations are given, e.g., those based on the determination of electrical, piezoelectric, colorimetric, fluorescent, and chemiluminescent properties. Likewise, the functioning of recently developed nanobiosensors is discussed, such as those based on local (SERS). Also, the applications of nanobiosensors in different fields of biomedicine and their fundamental importance to advance in the diagnosis of multiple pathologies as cancer are detailed. Finally, we discuss the state of the art and the future perspectives of scientific development.Fil: Romero, Marcelo Ricardo. Universidad Nacional de Córdoba. Instituto de Investigación y Desarrollo en Ingeniería de Procesos y Química Aplicada. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación y Desarrollo en Ingeniería de Procesos y Química Aplicada; ArgentinaFil: Picchio, Matías Luis. Universidad Nacional de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Steam locomotive K107, holiday special passenger train arriving at Noojee Station, Noojee, Victoria, April 1935 [picture] /

Part of collection: Buckland collection of railway transport photographs.; Title devised by cataloguer based on inscription and other reference sources.; Inscriptions: "K 107 Noojee 4/35"--In blue ink on verso; "Photograph by John Buckland"--Stamp on verso.; Condition: Good.; Also available in an electronic version via the Internet at: http://nla.gov.au/nla.pic-vn4196094