Summary
Lumpy skin disease, sheeppox and goatpox are high‐impact diseases of domestic ruminants with a devastating effect on cattle, sheep and goat farming industries in endemic regions. In this ...article, we review the current geographical distribution, economic impact of an outbreak, epidemiology, transmission and immunity of capripoxvirus. The special focus of the article is to scrutinize the use of currently available vaccines to investigate the resource needs and challenges that will have to be overcome to improve disease control and eradication, and progress on the development of safer and more effective vaccines. In addition, field evaluation of the efficacy of the vaccines and the genomic database available for poxviruses are discussed.
Injury to the meniscus is common and frequently leads to the development of post-traumatic osteoarthritis (PTOA). Many times meniscus injuries occur coincident with anterior cruciate ligament (ACL) ...injuries and lead to a bloody joint effusion. Hemarthrosis, or bleeding into the joint, has been implicated in degeneration of joint tissues. The goal of this review paper is to understand the pathophysiology of blood-induced joint damage, the possible effects of blood on meniscus tissue, and the implications for current meniscus repair techniques that involve the introduction of blood-derived products into the joint. In this review, we illustrate the similarities in the pathophysiology of joint damage due to hemophilic arthropathy (HA) and osteoarthritis (OA). Although numerous studies have revealed the harmful effects of blood on cartilage and synovium, there is currently a gap in knowledge regarding the effects of hemarthrosis on meniscus tissue homeostasis, healing, and the development of PTOA following meniscus injury. Given that many meniscus repair techniques utilize blood-derived and marrow-derived products, it is essential to understand the effects of these factors on meniscus tissue and the whole joint organ to develop improved strategies to promote meniscus tissue repair and prevent PTOA development.
Summary Zirconia is unique in its polymorphic crystalline makeup, reported to be sensitive to manufacturing and handling processes, and there is debate about which processing method is least harmful ...to the final product. Currently, zirconia restorations are manufactured by either soft or hard‐milling processes, with the manufacturer of each claiming advantages over the other. Chipping of the veneering porcelain is reported as a common problem and has been labelled as its main clinical setback. The objective of this systematic review is to report on the clinical success of zirconia‐based restorations fabricated by both milling processes, in regard to framework fractures and veneering porcelain chipping. A comprehensive review of the literature was completed for in vivo trials on zirconia restorations in MEDLINE and PubMed between 1950 and 2009. A manual hand search of relevant dental journals was also completed. Seventeen clinical trials involving zirconia‐based restorations were found, 13 were conducted on fixed partial dentures, two on single crowns and two on zirconia implant abutments, of which 11 were based on soft‐milled zirconia and six on hard‐milled zirconia. Chipping of the veneering porcelain was a common occurrence, and framework fracture was only observed in soft‐milled zirconia. Based on the limited number of short‐term in vivo studies, zirconia appears to be suitable for the fabrication of single crowns, and fixed partial dentures and implant abutments providing strict protocols during the manufacturing and delivery process are adhered to. Further long‐term prospective studies are necessary to establish the best manufacturing process for zirconia‐based restorations.
Summary
Both cat breeders and the lay public have interests in the origins of their pets, not only in the genetic identity of the purebred individuals, but also in the historical origins of common ...household cats. The cat fancy is a relatively new institution with over 85% of its 40–50 breeds arising only in the past 75 years, primarily through selection on single‐gene aesthetic traits. The short, yet intense cat breed history poses a significant challenge to the development of a genetic marker–based breed identification strategy. Using different breed assignment strategies and methods, 477 cats representing 29 fancy breeds were analysed with 38 short tandem repeats, 148 intergenic and five phenotypic single nucleotide polymorphisms. Results suggest the frequentist method of Paetkau (single nucleotide polymorphisms = 0.78, short tandem repeats = 0.88) surpasses the Bayesian method of Rannala and Mountain (single nucleotide polymorphisms = 0.56, short tandem repeats = 0.83) for accurate assignment of individuals to the correct breed. Additionally, a post‐assignment verification step with the five phenotypic single nucleotide polymorphisms accurately identified between 0.31 and 0.58 of the misassigned individuals raising the sensitivity of assignment with the frequentist method to 0.89 and 0.92 for single nucleotide polymorphisms and short tandem repeats respectively. This study provides a novel multistep assignment strategy and suggests that, despite their short breed history and breed family groupings, a majority of cats can be assigned to their proper breed or population of origin, that is, race.
Previous studies that have examined genetic influences on suicidal behaviour were confounded by genetic vulnerability for psychiatric risk factors. The present study examines genetic influences on ...suicidality (i.e. suicidal ideation and/or suicide attempt) after controlling for the inheritance of psychiatric disorders.
Sociodemographics, combat exposure, lifetime DSM-III-R major depression, bipolar disorder, childhood conduct disorder, adult antisocial personality disorder, panic disorder, post-traumatic stress disorder, drug dependence, alcohol dependence and lifetime suicidal ideation and attempt were assessed in 3372 twin pairs from the Vietnam Era Twin Registry who were assessed in 1987 and 1992. Genetic risk factors for suicidality were examined in a multinomial logistic regression model. Additive genetic, shared environmental and non-shared environmental effects on suicidality were estimated using structural equation modelling, controlling for other risk factors.
The prevalence of suicidal ideation and suicide attempt were 16.1% and 2.4% respectively. In a multinomial regression model, co-twin's suicidality, being white, unemployment, being other than married, medium combat exposure and psychiatric disorders were significant predictors for suicidal ideation. Co-twin's suicidality, unemployment, marital disruption, low education attainment and psychiatric disorders (except childhood conduct disorder) were significant predictors for suicide attempt. Model-fitting suggested that suicidal ideation was influenced by additive genetic (36%) and non-shared environmental (64%) effects, while suicide attempt was affected by additive genetic (17%), shared environmental (19%) and non-shared environmental (64%) effects.
There may be a genetic susceptibility specific to both suicidal ideation and suicide attempt in men, which is not explained by the inheritance of common psychiatric disorders.
Copy Number Variations (CNVs) have becoming very significant variants, representing a major source of genomic variation. CNVs involvement in phenotypic expression and different diseases has been ...widely demonstrated in humans as well as in many domestic animals. However, genome wide investigation on these structural variations is still missing in Felis catus. The present work is the first CNV mapping from a large data set of Next Generation Sequencing (NGS) data in the domestic cat, performed within the 99 Lives Consortium.
Reads have been mapped on the reference assembly_6.2 by Maverix Biomics. CNV detection with cn.MOPS and CNVnator detected 592 CNVs. These CNVs were used to obtain 154 CNV Regions (CNVRs) with BedTools, including 62 singletons. CNVRs covered 0.26% of the total cat genome with 129 losses, 19 gains and 6 complexes. Cluster Analysis and Principal Component Analysis of the detected CNVRs showed that breeds tend to cluster together as well as cats sharing the same geographical origins. The 46 genes identified within the CNVRs were annotated.
This study has improved the genomic characterization of 14 cat breeds and has provided CNVs information that can be used for studies of traits in cats. It can be considered a sound starting point for genomic CNVs identification in this species.
Summary
The domestic cat (Felis silvestris catus) is a valued companion animal throughout the world. Over 60 different cat breeds are accepted for competition by the cat fancy registries in different ...countries. Genetic markers, including short tandem repeats and SNPs, are available to evaluate and manage levels of inbreeding and genetic diversity, population and breed structure relationships, and individual identification for forensic and registration purposes. The International Society of Animal Genetics (ISAG) hosts the Applied Genetics in Companion Animals Workshop, which supports the standardization of genetic marker panels and genotyping for the identification of cats via comparison testing. SNP panels have been in development for many species, including the domestic cat. An ISAG approved core panel of SNPs for use in cat identification and parentage analyses is presented. SNPs (n = 121) were evaluated by different university‐based and commercial laboratories using 20 DNA samples as part of the ISAG comparison testing procedures. Different SNP genotyping technologies were examined, including DNA arrays, genotyping‐by‐sequencing and mass spectroscopy, to select a robust and efficient panel of 101 SNPs as the ISAG core panel for cats. The SNPs are distributed across all chromosomes including two on the X chromosome and an XY pseudo‐autosomal sexing marker (zinc‐finger XY; ZFXY). A population study demonstrated that the markers have an average polymorphic information content of 0.354 and a power of exclusion greater than 0.9999. The SNP panel should keep testing affordable while also allowing for the development of additional panels to monitor health, phenotypic traits, hybrid cats and highly inbred cats.
Severe climatic changes during the Pleistocene shaped the distributions of temperate‐adapted species. These species survived glaciations in classical southern refuges with more temperate climates, as ...well as in western and eastern peripheral Alpine temperate areas. We hypothesized that the European wildcat (Felis silvestris silvestris) populations currently distributed in Italy differentiated in, and expanded from two distinct glacial refuges, located in the southern Apennines and at the periphery of the eastern Alps. This hypothesis was tested by genotyping 235 presumed European wildcats using a panel of 35 domestic cat‐derived microsatellites. To provide support and controls for the analyses, 17 know wildcat x domestic cat hybrids and 17 Sardinian wildcats (F. s. libyca) were included. Results of Bayesian clustering and landscape genetic analyses showed that European wildcats in Italy are genetically subdivided into three well‐defined clusters corresponding to populations sampled in: (1) the eastern Alps, (2) the peninsular Apennines, and (3) the island of Sicily. Furthermore, the peninsular cluster is split into two subpopulations distributed on the eastern (Apennine mountains and hills) and western (Maremma hills and lowlands) sides of the Apennine ridge. Simulations indicated Alpine, peninsular, and Sicilian wildcats were isolated during the Last Glacial Maximum. Population subdivision in the peninsula cluster of central Italy arose as consequence of a more recent expansions of historically or ecologically distinct European wildcat subpopulations associated with distinct the Continental or Mediterranean habitats. This study identifies previously unknown European wildcat conservation units and supports a deep phylogeographical history for Italian wildcats.
Deep climatic changes during the Pleistocene shaped the distributions of temperate‐adapted species. The European wildcat (Felis s. silvestris) populations currently distributed in Italy differentiated in, and expanded from two distinct glacial refuges, respectively located in the southern Apennines and at the periphery of the eastern Alps.
Summary Objective Scottish fold cats, named for their unique ear shape, have a dominantly inherited osteochondrodysplasia involving malformation in the distal forelimbs, distal hindlimbs and tail, ...and progressive joint destruction. This study aimed to identify the gene and the underlying variant responsible for the osteochondrodysplasia. Design DNA samples from 44 Scottish fold and 54 control cats were genotyped using a feline DNA array and a case–control genome-wide association analysis conducted. The gene encoding a calcium permeable ion channel, transient receptor potential cation channel, subfamily V, member 4 ( TRPV4 ) was identified as a candidate within the associated region and sequenced. Stably transfected HEK293 cells were used to compare wild-type and mutant TRPV4 expression, cell surface localisation and responses to activation with a synthetic agonist GSK1016709A, hypo-osmolarity, and protease-activated receptor 2 stimulation. Results The dominantly inherited folded ear and osteochondrodysplasia in Scottish fold cats is associated with a p.V342F substitution (c.1024G>T) in TRPV4 . The change was not found in 648 unaffected cats. Functional analysis in HEK293 cells showed V342F mutant TRPV4 was poorly expressed at the cell surface compared to wild-type TRPV4 and as a consequence the maximum response to a synthetic agonist was reduced. Mutant TRPV4 channels had a higher basal activity and an increased response to hypotonic conditions. Conclusions Access to a naturally-occurring TRPV4 mutation in the Scottish fold cat will allow further functional studies to identify how and why the mutations affect cartilage and bone development.
Radiotherapy is an effective treatment of intermediate/high-risk locally advanced prostate cancer, however, >30% of patients relapse within 5 years. Clinicopathological parameters currently fail to ...identify patients prone to systemic relapse and those whom treatment intensification may be beneficial. The purpose of this study was to independently validate the performance of a 70-gene Metastatic Assay in a cohort of diagnostic biopsies from patients treated with radical radiotherapy and androgen deprivation therapy.
A bridging cohort of prostate cancer diagnostic biopsy specimens was profiled to enable optimization of the Metastatic Assay threshold before further independent clinical validation in a cohort of diagnostic biopsies from patients treated with radical radiotherapy and androgen deprivation therapy. Multivariable Cox proportional hazard regression analysis was used to assess assay performance in predicting biochemical failure-free survival (BFFS) and metastasis-free survival (MFS).
Gene expression analysis was carried out in 248 patients from the independent validation cohort and the Metastatic Assay applied. Ten-year MFS was 72% for Metastatic Assay positive patients and 94% for Metastatic Assay negative patients HR = 3.21 (1.35–7.67); P=0.003. On multivariable analysis the Metastatic Assay remained predictive for development of distant metastases HR = 2.71 (1.11–6.63); P=0.030. The assay retained independent prognostic performance for MFS when assessed with the Cancer of the Prostate Assessment Score (CAPRA) HR = 3.23 (1.22–8.59); P=0.019 whilst CAPRA itself was not significant HR = 1.88, (0.52–6.77); P=0.332. A high concordance 100% (61.5–100) for the assay result was noted between two separate foci taken from 11 tumours, whilst Gleason score had low concordance.
The Metastatic Assay demonstrated significant prognostic performance in patients treated with radical radiotherapy both alone and independent of standard clinical and pathological variables. The Metastatic Assay could have clinical utility when deciding upon treatment intensification in high-risk patients. Genomic and clinical data are available as a public resource.