Multi-environment QTL mapping in blackcurrant (Ribes nigrum L.) using mixed models.

The first genetic linkage map of blackcurrant, published by Brennan et al. (Euphytica 161:19-34, 2008), identified regions where quantitative trait loci (QTLs) for some important traits were located. The analysis was complicated by the fact that the mapping population was found to contain two subgroups, with segregation ratios consistent with these being crossed and selfed offspring. The QTL analysis was based on the trait mean over 3 years and focused on the crossed offspring. Here we proposed a mixed model multi-environment approach for this population. The 3 years are considered as three separate environments, the data from both the selfed and crossed offspring are combined and different residual terms are explored to model the correlation between the years. This permits tests for interactions between the QTLs, the year and the type of offspring (selfed or crossed). This is applied to re-analyse two important traits, anthocyanin concentration and budbreak. Several additional QTLs were identified, some affecting the trait in both the selfed and crossed offspring, others in just one.

Neurodevelopmental synaptopathies: Insights from behaviour in rodent models of synapse gene mutations.

The genomic revolution has begun to unveil the enormous complexity and heterogeneity of the genetic basis of neurodevelopmental disorders such as such epilepsy, intellectual disability, autism spectrum disorder and schizophrenia. Increasingly, human mutations in synapse genes are being identified across these disorders. These neurodevelopmental synaptopathies highlight synaptic homeostasis pathways as a convergence point underlying disease mechanisms. Here, we review some of the key pre- and postsynaptic genes in which penetrant human mutations have been identified in neurodevelopmental disorders for which genetic rodent models have been generated. Specifically, we focus on the main behavioural phenotypes that have been documented in these animal models, to consolidate our current understanding of how synapse genes regulate key behavioural and cognitive domains. These studies provide insights into better understanding the basis of the overlapping genetic and cognitive heterogeneity observed in neurodevelopmental disorders.

All troponins are not created equal.

Troponin measurement is central to the management and risk stratification of acute coronary syndromes. Decisions are made by categorizing troponin as positive or negative. We sought to evaluate categorical agreement between four troponin assays. Sixty blood samples were analysed by three troponin I assays (Centaur, Architect and point-of-care i-STAT) and one troponin T (TnT) assay (Roche Elecys). The upper reference limit was taken as the lowest value with a coefficient of variation of 10% or less. Continuous agreement between assays was good (Pearson's correlation coefficient 0.871-0.995). Categorical agreement assessed by Cohen's kappa varied from poor (between Architect and Centaur kappa = 0.37, and between TnT and Centaur kappa = 0.48) to good (between Architect and i-STAT kappa = 0.68, and between TnT and i-STAT kappa = 0.68). Percentage of positive results varied almost twofold, from 37% for the Centaur to 72% for the Architect. Comparison of four troponin assays showed up to twofold variations in the proportion of positive results. This implies that either a large proportion of troponin-positive diagnoses are missed by some assays or the assays with higher positivity are generating large numbers of false positives. Clinicians should evaluate troponin results in the clinical context and not base decisions solely on the 'normal range' of their local troponin assay.

Jansen's metaphyseal dysostosis.

A case of Jansen's metaphyseal dysostosis, a rare disorder of endochondral ossification, is described. This is the first case in which the severe radiographic manifestations of this disease were detected at birth. Linear growth is significantly retarded at 2 years of age. Nevertheless, because full ossification with trabeculae is anticipated, early recognition and appropriate management during the phase of active growth should minimize deformities.

Craniosynostosis associated with limb reduction malformations and cleft lip/palate: a distinct syndrome.

Craniosynostosis associated with short stature, radial and fibular aplasia, and cleft lip and/or palate represents a distinct syndrome. One original case and one previously undiagnosed case from the literature were found to have many distinct features in common, permitting them to be separated from craniosynostosis with radial or fibular aplasia, Robert's syndrome, pseudothalidomide or SC syndrome, and the hypomelia-hypotrichosis-facial hemangioma syndrome. Each had multiple craniofacial abnormalities: dysplastic ears, hypertelorism, strabismus, and malocclusion. Ulnae and humeri were hypoplastic; tibiae were bowed and hypoplastic. Testes were small. Associated mild to moderate mental retardation may be related to early institutionalization.

Acessory nerve function after surgical procedures in the posterior triangle.

Seventeen patients who had undergone surgical procedures in the posterior triangle of the neck were examined between one day and four years after operation. Eleven patients were studied with electromyography. Clinical and electromyographic evidence of 11th cranial nerve paresis was present in 12 patients. Partial nerve injuries and entrapments, as suggested by delayed symptoms and incomplete denervation on electromyographic studies, were frequent. Physiotherapy was effective in restoring a satisfactory, although in many cases an incomplete, return of function. The spinal accessory nerve appears to be vulnerable to injury despite careful preservation during surgical dissection.

Ingredients of a successful grant application to the National Institutes of Health.

Many factors determine the scientific merit of an NIH research grant application. This paper is intended to help optimize the organization and logical development of investigators' research ideas so that grant applications will be evaluated by the reviewers in as favorable a light as possible. The ingredients of a successful grant application are good ideas, good science, and a good application. The research should be based on a significant hypothesis and, if possible, oriented towards uncovering an important biological mechanism. Specific methods should be directly related to each aim of the project. Likewise, the specific aims should be related to each hypothesis. All aspects of the application should be clear and focused. It is best to define all assumptions, limitations, and alternative approaches. In general, the best philosophy is for the applicant to address all possible problems before the reviewers.

Matrix vesicle enzymes in human osteoarthritis.

The enzymatic activities and in vitro calcification properties of matrix vesicle fractions isolated from normal and osteoarthritic (OA) human articular cartilage were compared to determine the essential conditions for calcification in these tissues. Four groups of human cartilage were examined, I, normal articular cartilage from aged, nonOA joints; II, discolored or fibrillated cartilage from OA joints; III, osteophytic cartilage from OA joints; IV, loose body cartilage from OA joints. Fetal bovine growth plate cartilage was also studied. Both ATP- and 5'-AMP-dependent in vitro matrix vesicle calcification occurs in all cartilage groups examined and, for human articular cartilage, these activities increase progressively from Groups I to II to III. Calcification does not occur in the absence of either phosphate or pyrophosphate. Alkaline phosphatase, 5'-AMPase, and ATP:pyrophosphohydrolase activities are increased in Groups III and IV cartilage compared with Group I and are detected at high levels in fetal bovine growth plate cartilage. Pyrophosphatase activity occurs in only those cartilage groups juxtaposed to areas of new bone formation (osteophytic, loose body, and bovine growth plate). These results suggest that OA, growth plate, and even normal articular cartilage all have the potential to undergo calcification as long as both phosphate and pyrophosphate ions can be generated at sufficiently high levels. However, the capacity for cartilage to deposit hydroxyapatite, as it does during bone formation, may depend on the presence of pyrophosphatase activity.

Use of mesenchymal stem cells in a collagen matrix for Achilles tendon repair.

This investigation tested the hypothesis that delivering mesenchymal stem cell-seeded implants to a tendon gap model results in significantly improved repair biomechanics. Cultured, autologous, marrow-derived mesenchymal stem cells were suspended in a collagen gel delivery vehicle; the cell-gel composite was subsequently contracted onto a pretensioned suture. The resulting tissue prosthesis was then implanted into a 1-cm-long gap defect in the rabbit Achilles tendon. Identical procedures were performed on the contralateral tendon, but only the suture material was implanted. The tendon-implant constructs were evaluated 4, 8, and 12 weeks later by biomechanical and histological criteria. Significantly greater load-related structural and material properties were seen at all time intervals in the mesenchymal stem cell-treated tendons than in the contralateral, treated control repairs (p < 0.05), which contained suture alone with natural cell recruitment. The values were typically twice those for the control tissues at each time interval. Load-related material properties for the treated tissues also increased significantly over time (p < 0.05). The treated tissues had a significantly larger cross-sectional area (p < 0.05), and their collagen fibers appeared to be better aligned than those in the matched controls. The results indicate that delivering mesenchymal stem cell-contracted, organized collagen implants to large tendon defects can significantly improve the biomechanics, structure, and probably the function of the tendon after injury.

Residua of Guillain-Barré Polyneuritis in Children.

A study of the records from the period 1950 to 1970 at the Elizabethtown Hospital for Children and Youth produced twelve patients with the Guillain-Barré syndrome. These patients were contracted in 1975-76 and each was personally examined. Ten were found to have residual weakness but in several instances the weakness was so mild the patient was unaware of it. Good correlations were found between muscle examinations during the acute recovery period and at final follow-up. Six patients had undergone various surgical procedures, and all of them thought they had benefited.

Scapulothoracic dissociation (closed avulsion of the scapula, subclavian artery, and brachial plexus): a newly recognized variant, a new classification, and a review of the literature and treatment options.

Scapulothoracic (ST) dissociation is a closed complete traumatic forequarter amputation manifested by a flail pulseless arm and well-defined roentgenographic findings. These roentgenographic findings were previously reported to be lateral displacement of the scapula and either acromioclavicular separation (17) or displaced clavicular fracture (20). In this paper we present four patients with ST dissociation who had a previously unreported combination of roentgenographic findings: lateral displacement of the scapula and sternoclavicular separation. Polytrauma was present in all previously reported cases of patients with ST dissociation. We present one patient, however, in whom ST dissociation is an isolated finding. A review of the literature, and a review of treatment options that includes some combination of amputation, shoulder arthrodesis, prosthetic fitting, and reconstructive tendon transfers, are presented.

A review of basic science issues in low back pain.

This review article is based on a workshop, "New Horizons in Low Back Pain" that was held in November 1995 in San Diego, California. The current article follows the 1995 workshop format of a series of three case study models. Three classical clinical profiles were presented for consideration: lumbar radiculopathy, idiopathic (degenerative disk) low back pain, and degenerative stenosis. This article summarizes the basic science perspectives that were presented and discussed on each topic.

Lyme disease in children.

Lyme disease is becoming prevalent throughout the nation. This article will describe the etiology of Lyme disease, discuss ways of preventing the disease, and present methods for diagnosing and treating the disease.

An approach to the determination of winter chill requirements for different Ribes cultivars.

Winter chilling is critical for flowering and fruiting of many temperate fruits, with evidence that blackcurrant (Ribes nigrum L.) cropping has been adversely affected by warm winters. Accurate models of chill accumulation in blackcurrant are required so that breeding strategies can be formulated for the generation of new cultivars with resilience to future climates. Existing models for chill accumulation have largely been derived from statistical correlation; here we report the derivation of improved models for blackcurrant using controlled environment treatments. Hardwood cuttings from a diverse set of cultivars were exposed to constant or varying chilling temperatures and the effects on bud break after transfer to a warm, permissive environment evaluated. The impact of different combinations of temperature and chilling periods were described in terms of their overall 'Effectiveness' (E). Clear genotypic differences were found, with excessive chilling often inhibiting bud break. There was a significant interaction between observed chilling response and the period of low temperature exposure. A number of chilling models to explain observed interactions between chilling temperature and time of exposure on bud break were compared; the most effective involved an optimal response to increasing chill accumulation. The effects of varying temperatures during chilling on bud break were complex, with warm temperature breaks substantially inhibiting bud development and cooler temperature breaks tending to enhance bud burst. The relevance of these models to generic studies of endodormancy is discussed, together with their potential application to the development of phenotyping screens for future breeding using diverse blackcurrant germplasm.