Copy number variation burden does not predict severity of neurodevelopmental phenotype in children with a sex chromosome trisomy

Sex chromosome trisomies (SCTs) (XXX, XXY, and XYY karyotypes) are associated with an elevated risk of neurodevelopmental disorders. The range of severity of the phenotype is substantial. We considered whether this variable outcome was related to the presence of copy number variants (CNVs)—stretches of duplicated or deleted DNA. A sample of 125 children with an SCT were compared with 181 children of normal karyotype who had been given the same assessments. First, we compared the groups on measures of overall CNV burden: number of CNVs, total span of CNVs, and likely functional impact (probability of loss‐of‐function intolerance, pLI, summed over CNVs). Differences between groups were small relative to within‐group variance and not statistically significant on overall test. Next, we considered whether a measure of general neurodevelopmental impairment was predicted by pLI summed score, SCT versus comparison group, or the interaction between them. There was a substantial effect of SCT/comparison status but the pLI score was not predictive of outcomes in either group. We conclude that variable presence of CNVs is not a likely explanation for the wide phenotypic variation in children with SCTs. We discuss methodological challenges of testing whether CNVs are implicated in causing neurodevelopmental problems.     

Resistance mechanisms to plant viruses: an overview

To obtain virus-resistant host plants, a range of operational strategies can be followed nowadays. While for decades plant breeders have been able to introduce natural resistance genes in susceptible genotypes without knowing precisely what these resistance traits were, currently a growing number of (mostly) dominant resistance genes have been cloned and analyzed. This has led not only to a better understanding of the plant's natural defence systems, but also opened the way to use these genes beyond species borders. Besides using natural resistance traits, also several novel, "engineered" forms of virus resistance have been developed over the past 15 years. The first successes were obtained embarking from the principle of pathogen-derived resistance (PDR) by transforming host plants with viral genes or sequences with the purpose to block a specific step during virus multiplication in the plant. As an unforeseen spin-off of these investments, the phenomenon of post-translational gene silencing (PTGS) was discovered, which to date is by far the most successful way to engineer resistance. It is generally believed that PTGS reflects a natural defence system of the plant, and part of the hypothesized components required for PTGS have been identified. As counteracting strategy, and confirming PTGS to be a natural phenomenon, a considerable number of viruses have acquired gene functions by which they can suppress PTGS. In addition to PDR and PTGS, further strategies for engineered virus resistance have been explored, including the use of pokeweed antiviral protein (PAP), 2',5'-oligoadenylate synthetase and "plantibodies". This paper will give a brief overview of the major strategies that have become operational during the past 10 years.     

In situ localisation of beet necrotic yellow vein virus (BNYVV) in rootlets of susceptible and resistant beet plants

Summary Mechanisms of resistance to beet necrotic yellow vein virus (BNYVV) were studied by comparing the multiplication and distribution of BNYVV in root tissue of some beet accessions. Seedlings were infected either by soil containing resting spores ofPolymyxa betae with BNYVV, or by a viruliferous zoospore suspension. With both inoculation methods high virus concentrations were obtained in rootlets of the susceptible cultivar Regina. Using infested soil, low virus concentrations were found in the partially resistant cultivar Rima and in the resistant accessions Holly and WB42. When a zoospore suspension was used, similar virus concentrations occurred in Rima and Holly as in Regina, while a low virus concentration was found in WB42. By in situ localisation studies, using immunogold-silver labelling, virus was detected in Regina after infection by soil or a zoospore suspension, but it could only be detected in the resistant accessions after infection by a zoospore suspension. In rootlets of Regina, Rima and Holly, virus was found in the epidermis, cortex parenchyma, endodermis, and interstitial parenchyma, but in general not inside the vascular tissue. In WB42 the virus, occurring in small aggregates, seemed to be restricted to the epidermis and some cortex parenchyma cells. Comparing both the multiplication and distribution of BNYVV in rootlets of the accessions studied, it is concluded that the virus resistance mechanism in Rima and Holly is different from that in WB42.     

Physical activity and motor skill outcomes of a 10-week intervention for children with intellectual and developmental disabilities ages 4–13: A pilot study

BackgroundChildren with intellectual and developmental disabilities (IDD) often experience increased barriers to engaging in physical activity (PA) which can stem from lack of gross motor function (GMF) development. Intervening on GMF at an early age can create better opportunities for children with IDD to engage in regular PA. In turn, increased PA can improve health outcomes and increase social skills.ObjectiveThe primary objective of this pilot study was to explore the effectiveness of a community-based GMF-focused PA intervention for improving overall motor skills and PA for children with IDD.MethodsAll study participants (n = 24) engaged in 10 weeks of programming for 1 h each week. A convenience sample was utilized.ResultsResults indicated no statistically significant changes pre to post for motor skill scores. However, a visual analysis of mean changes showed a consistent pattern of increased scores from pre to post on most skills. Additionally, we found that a change in participant locomotor skills significantly predicted change in Moderate to Vigorous Physical Activity (MVPA), F (1,11) = 5.16, Adj R² = .26, p = .04.ConclusionsThese results suggest individualized attention on GMF may help to increase motor skills for children with IDD. This study adds to the small but growing amount of research examining the efficacy of community based adapted PA interventions. Further, study results should support continued exploration of effective approaches to address the motor delays experienced by children with IDD.     

Molecular cloning and sequence analysis of the 3′-terminal region of iris severe mosaic virus RNA

Summary Sequence analysis of iris severe mosaic potyvirus genomic RNA revealed an unusual E/G cleavage site between the deduced large nuclear-inclusion protein and coat protein sequences. The latter showed an N-terminus of only 15 amino acids. The 3 non-translated region of the viral RNA was 340 nucleotides long.     

The Role of the Medical Expert in the Retrospective Assessment of Testamentary Capacity

Objectives:Physicians and other mental health experts are increasingly called on to assist the courts with the determination of testamentary capacity. We aim to improve the understanding of the retrospective assessment of testamentary capacity for medical experts in order to provide more useful reports for the court’s determinations and to provide a methodology for the retrospective assessment of testamentary capacity.Method:Medical experts with experience in the retrospective assessment of testamentary capacity collaborated with lawyers who practice estate litigation. The medical literature on the assessment of testamentary capacity was reviewed and integrated. The medical experts provided a clinical perspective, while the lawyers ensured that the case law and legal perspective were integrated into this review.Results:The focus and limitations of the medical expert are outlined including the need to be objective, nonpartisan, and fair. For the benefit of the court, the medical expert should describe the nature and severity of relevant medical, psychiatric, and cognitive disorders, and how they may impact on the specific criteria for testamentary capacity as defined by the leading case of Banks v Goodfellow. Medical experts should opine only on the issue of vulnerability to influence and defer to the court to determine the facts of the case regarding any influence that may have been exerted.Conclusions:Although the ultimate determination of testamentary capacity is a legal one, medical experts can help the court achieve the most informed legal decision by providing relevant information on clinical issues that may impact the criteria for testamentary capacity.