Widespread genomic influences on phenotype in Dravet syndrome, a 'monogenic' condition

Dravet syndrome is an archetypal rare severe epilepsy, considered "monogenic", typically caused by loss-of-function SCN1A variants. Despite a recognisable core phenotype, its marked phenotypic heterogeneity is incompletely explained by differences in the causal SCN1A variant or clinical factors. In 34 adults with SCN1A-related Dravet syndrome, we show additional genomic variation beyond SCN1A contributes to phenotype and its diversity, with an excess of rare variants in epilepsy-related genes as a set and examples of blended phenotypes, including one individual with an ultra-rare DEPDC5 variant and focal cortical dysplasia. Polygenic risk scores for intelligence are lower, and for longevity, higher, in Dravet syndrome than in epilepsy controls. The causal, major-effect, SCN1A variant may need to act against a broadly compromised genomic background to generate the full Dravet syndrome phenotype, whilst genomic resilience may help to ameliorate the risk of premature mortality in adult Dravet syndrome survivors

Interplay between cell adhesion and growth factor receptors: from the plasma membrane to the endosomes

The emergence of multicellular animals could only take place once evolution had produced molecular mechanisms for cell adhesion and communication. Today, all metazoans express integrin-type adhesion receptors and receptors for growth factors. Integrins recognize extracellular matrix proteins and respective receptors on other cells and, following ligand binding, can activate the same cellular signaling pathways that are regulated by growth factor receptors. Recent reports have indicated that the two receptor systems also collaborate in many other ways. Here, we review the present information concerning the role of integrins as assisting growth factor receptors and the interplay between the receptors in cell signaling and in the orchestration of receptor recycling

Anisotropic nanomaterials: structure, growth, assembly, and functions

Comprehensive knowledge over the shape of nanomaterials is a critical factor in designing devices with desired functions. Due to this reason, systematic efforts have been made to synthesize materials of diverse shape in the nanoscale regime. Anisotropic nanomaterials are a class of materials in which their properties are direction-dependent and more than one structural parameter is needed to describe them. Their unique and fine-tuned physical and chemical properties make them ideal candidates for devising new applications. In addition, the assembly of ordered one-dimensional (1D), two-dimensional (2D), and three-dimensional (3D) arrays of anisotropic nanoparticles brings novel properties into the resulting system, which would be entirely different from the properties of individual nanoparticles. This review presents an overview of current research in the area of anisotropic nanomaterials in general and noble metal nanoparticles in particular. We begin with an introduction to the advancements in this area followed by general aspects of the growth of anisotropic nanoparticles. Then we describe several important synthetic protocols for making anisotropic nanomaterials, followed by a summary of their assemblies, and conclude with major applications

QCD and strongly coupled gauge theories : challenges and perspectives

We highlight the progress, current status, and open challenges of QCD-driven physics, in theory and in experiment. We discuss how the strong interaction is intimately connected to a broad sweep of physical problems, in settings ranging from astrophysics and cosmology to strongly coupled, complex systems in particle and condensed-matter physics, as well as to searches for physics beyond the Standard Model. We also discuss how success in describing the strong interaction impacts other fields, and, in turn, how such subjects can impact studies of the strong interaction. In the course of the work we offer a perspective on the many research streams which flow into and out of QCD, as well as a vision for future developments.Peer reviewe

The effects of rTMS on impulsivity in normal adults: a systematic review and meta-analysis

Background: Impulsivity is a multi-dimensional construct that is regarded as a symptom of many psychiatric disorders. Harm resulting from impulsive behaviour can be substantial for the individuals concerned, people around them and the society they live in. Therefore, the importance of developing therapeutic interventions to target impulsivity is paramount. Aims and methods: We conducted a systematic review and meta-analysis of the literature from AMED, Embase, Medline, and PsycINFO databases on the use of repetitive transcranial magnetic stimulation (rTMS) in healthy adults to modulate different subdomains (motor, temporal and reflection) of impulsivity. Results: The results indicated that rTMS has distinct effects on different impulsivity subdomains. It has a significant, albeit small, effect on modulating motor impulsivity (g = 0.30, 95% CI, 0.17 to 0.43, p < .001) and a moderate effect on temporal impulsivity (g = 0.59, 95% CI, 0.32 to 0.86, p < .001). Subgroup analyses (e.g., excitatory vs. inhibitory rTMS, conventional rTMS vs. theta burst stimulation, analyses by stimulation sites, and type of outcome measure used) identified key parameters associated with the effects of rTMS on motor and temporal impulsivity. Age, sex, stimulation intensity and the number of pulses were not significant moderators for effects of rTMS on motor impulsivity. Due to lack of sufficient data to inform a meta-analysis, it has not been possible to assess the effects of rTMS on reflection impulsivity. Conclusions: The present findings provide preliminary evidence that rTMS can be used to modulate motor and temporal impulsivity in healthy individuals. Further studies are required to extend the use of rTMS to modulate impulsivity in those at most risk of engaging in harmful behaviour as a result of impulsivity, such as patients with offending histories and those with a history of self-harming behaviour