Cell adhesion marker expression dynamics during fusion of the optic fissure.

Tissue fusion is a critical process that is repeated in multiple contexts during embryonic development and shares common attributes to processes such as wound healing and metastasis. Ocular coloboma is a developmental eye disorder that presents as a physical gap in the ventral eye, and is a major cause of childhood blindness. Coloboma results from fusion failure between opposing ventral retinal epithelia, but there are major knowledge gaps in our understanding of this process at the molecular and cell behavioural levels.

Detailed analysis of chick optic fissure closure reveals Netrin-1 as an essential mediator of epithelial fusion.

Epithelial fusion underlies many vital organogenic processes during embryogenesis. Disruptions to these cause a significant number of human birth defects, including ocular coloboma. We provide robust spatial-temporal staging and unique anatomical detail of optic fissure closure (OFC) in the embryonic chick, including evidence for roles of apoptosis and epithelial remodelling.

Copy number variation of in familial dystonic tremor.

Objective: To elucidate the genetic cause of a large 5 generation South Indian family with multiple individuals with predominantly an upper limb postural tremor and posturing in keeping with another form of tremor, namely, dystonic tremor.

Methods: Whole-genome single nucleotide polymorphism (SNP) microarray analysis was undertaken to look for copy number variants in the affected individuals.

Results: Whole-genome SNP microarray studies identified a tandem duplicated genomic segment of chromosome 15q24 present in all affected family members.

Mutation in the intracellular chloride channel CLCC1 associated with autosomal recessive retinitis pigmentosa.

We identified a homozygous missense alteration (c.75C>A, p.D25E) in CLCC1, encoding a presumptive intracellular chloride channel highly expressed in the retina, associated with autosomal recessive retinitis pigmentosa (arRP) in eight consanguineous families of Pakistani descent.

Truncating mutations underlie a spectrum of dominant hereditary motor neuropathies.

Objective: To identify the genetic cause of disease in 2 previously unreported families with forms of distal hereditary motor neuropathies (dHMNs).

Methods: The first family comprises individuals affected by dHMN type V, which lacks the cardinal clinical feature of vocal cord paralysis characteristic of dHMN-VII observed in the second family. Next-generation sequencing was performed on the proband of each family.

Choline transporter mutations in severe congenital myasthenic syndrome disrupt transporter localization.

The presynaptic, high-affinity choline transporter is a critical determinant of signalling by the neurotransmitter acetylcholine at both central and peripheral cholinergic synapses, including the neuromuscular junction. Here we describe an autosomal recessive presynaptic congenital myasthenic syndrome presenting with a broad clinical phenotype due to homozygous choline transporter missense mutations. The clinical phenotype ranges from the classical presentation of a congenital myasthenic syndrome in one patient (p.

How does calcium interact with the cytoskeleton to regulate growth cone motility during axon pathfinding?

The precision with which neurons form connections is crucial for the normal development and function of the nervous system. The development of neuronal circuitry in the nervous system is accomplished by axon pathfinding: a process where growth cones guide axons through the embryonic environment to connect with their appropriate synaptic partners to form functional circuits. Despite intense efforts over many years to understand how this process is regulated, the complete repertoire of molecular mechanisms that govern the growth cone cytoskeleton and hence motility, remain unresolved.

Drebrin coordinates the actin and microtubule cytoskeleton during the initiation of axon collateral branches.

Drebrin is a cytoskeleton-associated protein which can interact with both actin filaments and the tips of microtubules. Its roles have been studied mostly in dendrites, and the functions of drebrin in axons are less well understood. In this study, we analyzed the role of drebrin, through shRNA-mediated depletion and overexpression, in the collateral branching of chicken embryonic sensory axons.

Views of newly-qualified GPs about their training and preparedness: lessons for extended generalist training.

Background: General practice is becoming increasingly complex due to an ageing population with multiple morbidities and the shift of services from secondary to primary care, yet GP training remains largely the same. Extended training is now recommended, initially proposed as a fourth GP specialty trainee year, but more recently as a broad-based 4-year specialty training programme.

Aim: To explore the views of newly-qualified GPs about their training and preparedness for specific aspects of the GP's role.

Prepared for commissioning? A qualitative study into the views of recently qualified GPs.

Background: Expectations of the latest manifestation of GPled commissioning, in delivering cost-savings and improved services, are considerable. However, previous models suggest clinical engagement and other factors may hinder its success. It is timely to explore the views of the newest generation of GPs about involvement in commissioning, to inform plans for preparing the future workforce.

Probiotics, prebiotics and immunomodulation of gut mucosal defences: homeostasis and immunopathology.

Probiotics are beneficial microbes that confer a realistic health benefit on the host, which in combination with prebiotics, (indigestible dietary fibre/carbohydrate), also confer a health benefit on the host via products resulting from anaerobic fermentation. There is a growing body of evidence documenting the immune-modulatory ability of probiotic bacteria, it is therefore reasonable to suggest that this is potentiated via a combination of prebiotics and probiotics as a symbiotic mix. The need for probiotic formulations has been appreciated for the health benefits in "topping up your good bacteria" or indeed in an attempt to normalise the dysbiotic microbiota associated with immunopathology.