Dietary fatty acids and chylomicron synthesis and secretion

There is currently considerable interest in potential atherogenic and thrombogenic consequences of elevated concentrations of triacylglycerols, especially in the post-prandial state. Despite this, there is limited information on the effects of dietary fatty acids on the synthesis, secretion and metabolism of chylomicrons, the large triacylglycerol-rich lipoproteins synthesized in the enterocyte following the digestion and absorption of dietary fat. This brief review considers current approaches to the investigation of chylomicron synthesis and summarizes some of the human, cell and animal studies that have investigated effects of different fatty acids on these pathways. Potential sites for modulatory effects of dietary fatty acids on the molecular events of chylomicron synthesis are proposed in the light of the recent model that has been developed from cell and animal studies and observations based on abnormalities in chylomicron formation in human inherited autosomal recessive diseases.

TRIM32 regulates skeletal muscle stem cell differentiation and is necessary for normal adult muscle regeneration

Limb girdle muscular dystrophy type 2H (LGMD2H) is an inherited autosomal recessive disease of skeletal muscle caused by a mutation in the TRIM32 gene. Currently its pathogenesis is entirely unclear. Typically the regeneration process of adult skeletal muscle during growth or following injury is controlled by a tissue specific stem cell population termed satellite cells. Given that TRIM32 regulates the fate of mammalian neural progenitor cells through controlling their differentiation, we asked whether TRIM32 could also be essential for the regulation of myogenic stem cells. Here we demonstrate for the first time that TRIM32 is expressed in the skeletal muscle stem cell lineage of adult mice, and that in the absence of TRIM32, myogenic differentiation is disrupted. Moreover, we show that the ubiquitin ligase TRIM32 controls this process through the regulation of c-Myc, a similar mechanism to that previously observed in neural progenitors. Importantly we show that loss of TRIM32 function induces a LGMD2H-like phenotype and strongly affects muscle regeneration in vivo. Our studies implicate that the loss of TRIM32 results in dysfunctional muscle stem cells which could contribute to the development of LGMD2H.

Genetic and phenotypic characterization of complex hereditary spastic paraplegia

The hereditary spastic paraplegias are a heterogeneous group of degenerative disorders that are clinically classified as either pure with predominant lower limb spasticity, or complex where spastic paraplegia is complicated with additional neurological features, and are inherited in autosomal dominant, autosomal recessive or X-linked patterns. Genetic defects have been identified in over 40 different genes, with more than 70 loci in total. Complex recessive spastic paraplegias have in the past been frequently associated with mutations in SPG11 (spatacsin), ZFYVE26/SPG15, SPG7 (paraplegin) and a handful of other rare genes, but many cases remain genetically undefined. The overlap with other neurodegenerative disorders has been implied in a small number of reports, but not in larger disease series. This deficiency has been largely due to the lack of suitable high throughput techniques to investigate the genetic basis of disease, but the recent availability of next generation sequencing can facilitate the identification of disease- causing mutations even in extremely heterogeneous disorders. We investigated a series of 97 index cases with complex spastic paraplegia referred to a tertiary referral neurology centre in London for diagnosis or management. The mean age of onset was 16 years (range 3 to 39). The SPG11 gene was first analysed, revealing homozygous or compound heterozygous mutations in 30/97 (30.9%) of probands, the largest SPG11 series reported to date, and by far the most common cause of complex spastic paraplegia in the UK, with severe and progressive clinical features and other neurological manifestations, linked with magnetic resonance imaging defects. Given the high frequency of SPG11 mutations, we studied the autophagic response to starvation in eight affected SPG11 cases and control fibroblast cell lines, but in our restricted study we did not observe correlations between disease status and autophagic or lysosomal markers. In the remaining cases, next generation sequencing was carried out revealing variants in a number of other known complex spastic paraplegia genes, including five in SPG7 (5/97), four in FA2H (also known as SPG35) (4/97) and two in ZFYVE26/SPG15. Variants were identified in genes usually associated with pure spastic paraplegia and also in the Parkinson’s disease-associated gene ATP13A2, neuronal ceroid lipofuscinosis gene TPP1 and the hereditary motor and sensory neuropathy DNMT1 gene, highlighting the genetic heterogeneity of spastic paraplegia. No plausible genetic cause was identified in 51% of probands, likely indicating the existence of as yet unidentified genes.

How level and type of deafness affects user perception of multimedia video clips

Our research investigates the impact that hearing has on the perception of digital video clips, with and without captions, by discussing how hearing loss, captions and deafness type affects user QoP (Quality of Perception). QoP encompasses not only a user's satisfaction with the quality of a multimedia presentation, but also their ability to analyse, synthesise and assimilate informational content of multimedia . Results show that hearing has a significant effect on participants’ ability to assimilate information, independent of video type and use of captions. It is shown that captions do not necessarily provide deaf users with a ‘greater level of information’ from video, but cause a change in user QoP, depending on deafness type, which provides a ‘greater level of context of the video’. It is also shown that post-lingual mild and moderately deaf participants predict less accurately their level of information assimilation than post-lingual profoundly deaf participants, despite residual hearing. A positive correlation was identified between level of enjoyment (LOE) and self-predicted level of information assimilation (PIA), independent of hearing level or hearing type. When this is considered in a QoP quality framework, it puts into question how the user perceives certain factors, such as ‘informative’ and ‘quality’.

Facilitating and disrupting speech perception in word deafness

Background: Word deafness is a rare condition where pathologically degraded speech perception results in impaired repetition and comprehension but otherwise intact linguistic skills. Although impaired linguistic systems in aphasias resulting from damage to the neural language system (here termed central impairments), have been consistently shown to be amenable to external influences such as linguistic or contextual information (e.g. cueing effects in naming), it is not known whether similar influences can be shown for aphasia arising from damage to a perceptual system (here termed peripheral impairments). Aims: This study aimed to investigate the extent to which pathologically degraded speech perception could be facilitated or disrupted by providing visual as well as auditory information. Methods and Procedures: In three word repetition tasks, the participant with word deafness (AB) repeated words under different conditions: words were repeated in the context of a pictorial or written target, a distractor (semantic, unrelated, rhyme or phonological neighbour) or a blank page (nothing). Accuracy and error types were analysed. Results: AB was impaired at repetition in the blank condition, confirming her degraded speech perception. Repetition was significantly facilitated when accompanied by a picture or written example of the word and significantly impaired by the presence of a written rhyme. Errors in the blank condition were primarily formal whereas errors in the rhyme condition were primarily miscues (saying the distractor word rather than the target). Conclusions: Cross-modal input can both facilitate and further disrupt repetition in word deafness. The cognitive mechanisms behind these findings are discussed. Both top-down influence from the lexical layer on perceptual processes as well as intra-lexical competition within the lexical layer may play a role.