The use of blended learning to teach metabolism

We have developed a blended program for teaching Biochemistry, in particular metabolism, to undergraduate students undertaking the degrees of Bachelor of Science, Biomedical Science and Nutrition and Dietetics. In these degrees, where graduates develop scientific skills and clinical skills when appropriate, a thorough understanding of biochemistry is essential. Blended learning approaches aim to bring together face to face and online learning modalities in combinations which will enhance student learning (‘Blended learning’ 2005; Aycock, Garnham and Kaleta 2002; Garnham and Kaleta 2002). Our aim in designing blended biochemistry units was to integrate the various components of the units into single continuous entities with the components being linked and interdependent. We therefore developed an integrated blend (Clark 2003) delivered both online (WebCT-Vista) and offline (face to face lectures and tutorials, distributable print media, CDs). A range of interactive multimedia learning modalities and face to face learning exposures are thus used to promote interactive, active, student-centred learning and enhance students’ problemsolving skills. Blended learning was introduced to: 1. cater for a range of learning styles and engage students at a higher level of learning; 2. integrate in-class and out-of-class learning; 3. improve students’ ability to master and integrate biochemical concepts which are fundamental to understanding metabolism; 4. allow students to work at their own time and pace using online learning; and 5. encourage students to assess their knowledge and understanding through electronic quizzes and to provide prompt and direct feedback on their performance

Reconsidering the causality of TIA1 mutations in ALS

International audienc

Structural variation analysis of 6,500 whole genome sequences in amyotrophic lateral sclerosis

There is a strong genetic contribution to Amyotrophic lateral sclerosis (ALS) risk, with heritability estimates of up to 60%. Both Mendelian and small effect variants have been identified, but in common with other conditions, such variants only explain a little of the heritability. Genomic structural variation might account for some of this otherwise unexplained heritability. We therefore investigated association between structural variation in a set of 25 ALS genes, and ALS risk and phenotype. As expected, the repeat expansion in the C9orf72 gene was identified as associated with ALS. Two other ALS-associated structural variants were identified: inversion in the VCP gene and insertion in the ERBB4 gene. All three variants were associated both with increased risk of ALS and specific phenotypic patterns of disease expression. More than 70% of people with respiratory onset ALS harboured ERBB4 insertion compared with 25% of the general population, suggesting respiratory onset ALS may be a distinct genetic subtype

Telomere length analysis in amyotrophic lateral sclerosis using large-scale whole genome sequence data

Background: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the loss of upper and lower motor neurons, leading to progressive weakness of voluntary muscles, with death following from neuromuscular respiratory failure, typically within 3 to 5 years. There is a strong genetic contribution to ALS risk. In 10% or more, a family history of ALS or frontotemporal dementia is obtained, and the Mendelian genes responsible for ALS in such families have now been identified in about 50% of cases. Only about 14% of apparently sporadic ALS is explained by known genetic variation, suggesting that other forms of genetic variation are important. Telomeres maintain DNA integrity during cellular replication, differ between sexes, and shorten naturally with age. Sex and age are risk factors for ALS and we therefore investigated telomere length in ALS. Methods: Samples were from Project MinE, an international ALS whole genome sequencing consortium that includes phenotype data. For validation we used donated brain samples from motor cortex from people with ALS and controls. Ancestry and relatedness were evaluated by principal components analysis and relationship matrices of DNA microarray data. Whole genome sequence data were from Illumina HiSeq platforms and aligned using the Isaac pipeline. TelSeq was used to quantify telomere length using whole genome sequence data. We tested the association of telomere length with ALS and ALS survival using Cox regression. Results: There were 6,580 whole genome sequences, reducing to 6,195 samples (4,315 from people with ALS and 1,880 controls) after quality control, and 159 brain samples (106 ALS, 53 controls). Accounting for age and sex, there was a 20% (95% CI 14%, 25%) increase of telomere length in people with ALS compared to controls (p = 1.1 × 10−12), validated in the brain samples (p = 0.03). Those with shorter telomeres had a 10% increase in median survival (p = 5.0×10−7). Although there was no difference in telomere length between sporadic ALS and familial ALS (p=0.64), telomere length in 334 people with ALS due to expanded C9orf72 repeats was shorter than in those without expanded C9orf72 repeats (p = 5.0×10−4). Discussion: Although telomeres shorten with age, longer telomeres are a risk factor for ALS and worsen prognosis. Longer telomeres are associated with ALS