PiggyBac-ing on a Primate Genome: Novel Elements, Recent Activity and Horizontal Transfer

To better understand the extent of Class II transposable element activity in mammals, we investigated the mouse lemur, Microcebus murinus, whole genome shotgun (2X) draft assembly. Analysis of this strepsirrhine primate extended previous research that targeted anthropoid primates and found no activity within the last 37 Myr. We tested the hypothesis that members of the piggyBac Class II superfamily have been inactive in the strepsirrhine lineage of primates during the same period. Evidence against this hypothesis was discovered in the form of three nonautonomous piggyBac elements with activity periods within the past 40 Myr and possibly into the very recent past. In addition, a novel family of piggyBac transposons was identified, suggesting introduction via horizontal transfer. A second autonomous element was also found with high similarity to an element recently described from the little brown bat, Myotis lucifugus, further implicating horizontal transfer in the evolution of this genome. These findings indicate a more complex history of transposon activity in mammals rather than a uniform shutdown of Class II transposition, which had been suggested by analyses of more common model organisms

Mobile DNA in Old World monkeys: A glimpse through the rhesus macaque genome

The completion of the draft sequence of the rhesus macaque genome allowed us to study the genomic composition and evolution of transposable elements in this representative of the Old World monkey lineage, a group of diverse primates closely related to humans. The L1 family of long interspersed elements appears to have evolved as a single lineage, and Alu elements have evolved into four currently active lineages. We also found evidence of elevated horizontal transmissions of retroviruses and the absence of DNA transposon activity in the Old World monkey lineage. In addition, ∼100 precursors of composite SVA (short interspersed element, variable number of tandem repeat, and Alu) elements were identified, with the majority being shared by the common ancestor of humans and rhesus macaques. Mobile elements compose roughly 50% of primate genomes, and our findings illustrate their diversity and strong influence on genome evolution between closely related species

Reductions in co-contraction following neuromuscular re-education in people with knee osteoarthritis

Background Both increased knee muscle co-contraction and alterations in central pain processing have been suggested to play a role in knee osteoarthritis pain. However, current interventions do not target either of these mechanisms. The Alexander Technique provides neuromuscular re-education and may also influence anticipation of pain. This study therefore sought to investigate the potential clinical effectiveness of the AT intervention in the management of knee osteoarthritis and also to identify a possible mechanism of action. Methods A cohort of 21 participants with confirmed knee osteoarthritis were given 20 lessons of instruction in the Alexander Technique. In addition to clinical outcomes EMG data, quantifying knee muscle co-contraction and EEG data, characterising brain activity during anticipation of pain, were collected. All data were compared between baseline and post-intervention time points with a further 15-month clinical follow up. In addition, biomechanical data were collected from a healthy control group and compared with the data from the osteoarthritis subjects. Results: Following AT instruction the mean WOMAC pain score reduced by 56% from 9.6 to 4.2 (P<0.01) and this reduction was maintained at 15 month follow up. There was a clear decrease in medial co-contraction at the end of the intervention, towards the levels observed in the healthy control group, both during a pre-contact phase of gait (p<0.05) and during early stance (p<0.01). However, no changes in pain-anticipatory brain activity were observed. Interestingly, decreases in WOMAC pain were associated with reductions in medial co-contraction during the pre-contact phase of gait. Conclusions: This is the first study to investigate the potential effectiveness of an intervention aimed at increasing awareness of muscle behaviour in the clinical management of knee osteoarthritis. These data suggest a complex relationship between muscle contraction, joint loading and pain and support the idea that excessive muscle co-contraction may be a maladaptive response in this patient group. Furthermore, these data provide evidence that, if the activation of certain muscles can be reduced during gait, this may lead to positive long-term clinical outcomes. This finding challenges clinical management models of knee osteoarthritis which focus primarily on muscle strengthening

The health and housing in transition study: A longitudinal study of the health of homeless and vulnerably housed adults in three Canadian cities

Objectives: While substantial research has demonstrated the poor health status of homeless populations, the health status of vulnerably housed individuals is largely unknown. Furthermore, few longitudinal studies have assessed the impact of housing transitions on health. The health and housing in transition (HHiT) study is a prospective cohort study that aims to track the health and housing status of a representative sample of homeless and vulnerably housed single adults in three Canadian cities (Toronto, Ottawa, and Vancouver). This paper discusses the HHiT study methodological recruitment strategies and follow-up procedures, including a discussion of the limitations and challenges experienced to date. Methods: Participants (n = 1,192) were randomly selected at shelters, meal programmes, community health centres, drop-in centres, rooming houses, and single-room occupancy hotels from January to December 2009 and are being re-interviewed every 12 months for a 2-year period. Results: At baseline, over 85% of participants reported having at least one chronic health condition, and over 50% reported being diagnosed with a mental health problem. Conclusions: Our findings suggest that, regardless of housing status, participants had extremely poor overall health

Older People, Sense of Coherence and Community

Population ageing is a global trend and even though years added to life often are lived in good health; it will have an impact on healthcare, housing and facilities, and social security costs. Healthy ageing in place, especially in one’s own home and community, increasingly receives attention from health professionals, researchers, and policymakers. In this chapter, we first discuss the meaning of the concept of healthy ageing, and how Sense of Coherence contributes to this process. Next, we discuss the characteristics of the community in which older people live their lives and how the community can provide resources (GRR and SRR) to strengthen Sense of Coherence and hence perceived well-being and quality of life

Mapping and phasing of structural variation in patient genomes using nanopore sequencing

Despite improvements in genomics technology, the detection of structural variants (SVs) from short-read sequencing still poses challenges, particularly for complex variation. Here we analyse the genomes of two patients with congenital abnormalities using the MinION nanopore sequencer and a novel computational pipeline—NanoSV. We demonstrate that nanopore long reads are superior to short reads with regard to detection of de novo chromothripsis rearrangements. The long reads also enable efficient phasing of genetic variations, which we leveraged to determine the parental origin of all de novo chromothripsis breakpoints and to resolve the structure of these complex rearrangements. Additionally, genome-wide surveillance of inherited SVs reveals novel variants, missed in short-read data sets, a large proportion of which are retrotransposon insertions. We provide a first exploration of patient genome sequencing with a nanopore sequencer and demonstrate the value of long-read sequencing in mapping and phasing of SVs for both clinical and research applications