Computational Analysis and Integration of MeDIP-seq Methylome Data

The combinatorial number of possible methylomes in biological time and space is astronomical. Consequently, the computational analysis of methylomes needs to cater for a variety of data, throughput and resolution. Here, we review recent advances in 2nd generation sequencing (2GS) with a focus on the different methods used for the analysis of MeDIP-seq data. The challenges and opportunities presented by the integration of methylation data with other genomic data types are discussed as is the potential impact of emerging 3rd generation sequencing (3GS) based technologies on methylation analysis

Human-specific CpG 'beacons' identify human-specific prefrontal cortex H3K4me3 chromatin peaks

Therefore, CpG-focused comparative sequence analysis can precisely pinpoint chromatin structures that contribute to the human-specific phenotype and further supports an integrated approach in genomic and epigenomic studie

A biomechanical comparison of initial sprint acceleration performance and technique in an elite athlete with cerebral palsy and able-bodied sprinters

Cerebral palsy is known to generally limit range of motion and force producing capability during movement. It also limits sprint performance, but the exact mechanisms underpinning this are not well known. One elite male T36 multiple-Paralympic sprint medallist (T36) and 16 well-trained able-bodied (AB) sprinters each performed 5–6 maximal sprints from starting blocks. Whole-body kinematics (250 Hz) in the block phase and first two steps, and synchronised external forces (1,000 Hz) in the first stance phase after block exit were combined to quantify lower limb joint kinetics. Sprint performance (normalised average horizontal external power in the first stance after block exit) was lower in T36 compared to AB. T36 had lower extensor range of motion and peak extensor angular velocity at all lower limb joints in the first stance after block exit. Positive work produced at the knee and hip joints in the first stance was lower in T36 than AB, and the ratio of positive:negative ankle work produced was lower in T36 than AB. These novel results directly demonstrate the manner in which cerebral palsy limits performance in a competition-specific sprint acceleration movement, thereby improving understanding of the factors that may limit performance in elite sprinters with cerebral palsy

Asthma, body mass and aerobic fitness, the relationship in adolescents: The exercise for asthma with commando Joe’s® (X4ACJ) trial

Although an association has been suggested between asthma, obesity, fitness and physical activity, the relationship between these parameters remains to be elucidated in adolescents. Six-hundred and sixteen adolescents were recruited (334 boys; 13.0 ± 1.1years; 1.57 ± 0.10m; 52.6 ± 12.9kg), of which 155 suffered from mild-to-moderate asthma (78 boys). Participants completed a 20-metre shuttle run test, lung function and 7-day objective physical activity measurements and completed asthma control and quality of life questionnaires. Furthermore, 69 adolescents (36 asthma; 21 boys) completed an incremental ramp cycle ergometer test. Although participants with asthma completed significantly fewer shuttle runs than their peers, peak V̇O2 did not differ between the groups. However, adolescents with asthma engaged in less physical activity (53.9 ± 23.5 vs 60.5 ± 23.6minutes) and had higher BMI (22.2 ± 4.8 vs 20.4 ± 3.7kg·m-2), than their peers. Whilst a significant relationship was found between quality of life and cardiorespiratory fitness according to peak V̇O2, only BMI was revealed as a significant predictor of asthma status. The current findings highlight the need to use accurate measures of cardiorespiratory fitness rather than indirect estimates to assess the influence of asthma during adolescence. Furthermore, the present study suggests that BMI and fitness may be key targets for future interventions seeking to improve asthma quality of life

An improved quantitative measure of the tendency for volcanic ash plumes to form in water: implications for the deposition of marine ash beds

Laboratory experiments and numerical simulations have shown that volcanic ash particles immersed in water can either settle slowly and individually, or rapidly and collectively as particle-laden plumes. The ratio of timescales for individual and collective settling, in the form of analytical expressions, provides a dimensionless quantitative measure of the tendency for such plumes to grow and persist which has important implications for determining particle residence times and deposition rates. However, existing measures in the literature assume that collective settling obeys Stokes' law and is therefore controlled by the balance between gravitational forces and viscous drag, despite plume development actually being controlled by the balance between gravitational forces and inertial drag even in the absence of turbulence during early times. This paper presents a new measure for plume onset which takes into account the inertial drag-controlled (rather than viscous drag-controlled) nature of plume growth and descent. A parameter study comprising a set of numerical simulations of small-scale volcanic ash particle settling experiments highlights the effectiveness of the new measure and, by comparison with an existing measure in the literature, also demonstrates that the timescale of collective settling is grossly under-estimated when assuming that plume development is slowed by viscous drag. Furthermore, the formulation of the new measure means that the tendency for plumes to form can be estimated from the thickness and concentration of the final deposit; the magnitude and duration of particle flux across the water's surface do not need to be known. The measure therefore permits the residence times of particles in a large body of water to be more accurately and practically determined, and allows the improved interpretation of layers of volcaniclastic material deposited at the seabed

Absence of glaucoma in DBA/2J mice homozygous for wild-type versions of Gpnmb and Tyrp1

BACKGROUND: The glaucomas are a common but incompletely understood group of diseases. DBA/2J mice develop a pigment liberating iris disease that ultimately causes elevated intraocular pressure (IOP) and glaucoma. We have shown previously that mutations in two genes, Gpnmb and Tyrp1, initiate the iris disease. However, mechanisms involved in the subsequent IOP elevation and optic nerve degeneration remain unclear. RESULTS: Here we present new mouse strains with Gpnmb and/or Tyrp1 genes of normal function and with a DBA/2J genetic background. These strains do not develop elevated IOP or glaucoma with age. CONCLUSION: These strains provide much needed controls for studying pathogenic mechanisms of glaucoma using DBA/2J mice. Given the involvement of Gpnmb and/or Tyrp1 in areas such as immunology and tumor development and progression, these strains are also important in other research fields

Host-linked soil viral ecology along a permafrost thaw gradient

Climate change threatens to release abundant carbon that is sequestered at high latitudes, but the constraints on microbial metabolisms that mediate the release of methane and carbon dioxide are poorly understood1,2,3,4,5,6,7. The role of viruses, which are known to affect microbial dynamics, metabolism and biogeochemistry in the oceans8,9,10, remains largely unexplored in soil. Here, we aimed to investigate how viruses influence microbial ecology and carbon metabolism in peatland soils along a permafrost thaw gradient in Sweden. We recovered 1,907 viral populations (genomes and large genome fragments) from 197 bulk soil and size-fractionated metagenomes, 58% of which were detected in metatranscriptomes and presumed to be active. In silico predictions linked 35% of the viruses to microbial host populations, highlighting likely viral predators of key carbon-cycling microorganisms, including methanogens and methanotrophs. Lineage-specific virus/host ratios varied, suggesting that viral infection dynamics may differentially impact microbial responses to a changing climate. Virus-encoded glycoside hydrolases, including an endomannanase with confirmed functional activity, indicated that viruses influence complex carbon degradation and that viral abundances were significant predictors of methane dynamics. These findings suggest that viruses may impact ecosystem function in climate-critical, terrestrial habitats and identify multiple potential viral contributions to soil carbon cycling