Evolving DNA motifs to predict GeneChip probe performance

Background: Affymetrix High Density Oligonuclotide Arrays (HDONA) simultaneously measure expression of thousands of genes using millions of probes. We use correlations between measurements for the same gene across 6685 human tissue samples from NCBI's GEO database to indicated the quality of individual HG-U133A probes. Low correlation indicates a poor probe. Results: Regular expressions can be automatically created from a Backus-Naur form (BNF) context-free grammar using strongly typed genetic programming. Conclusion: The automatically produced motif is better at predicting poor DNA sequences than an existing human generated RE, suggesting runs of Cytosine and Guanine and mixtures should all be avoided. © 2009 Langdon and Harrison; licensee BioMed Central Ltd

Effect of parasympathetic stimulation on brain activity during appraisal of fearful expressions

Autonomic nervous system activity is an important component of human emotion. Mental processes influence bodily physiology, which in turn feeds back to influence thoughts and feelings. Afferent cardiovascular signals from arterial baroreceptors in the carotid sinuses are processed within the brain and contribute to this two-way communication with the body. These carotid baroreceptors can be stimulated non-invasively by externally applying focal negative pressure bilaterally to the neck. In an experiment combining functional neuroimaging (fMRI) with carotid stimulation in healthy participants, we tested the hypothesis that manipulating afferent cardiovascular signals alters the central processing of emotional information (fearful and neutral facial expressions). Carotid stimulation, compared with sham stimulation, broadly attenuated activity across cortical and brainstem regions. Modulation of emotional processing was apparent as a significant expression-by-stimulation interaction within left amygdala, where responses during appraisal of fearful faces were selectively reduced by carotid stimulation. Moreover, activity reductions within insula, amygdala, and hippocampus correlated with the degree of stimulation-evoked change in the explicit emotional ratings of fearful faces. Across participants, individual differences in autonomic state (heart rate variability, a proxy measure of autonomic balance toward parasympathetic activity) predicted the extent to which carotid stimulation influenced neural (amygdala) responses during appraisal and subjective rating of fearful faces. Together our results provide mechanistic insight into the visceral component of emotion by identifying the neural substrates mediating cardiovascular influences on the processing of fear signals, potentially implicating central baroreflex mechanisms for anxiolytic treatment targets

Pilates based core stability training in ambulant individuals with multiple sclerosis: protocol for a multi-centre randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>People with Multiple Sclerosis (MS) frequently experience balance and mobility impairments, including reduced trunk stability. Pilates-based core stability training, which is aimed at improving control of the body's stabilising muscles, is popular as a form of exercise with people with MS and therapists. A replicated single case series study facilitated by the Therapists in MS Group in the United Kingdom (UK) provides preliminary evidence that this approach can improve balance and mobility in ambulant people with MS; further evidence is needed to substantiate these findings to ensure that limited time, energy, finances and resources are used to best effect.</p> <p>This study builds upon the pilot work undertaken in the case series study by implementing a powered randomised controlled study, with the aims of:</p> <p>1 Establishing the effectiveness of core stability training</p> <p>2 Comparing core stability training with standardised physiotherapy exercise</p> <p>3 Exploring underlying mechanisms of change associated with this intervention</p> <p>Methods</p> <p>This is a multi-centre, double blind, block randomised, controlled trial. Eligible participants will be recruited from 4 UK centres. Participants will be randomly allocated to one of three groups: Pilates based core stability training, standardised physiotherapy exercise or contract-relax relaxation sessions (placebo control). All will receive face to face training sessions over a 12 week period; together with a 15 minute daily home programme. All will be assessed by a blinded assessor before training, at the end of the 12 week programme and at 4 week follow-up. The primary outcome measure is the 10 metre timed walk. Secondary outcome measures are the MS walking Scale (MSWS-12), the Functional Reach (forwards and lateral), a 10 point Numerical Rating Scale to determine "Difficulty in carrying a drink when walking", and the Activities-specific Balance Confidence (ABC) Scale. In addition, ultrasound imaging of the abdominal muscles will be performed before and after intervention to assess changes in abdominal musculature at one of the four centres (Plymouth).</p> <p>Discussion</p> <p>This pragmatic trial will assess the effect of these exercise programmes on ambulatory people with MS. It may not be possible to extrapolate the conclusions to those who are non-ambulatory.</p> <p>Trial registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01414725">NCT01414725</a></p

Bioinformatics on the Cloud Computing Platform Azure

We discuss the applicability of the Microsoft cloud computing platform, Azure, for bioinformatics. We focus on the usability of the resource rather than its performance. We provide an example of how R can be used on Azure to analyse a large amount of microarray expression data deposited at the public database ArrayExpress. We provide a walk through to demonstrate explicitly how Azure can be used to perform these analyses in Appendix S1 and we offer a comparison with a local computation. We note that the use of the Platform as a Service (PaaS) offering of Azure can represent a steep learning curve for bioinformatics developers who will usually have a Linux and scripting language background. On the other hand, the presence of an additional set of libraries makes it easier to deploy software in a parallel (scalable) fashion and explicitly manage such a production run with only a few hundred lines of code, most of which can be incorporated from a template. We propose that this environment is best suited for running stable bioinformatics software by users not involved with its development. © 2014 Shanahan et al

Paratuberculosis sero-status and milk production, SCC and calving interval in Irish dairy herds

The objective of this study was to investigate the impact of paratuberculosis sero-status on milk yield, fat, protein, somatic cell count and calving interval in Irish dairy herds. Serum from all animals over 12 months of age (n = 2,602) in 34 dairy herds was tested for antibodies to Mycobacterium avium subsp. paratuberculosis using an ELISA. Herds were categorised by sero-status into positive, non-negative and negative, where a positive herd contained two or more positive cows, a non-negative herd contained only one positive cow and a negative herd contained no positive cows. Data at animal, parity and herd-level were analysed by multiple regression using general linear models. Positive herds (mean herd size = 129 cows) and non-negative herds (81 cows) were larger than negative herds (72 cows) (P < 0.01). Negative herds had the highest economic breeding index (EBI), while positive herds had the highest estimated breeding value (EBV) for milk yield. There was no significant effect of paratuberculosis sero-status at animal, parity or herd-level on milk yield, milk fat or protein production, somatic cell count score (SCCS) or calving interval. Negative herds tended to have a lower SCCS than positive and nonnegative herds (P = 0.087). This study only examined the effects of paratuberculosis sero-status but did not examine the clinical effects of Johne's disease at the farm or dairy industry levels

Virological and serological surveillance for type A influenza in the black-legged kittiwake (Rissa tridactyla)

<p>Abstract</p> <p>Background</p> <p>The epidemiology of avian influenza viruses (AIVs) in gulls is only partially known. The role of the world's most numerous gull species, the black-legged kittiwake (<it>Rissa tridactyla</it>), as a potential AIV reservoir species has been unclear. The prevalence of AIV and humoral response against AIV were therefore studied in a colony of apparently healthy black-legged kittiwakes breeding in a nesting cliff in the South West Barents Region of Norway (70°22' N, 31°10' E), in 2008 and 2009.</p> <p>Results</p> <p>AIVs were detected from the oropharynx and cloaca in low amounts, with prevalences of 15% and 5%, in 2008 and 2009, respectively. Direct, partial sequencing of the hemagglutinin (HA) gene revealed that the H4 subtype was present. In 2009, antibodies to influenza A virus were detected in sera from 57 of 80 adult birds. In contrast, none of the three-week-old chicks (n = 18) tested seropositive. Hemagglutination inhibition (HI) assays demonstrated that the adult kittiwakes primarily had antibodies specific to the gull-associated H13 and H16 subtypes, with antibodies to H16 being most common.</p> <p>Conclusions</p> <p>These results support that the highly pelagic black-legged kittiwake is a reservoir of AIV. The serological findings suggest that H16 might be the main AIV subtype in the black-legged kittiwake. Further studies are needed to understand the ecology of AIV in the black-legged kittiwake and in gulls in general.</p

Resequencing of genes for transforming growth factor β1 (TGFB1) type 1 and 2 receptors (TGFBR1, TGFBR2), and association analysis of variants with diabetic nephropathy

BACKGROUND: Diabetic nephropathy is the leading cause of end stage renal failure in the western world. There is substantial epidemiological evidence supporting a genetic predisposition to diabetic nephropathy, however the exact molecular mechanisms remain unknown. Transforming growth factor (TGFβ1) is a crucial mediator in the pathogenesis of diabetic nephropathy. METHODS: We investigated the role of five known single nucleotide polymorphisms (SNPs) in the TGFB1 gene for their association with diabetic nephropathy in an Irish, type 1 diabetic case (n = 272) control (n = 367) collection. The activity of TGFβ1 is facilitated by the action of type 1 and type 2 receptors, with both receptor genes (TGFBR1 and TGFBR2) shown to be upregulated in diabetic kidney disease. We therefore screened TGFBR1 and TGFBR2 genes for genomic variants using WAVE™ (dHPLC) technology and confirmed variants by direct capillary sequencing. Allele frequencies were determined in forty-eight healthy individuals. Data for all SNPs was assessed for Hardy Weinberg equilibrium, with genotypes and allele frequencies compared using the χ(2 )test for contingency tables. Patterns of linkage disequilibrium were established and common haplotypes estimated. RESULTS: Fifteen variants were identified in these genes, seven of which are novel, and putatively functional SNPs were subsequently genotyped using TaqMan™, Invader™ or Pyrosequencing(® )technology. No significant differences (p > 0.1) were found in genotype or allele distributions between cases and controls for any of the SNPs assessed. CONCLUSION: Our results suggest common variants in TGFB1, TGFBR1 and TGFBR2 genes do not strongly influence genetic susceptibility to diabetic nephropathy in an Irish Caucasian population

Seabird Modulations of Isotopic Nitrogen on Islands

The transport of nutrients by migratory animals across ecosystem boundaries can significantly enrich recipient food webs, thereby shaping the ecosystems’ structure and function. To illustrate the potential role of islands in enabling the transfer of matter across ecosystem boundaries to be gauged, we investigated the influence of seabirds on nitrogen input on islands. Basing our study on four widely differing islands in terms of their biogeography and ecological characteristics, sampled at different spatial and temporal intervals, we analyzed the nitrogen isotopic values of the main terrestrial ecosystem compartments (vascular plants, arthropods, lizards and rodents) and their relationship to seabird values. For each island, the isotopic values of the ecosystem were driven by those of seabirds, which ultimately corresponded to changes in their marine prey. First, terrestrial compartments sampled within seabird colonies were the most enriched in δ15N compared with those collected at various distances outside colonies. Second, isotopic values of the whole terrestrial ecosystems changed over time, reflecting the values of seabirds and their prey, showing a fast turnover throughout the ecosystems. Our results demonstrate that seabird-derived nutrients not only spread across the terrestrial ecosystems and trophic webs, but also modulate their isotopic values locally and temporally on these islands. The wealth of experimental possibilities in insular ecosystems justifies greater use of these model systems to further our understanding of the modalities of trans-boundary nutrient transfers