Do synaesthesia and mental imagery tap into similar cross-modal processes?

Synaesthesia has previously been linked with imagery abilities, although an understanding of a causal role for mental imagery in broader synaesthetic experiences remains elusive. This can be partly attributed to our relatively poor understanding of imagery in sensory domains beyond vision. Investigations into the neural and behavioural underpinnings of mental imagery have nevertheless identified an important role for imagery in perception, particularly in mediating cross-modal interactions. However, the phenomenology of synaesthesia gives rise to the assumption that associated cross-modal interactions may be encapsulated and specific to synaesthesia. As such, evidence for a link between imagery and perception may not generalize to synaesthesia. Here, we present results that challenge this idea: first, we found enhanced somatosensory imagery evoked by visual stimuli of body parts in mirror-touch synaesthetes, relative to other synaesthetes or controls. Moreover, this enhanced imagery generalized to tactile object properties not directly linked to their synaesthetic associations. Second, we report evidence that concurrent experience evoked in grapheme-colour synaesthesia was sufficient to trigger visual-to-tactile correspondences that are common to all. Together, these findings show that enhanced mental imagery is a consistent hallmark of synaesthesia, and suggest the intriguing possibility that imagery may facilitate the cross-modal interactions that underpin synaesthesic experiences. This article is part of a discussion meeting issue 'Bridging senses: novel insights from synaesthesia'

Genetic and economic benefits of foreign sire contributions to a domestic sheep industry; including an Ireland-New Zealand case study

peer-reviewedBackground Importation of foreign genetics is a widely used genetic improvement strategy. However, even if the foreign genetic merit is currently greater than the domestic genetic merit, differences in foreign and domestic trends mean that the long-term competitiveness of an importation strategy cannot be guaranteed. Gene flow models are used to quantify the impact that a specific subpopulation, such as foreign genetics, can have over time on the genetic or economic benefit of a domestic industry. Methods We used a deterministic recursive gene flow model to predict the commercial performance of lambs born across various subpopulations. Numerous breeding strategies were evaluated by varying market share, proportions of rams selected for mating, genetic trend, superiority of foreign genetics over domestic genetics and frequency of importation. Specifically, an Ireland-New Zealand case study was simulated to quantify the potential gain that could be made by using foreign sire contributions (New Zealand) in a domestic sheep industry (Ireland). Results Genetic and economic gains were generated from alternative breeding strategies. The ‘base scenario’ (i.e. representing the current industry) predicted an average genetic merit value of €2.51 for lambs born and an annualised cumulative benefit of €45 million (m) after 20 years. Maximum genetic (€9.45 for lambs born) and economic (annualised cumulative benefit of €180 m after 20 years) benefits were achieved by implementing the ‘PRO-intense-market scenario’ which involved shifting market share away from conservative domestic breeders and reducing the proportion of rams that were selected for mating by progressive domestic breeders from the top 40% to the top 20%, without the use of any foreign genetics. The ‘PROFOR scenario’, which considered the use of foreign and progressive domestic genetics, predicted an average genetic merit value of €7.37 for lambs born and an annualised cumulative benefit of €144 m, after 20 years. Conclusions Our results demonstrate that there is opportunity for a domestic industry to increase industry benefits without the use of foreign genetics but through an attempt to shift the market share away from conservative domestic breeders towards progressive domestic breeders. However, the importation and use of progressive foreign genetics may be an effective method to trigger a change in behaviour of conservative domestic breeders towards the use of progressive genetics

Investigation of intra-day variability of gaseous measurements in sheep using portable accumulation chambers

peer-reviewedPortable accumulation chambers (PAC) enable short-term spot measurements of gaseous emissions including methane (CH4), carbon dioxide (CO2), and oxygen (O2) consumption from small ruminants. To date the differences in morning and evening gaseous measurements in the PAC have not been investigated. The objectives of this study were to investigate: 1) the optimal measurement time in the PAC, 2) the appropriate method of accounting for the animal’s size when calculating the animal’s gaseous output, and 3) the intra-day variability of gaseous measurements. A total of 12 ewe lambs (c. 10 to 11 months of age) were randomly selected each day from a cohort of 48 animals over nine consecutive days. Methane emissions from the 12 lambs were measured in 12 PAC during two measurement runs daily, AM (8 to 10 h) and PM (14 to 16 h). Animals were removed from Perennial ryegrass silage for at least 1 h prior to measurements in the PAC and animals were assigned randomly to each of the 12 chambers. Methane (ppm) concentration, O2 and CO2 percentage were measured at 5 time points (T1 = 0.0 min, T2 = 12.5 min, T3 = 25.0 min, T4 = 37.5 min, and T5 = 50.0 min from entry of the first animal into the first chamber) using an Eagle 2 monitor. The correlation between time points T5-T1 (i.e., 50 min minus 0 min after entry of the animal to the chamber) and T4-T1 was 0.95, 0.92, and 0.77 for CH4, O2, and CO2, respectively (P < 0.01). The correlation between CH4 and CO2 output and O2 consumption, calculated with live-weight and with body volume was 0.99 (P < 0.001). The correlation between the PAC measurement recorded on the same animal in the AM and PM measurement runs was 0.73. Factors associated with CH4 production included: day and time of measurement, the live-weight of the animal and the hourly relative humidity. Results from this study suggest that the optimal time for measuring an animal’s gaseous output in the PAC is 50 min, that live-weight should be used in the calculation of gaseous output from an animal and that the measurement of an animal’s gaseous emissions in either the AM or PM does not impact on the ranking of animals when gaseous emissions are measured using the feeding and measurement protocol outlined in the present study.Irish Department of Agricultur

Age-Related Sexual Dimorphism in Temporal Discrimination and in Adult-Onset Dystonia Suggests GABAergic Mechanisms

Background: Adult-onset isolated focal dystonia (AOIFD) presenting in early adult life is more frequent in men, whereas in middle age it is female predominant. Temporal discrimination, an endophenotype of adult-onset idiopathic isolated focal dystonia, shows evidence of sexual dimorphism in healthy participants. Objectives: We assessed the distinctive features of age-related sexual dimorphism of (i) sex ratios in dystonia phenotypes and (ii) sexual dimorphism in temporal discrimination in unaffected relatives of cervical dystonia patients. Methods: We performed (i) a meta-regression analysis of the proportion of men in published cohorts of phenotypes of adult-onset dystonia in relation to their mean age of onset and (ii) an analysis of temporal discrimination thresholds in 220 unaffected first-degree relatives (125 women) of cervical dystonia patients. Results: In 53 studies of dystonia phenotypes, the proportion of men showed a highly significant negative association with mean age of onset (p \u3c 0.0001, pseudo-R2 = 59.6%), with increasing female predominance from 40 years of age. Age of onset and phenotype together explained 92.8% of the variance in proportion of men. Temporal discrimination in relatives under the age of 35 years is faster in women than men but the age-related rate of deterioration in women is twice that of men; after 45 years of age, men have faster temporal discrimination than women. Conclusion: Temporal discrimination in unaffected relatives of cervical dystonia patients and sex ratios in adult-onset dystonia phenotypes show similar patterns of age-related sexual dimorphism. Such age-related sexual dimorphism in temporal discrimination and adult-onset focal dystonia may reflect common underlying mechanisms. Cerebral GABA levels have been reported to show similar age-related sexual dimorphism in healthy participants and may be the mechanism underlying the observed age-related sexual dimorphism in temporal discrimination and the sex ratios in AOIFD

Postal survey of physicians and laboratories: Practices and perceptions of molecular oncology testing

<p>Abstract</p> <p>Background</p> <p>Molecular oncology testing (MOT) to detect genomic alterations underlying cancer holds promise for improved cancer care. Yet knowledge limitations regarding the delivery of testing services may constrain the translation of scientific advancements into effective health care.</p> <p>Methods</p> <p>We conducted a cross-sectional, self-administered, postal survey of active cancer physicians in Ontario, Canada (N = 611) likely to order MOT, and cancer laboratories (N = 99) likely to refer (i.e., referring laboratories) or conduct (i.e., testing laboratories) MOT in 2006, to assess respondents' perceptions of the importance and accessibility of MOT and their preparedness to provide it.</p> <p>Results</p> <p>54% of physicians, 63% of testing laboratories and 60% of referring laboratories responded. Most perceived MOT to be important for treatment, diagnosis or prognosis now, and in 5 years (61% – 100%). Yet only 45% of physicians, 59% of testing labs and 53% of referring labs agreed that patients in their region were receiving MOT that is indicated as a standard of care. Physicians and laboratories perceived various barriers to providing MOT, including, among 70% of physicians, a lack of clear guidelines regarding clinical indications, and among laboratories, a lack of funding (73% – 100%). Testing laboratories were confident of their ability to determine whether and which MOT was indicated (77% and 82% respectively), and perceived that key elements of formal and continuing education were helpful (75% – 100%). By contrast, minorities of physicians were confident of their ability to assess whether and which MOT was indicated (46% and 34% respectively), and while majorities considered various continuing educational resources helpful (68% – 75%), only minorities considered key elements of formal education helpful in preparing for MOT (17% – 43%).</p> <p>Conclusion</p> <p>Physicians and laboratory professionals were enthusiastic about the value of MOT for cancer care but most did not believe patients were gaining adequate access to clinically necessary testing. Further, our results suggest that many were ill equipped as individual stakeholders, or as a coordinated system of referral and interpretation, to provide MOT. These challenges should inspire educational, training and other interventions to ensure that developments in molecular oncology can result in optimal cancer care.</p

CD40: Novel Association with Crohn's Disease and Replication in Multiple Sclerosis Susceptibility

Background: A functional polymorphism located at 21 from the start codon of the CD40 gene, rs1883832, was previously reported to disrupt a Kozak sequence essential for translation. It has been consistently associated with Graves’ disease risk in populations of different ethnicity and genetic proxies of this variant evaluated in genome-wide association studies have shown evidence of an effect in rheumatoid arthritis and multiple sclerosis (MS) susceptibility. However, the protective allele associated with Graves’ disease or rheumatoid arthritis has shown a risk role in MS, an effect that we aimed to replicate in the present work. We hypothesized that this functional polymorphism might also show an association with other complex autoimmune condition such as inflammatory bowel disease, given the CD40 overexpression previously observed in Crohn’s disease (CD) lesions. Methodology: Genotyping of rs1883832C.T was performed in 1564 MS, 1102 CD and 969 ulcerative colitis (UC) Spanish patients and in 2948 ethnically matched controls by TaqMan chemistry. Principal Findings: The observed effect of the minor allele rs1883832T was replicated in our independent Spanish MS cohort [p= 0.025; OR (95% CI)= 1.12 (1.01–1.23)]. The frequency of the minor allele was also significantly higher in CD patients than in controls [p= 0.002; OR (95% CI)= 1.19 (1.06–1.33)]. This increased predisposition was not detected in UC patients [p= 0.5; OR (95% CI)= 1.04 (0.93–1.17)]. Conclusion: The impact of CD40 rs1883832 on MS and CD risk points to a common signaling shared by these autoimmune conditions.Peer reviewe

NOX1 loss-of-function genetic variants in patients with inflammatory bowel disease.

Genetic defects that affect intestinal epithelial barrier function can present with very early-onset inflammatory bowel disease (VEOIBD). Using whole-genome sequencing, a novel hemizygous defect in NOX1 encoding NAPDH oxidase 1 was identified in a patient with ulcerative colitis-like VEOIBD. Exome screening of 1,878 pediatric patients identified further seven male inflammatory bowel disease (IBD) patients with rare NOX1 mutations. Loss-of-function was validated in p.N122H and p.T497A, and to a lesser degree in p.Y470H, p.R287Q, p.I67M, p.Q293R as well as the previously described p.P330S, and the common NOX1 SNP p.D360N (rs34688635) variant. The missense mutation p.N122H abrogated reactive oxygen species (ROS) production in cell lines, ex vivo colonic explants, and patient-derived colonic organoid cultures. Within colonic crypts, NOX1 constitutively generates a high level of ROS in the crypt lumen. Analysis of 9,513 controls and 11,140 IBD patients of non-Jewish European ancestry did not reveal an association between p.D360N and IBD. Our data suggest that loss-of-function variants in NOX1 do not cause a Mendelian disorder of high penetrance but are a context-specific modifier. Our results implicate that variants in NOX1 change brush border ROS within colonic crypts at the interface between the epithelium and luminal microbes

Large-scale association analysis identifies new lung cancer susceptibility loci and heterogeneity in genetic susceptibility across histological subtypes.

Although several lung cancer susceptibility loci have been identified, much of the heritability for lung cancer remains unexplained. Here 14,803 cases and 12,262 controls of European descent were genotyped on the OncoArray and combined with existing data for an aggregated genome-wide association study (GWAS) analysis of lung cancer in 29,266 cases and 56,450 controls. We identified 18 susceptibility loci achieving genome-wide significance, including 10 new loci. The new loci highlight the striking heterogeneity in genetic susceptibility across the histological subtypes of lung cancer, with four loci associated with lung cancer overall and six loci associated with lung adenocarcinoma. Gene expression quantitative trait locus (eQTL) analysis in 1,425 normal lung tissue samples highlights RNASET2, SECISBP2L and NRG1 as candidate genes. Other loci include genes such as a cholinergic nicotinic receptor, CHRNA2, and the telomere-related genes OFBC1 and RTEL1. Further exploration of the target genes will continue to provide new insights into the etiology of lung cancer

Comparative Susceptibility of Sheep of Different Origins, Breeds and PRNP Genotypes to Challenge with Bovine Spongiform Encephalopathy and Scrapie

Sheep are natural hosts of the prion disease, scrapie. They are also susceptible to experimental challenge with various scrapie strains and with bovine spongiform encephalopathy (BSE), which affects cattle and has been accidentally transmitted to a range of other species, including man. Incidence and incubation period of clinical disease in sheep following inoculation is controlled by the PRNP gene, which has different alleles defined on the basis of polymorphisms, particularly at codons 136, 154 and 171, although other codons are associated with survival time, and the exact responses of the sheep may be influenced by other breed-related differences. Here we report the results of a long term single study of experimental scrapie and BSE susceptibility of sheep of Cheviot, Poll Dorset and Suffolk breeds, originating from New Zealand and of a wide range of susceptible and resistant PRNP genotypes. Responses were compared with those of sheep from a closed Cheviot flock of UK origin (Roslin Cheviot flock). The unusually long observation period (6-8 years for most, but up to 12 years for others) allows us to draw robust conclusions about rates of survival of animals previously regarded as resistant to infection, particularly PRNP heterozygotes, and is the most comprehensive such study reported to date. BSE inoculation by an intracerebral route produced disease in all genotype groups with differing incubation periods, although M112T and L141F polymorphisms seemed to give some protection. Scrapie isolate SSBP/1, which has the shortest incubation period in sheep with at least one VRQ PRNP allele, also produced disease following sub-cutaneous inoculation in ARQ/ARQ animals of New Zealand origin, but ARQ/ARQ sheep from the Roslin flock survived the challenge. Our results demonstrate that the links between PRNP genotype and clinical prion disease in sheep are much less secure than previously thought, and may break down when, for example, a different breed of sheep is moved into a new flock