Transient expression analysis of allelic variants of a VNTR in the dopamine transporter gene (DAT1)

BACKGROUND: The 10-repeat allele of a variable number tandem repeat (VNTR) polymorphism in the 3'-untranslated region of the dopamine transporter gene (DAT1) has been associated with a range of psychiatric phenotypes, most notably attention-deficit hyperactivity disorder. The mechanism for this association is not yet understood, although several lines of evidence implicate variation in gene expression. In this study we have characterised the genomic structure of the 9- and 10-repeat VNTR alleles, and directly examined the role of the polymorphism in mediating gene expression by measuring comparative in vitro cellular expression using a reporter-gene assay system. RESULTS: Differences in the sequence of the 9- and 10- repeat alleles were confirmed but no polymorphic differences were observed between individuals. There was no difference in expression of reporter gene constructs containing the two alleles. CONCLUSIONS: Our data suggests that this VNTR polymorphism may not have a direct effect on DAT1 expression and that the associations observed with psychiatric phenotypes may be mediated via linkage disequilibrium with other functional polymorphisms

The large-scale removal of mammalian invasive alien species in Northern Europe

Peer reviewedPublisher PD

Player responses to match and training demands during an intensified fixture schedule in professional rugby league: A case study.

As accepted for publicationPlayer loads and fatigue responses are reported in 15 professional rugby league players (24.3 ± 3.8 y) during a period of intensified fixtures. Repeated measures of internal and external loads, perceived well-being, and jump flight time were recorded across 22 d, comprising 9 training sessions and matches on days 5, 12, 15, and 21 (player exposure: 3.6 ± 0.6 matches). Mean training loads (session rating of perceived exertion × duration) between matches were 1177, 1083, 103, and 650 AU. Relative distance in match 1 (82 m/min) and match 4 (79 m/min) was very likely lower in match 2 (76 m/min) and likely higher in match 3 (86 m/min). High-intensity running (≥5.5 m/s) was likely to very likely lower than match 1 (5 m/min) in matches 2–4 (2, 4, and 3 m/min, respectively). Low-intensity activity was likely to very likely lower than match 1 (78 m/min) in match 2 (74 m/min) and match 4 (73 m/min) but likely higher in match 3 (81 m/min). Accumulated accelerometer loads for matches 1–4 were 384, 473, 373, and 391 AU, respectively. Perceived well-being returned to baseline values (~21 AU) before all matches but was very likely to most likely lower the day after each match (~17 AU). Prematch jump flight times were likely to most likely lower across the period, with mean values of 0.66, 0.65, 0.62, and 0.64 s before matches 1–4, respectively. Across a 22-d cycle with fixture congestion, professional rugby league players experience cumulative neuromuscular fatigue and impaired match running performance

Epigenomic and transcriptomic signatures of a Klinefelter syndrome (47,XXY) karyotype in the brain

Klinefelter syndrome (KS) is the most common sex-chromosome aneuploidy in humans. Most affected individuals carry one extra X-chromosome (47,XXY karyotype) and the condition presents with a heterogeneous mix of reproductive, physical and psychiatric phenotypes. Although the mechanism(s) by which the supernumerary X-chromosome determines these features of KS are poorly understood, skewed X-chromosome inactivation (XCI), gene-dosage dysregulation, and the parental origin of the extra X-chromosome have all been implicated, suggesting an important role for epigenetic processes. We assessed genomic, methylomic and transcriptomic variation in matched prefrontal cortex and cerebellum samples identifying an individual with a 47,XXY karyotype who was comorbid for schizophrenia and had a notably reduced cerebellum mass compared with other individuals in the study (n = 49). We examined methylomic and transcriptomic differences in this individual relative to female and male samples with 46,XX or 46,XY karyotypes, respectively, and identified numerous locus-specific differences in DNA methylation and gene expression, with many differences being autosomal and tissue-specific. Furthermore, global DNA methylation, assessed via the interrogation of LINE-1 and Alu repetitive elements, was significantly altered in the 47,XXY patient in a tissue-specific manner with extreme hypomethylation detected in the prefrontal cortex and extreme hypermethylation in the cerebellum. This study provides the first detailed molecular characterization of the prefrontal cortex and cerebellum from an individual with a 47,XXY karyotype, identifying widespread tissue-specific epigenomic and transcriptomic alterations in the brain. © 2014 Landes Bioscience

Assessing a potential non-invasive method for viral diagnostic purposes in European squirrels.

Viral infections globally threaten wild and captive mammal populations, with surveillance options limited by a lack of non-invasive diagnostics; especially when infection is asymptomatic in nature. We explored the potential for hair samples collected from red (Sciurus vulgaris) and grey (Sciurus carolinensis) squirrels to provide a means of screening for adenovirus (ADV) and squirrelpox virus (SQPV) using evolving polymerase chain reaction (PCR) assays. An initial pilot study phase utilised samples opportunistically harvested from grey squirrels controlled in Gwynedd, United Kingdom (UK). The screening of 319 grey squirrel carcasses revealed 58% spleen ADV DNA qPCR and 69% SQPV antibody enzyme linked immunosorbent assay (ELISA) positives. We developed new nested ADV and SQPV qPCRs and examined tail hair samples from a sub-set of 80 of these 319 sampled squirrels and these assays amplified ADV and SQPV DNA in a higher proportion of animals than the original qPCR (94% and 21% respectively). Tail hair samples obtained from six Cumbrian red squirrels which had died from squirrelpox disease also revealed 100% SQPV and 50% ADV DNA positive by the nested qPCR assays. These findings indicate enhanced sensitivity for the new platform. The integration of this non-invasive approach in assessing viral infection has wide application in epidemiological studies of wild mammal populations, in particular, during conservation translocations, where asymptomatic infections are of concern

COUNTERFACTUALS AND THE ANALYSIS OF NECESSITY *

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73782/1/j.1520-8583.2006.00108.x.pd