• Adaptive radiation-induced epigenetic alterations mitigated by antioxidants

      Bernal, Autumn J.; Dolinoy, Dana C.; Huang, Dale; Skaar, David A.; Weinhouse, Caren; Jirtle, Randy L. (Federation of American Society of Experimental Biology, 2012)
      Humans are exposed to low-dose ionizing radiation (LDIR) from a number of environmental and medical sources. In addition to inducing genetic mutations, there is concern that LDIR may also alter the epigenome. Such heritable effects early in life can either be positively adaptive or result in the enhanced formation of diseases, including cancer, diabetes, and obesity. Herein, we show that LDIR significantly increased DNA methylation at the viable yellow agouti (A(vy)) locus in a sex-specific manner (P=0.004). Average DNA methylation was significantly increased in male offspring exposed to doses between 0.7 and 7.6 cGy, with maximum effects at 1.4 and 3.0 cGy (P<0.01). Offspring coat color was concomitantly shifted toward pseudoagouti (P<0.01). Maternal dietary antioxidant supplementation mitigated both the DNA methylation changes and coat color shift in the irradiated offspring. Thus, LDIR exposure during gestation elicits epigenetic alterations that lead to positive adaptive phenotypic changes that are negated with antioxidants, indicating they are mediated in part by oxidative stress. These findings provide evidence that in the isogenic A(vy) mouse model, epigenetic alterations resulting from LDIR play a role in radiation hormesis, bringing into question the assumption that every dose of radiation is harmful.
    • The affective paradox: an emotion regulatory account of ethnic differences in self-reported anger

      Consedine, Nathan S.; Magai, C.; Horton, D.; Brown, William Michael; University of Bedfordshire (2012-05-23)
    • Androgens affect myogenesis in vitro and increase local IGF-1 expression

      Sculthorpe, Nicholas; Solomon, Andrew M.; Sinanan, Andrea C.M.; Bouloux, Pierre-Marc G.; Grace, Fergal; Lewis, Mark P.; University of Bedfordshire (2012-04)
      The mechanism whereby anabolic androgens are associated with hypertrophy of skeletal muscle is incompletely understood but may involve an interaction with locally generated insulin-like growth factor (IGF) 1. The present investigation utilized a cell culture model of human skeletal muscle-derived cell maturation to test the hypothesis that androgens increase differentiation of human muscle precursor cells in vitro and to assess effects of androgen with or without IGF-1 on IGF-1 messenger RNA (mRNA) expression in human muscle precursor cells.
    • C2 and C2C12 murine skeletal myoblast models of atrophic and hypertrophic potential: relevance to disease and ageing?

      Sharples, Adam P.; Al-Shanti, Nasser; Stewart, Claire E.; Manchester Metropolitan University (2010-10)
      Reduced muscle mass and increased susceptibility to TNF-induced degradation accompany inflamed ageing and chronic diseases. Furthermore, C(2) myoblasts display diminished differentiation and increased susceptibility to TNF-alpha-induced cell death versus subcloned C(2)C(12) cells, providing relevant models to assess: differentiation (creatine kinase), growth (protein), death (trypan-blue) and anabolic/catabolic parameters (RT-PCR) over 72 h +/- TNF-alpha (20 ng ml(-1)). At 48 and 72 h, respectively, larger myotubes and significantly higher CK activity (320.26 +/- 6.82 vs. 30.71 +/- 2.5, P < 0.05; 544.94 +/- 27.7 vs. 39.4 +/- 3.37 mU mg ml(-1), P < 0.05), fold increases in myoD (21.45 +/- 3.12 vs. 3.97 +/- 1.76, P < 0.05; 31.07 +/- 3.1 vs. 6.82 +/- 1.93, P < 0.05) and myogenin mRNA (241.8 +/- 40 vs. 36.80 +/- 19.3, P < 0.05; 440 +/- 100.5 vs. 201.1 +/- 86, P < 0.05) were detected in C(2)C(12) versus C(2). C(2)C(12) showed significant increases in IGF-I mRNA (243.05 +/- 3.87 vs. 105.75 +/- 21.95, P < 0.05), reduced proliferation and significantly lower protein expression (1.21 +/- 0.28 vs. 1.79 +/- 0.29 mg ml(-1), P < 0.05) at 72 h versus C(2) cells. Significant temporal reductions in C(2)C(12) IGFBP2 mRNA (28.02 +/- 15.44, 13.82 +/- 8.07, 6.92 +/- 4.37, P < 0.05) contrasted increases in C(2)s (4.31 +/- 3.31, 13.02 +/- 9.92, 82.9 +/- 58.9, P < 0.05) at 0, 48 and 72 h, respectively. TNF-alpha increased cell death in C(2)s (2.67 +/- 1.54%, 34.42 +/- 5.39%, 29.71 +/- 5.79% (0, 48, 72 h), P < 0.05), yet was without effect in C(2)C(12)s at 48 h but caused a small significant increase at 72 h (9.88 +/- 4.02% (TNF-alpha) vs. 6.17 +/- 0.749% (DM), 72 h). TNF-alpha and TNFRI mRNA were unchanged; however, larger reductions in IGF-I (8.2- and 7.5-fold vs. 4.5- and 4.1-fold (48, 72 h)), IGF-IR (2-fold vs. no-significant reduction (72 h)) and IGFBP5 (3.24 vs. 1.38 (48 h) and 2.21 vs. 1.71 (72 h), P < 0.05) mRNA were observed in C(2) versus C(2)C(12) with TNF-alpha. This investigation provides insight into regulators of altered basal hypertrophy and TNF-induced atrophy, providing a model for future investigation into therapeutic initiatives for ageing/wasting disorders.
    • The effect of short-term creatine loading on active range of movement

      Sculthorpe, Nicholas; Grace, Fergal; Jones, Peter; Fletcher, Iain M.; University of Bedfordshire (2010-08)
      During high-intensity exercise, intracellular creatine phosphate (PCr) is rapidly broken down to maintain adenosine triphosphate turnover. This has lead to the widespread use of creatine monohydrate as a nutritional ergogenic aid. However, the increase in intracellular PCr and the concomitant increase in intracellular water have not been investigated with regard to their effect on active range of movement (ROM). Forty male subjects (age, 24+/-3.2 years) underwent restricted randomization into 2 equal groups, either an intervention group (CS) or a control group (C). The CS group ingested 25 g.day(-1) of creatine monohydrate for 5 days, followed by 5 g.day(-1) for a further 3 days. Before (24 h before starting supplementation (PRE) and after (on the 8th day of supplementation (POST)) this loading phase, both groups underwent goniometry measurement of the shoulder, elbow, hip, and ankle. Data indicated significant reductions in active ROM in 3 movements: shoulder extension (57+/-11.3 degrees PRE vs. 48+/-11.2 degrees POST, p<0.01), shoulder abduction (183.4+/-6.8 degrees PRE vs. 180.3+/-5.1 degrees POST, p<0.05), and ankle dorsiflexion (14.2+/-4.7 degrees PRE vs. 12.1+/-6.4 degrees POST, p<0.01). There was also a significant increase in body mass for the CS group (83.6+/-6.2 kg vs. 85.2+/-6.3 kg, p<0.05). The results suggest that short-term supplementation with creatine monohydrate reduces the active ROM of shoulder extension and abduction and of ankle dorsiflexion. Although the mechanism for this is not fully understood, it may be related to the asymmetrical distribution of muscle mass around those joints.
    • Evidence of altered cardiac electrophysiology following prolonged androgenic anabolic steroid use.

      Sculthorpe, Nicholas; Grace, Fergal; Jones, Peter; Davies, Bruce; University of Bedfordshire (2010-12)
      The non-therapeutic use of androgenic anabolic steroids (AAS) is associated with sudden cardiac death. Despite this, there is no proposed mechanism by which this may occur. Signal-averaged ECG (SAECG) allows the assessment of cardiac electrical stability, reductions of which are a known risk factor for cardiac arrhythmias. The aim of the present study was to examine cardiac electrical stability using SAECG in a group (n = 15) of long-term AAS users (AAS use 21.3 ± 3.1 years) compared with a group (n = 15) of age-matched weight lifters (WL) and age-matched sedentary controls [C (n = 15)]. AS, WL and C underwent SAECG analysis at rest and following an acute bout of exercise to volitional exhaustion. SAECGs were analyzed using a 40 Hz filter and were averaged over 200 beats. Results indicate a non-significant trend for increased incidence of abnormal SAECG measures at rest in AS (P = 0.55). However, AS demonstrated a significantly higher incidence of abnormalities of SAECG following exercise than C or WL (P < 0.05). In conclusion, the higher incidence of abnormal SAECG measurements immediately post-exercise in the AAS group places them at a greater risk of sudden death. The present study provides a strong contraindication to the use of AAS.
    • Exercise-associated DNA methylation change in skeletal muscle and the importance of imprinted genes: a bioinformatics meta-analysis

      Brown, William Michael; University of Bedfordshire (BMJ Publishing Group Limited, 2015-03-30)
      BACKGROUND: Epigenetics is the study of processes-beyond DNA sequence alteration-producing heritable characteristics. For example, DNA methylation modifies gene expression without altering the nucleotide sequence. A well-studied DNA methylation-based phenomenon is genomic imprinting (ie, genotype-independent parent-of-origin effects). OBJECTIVE: We aimed to elucidate: (1) the effect of exercise on DNA methylation and (2) the role of imprinted genes in skeletal muscle gene networks (ie, gene group functional profiling analyses). DESIGN: Gene ontology (ie, gene product elucidation)/meta-analysis. DATA SOURCES: 26 skeletal muscle and 86 imprinted genes were subjected to g:Profiler ontology analysis. Meta-analysis assessed exercise-associated DNA methylation change. DATA EXTRACTION: g:Profiler found four muscle gene networks with imprinted loci. Meta-analysis identified 16 articles (387 genes/1580 individuals) associated with exercise. Age, method, sample size, sex and tissue variation could elevate effect size bias. DATA SYNTHESIS: Only skeletal muscle gene networks including imprinted genes were reported. Exercise-associated effect sizes were calculated by gene. Age, method, sample size, sex and tissue variation were moderators. RESULTS: Six imprinted loci (RB1, MEG3, UBE3A, PLAGL1, SGCE, INS) were important for muscle gene networks, while meta-analysis uncovered five exercise-associated imprinted loci (KCNQ1, MEG3, GRB10, L3MBTL1, PLAGL1). DNA methylation decreased with exercise (60% of loci). Exercise-associated DNA methylation change was stronger among older people (ie, age accounted for 30% of the variation). Among older people, genes exhibiting DNA methylation decreases were part of a microRNA-regulated gene network functioning to suppress cancer. CONCLUSIONS: Imprinted genes were identified in skeletal muscle gene networks and exercise-associated DNA methylation change. Exercise-associated DNA methylation modification could rewind the 'epigenetic clock' as we age. TRIAL REGISTRATION NUMBER: CRD42014009800.
    • Fluctuating asymmetry and preferences for sex-typical bodily characteristics

      Brown, William Michael; Price, M.E.; Kang, J.; Pound, N.; Zhao, Y.; Yu, H.; Brunel University; Higher Education Funding Council; British Academy Grant (2012-05-23)
      Body size and shape seem to have been sexually selected in a variety of species, including humans, but little is known about what attractive bodies signal about underlying genotypic or phenotypic quality. A widely used indicator of phenotypic quality in evolutionary analyses is degree of symmetry (i.e., fluctuating asymmetry, FA) because it is a marker of developmental stability, which is defined as an organism's ability to develop toward an adaptive end-point despite perturbations during its ontogeny. Here we sought to establish whether attractive bodies signal low FA to observers, and, if so, which aspects of attractive bodies are most predictive of lower FA. We used a 3D optical body scanner to measure FA and to isolate size and shape characteristics in a sample of 77 individuals (40 males and 37 females). From the 3D body scan data, 360° videos were created that separated body shape from other aspects of visual appearance (e.g., skin color and facial features). These videos then were presented to 87 evaluators for attractiveness ratings. We found strong negative correlations between FA and bodily attractiveness in both sexes. Further, sex-typical body size and shape characteristics were rated as attractive and correlated negatively with FA. Finally, geometric morphometric analysis of joint configurations revealed that sex-typical joint configurations were associated with both perceived attractiveness and lower FA for male but not for female bodies. In sum, body size and shape seem to show evidence of sexual selection and indicate important information about the phenotypic quality of individuals.
    • H55N polymorphism as a likely cause of variation in citrate synthase activity of mouse skeletal muscle

      Ratkevicius, Aivaras; Carroll, Andrew M.; Kilikevicius, Audrius; Venckunas, Tomas; McDermott, Kevin T.; Gray, Stuart R.; Wackerhage, Henning; Lionikas, Arimantas (American Physiological Society, 2010)
      The aim of this study was to investigate the mechanisms underlying low activity of citrate synthase (CS) in A/J mice compared with other inbred strains of mice. Enzyme activity, protein content, and mRNA levels of CS were studied in the quadriceps muscles of A/J, BALB/cByJ, C57BL/6J, C3H/HeJ, DBA/2J, and PWD/PhJ strains of mice. Cytochrome c protein content was also measured. The results of the study indicate that A/J mice have a 50–65% reduction in CS activity compared with other strains despite similar levels of Cs mRNA and lack of differences in CS and cytochrome c protein content. CS from A/J mice also showed lower Michaelis constant (Km) for both acetyl CoA and oxaloacetate compared with the other strains of mice.
    • The human imprintome: regulatory mechanisms, methods of ascertainment, and roles in disease susceptibility

      Skaar, David A.; Li, Yue; Bernal, Autumn J.; Hoyo, Cathrine; Murphy, Susan K.; Jirtle, Randy L. (National Academy of Sciences, 2012-12)
      Imprinted genes form a special subset of the genome, exhibiting monoallelic expression in a parent-of-origin-dependent fashion. This monoallelic expression is controlled by parental-specific epigenetic marks, which are established in gametogenesis and early embryonic development and are persistent in all somatic cells throughout life. We define this specific set of cis-acting epigenetic regulatory elements as the imprintome, a distinct and specially tasked subset of the epigenome. Imprintome elements contain DNA methylation and histone modifications that regulate monoallelic expression by affecting promoter accessibility, chromatin structure, and chromatin configuration. Understanding their regulation is critical because a significant proportion of human imprinted genes are implicated in complex diseases. Significant species variation in the repertoire of imprinted genes and their epigenetic regulation, however, will not allow model organisms solely to be used for this crucial purpose. Ultimately, only the human will suffice to accurately define the human imprintome.
    • Hypoxia-mediated prior induction of monocyte-expressed HSP72 and HSP32 provides protection to the disturbances to redox balance associated with human sub-maximal aerobic exercise.

      Taylor, Lee; Hillman, Angela R.; Midgley, Adrian W.; Peart, Daniel J.; Chrismas, Bryna C.; McNaughton, Lars R.; University of Bedfordshire (2012-03-23)
      HSP72 is rapidly expressed in response to a variety of stressors in vitro and in vivo (including hypoxia). This project sought a hypoxic stimulus to elicit increases in HSP72 and HSP32 in attempts to confer protection to the sub-maximal aerobic exercise-induced disturbances to redox balance. Eight healthy recreationally active male subjects were exposed to five consecutive days of once-daily hypoxia (2,980 m, 75 min). Seven days prior to the hypoxic acclimation period, subjects performed 60 min of cycling on a cycle ergometer (exercise bout 1-EXB1), and this exercise bout was repeated 1 day post-cessation of the hypoxic period (exercise bout 2-EXB2). Blood samples were taken immediately pre- and post-exercise and 1, 4 and 8 h post-exercise for HSP72 and immediately pre, post and 1 h post-exercise for HSP32, TBARS and glutathione [reduced (GSH), oxidised (GSSG) and total (TGSH)], with additional blood samples obtained immediately pre-day 1 and post-day 5 of the hypoxic acclimation period for the same indices. Monocyte-expressed HSP32 and HSP72 were analysed by flow cytometry, with measures of oxidative stress accessed by commercially available kits. There were significant increases in HSP72 (P < 0.001), HSP32 (P = 0.03), GSSG (t = 9.5, P < 0.001) and TBARS (t = 5.6, P = 0.001) in response to the 5-day hypoxic intervention, whereas no significant changes were observed for GSH (P = 0.22) and TGSH (P = 0.25). Exercise-induced significant increases in HSP72 (P < 0.001) and HSP32 (P = 0.003) post-exercise in EXB1; this response was absent for HSP72 (P ≥ 0.79) and HSP32 (P ≥ 0.99) post-EXB2. The hypoxia-mediated increased bio-available HSP32 and HSP72 and favourable alterations in glutathione redox, prior to exercise commencing in EXB2 compared to EXB1, may acquiesce the disturbances to redox balance encountered during the second physiologically identical exercise bout.
    • An investigation into the effect of a pre-performance strategy on jump performance

      Fletcher, Iain M. (Lippincott, Williams & Wilkins, 2013)
      The aim of this study was to explore the effect that different components, making up a commonly used pre-performance preparation strategy, have on jump height performance. Sixteen male collegiate athletes (age, 21.38 ± 0.52 years; height, 1.79 ± 0.07 m; and body mass, 75.1 ± 5.26 kg) performed a preparation strategy involving a cycle ergometer warm-up, followed by a dynamic stretch component, and finishing with heavy back squats. This intervention was repeated to test countermovement, squat or drop jump performance after each component of the preparation strategy, with electromyographic activity measured during each jump test. Significant increases (p < 0.05) in jump height and electromyographic activity were noted, with a stepwise increase in performance from pre- to post-warm-up, increased further by the dynamic stretch component and again increased after the back squat.
    • Just how happy is the happy puppet? An emotion signaling and kinship theory perspective on the behavioral phenotype of children with Angelman syndrome.

      Brown, William Michael; Consedine, Nathan S.; Long Island University (2004)
      The favored level of parental investment in a child may differ for genes of maternal and paternal origin in the child. This conflict can be expressed in the phenomenon of genomic imprinting that refers to situations in which the same gene is differentially expressed depending on its parent of origin. Two disorders that show the effects of genomic imprinting--both at 15q11-q13--are Angelman Syndrome (AS) which is due to the absence of expression of maternally-inherited genes and Prader-Willi syndromes (PWS) which is due to the absence of expression of paternally-inherited genes. However, although both disorders can arise from the deletion of the same genetic region, the gustatory, behavioral, and affective characteristics of AS and PWS children are remarkably distinct. Recent research inspired by kinship theory has suggested the origins of these phenotypic differences may lie in the differential investment of each parent's genome in the AS or PWS child. Specifically, it is thought that each set of parental genes have different 'ideas' regarding how the child should behave towards the mother and how much investment they should look to extract. In normal cases, the trade-off between the competing parental genomes produces a behavioral equilibrium in the child. However, in pathological instances, particularly where gene expression is one-sided, the evolved behavioral strategies favored by the contributing genome will dominate the child's behavior. To date, research in the area of genomic conflict in AS and PWS children has primarily focusing on differences in post-natal nutrition-related behaviors. The current paper extends this framework by offering an emotion and evolutionary signaling interpretation of the affective characteristics of AS children. A review of the affective characteristics of the two syndromes (PWS and AS) is presented before kinship and emotions theory are used to examine the functions that differential affect expression may serve in altering maternal investment. We expected that because the ultimate goal of paternal genes is to increase the child rearing burden of mothers, the Angelman behavioral phenotype should exhibit the emotion signaling characteristics that elicit levels of investment more consistent with paternal genetic interests. AS children display more positive, relative to negative, affect expressions (i.e. AS children laugh and smile more frequently than PWS children). In affect signaling theories, positive affect signals (i.e., smiling, laughing) have evolved to manipulate the sensory systems of receivers to increase social resources. In contrast, because the expression of some negative affects may indicate to the mother that the infant is not viable, negative affect expression is characteristically low among AS children. However, AS children may nonetheless have high levels of non-expressed anxiety because of its role in assisting the child (and its paternal genome) to maintain vigilance for changes in investment on the part of the mother. Overall, our kinship and emotion signaling analysis of AS children suggests that their global pattern of affect signaling represents one manifestation of an array of possible evolved strategies within the parental genome. Specifically, because AS exhibits the effects of paternally-inherited genes unhindered by the expression of maternally-inherited genes, the AS infant manifests a pattern of expression and non-expression that maximize maternal investment and thus paternal fitness. This theory is a significant departure from the standard but erroneous conjecture that a mother and child's inclusive fitness interests are one and the same.
    • The missing risk: MRI and MRS phenotyping of abdominal adiposity and ectopic fat.

      Thomas, E. Louise; Parkinson, James R.; Frost, Gary S.; Goldstone, Anthony P.; Doré, Caroline J.; McCarthy, John; Collins, Adam L.; Fitzpatrick, Julie; Durighel, Giuliana; Taylor-Robinson, Simon D.; et al. (Wiley, 2012-01)
      Individual compartments of abdominal adiposity and lipid content within the liver and muscle are differentially associated with metabolic risk factors, obesity and insulin resistance. Subjects with greater intra-abdominal adipose tissue (IAAT) and hepatic fat than predicted by clinical indices of obesity may be at increased risk of metabolic diseases despite their "normal" size. There is a need for accurate quantification of these potentially hazardous depots and identification of novel subphenotypes that recognize individuals at potentially increased metabolic risk. We aimed to calculate a reference range for total and regional adipose tissue (AT) as well as ectopic fat in liver and muscle in healthy subjects. We studied the relationship between age, body-mass, BMI, waist circumference (WC), and the distribution of AT, using whole-body magnetic resonance imaging (MRI), in 477 white volunteers (243 male, 234 female). Furthermore, we used proton magnetic resonance spectroscopy (MRS) to determine intrahepatocellular (IHCL) and intramyocellular (IMCL) lipid content. The anthropometric variable which provided the strongest individual correlation for adiposity and ectopic fat stores was WC in men and BMI in women. In addition, we reveal a large variation in IAAT, abdominal subcutaneous AT (ASAT), and IHCL depots not fully predicted by clinically obtained measurements of obesity and the emergence of a previously unidentified subphenotype. Here, we demonstrate gender- and age-specific patterns of regional adiposity in a large UK-based cohort and identify anthropometric variables that best predict individual adiposity and ectopic fat stores. From these data we propose the thin-on-the-outside fat-on-the-inside (TOFI) as a subphenotype for individuals at increased metabolic risk.
    • Myoblast models of skeletal muscle hypertrophy and atrophy.

      Sharples, Adam P.; Stewart, Claire E.; University of Bedfordshire; Manchester Metropolitan University (2011-05)
      To highlight recent breakthroughs and controversies in the use of myoblast models to uncover cellular and molecular mechanisms regulating skeletal muscle hypertrophy and atrophy.
    • Novel retrotransposed imprinted locus identified at human 6p25

      Zhang, Aiping; Skaar, David A.; Li, Yue; Huang, Dale; Price, Thomas M.; Murphy, Susan K.; Jirtle, Randy L. (Oxford University Press, 2011)
      Differentially methylated regions (DMRs) are stable epigenetic features within or in proximity to imprinted genes. We used this feature to identify candidate human imprinted loci by quantitative DNA methylation analysis. We discovered a unique DMR at the 50-end of FAM50B at 6p25.2. We determined that sense transcripts originating from the FAM50B locus are expressed from the paternal allele in all human tissues investigated except for ovary, in which expression is biallelic. Furthermore, an antisense transcript, FAM50B-AS, was identified to be monoallelically expressed from the paternal allele in a variety of tissues. Comparative phylogenetic analysis showed that FAM50B orthologs are absent in chicken and platypus, but are present and biallelically expressed in opossum and mouse.
    • The parental antagonism theory of language evolution: preliminary evidence for the proposal.

      Brown, William Michael; Queen Mary University of London (2011-04)
      Language--as with most communication systems--likely evolved by means of natural selection. Accounts for the genetical selection of language can usually be divided into two scenarios, either of which used in isolation of the other appear insufficient to explain the phenomena: (1) there are group benefits from communicating, and (2) there are individual benefits from being a better communicator. In contrast, it is hypothesized that language phenotypes emerged during a coevolutionary struggle between parental genomes via genomic imprinting, which is differential gene expression depending on parental origin of the genetic element. It is hypothesized that relatedness asymmetries differentially selected for patrigene-caused language phenotypes to extract resources from mother (early in development) and matrigene-caused language phenotypes to influence degree of cooperativeness among asymmetric kin (later in development). This paper reports that imprinted genes have a high frequency of involvement in language phenotypes (~36%), considering their presumed rarity in the human genome (~2%). For example, two well-studied genes associated with language impairments (FOXP2 and UBE3A) exhibit parent-of- origin effects. Specifically, FOXP2 is putatively paternally expressed, whereas UBE3A is a maternally expressed imprinted gene. It is also hypothesized that the more unique and cooperative aspects of human language emerged to the benefit of matrilineal inclusive fitness. Consistent with this perspective, it is reported here that the X-chromosome has higher involvement in loci that have associations with language than would be expected by chance. It is also reported, for the first time, that human and chimpanzee maternally expressed overlapping imprinted genes exhibit greater evolutionary divergence (in terms of the degree of overlapping transcripts) than paternally expressed overlapping imprinted genes. Finally, an analysis of global language patterns reveals that paternally but not maternally silenced Alu elements are positively correlated with language diversity. Furthermore, there is a much higher than expected frequency of Alu elements inserted into the protein-coding machinery of imprinted and X-chromosomal language loci compared with nonimprinted language loci. Taken together these findings provide some support for parental antagonism theory. Unlike previous theories for language evolution, parental antagonism theory generates testable predictions at the proximate (e.g., neurocognitive areas important for social transmission and language capacities), ontogenetic (e.g., the function of language at different points of development), ultimate (e.g., inclusive fitness), and phylogenetic levels (e.g., the spread of maternally derived brain components in mammals, particularly in the hominin lineage), thus making human capacities for culture more tractable than previously thought.
    • Paternal obesity is associated with IGF2 hypomethylation in newborns: results from a Newborn Epigenetics Study (NEST) cohort

      Soubry, Adelheid; Schildkraut, Joellen M.; Murtha, Amy; Wang, Frances; Huang, Zhiqing; Bernal, Autumn J.; Kurtzberg, Joanne; Jirtle, Randy L.; Murphy, Susan K.; Hoyo, Cathrine; et al. (BioMed Central, 2013)
      Data from epidemiological and animal model studies suggest that nutrition during pregnancy may affect the health status of subsequent generations. These transgenerational effects are now being explained by disruptions at the level of the epigenetic machinery. Besides in vitro environmental exposures, the possible impact on the reprogramming of methylation profiles at imprinted genes at a much earlier time point, such as during spermatogenesis or oogenesis, has not previously been considered. In this study, our aim was to determine associations between preconceptional obesity and DNA methylation profiles in the offspring, particularly at the differentially methylated regions (DMRs) of the imprinted Insulin-like Growth Factor 2 (IGF2) gene.
    • Proton magnetic resonance spectroscopy and ultrasound for hepatic fat quantification

      Mehta, Sanjeev R.; Louise Thomas, Elizabeth; Patel, Nayna; Crofton, Mary E.; McCarthy, John; Eliahoo, Joseph; Morin, Stanislas X.; Fitzpatrick, Julie; Durighel, Giuliana; Goldstone, Anthony P.; et al. (Wiley, 2010-04)
      Aim:  The increasing prevalence of fatty liver disease requires routine assessment methods. Proton magnetic resonance spectroscopy (1H MRS) is increasingly used for steatosis measurement, but due to cost, is unlikely to become a widely-used screening tool. Ultrasound is cheaper and more widely available, although subject to observer variability. Our aim was to determine the sensitivity and specificity of ultrasound against 1H MRS, using MRS as a gold standard, for the detection and quantification of hepatic fat content. Methods:  Fifty adults participated (43 men, seven women) in this study. Hepatic steatosis was assessed by ultrasound and 1H MRS. Images were graded by two independent radiologists to classify severity and distribution of liver fat. Results:  Ultrasound detected liver fat infiltration in 82% of cases measurable by 1H MRS, while liver fat was detectable in 44% of cases graded absent by ultrasound. Ultrasound grading was subjective, with the radiologists in agreement in 53% of cases (κ = 0.39, P = 0.002). Considerable overlap in intrahepatocellular lipid content was observed between different grades: absent (0.0–1.58%), mild (2.2–16.2%), moderate (4.9–26.7%) and severe (8.1–76.8%) steatosis. Ultrasound could not detect liver fat levels below 2% as measured by 1H MRS Conclusion:  Ultrasound is less sensitive than 1H MRS in detecting very low levels of liver fat content, but is sensitive to fatty infiltration greater than 2%. There is a tendency of higher ultrasound grades to correlate with higher degrees of fatty infiltration, although some overlap exists. Our findings are still consistent with ultrasound being useful as a low cost screening tool.