Do variations in substitution rates and male mutation bias correlate with life-history traits? A study of 32 mammalian genomes

Life-history traits vary substantially across species, and have been demonstrated to affect substitution rates. We compute genomewide, branch-specific estimates of male mutation bias (the ratio of male-to-female mutation rates) across 32 mammalian genomes and study how these vary with life-history traits (generation time, metabolic rate, and sperm competition). We also investigate the influence of life-history traits on substitution rates at unconstrained sites across a wide phylogenetic range. We observe that increased generation time is the strongest predictor of variation in both substitution rates (for which it is a negative predictor) and male mutation bias (for which it is a positive predictor). Although less significant, we also observe that estimates of metabolic rate, reflecting replication-independent DNA damage and repair mechanisms, correlate negatively with autosomal substitution rates, and positively with male mutation bias. Finally, in contrast to expectations, we find no significant correlation between sperm competition and either autosomal substitution rates or male mutation bias. Our results support the important but frequently opposite effects of some, but not all, life history traits on substitution rates. KEY WORDS: Generation time, genome evolution, metabolic rate, sperm competition.

“The suffering black male body and the threatened white female body": ambiguous bodies in Candyman

This article explores the roles of monster and victim as experienced through the body, and considers how the relationship between violence and the body affects the presentation of these roles through close analysis of performance in Candyman (Bernard Rose, 1992). I aim to demonstrate that commitment to such a detailed approach, offers a more intricate and rewarding critical interaction, reflecting the complexity of narrative film. Consideration of the particulars of performance is crucial, in its affect on our engagement with the performer and their physical presence. Through this attention I intend to demonstrate how the seemingly fixed role of monster is in fact more fluid than first apparent, that monster and victim can co-exist in the same body. Candyman’s physicality and the way it is presented foregrounds the oscillations between violence and suffering, the relationship between the body and the violence inflicted on and by it, ambiguities which are also found in the heroine’s development, thus enhancing the film’s striking preoccupation with the shifting parallels between monster and victim.

The neuropsychology of male adults with High-Functioning Autism or Asperger Syndrome

Autism Spectrum Disorder (ASD) is diagnosed on the basis of behavioral symptoms, but cognitive abilities may also be useful in characterizing individuals with ASD. One hundred seventy-eight high-functioning male adults, half with ASD and half without, completed tasks assessing IQ, a broad range of cognitive skills, and autistic and comorbid symptomatology. The aims of the study were, first, to determine whether significant differences existed between cases and controls on cognitive tasks, and whether cognitive profiles, derived using a multivariate classification method with data from multiple cognitive tasks, could distinguish between the two groups. Second, to establish whether cognitive skill level was correlated with degree of autistic symptom severity, and third, whether cognitive skill level was correlated with degree of comorbid psychopathology. Fourth, cognitive characteristics of individuals with Asperger Syndrome (AS) and high-functioning autism (HFA) were compared. After controlling for IQ, ASD and control groups scored significantly differently on tasks of social cognition, motor performance, and executive function (P's < 0.05). To investigate cognitive profiles, 12 variables were entered into a support vector machine (SVM), which achieved good classification accuracy (81%) at a level significantly better than chance (P < 0.0001). After correcting for multiple correlations, there were no significant associations between cognitive performance and severity of either autistic or comorbid symptomatology. There were no significant differences between AS and HFA groups on the cognitive tasks. Cognitive classification models could be a useful aid to the diagnostic process when used in conjunction with other data sources-including clinical history.

Analysis and manipulation of the structure of odor plumes from a piezo-electric release system and measurements of upwind flight of male Almond Moths, Cadra cautella, to pheromone plumes

We investigated the plume structure of a piezo-electric sprayer system, set up to release ethanol in a wind tunnel, using a fast response mini-photoionizaton detector. We recorded the plume structure of four different piezo-sprayer configurations: the sprayer alone; with a 1.6-mm steel mesh shield; with a 3.2-mm steel mesh shield; and with a 5 cm circular upwind baffle. We measured a 12 × 12-mm core at the center of the plume, and both a horizontal and vertical cross-section of the plume, all at 100-, 200-, and 400-mm downwind of the odor source. Significant differences in plume structure were found among all configurations in terms of conditional relative mean concentration, intermittency, ratio of peak concentration to conditional mean concentration, and cross-sectional area of the plume. We then measured the flight responses of the almond moth, Cadra cautella, to odor plumes generated with the sprayer alone, and with the upwind baffle piezo-sprayer configuration, releasing a 13:1 ratio of (9Z,12E)-tetradecadienyl acetate and (Z)-9-tetradecenyl acetate diluted in ethanol at release rates of 1, 10, 100, and 1,000 pg/min. For each configuration, differences in pheromone release rate resulted in significant differences in the proportions of moths performing oriented flight and landing behaviors. Additionally, there were apparent differences in the moths’ behaviors between the two sprayer configurations, although this requires confirmation with further experiments. This study provides evidence that both pheromone concentration and plume structure affect moth orientation behavior and demonstrates that care is needed when setting up experiments that use a piezo-electric release system to ensure the optimal conditions for behavioral observations.

The application of social marketing in reducing road traffic accidents amoung young male drivers: an investigation using physical fear threat appeals

There were 338 road fatalities on Irish roads in 2007. Research in 2007 by the Road Safety Authority in Ireland states that young male drivers (17 – 25 years) are seven times more likely to be killed on Irish roads than other road users. The car driver fatality rate was found to be approximately 10 times higher for young male drivers than for female drivers in 2000. Young male drivers in particular demonstrate a high proclivity for risky driving behaviours. These risky behaviours include drink driving, speeding, rug-driving and engaging in aggressive driving. Speed is the single largest contributing factor to road deaths in Ireland. Approximately 40% of fatal accidents are caused by excessive or inappropriate speed. This study focuses on how dangerous driving behaviours may be addressed through social marketing. This study analyses the appropriate level of fear that needs to be induced in order to change young male driving behaviour.

Orexin restores aging-related brown adipose tissue dysfunction in male mice

The aging process causes an increase in percent body fat, but the mechanism remains unclear. In the present study we examined the impact of aging on brown adipose tissue (BAT) thermogenic activity as potential cause for the increase in adiposity. We show that aging is associated with interscapular BAT morphologic abnormalities and thermogenic dysfunction. In vitro experiments revealed that brown adipocyte differentiation is defective in aged mice. Interscapular brown tissue in aged mice is progressively populated by adipocytes bearing white morphologic characteristics. Aged mice fail to mobilize intracellular fuel reserves from brown adipocytes and exhibit deficiency in homeothermy. Our results suggest a role for orexin (OX) signaling in the regulation of thermogenesis during aging. Brown fat dysfunction and age-related assimilation of fat mass were accelerated in mice in which OX-producing neurons were ablated. Conversely, OX injections in old mice increased multilocular morphology, increased core body temperature, improved cold tolerance, and reduced adiposity. These results argue that BAT can be targeted for interventions to reverse age-associated increase in fat mass.

Atypically rightward cerebral asymmetry in male adults with autism stratifies individuals with and without language delay

In humans, both language and fine motor skills are associated with left-hemisphere specialization, whereas visuospatial skills are associated with right-hemisphere specialization. Individuals with autism spectrum conditions (ASC) show a profile of deficits and strengths that involves these lateralized cognitive functions. Here we test the hypothesis that regions implicated in these functions are atypically rightward lateralized in individuals with ASC and, that such atypicality is associated with functional performance. Participants included 67 male, right-handed adults with ASC and 69 age- and IQ-matched neurotypical males. We assessed group differences in structural asymmetries in cortical regions of interest with voxel-based analysis of grey matter volumes, followed by correlational analyses with measures of language, motor and visuospatial skills. We found stronger rightward lateralization within the inferior parietal lobule and reduced leftward lateralization extending along the auditory cortex comprising the planum temporale, Heschl's gyrus, posterior supramarginal gyrus, and parietal operculum, which was more pronounced in ASC individuals with delayed language onset compared to those without. Planned correlational analyses showed that for individuals with ASC, reduced leftward asymmetry in the auditory region was associated with more childhood social reciprocity difficulties. We conclude that atypical cerebral structural asymmetry is a potential candidate neurophenotype of ASC

Variance in male reproductive success and sexual size dimorphism in pinnipeds: testing an assumption of sexual selection theory

The theory of evolution by sexual selection for sexual size dimorphism (SSD) postulates that SSD primarily reflects the adaptation of males and females to their different reproductive roles. For example, competition among males for access to females increases male body size because larger males are better able to maintain dominant status than smaller males. Larger dominant males sire most offspring while smaller subordinate males are unsuccessful, leading to skew in reproductive success. Therefore, species with male-biased SSD are predicted to have greater variance in male reproductive success than those in which both sexes are similar in size. We tested this prediction among the Pinnipedia, a mammalian group with a great variation in SSD. From a literature review, we identified genetic estimates of male reproductive success for 10 pinniped taxa (eight unique species and two subspecies of a ninth species) that range from seals with similarly sized males and females to species in which males are more than four times as large as females. We found no support for a positive relationship between variance in reproductive success and SSD among pinnipeds after excluding the elephant seals Mirounga leonina and Mirounga angustirostris, which we discuss as distinctive cases. Several explanations for these results are presented, including the revival of one of Darwin's original ideas. Darwin proposed that natural selection may explain SSD based on differences in energetic requirements between sexes and the potential for sexual niche segregation. Males may develop larger bodies to exploit resources that remain unavailable to females due to the energetic constraints imposed on female mammals by gestation and lactation. The importance of this alternative explanation remains to be tested.

Retinoid-Related Receptor (ROR) alpha mRNA Expression Is Altered in the Brain of Male Mice Lacking All Ligand-Binding Thyroid Hormone Receptor (TR) Isoforms

In the vertebrate brain, the thalamus serves as a relay and integration station for diverse neuronal information en route from the periphery to the cortex. Deficiency of TH during development results in severe cerebral abnormalities similar to those seen in the mouse when the retinoic acid receptor (ROR)α gene is disrupted. To investigate the effect of the thyroid hormone recep-tors (TRs) on RORalpha gene expression, we used intact male mice, in which the genes encoding the α and beta TRs have been deleted. In situ hybridization for RORalpha mRNA revealed that this gene is expressed in specific areas of the brain including the thalamus, pons, cerebellum, cortex, and hippocampus. Our quantitative data showed differences in RORalpha mRNA expression in different subthalamic nuclei between wild-type and knock-out mice. For example, the centromedial nucleus of the thalamus, which plays a role in mediating nociceptive and visceral information from the brainstem to the basal ganglia and cortical regions, has less expression of RORalpha mRNA in the knockout mice (-37%) compared to the wild-type controls. Also, in the dorsal geniculate (+72%) and lateral posterior nuclei (+58%) we found more RORalpha mRNA in dKO as compared to dWT animals. Such differences in RORalpha mRNA expression may play a role in the behavioral alterations resulting from congenital hypothyroidism.

Distinct behavioral phenotypes in male mice lacking the thyroid hormone receptor alpha1 or beta isoforms

Thyroid hormones influence both neuronal development and anxiety via the thyroid hormone receptors (TRs). The TRs are encoded by two different genes, TRalpha and TRbeta. The loss of TRalpha1 is implicated in increased anxiety in males, possibly via a hippocampal increase in GABAergic activity. We compared both social behaviors and two underlying and related non-social behaviors, state anxiety and responses to acoustic and tactile startle in the gonadally intact TRalpha1 knockout (alpha1KO) and TRbeta (betaKO) male mice to their wild-type counterparts. For the first time, we show an opposing effect of the two TR isoforms, TRalpha1 and TRbeta, in the regulation of state anxiety, with alpha1 knockout animals (alpha1KO) showing higher levels of anxiety and betaKO males showing less anxiety compared to respective wild-type mice. At odds with the increased anxiety in non-social environments, alpha1KO males also show lower levels of responsiveness to acoustic and tactile startle stimuli. Consistent with the data that T4 is inhibitory to lordosis in female mice, we show subtly increased sex behavior in alpha1KO male mice. These behaviors support the idea that TRalpha1 could be inhibitory to ERalpha driven transcription that ultimately impacts ERalpha driven behaviors such as lordosis. The behavioral phenotypes point to novel roles for the TRs, particularly in non-social behaviors such as state anxiety and startle.

Thyroid hormones regulate anxiety in the male mouse

Thyroid hormone levels are implicated in mood disorders in the adult human but the mechanisms remain unclear partly because, in rodent models, more attention has been paid to the consequences of perinatal hypo and hyperthyroidism. Thyroid hormones act via the thyroid hormone receptor (TR) alpha and beta isoforms, both of which are expressed in the limbic system. TR's modulate gene expression via both unliganded and liganded actions. Though the thyroid hormone receptor (TR) knockouts and a transgenic TRalpha1 knock-in mouse have provided us valuable insight into behavioral phenotypes such as anxiety and depression, it is not clear if this is because of the loss of unliganded actions or liganded actions of the receptor or due to locomotor deficits. We used a hypothyroid mouse model and supplementation with tri-iodothyronine (T3) or thyroxine (T4) to investigate the consequences of dysthyroid hormone levels on behaviors that denote anxiety. Our data from the open field and the light-dark transition tests suggest that adult onset hypothyroidism in male mice produces a mild anxiogenic effect that is possibly due to unliganded receptor actions. T3 or T4 supplementation reverses this phenotype and euthyroid animals show anxiety that is intermediate between the hypothyroid and thyroid hormone supplemented groups. In addition, T3 but not T4 supplemented animals have lower spine density in the CA1 region of the hippocampus and in the central amygdala suggesting that T3-mediated rescue of the hypothyroid state might be due to lower neuronal excitability in the limbic circuit.