34 research outputs found

    Oxytocin enhances basolateral amygdala activation and functional connectivity while processing emotional faces: preliminary findings in autistic versus non-autistic women

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    Oxytocin is hypothesized to promote social interactions by enhancing the salience of social stimuli. While previous neuroimaging studies have reported that oxytocin enhances amygdala activation to face stimuli in autistic men, effects in autistic women remain unclear. In this study, the influence of intranasal oxytocin on activation and functional connectivity of the basolateral amygdala – the brain’s “salience detector” – while processing emotional faces vs. shapes was tested in 16 autistic and 21 non-autistic women by fMRI in a placebo-controlled, within-subjects, cross-over design. In the placebo condition, minimal activation differences were observed between autistic and non-autistic women. However, significant drug × group interactions were observed for both basolateral amygdala activation and functional connectivity. Oxytocin increased left basolateral amygdala activation among autistic women (35 voxel cluster, MNI coordinates of peak voxel= -22 -10 -28; mean change=+0.079%, t=3.159, ptukey=0.0166), but not non-autistic women (mean change =+0.003%, t=0.153, ptukey=0.999). Furthermore, oxytocin increased functional connectivity of the right basolateral amygdala with brain regions associated with socio-emotional information processing in autistic women, but not non-autistic women, attenuating group differences in the placebo condition. Taken together, these findings extend evidence of oxytocin’s effects on the amygdala to specifically include autistic women and specify the subregion of the effect.TLP was supported by the Autism Research Trust, Cambridge Trust, and Natural Sciences and Engineering Research Council of Canada. MVL was supported by an ERC Starting Grant (ERC-2017-STG; 755816). MCL was supported by a Canadian Institutes of Health Research (CIHR) Sex and Gender Science Chair (GSB 171373), the O’Brien Scholars Program within the Child and Youth Mental Health Collaborative at the Centre for Addiction and Mental Health (CAMH) and The Hospital for Sick Children, Toronto, the Academic Scholars Award from the Department of Psychiatry, University of Toronto, the CAMH Foundation, and the Ontario Brain Institute. SBC received funding from the Wellcome Trust 214322\Z\18\Z. For the purpose of Open Access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. SBC also received funding from the Autism Centre of Excellence, SFARI, the Templeton World Charitable Fund, the MRC, and the National Institute for Health Research (NIHR). Any views expressed are those of the author(s) and not necessarily those of the funder. RB was supported by the MRC UK, Pinsent Darwin Trust and British Academy post-doctoral fellowship

    Precise age of Bangiomorpha pubescens dates the origin of eukaryotic photosynthesis

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    Although the geological record indicates that eukaryotes evolved by 1.9–1.4 Ga, their early evolution is poorly resolved taxonomically and chronologically. The fossil red alga Bangiomorpha pubescens is the only recognized crown-group eukaryote older than ca. 0.8 Ga and marks the earliest known expression of extant forms of multicellularity and eukaryotic photosynthesis. Because it postdates the divergence between the red and green algae and the prior endosymbiotic event that gave rise to the chloroplast, B. pubescens is uniquely important for calibrating eukaryotic evolution. However, molecular clock estimates for the divergence between the red and green algae are highly variable, and some analyses estimate this split to be younger than the widely inferred but poorly constrained first appearance age of 1.2 Ga for B. pubescens. As a result, many molecular clock studies reject this fossil ex post facto. Here we present new Re-Os isotopic ages from sedimentary rocks that stratigraphically bracket the occurrence of B. pubescens in the Bylot Supergroup of Baffin Island and revise its first appearance to 1.047 +0.013/–0.017 Ga. This date is 150 m.y. younger than commonly held interpretations and permits more precise estimates of early eukaryotic evolution. Using cross-calibrated molecular clock analyses with the new fossil age, we calculate that photosynthesis within the Eukarya emerged ca. 1.25 Ga. This date for primary plastid endosymbiosis serves as a benchmark for interpreting the fossil record of early eukaryotes and evaluating their role in the Proterozoic biosphere

    Effects of oxytocin administration on salivary sex hormone levels in autistic and neurotypical women

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    Abstract: Background: Oxytocin administration, which may be of therapeutic value for individuals with social difficulties, is likely to affect endogenous levels of other socially relevant hormones. However, to date, the effects of oxytocin administration on endogenous hormones have only been examined in neurotypical individuals. The need to consider multi-hormone interactions is particularly warranted in oxytocin trials for autism due to evidence of irregularities in both oxytocin and sex steroid systems. Methods: In this double-blind cross-over study, saliva samples were collected from 16 autistic and 29 neurotypical women before and after intranasal administration of 24 IU oxytocin or placebo. Oestradiol, testosterone, and oxytocin levels were quantified in saliva samples. Participants also completed the Autism-Spectrum Quotient (AQ) and Empathy Quotient (EQ) questionnaires. Results: Distinct patterns of change in testosterone and oestradiol levels pre- to-post-administration were observed in autistic relative to neurotypical women (ANCOVA, p < 0.05 main effect of Group), controlling for sample collection time. The mean percent change oestradiol was + 8.8% for the autism group and − 13.0% for the neurotypical group (t = 1.81, p = 0.08), while the mean percent change testosterone was + 1.1% in the autism group and − 12.6% in the neurotypical group (t = 1.26, p = 0.22). In the oxytocin condition, the mean percent change oestradiol was + 12.6% in the autism group and − 6.9% in the neurotypical group (t = 1.78, p = 0.08), while the mean percent change testosterone was + 14.4% in the autism group and − 15.2% in the neurotypical group (t = 3.00, p = 0.006). Robust regression confirmed that group differences in percent change hormone levels were not driven by a small number of influential individuals. Baseline hormone levels did not differ between groups when considered individually. However, baseline testosterone relative to oestradiol (T:E2 ratio) was higher in autistic women (p = 0.023, Cohen’s d = 0.63), and this ratio correlated positively and negatively with AQ and EQ scores, respectively, in the combined sample. Limitations: Further studies with larger and more diverse autistic sample are warranted to confirm these effects. Conclusions: This study provides the first evidence that oxytocin influences endogenous testosterone levels in autistic individuals, with autistic women showing increases similar to previous reports of neurotypical men. These findings highlight the need to consider sex steroid hormones as a variable in future oxytocin trials

    Precise age of Bangiomorpha pubescens dates the origin of eukaryotic photosynthesis

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    Although the geological record indicates that eukaryotes evolved by 1.9–1.4 Ga, their early evolution is poorly resolved taxonomically and chronologically. The fossil red alga Bangiomorpha pubescens is the only recognized crown-group eukaryote older than ca. 0.8 Ga and marks the earliest known expression of extant forms of multicellularity and eukaryotic photosynthesis. Because it postdates the divergence between the red and green algae and the prior endosymbiotic event that gave rise to the chloroplast, B. pubescens is uniquely important for calibrating eukaryotic evolution. However, molecular clock estimates for the divergence between the red and green algae are highly variable, and some analyses estimate this split to be younger than the widely inferred but poorly constrained first appearance age of 1.2 Ga for B. pubescens. As a result, many molecular clock studies reject this fossil ex post facto. Here we present new Re-Os isotopic ages from sedimentary rocks that stratigraphically bracket the occurrence of B. pubescens in the Bylot Supergroup of Baffin Island and revise its first appearance to 1.047 +0.013/–0.017 Ga. This date is 150 m.y. younger than commonly held interpretations and permits more precise estimates of early eukaryotic evolution. Using cross-calibrated molecular clock analyses with the new fossil age, we calculate that photosynthesis within the Eukarya emerged ca. 1.25 Ga. This date for primary plastid endosymbiosis serves as a benchmark for interpreting the fossil record of early eukaryotes and evaluating their role in the Proterozoic biosphere

    Genome-wide linkage screen for testicular germ cell tumour susceptibility loci

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    A family history of disease is a strong risk factor for testicular germ cell tumour (TGCT). In order to identify the location of putative TGCT susceptibility gene(s) we conducted a linkage search in 237 pedigrees with two or more cases of TGCT. One hundred and seventy-nine pedigrees were evaluated genome-wide with an average inter-marker distance of 10 cM. An additional 58 pedigrees were used to more intensively investigate several genomic regions of interest. Genetic linkage analysis was performed with the ALLEGRO software using two model-based parametric analyses and a non-parametric analysis. Six genomic regions on chromosomes 2p23, 3p12, 3q26, 12p13-q21, 18q21-q23 and Xq27 showed heterogeneity LOD (HLOD) scores of greater than 1, with a maximum HLOD of 1.94 at 3q26. Genome-wide simulation studies indicate that the observed number of HLOD peaks greater than one does not differ significantly from that expected by chance. A TGCT locus at Xq27 has been previously reported. Of the 237 pedigrees examined in this study, 66 were previously unstudied at Xq27, no evidence for linkage to this region was observed in this new pedigree set. Overall, the results indicate that no single major locus can account for the majority of the familial aggregation of TGCT, and suggests that multiple susceptibility loci with weak effects contribute to the diseas

    Genetic risk for neurodegenerative disorders, and its overlap with cognitive ability and physical function

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    Neurodegenerative disorders are associated with impaired cognitive function and worse physical health outcomes. This study aims to test whether polygenic risk for Alzheimer’s disease, Amyotrophic Lateral Sclerosis (ALS), or frontotemporal dementia (FTD) is associated with cognitive function and physical health in the UK Biobank, a cohort of healthy individuals. Group-based analyses were then performed to compare the top and bottom 10% for the three neurodegenerative polygenic risk scores; these groups were compared on the cognitive and physical health variables. Higher polygenic risk for AD, ALS, and FTD was associated with lower cognitive performance. Higher polygenic risk for FTD was also associated with increased forced expiratory volume in 1s and peak expiratory flow. A significant group difference was observed on the symbol digit substitution task between individuals with high polygenic risk for FTD and high polygenic risk for ALS. The results suggest some overlap between polygenic risk for neurodegenerative disorders, cognitive function and physical health

    Small to Mid-Size Sporting Events: Are We Prepared to Recover from an Attack?

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    This article describes a fictional deadly attack by a lone-wolf terrorist during a high school football event in a small town, here in the United States. The authors begin by describing an attack and then focus on the response from the medical community, city, county, state, and federal government officials. Next, the authors make several recommendations on what actions are needed to develop an effective plan to combat terrorist activities during a small- to mid-size sports event. Among the actions needed, the authors focus on the following: response planning, emergency action plan, incident command, policies and procedures, and security staff training
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