A reappraisal of the problematic European, Late Cretaceous brachiopod <i>Leptothyrellopsis polonicus</i> Bitner & Pisera, 1979

This short note presents an emended description of Leptothyrellopsis polonicus BITNER & PISERA, 1979 based on new and well-preserved materia] from Cuesmes and Ciply (Mons Basin, Hainaut, Belgium), as well as re-examination of type and additional material from Mielnik, eastern Poland. The stratigraphic range of L. polonicus is defined as from Lower Campanian to Upper Maastrichtian. On the basis of comparisons between Leptothyrellopsis polonicus and various other similar-looking brachiopods, including the Recent Leptothyrella MUIR-WOOD, Leptothyrellopsis polonicus is retained, meantime, in Incertae sedis

Identification of common genetic risk variants for autism spectrum disorder

Autism spectrum disorder (ASD) is a highly heritable and heterogeneous group of neurodevelopmental phenotypes diagnosed in more than 1% of children. Common genetic variants contribute substantially to ASD susceptibility, but to date no individual variants have been robustly associated with ASD. With a marked sample-size increase from a unique Danish population resource, we report a genome-wide association meta-analysis of 18,381 individuals with ASD and 27,969 controls that identified five genome-wide-significant loci. Leveraging GWAS results from three phenotypes with significantly overlapping genetic architectures (schizophrenia, major depression, and educational attainment), we identified seven additional loci shared with other traits at equally strict significance levels. Dissecting the polygenic architecture, we found both quantitative and qualitative polygenic heterogeneity across ASD subtypes. These results highlight biological insights, particularly relating to neuronal function and corticogenesis, and establish that GWAS performed at scale will be much more productive in the near term in ASD.Peer reviewe

Integrated analysis of environmental and genetic influences on cord blood DNA methylation in new-borns

Epigenetic processes, including DNA methylation (DNAm), are among the mechanisms allowing integration of genetic and environmental factors to shape cellular function. While many studies have investigated either environmental or genetic contributions to DNAm, few have assessed their integrated effects. Here we examine the relative contributions of prenatal environmental factors and genotype on DNA methylation in neonatal blood at variably methylated regions (VMRs) in 4 independent cohorts (overall n = 2365). We use Akaike’s information criterion to test which factors best explain variability of methylation in the cohort-specific VMRs: several prenatal environmental factors (E), genotypes in cis (G), or their additive (G + E) or interaction (GxE) effects. Genetic and environmental factors in combination best explain DNAm at the majority of VMRs. The CpGs best explained by either G, G + E or GxE are functionally distinct. The enrichment of genetic variants from GxE models in GWAS for complex disorders supports their importance for disease risk

Stereology of cerebral cortex after traumatic brain injury matched to the Glasgow Outcome Score

Magnetic resonance imaging provides evidence for loss of both white and grey matter, in terms of tissue volume, from the cerebral hemispheres after traumatic brain injury. However, quantitative histopathological data are lacking. From the archive of the Department of Neuropathology at Glasgow, the cerebral cortex of 48 patients was investigated using stereology. Patients had survived 3 months after traumatic brain injury and were classified using the Glasgow Outcome Scale as follows: moderately disabled (n = 13), severely disabled (n = 12) and vegetative state (n = 12); and controls. Some patients from the archive were diagnosed with diffuse axonal injury post-mortem. Comparisons of changes in cortical neuron population across Glasgow Outcome Scale groups between diffuse axonal injury and non-diffuse axonal injury patients were undertaken using effect size analyses. The hypotheses tested were that (i) thinning of the cerebral cortex occurred after traumatic brain injury; (ii) changes in thickness of cortical layers in Brodmann areas 11, 10, 24a and 4 differed; and (iii) different changes occurred for neuronal number, their size and nearest neighbour index across Glasgow Outcome Scale groups. There was a greater loss of large pyramidal and large non-pyramidal neurons with a more severe score on the Glasgow Outcome Scale from all four cortical regions, with the greatest loss of neurons from the prefrontal cortex of patients with diffuse axonal injury. There were differences in the changes of number of medium and small pyramidal and non-pyramidal neurons between different cortical regions, and between patients with and without diffuse axonal injury. Generally, a decrease in the somatic diameter of pyramidal and non-pyramidal neurons was associated with a more severe clinical outcome. However, in the motor cortex a more severe Glasgow Outcome Scale was associated with an increased diameter of medium pyramidal neurons and small non-pyramidal cells. Pyramidal and non-pyramidal neurons did not follow a Poisson distribution within the neuropil of control patients. Pyramidal neurons were usually scattered while medium and small non-pyramidal neurons were clustered. An increased spacing between remaining neurons usually occurred across Glasgow Outcome Scale groups. It is concluded that loss of neurons resulted in reduced executive and integrative capability in patients after traumatic head injur

No evidence for the presence of apolipoprotein epsilon-4, interleukin-1 alpha allele 2 and interleukin-1 beta allele 2 cause an increase in programmed cell death following traumatic brain injury in humans

Background: Brain injury after trauma is an important cause of mortality and morbidity in society. There is evidence in both man and laboratory animals that in addition to necrosis, cell loss may occur as a result of programmed cell death (PCD). The cellular and molecular responses after head injury are partly influenced by genetic polymorphisms of apolipoprotein E and the proinflammatory cytokine IL-1. Aim: The principal aim of this study was to determine whether the presence of the ApoE epsilon(4), IL-1(alpha 2) or IL-I beta(2) allele types influenced the amounts of PCD after head injury compared with controls. Methods: Paraffin sections from the hippocampus of 38 patients (32 M : 6 F, aged 15-75, mean 38 years, survival 7-576 hours; mean 36 hours) who died after a head injury were stained by Tunel histochemistry and quantified, and genotyping was undertaken by PCR "blind" to clinical detail. Results: There were more Tunel+ cells (neurons and glia) after head injury than in controls with statistically increased numbers in all sectors of the hippocampus including the dentate fascia. However, there was no correlation between ApoE epsilon(4), IL-1 alpha allele 2 and IL-1 beta allele 2 and the amount of Tunel positivity. Conclusion: Given that both the ApoE and IL-1 influence outcome after various forms of acute brain injury, further work will be required to determine the mechanism underlying this relationshi