From genes to folds: a review of cortical gyrification theory.

Cortical gyrification is not a random process. Instead, the folds that develop are synonymous with the functional organization of the cortex, and form patterns that are remarkably consistent across individuals and even some species. How this happens is not well understood. Although many developmental features and evolutionary adaptations have been proposed as the primary cause of gyrencephaly, it is not evident that gyrification is reducible in this way. In recent years, we have greatly increased our understanding of the multiple factors that influence cortical folding, from the action of genes in health and disease to evolutionary adaptations that characterize distinctions between gyrencephalic and lissencephalic cortices. Nonetheless it is unclear how these factors which influence events at a small-scale synthesize to form the consistent and biologically meaningful large-scale features of sulci and gyri. In this article, we review the empirical evidence which suggests that gyrification is the product of a generalized mechanism, namely the differential expansion of the cortex. By considering the implications of this model, we demonstrate that it is possible to link the fundamental biological components of the cortex to its large-scale pattern-specific morphology and functional organization.This work was funded by the Bernard Wolfe Health Neuroscience Fund and the Wellcome Trust.This is the final version of the article. It first appeared from Springer via http://dx.doi.org/10.1007/s00429-014-0961-

Passive sampling for emerging compounds: An Irish perspective

A collaborative project investigating the potential of passive sampling technologies and integrative sampling to meet chemical monitoring requirements of the Water Framework Directive (2000/60/EC) in Ireland began in February 2013. Polar (POCIS) and non-­‐polar (silicon rubber) passive sampling, grab samples and biota samples are being collected at ten sites across Ireland over two years. The first five sites (Fig. 1) are taking a catchment approach. All samples will be tested for emerging and priority compounds listed in the Environmental Quality Standard (EQS) Directive (2008/105/EC) and its 2012 amendment

Childhood Obesity, Cortical Structure, and Executive Function in Healthy Children.

The development of executive function is linked to maturation of prefrontal cortex (PFC) in childhood. Childhood obesity has been associated with changes in brain structure, particularly in PFC, as well as deficits in executive functions. We aimed to determine whether differences in cortical structure mediate the relationship between executive function and childhood obesity. We analyzed MR-derived measures of cortical thickness for 2700 children between the ages of 9 and 11 years, recruited as part of the NIH Adolescent Brain and Cognitive Development (ABCD) study. We related our findings to measures of executive function and body mass index (BMI). In our analysis, increased BMI was associated with significantly reduced mean cortical thickness, as well as specific bilateral reduced cortical thickness in prefrontal cortical regions. This relationship remained after accounting for age, sex, race, parental education, household income, birth-weight, and in-scanner motion. Increased BMI was also associated with lower executive function. Reduced thickness in the rostral medial and superior frontal cortex, the inferior frontal gyrus, and the lateral orbitofrontal cortex partially accounted for reductions in executive function. These results suggest that childhood obesity is associated with compromised executive function. This relationship may be partly explained by BMI-associated reduced cortical thickness in the PFC.Wellcome Trust Bernard Wolfe Health Neuroscience Fun

Cortical thickness gradients in structural hierarchies.

MRI, enabling in vivo analysis of cortical morphology, offers a powerful tool in the assessment of brain development and pathology. One of the most ubiquitous measures used-the thickness of the cortex-shows abnormalities in a number of diseases and conditions, but the functional and biological correlates of such alterations are unclear. If the functional connotations of structural MRI measures are to be understood, we must strive to clarify the relationship between measures such as cortical thickness and their cytoarchitectural determinants. We therefore sought to determine whether patterns of cortical thickness mirror a key motif of the cortex, specifically its structural hierarchical organisation. We delineated three sensory hierarchies (visual, somatosensory and auditory) in two species-macaque and human-and explored whether cortical thickness was correlated with specific cytoarchitectural characteristics. Importantly, we controlled for cortical folding which impacts upon thickness and may obscure regional differences. Our results suggest that an easily measurable macroscopic brain parameter, namely, cortical thickness, is systematically related to cytoarchitecture and to the structural hierarchical organisation of the cortex. We argue that the measurement of cortical thickness gradients may become an important way to develop our understanding of brain structure-function relationships. The identification of alterations in such gradients may complement the observation of regionally localised cortical thickness changes in our understanding of normal development and neuropsychiatric illnesses.We thank Claus Hilgetag and Sarah Beul for valuable input and Helen Barbas for providing macaque data. Human data were provided by the Human Connectome Project, WU-Minn Consortium (Principal Investi- gators: David Van Essen and Kamil Ugurbil; 1U54MH091657) funded by the 16 NIH Institutes and Centers that support the NIH Blueprint for Neuroscience Research, and by the McDonnell Center for Systems Neuroscience at Washington University. KW is supported by the Wellcome Trust and the University of Cambridge MB/PhD Programme, IG by a Wellcome Trust Strategic Award (RNAG/260) and LR and PF by the Bernard Wolfe Health Neuroscience Fund and Wellcome Trust.This is the final published manuscript. It first appeared at http://www.sciencedirect.com/science/article/pii/S1053811915001378

Subjective Impact of the COVID-19 Pandemic on Schizotypy and General Mental Health in Germany and the United Kingdom, for Independent Samples in May and in October 2020.

Studies reported a strong impact on mental health during the first wave of the COVID-19 pandemic in March-June, 2020. In this study, we assessed the impact of the pandemic on mental health in general and on schizotypal traits in two independent general population samples of the United Kingdom (May sample N: 239, October sample N: 126; participation at both timepoints: 21) and in two independent general population samples of Germany (May sample N: 543, October sample N: 401; participation at both timepoints: 100) using online surveys. Whereas general psychological symptoms (global symptom index, GSI) and percentage of responders above clinical cut-off for further psychological investigation were higher in the May sample compared to the October sample, schizotypy scores (Schizotypal Personality Questionnaire) were higher in the October sample. We investigated potential associations, using general linear regression models (GLM). For schizotypy scores, we found that loneliness, use of drugs, and financial burden were more strongly corrected with schizotypy in the October compared to the May sample. We identified similar associations for GSI, as for schizotypy scores, in the May and October samples. We furthermore found that living in the United Kingdom was related to higher schizotypal scores or GSI. However, individual estimates of the GLM are highly comparable between the two countries. In conclusion, this study shows that while the general psychological impact is lower in the October than the May sample, potentially showing a normative response to an exceptional situation; schizotypy scores are higher at the second timepoint, which may be due to a stronger impact of estimates of loneliness, drug use, and financial burden. The ongoing, exceptional circumstances within this pandemic might increase the risk for developing psychosis in some individuals. The development of general psychological symptoms and schizotypy scores over time requires further attention and investigation

Passive sampling as a screening tool in Ireland for new and emerging chemicals

The challenges of monitoring our waters for compliance with WFD and the expansion of the list of organic chemicals that are to be added for monitoring, provides impetus for investigation of alternative monitoring approaches such as passive sampling. The work being carried out represents an important collaboration between two research centres (DCU & MI) together with agency (EA UK and Inland Fisheries Ireland) and industry (TelLab) to assess the potential of passive sampling in monitoring priority pollutants in Ireland. This work is underpinned by a some studies carried out in Ireland already by the Marine Institute and a vast array of literature in the area of priority pollutant monitoring. The impact of this study may lie in the establishment of a capability to utilise passive sampling in the monitoring programme in Ireland for WFD. This project pilots the use of passive sampling technology (PDMS and POCIS) combined with biota monitoring to assess the presence of priority substances in Irish surface waters. The project focuses in particular on new pollutants earmarked as candidates for the Annex X priority substances list under the EU Water Framework Directive e.g. E2 and EE2, pharmaceuticals, pesticides, PFOS etc. This considers the implications for compliance with current and proposed EQS and investigates the potential for incorporating passive sampling and biota testing in future compliance, investigative and trend monitoring. Results of water, biota and passive sampling will be presented together with an outline of the project over the next 12 months. Keywords: passive sampling, surface waters, coastal waters, WFD

Convergent evolution of pregnancy-specific glycoproteins in human and horse

Pregnancy-specific glycoproteins (PSGs) are members of the carcinoembryonic antigen cell adhesion molecule (CEACAM) family that are secreted by trophoblast cells. PSGs may modulate immune, angiogenic and platelet responses during pregnancy. Until now, PSGs are only found in species that have a highly invasive (hemochorial) placentation including humans, mice and rats. Surprisingly, analyzing the CEACAM gene family of the horse, which has a non-invasive epitheliochorial placenta, with the exception of the transient endometrial cups, we identified equine CEACAM family members that seem to be related to PSGs of rodents and primates. We identified seven genes that encode secreted PSG-like CEACAMs. Phylogenetic analyses indicate that they evolved independently from an equine CEACAM1-like ancestor rather than from a common PSG-like ancestor with rodents and primates. Significantly, expression of PSG-like genes (CEACAM44, CEACAM48, CEACAM49 and CEACAM55) was found in non-invasive as well as invasive trophoblast cells such as purified chorionic girdle cells and endometrial cup cells. Chorionic girdle cells are highly invasive trophoblast cells that invade the endometrium of the mare where they form endometrial cups and are in close contact with maternal immune cells. Therefore, the microenvironment of invasive equine trophoblast cells has striking similarities to the microenvironment of trophoblast cells in hemochorial placentas, suggesting that equine PSG-like CEACAMs and rodent and primate PSGs have undergone convergent evolution. This is supported by our finding that equine PSG-like CEACAM49 exhibits similar activity to certain rodent and human PSGs in a functional assay of platelet–fibrinogen binding. Our results have implications for understanding the evolution of PSGs and their functions in maternal–fetal interactions

Obesity associated with increased brain age from midlife.

Common mechanisms in aging and obesity are hypothesized to increase susceptibility to neurodegeneration, however, direct evidence in support of this hypothesis is lacking. We therefore performed a cross-sectional analysis of magnetic resonance image-based brain structure on a population-based cohort of healthy adults. Study participants were originally part of the Cambridge Centre for Ageing and Neuroscience (Cam-CAN) and included 527 individuals aged 20-87 years. Cortical reconstruction techniques were used to generate measures of whole-brain cerebral white-matter volume, cortical thickness, and surface area. Results indicated that cerebral white-matter volume in overweight and obese individuals was associated with a greater degree of atrophy, with maximal effects in middle-age corresponding to an estimated increase of brain age of 10 years. There were no similar body mass index-related changes in cortical parameters. This study suggests that at a population level, obesity may increase the risk of neurodegeneration.This work was supported by the Bernard Wolfe Health Neuroscience Fund and the Wellcome Trust (grant number RNAG/259). The Cambridge Centre for Ageing and Neuroscience (Cam-CAN) research was supported by the Biotechnology and Biological Sciences Research Council (grant number BB/H008217/1).This is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.neurobiolaging.2016.07.01

Catchment approach to passive sampling of Irish waters

The challenges of monitoring our waters for compliance with WFD and the expansion of the list of organic chemicals that are to be added for monitoring, provides impetus for investigation of alternative monitoring approaches such as passive sampling. The work being carried out represents an important collaboration between two research centres (DCU & MI) together with agency (EA UK and Inland Fisheries Ireland) and industry (TelLab) to assess the potential of passive sampling in monitoring priority pollutants in Ireland. The impact of this study may lie in the establishment of a capability to utilise passive sampling in the monitoring programme in Ireland for WFD. This project pilots the use of passive sampling technology (PDMS and POCIS) combined with biota monitoring to assess the presence of priority substances in Irish surface waters. The project focuses in particular on new pollutants earmarked as candidates for the Annex X priority substances list under the EU Water Framework Directive e.g. E2 and EE2, pharmaceuticals, pesticides, PFOS etc. This considers the implications for compliance with current and proposed EQS and investigates the potential for incorporating passive sampling and biota testing in future compliance, investigative and trend monitoring. . Results of water, biota and passive sampling will be presented together for samples collected in the Dublin catchment. A separate study on the occurrence of the pyrethroid pesticide cypermethrin was also conducted. Several sites along the River Liffey, Dublin, were sampled for pharmaceutical as well as other organic pollutants. A POCIS device was deployed at each location and water samples were collected at T-0 and T-4weeks. There are a number of potential point sources of pollution to this catchment with 3 wastewater treatment plants in the area. Pyrethroids have a low toxicity relative to other pesticides (specifically the organochlorines) so have recently been used in place of more toxic pesticides. Cypermethrin has been shown to accumulate in passive sampling devices. This study involved collection of water samples alongside PDMS and SPMD samplers. Cypermethrin was detected in high levels in the water and PDMS samplers. Passive sampling devices can be a useful supporting technique in a ‘toolbox’ for monitoring within the WFD and other environmental programs. From the investigation of work to date it is clear that passive sampling can play an important role in screening of waters for emerging contaminants, especially for hydrophobic subtances where they could be incorporated into a risk based approach to monitoring. Also, passive sampling has demonstrated that it has a role to play in trend monitoring to illustrate where waters are improving in quality over time, thereby offering the WFD monitoring programme a valuable tool. Keywords: passive sampling, surface waters, coastal waters, WFD