Mapping the structural organization of the brain in conduct disorder: replication of findings in two independent samples.

BACKGROUND: Neuroimaging methods that allow researchers to investigate structural covariance between brain regions are increasingly being used to study psychiatric disorders. Structural covariance analyses are particularly well suited for studying disorders with putative neurodevelopmental origins as they appear sensitive to changes in the synchronized maturation of different brain regions. We assessed interregional correlations in cortical thickness as a measure of structural covariance, and applied this method to investigate the coordinated development of different brain regions in conduct disorder (CD). We also assessed whether structural covariance measures could differentiate between the childhood-onset (CO-CD) and adolescence-onset (AO-CD) subtypes of CD, which may differ in terms of etiology and adult outcomes. METHODS: We examined interregional correlations in cortical thickness in male youths with CO-CD or AO-CD relative to healthy controls (HCs) in two independent datasets. The age range in the Cambridge sample was 16-21 years (mean: 18.0), whereas the age range of the Southampton sample was 13-18 years (mean: 16.7). We used FreeSurfer to perform segmentations and applied structural covariance methods to the resulting parcellations. RESULTS: In both samples, CO-CD participants displayed a strikingly higher number of significant cross-cortical correlations compared to HC or AO-CD participants, whereas AO-CD participants presented fewer significant correlations than HCs. Group differences in the strength of the interregional correlations were observed in both samples, and each set of results remained significant when controlling for IQ and comorbid attention-deficit/hyperactivity disorder symptoms. CONCLUSIONS: This study provides new evidence for quantitative differences in structural brain organization between the CO-CD and AO-CD subtypes, and supports the hypothesis that both subtypes of CD have neurodevelopmental origins.This research was funded by Wellcome Trust grant 083140 (Fairchild, Goodyer), Medical Research Council project U.1055.02.001.00001.01 (Calder), an Adventure in Research grant from Southampton University (Fairchild), a PhD studentship from Southampton University (Sully), and the Betty Behrens Research Fellowship at Clare Hall, Cambridge University (Passamonti).This is the final version of the article. It first appeared from Wiley via http://dx.doi.org/10.1111/jcpp.1258

Cryotomography of budding influenza a virus reveals filaments with diverse morphologies that mostly do not bear a genome at their distal end

Influenza viruses exhibit striking variations in particle morphology between strains. Clinical isolates of influenza A virus have been shown to produce long filamentous particles while laboratory-adapted strains are predominantly spherical. However, the role of the filamentous phenotype in the influenza virus infectious cycle remains undetermined. We used cryo-electron tomography to conduct the first three-dimensional study of filamentous virus ultrastructure in particles budding from infected cells. Filaments were often longer than 10 microns and sometimes had bulbous heads at their leading ends, some of which contained tubules we attribute to M1 while none had recognisable ribonucleoprotein (RNP) and hence genome segments. Long filaments that did not have bulbs were infrequently seen to bear an ordered complement of RNPs at their distal ends. Imaging of purified virus also revealed diverse filament morphologies; short rods (bacilliform virions) and longer filaments. Bacilliform virions contained an ordered complement of RNPs while longer filamentous particles were narrower and mostly appeared to lack this feature, but often contained fibrillar material along their entire length. The important ultrastructural differences between these diverse classes of particles raise the possibility of distinct morphogenetic pathways and functions during the infectious process

Scintigraphic assessment of bone status at one year following hip resurfacing : comparison of two surgical approaches using SPECT-CT scan

Objectives: To study the vascularity and bone metabolism of the femoral head/neck following hip resurfacing arthroplasty, and to use these results to compare the posterior and the trochanteric-flip approaches. Methods: In our previous work, we reported changes to intra-operative blood flow during hip resurfacing arthroplasty comparing two surgical approaches. In this study, we report the vascularity and the metabolic bone function in the proximal femur in these same patients at one year after the surgery. Vascularity and bone function was assessed using scintigraphic techniques. Of the 13 patients who agreed to take part, eight had their arthroplasty through a posterior approach and five through a trochanteric-flip approach. Results: One year after surgery, we found no difference in the vascularity (vascular phase) and metabolic bone function (delayed phase) at the junction of the femoral head/neck between the two groups of patients. Higher radiopharmaceutical uptake was found in the region of the greater trochanter in the trochanteric-flip group, related to the healing osteotomy. Conclusions: Our findings using scintigraphic techniques suggest that the greater intra-operative reduction in blood flow to the junction of the femoral head/neck, which is seen with the posterior approach compared with trochanteric flip, does not result in any difference in vascularity or metabolic bone function one year after surgery

Anti-Allergic Cromones Inhibit Histamine and Eicosanoid Release from Activated Human and Murine Mast Cells by Releasing Annexin A1

PMCID: PMC3601088This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Computational modelling of cancerous mutations in the EGFR/ERK signalling pathway

This article has been made available through the Brunel Open Access Publishing Fund - Copyright @ 2009 Orton et al.BACKGROUND: The Epidermal Growth Factor Receptor (EGFR) activated Extracellular-signal Regulated Kinase (ERK) pathway is a critical cell signalling pathway that relays the signal for a cell to proliferate from the plasma membrane to the nucleus. Deregulation of the EGFR/ERK pathway due to alterations affecting the expression or function of a number of pathway components has long been associated with numerous forms of cancer. Under normal conditions, Epidermal Growth Factor (EGF) stimulates a rapid but transient activation of ERK as the signal is rapidly shutdown. Whereas, under cancerous mutation conditions the ERK signal cannot be shutdown and is sustained resulting in the constitutive activation of ERK and continual cell proliferation. In this study, we have used computational modelling techniques to investigate what effects various cancerous alterations have on the signalling flow through the ERK pathway. RESULTS: We have generated a new model of the EGFR activated ERK pathway, which was verified by our own experimental data. We then altered our model to represent various cancerous situations such as Ras, B-Raf and EGFR mutations, as well as EGFR overexpression. Analysis of the models showed that different cancerous situations resulted in different signalling patterns through the ERK pathway, especially when compared to the normal EGF signal pattern. Our model predicts that cancerous EGFR mutation and overexpression signals almost exclusively via the Rap1 pathway, predicting that this pathway is the best target for drugs. Furthermore, our model also highlights the importance of receptor degradation in normal and cancerous EGFR signalling, and suggests that receptor degradation is a key difference between the signalling from the EGF and Nerve Growth Factor (NGF) receptors. CONCLUSION: Our results suggest that different routes to ERK activation are being utilised in different cancerous situations which therefore has interesting implications for drug selection strategies. We also conducted a comparison of the critical differences between signalling from different growth factor receptors (namely EGFR, mutated EGFR, NGF, and Insulin) with our results suggesting the difference between the systems are large scale and can be attributed to the presence/absence of entire pathways rather than subtle difference in individual rate constants between the systems.This work was funded by the Department of Trade and Industry (DTI), under their Bioscience Beacon project programme. AG was funded by an industrial PhD studentship from Scottish Enterprise and Cyclacel

Amygdala Engagement in Response to Subthreshold Presentations of Anxious Face Stimuli in Adults with Autism Spectrum Disorders: Preliminary Insights

Current theoretical models of autism spectrum disorders (ASD) have proposed that impairments in the processing of social/emotional information may be linked to amygdala dysfunction. However, the extent to which amygdala functions are compromised in ASD has become a topic of debate in recent years. In a jittered functional magnetic resonance imaging study, sub-threshold presentations of anxious faces permitted an examination of amygdala recruitment in 12 high functioning adult males with ASD and 12 matched controls. We found heightened neural activation of the amygdala in both high functioning adults with ASD and matched controls. Neither the intensity nor the time-course of amygdala activation differed between the groups. However, the adults with ASD showed significantly lower levels of fusiform activation during the trials compared to controls. Our findings suggest that in ASD, the transmission of socially salient information along sub-cortical pathways is intact: and yet the signaling of this information to structures downstream may be impoverished, and the pathways that facilitate subsequent processing deficient

A Computational Model of the Development of Separate Representations of Facial Identity and Expression in the Primate Visual System

Experimental studies have provided evidence that the visual processing areas of the primate brain represent facial identity and facial expression within different subpopulations of neurons. For example, in non-human primates there is evidence that cells within the inferior temporal gyrus (TE) respond primarily to facial identity, while cells within the superior temporal sulcus (STS) respond to facial expression. More recently, it has been found that the orbitofrontal cortex (OFC) of non-human primates contains some cells that respond exclusively to changes in facial identity, while other cells respond exclusively to facial expression. How might the primate visual system develop physically separate representations of facial identity and expression given that the visual system is always exposed to simultaneous combinations of facial identity and expression during learning? In this paper, a biologically plausible neural network model, VisNet, of the ventral visual pathway is trained on a set of carefully-designed cartoon faces with different identities and expressions. The VisNet model architecture is composed of a hierarchical series of four Self-Organising Maps (SOMs), with associative learning in the feedforward synaptic connections between successive layers. During learning, the network develops separate clusters of cells that respond exclusively to either facial identity or facial expression. We interpret the performance of the network in terms of the learning properties of SOMs, which are able to exploit the statistical indendependence between facial identity and expression

Limited Effect of Dietary Saturated Fat on Plasma Saturated Fat in the Context of a Low Carbohydrate Diet

We recently showed that a hypocaloric carbohydrate restricted diet (CRD) had two striking effects: (1) a reduction in plasma saturated fatty acids (SFA) despite higher intake than a low fat diet, and (2) a decrease in inflammation despite a significant increase in arachidonic acid (ARA). Here we extend these findings in 8 weight stable men who were fed two 6-week CRD (12%en carbohydrate) varying in quality of fat. One CRD emphasized SFA (CRD-SFA, 86 g/d SFA) and the other, unsaturated fat (CRD-UFA, 47 g SFA/d). All foods were provided to subjects. Both CRD decreased serum triacylglycerol (TAG) and insulin, and increased LDL-C particle size. The CRD-UFA significantly decreased plasma TAG SFA (27.48 ± 2.89 mol%) compared to baseline (31.06 ± 4.26 mol%). Plasma TAG SFA, however, remained unchanged in the CRD-SFA (33.14 ± 3.49 mol%) despite a doubling in SFA intake. Both CRD significantly reduced plasma palmitoleic acid (16:1n-7) indicating decreased de novo lipogenesis. CRD-SFA significantly increased plasma phospholipid ARA content, while CRD-UFA significantly increased EPA and DHA. Urine 8-iso PGF2α, a free radical-catalyzed product of ARA, was significantly lower than baseline following CRD-UFA (−32%). There was a significant inverse correlation between changes in urine 8-iso PGF2α and PL ARA on both CRD (r = −0.82 CRD-SFA; r = −0.62 CRD-UFA). These findings are consistent with the concept that dietary saturated fat is efficiently metabolized in the presence of low carbohydrate, and that a CRD results in better preservation of plasma ARA

Facial expression training optimises viewing strategy in children and adults

This study investigated whether training-related improvements in facial expression categorization are facilitated by spontaneous changes in gaze behaviour in adults and nine-year old children. Four sessions of a self-paced, free-viewing training task required participants to categorize happy, sad and fear expressions with varying intensities. No instructions about eye movements were given. Eye-movements were recorded in the first and fourth training session. New faces were introduced in session four to establish transfer-effects of learning. Adults focused most on the eyes in all sessions and increased expression categorization accuracy after training coincided with a strengthening of this eye-bias in gaze allocation. In children, training-related behavioural improvements coincided with an overall shift in gaze-focus towards the eyes (resulting in more adult-like gaze-distributions) and towards the mouth for happy faces in the second fixation. Gaze-distributions were not influenced by the expression intensity or by the introduction of new faces. It was proposed that training enhanced the use of a uniform, predominantly eyes-biased, gaze strategy in children in order to optimise extraction of relevant cues for discrimination between subtle facial expressions

Detection of Babesia divergens in southern Norway by using an immunofluorescence antibody test in cow sera

<p>Abstract</p> <p>Background</p> <p>The incidence of bovine babesiosis, caused by <it>Babesia divergens </it>(Apicomplexa: Piroplasmida) has decreased markedly since the 1930 s, but may re-emerge as a consequence of climate change and changes in legislation and pasturing practices. This is a potentially serious disease, with both economical and animal welfare consequences. Therefore, there is a need to survey the distribution of <it>B. divergens</it>.</p> <p>Methods</p> <p>We tested sera from 306 healthy pastured cows from 24 farms along the southern Norwegian coast by using an indirect immunofluorescence IgG antibody test (IFAT). Fractions of seropositive cows were compared by calculating 95% CI.</p> <p>Results</p> <p>The results of this test showed that 27% of the sera were positive for <it>B. divergens </it>antibodies. The fraction of antibody-positive sera that we detected showed a two-humped distribution, with a high fraction of positives being found in municipalities in the western and eastern parts of the study area, while the municipalities between these areas had few or no positive serum samples.</p> <p>Conclusions</p> <p>Neither the farmers' observations nor the Norwegian Dairy Herd Recording System give an adequate picture of the distribution of bovine babesiosis. Serological testing of cows by using IFAT is a convenient way of screening for the presence of <it>B. divergens </it>in an area.</p