Multi-scale correlation structure of gene expression in the brain

The mammalian brain is best understood as a multi-scale hierarchical neural system, in the sense that connection and function occur on multiple scales from micro to macro. Modern genomic-scale expression profiling can provide insight into methodologies that elucidate this architecture. We present a methodology for understanding the relationship of gene expression and neuroanatomy based on correlation between gene expression profiles across tissue samples. A resulting tool, NeuroBlast, can identify networks of genes co-expressed within or across neuroanatomic structures. The method applies to any data modality that can be mapped with sufficient spatial resolution, and provides a computation technique to elucidate neuroanatomy via patterns of gene expression on spatial and temporal scales. In addition, from the perspective of spatial location, we discuss a complementary technique that identifies gene classes that contribute to defining anatomic patterns.     

Maturation of limbic regions in Asperger syndrome: a preliminary study using proton magnetic resonance spectroscopy and structural magnetic resonance imaging

People with autistic spectrum disorders (ASD, including Asperger syndrome) may have developmental abnormalities in the amygdala-hippocampal complex (AHC). However, in vivo, age-related comparisons of both volume and neuronal integrity of the AHC have not yet been carried out in people with Asperger syndrome (AS) versus controls. We compared structure and metabolic activity of the right AHC of 22 individuals with AS and 22 healthy controls aged 10-50 years and examined the effects of age between groups. We used structural magnetic resonance imaging (sMRI) to measure the volume of the AHC, and magnetic resonance spectroscopy ((1)H-MRS) to measure concentrations of N-acetyl aspartate (NAA), creatine+phosphocreatine (Cr+PCr), myo-inositol (mI) and choline (Cho). The bulk volume of the amygdala and the hippocampus did not differ significantly between groups, but there was a significant difference in the effect of age on the hippocampus in controls. Compared with controls, young (but not older) people with AS had a significantly higher AHC concentration of NAA and a significantly higher NAA/Cr ratio. People with AS, but not controls, had a significant age-related reduction in NAA and the NAA/Cr ratio. Also, in people with AS, but not controls, there was a significant relationship between concentrations of choline and age so that choline concentrations reduced with age. We therefore suggest that people with AS have significant differences in neuronal and lipid membrane integrity and maturation of the AHC.     

Bridging the gap between best evidence and best practice in mental health

Clinical psychology is in a unique position to move beyond a simplistic agenda of outcome assessment to translating that information into a sustainable model of evidence-based practice. The scientist–practitioner model is no longer limited to use of evidence-based treatments in practice, but can extend to using innovative methodologies to assess rates of recovery, monitor patient progress, intervene in the face of poor response, and contribute to the benchmarking of risk-adjusted outcomes. As the scientific conversation about outcomes moves to encompass feedback of information in order to refine management and practice; researchers, policy-makers, clinicians and patients are poised to look further than average group effects. A new emphasis on individual outcome, taking account of clinical characteristics and risk variables, has generated a clinical outcomes agenda that may be directly translated from “bench to bedside”. The current paper addresses the status of evidence-based treatments, measurement of change, patient-focused research and the public availability of risk-adjusted outcomes data; as well as challenges that remain.     

Expression and activity of transglutaminase II in spontaneous tumours of dogs and cats

Tissue transglutaminase II (TGase II) is a dual function protein with both transamidating and guanidine triphosphate (GTP)-binding capabilities. Previous studies have implicated TGase as a pro-apoptotic molecule; however, our recent findings indicate that TGase II may act as a survival factor in various cell types. The purpose of this study was to survey TGase II expression in normal tissue and spontaneous tumours of dogs and cats, by Western blotting and immunohistochemistry. Bladder, liver and adrenal gland exhibited prominent expression of TGase II while other tissues, including mammary gland, displayed limited expression and activity. TGase II GTP-binding in normal tissues was proportional to the level of expression in all tissues examined. Normal mammary tissue and that showing benign hyperplasia did not express TGase II. However, 11/25 (44%) of canine mammary carcinomas and 10/12 (83%) of feline mammary carcinomas strongly expressed TGase II in either a stromal, cellular or combined pattern. The pattern of expression was not related to the classification of mammary carcinoma (solid, tubulopapillary, complex or anaplastic), except that two anaplastic canine mammary carcinomas showed prominent TGase II expression. Two canine mammary carcinoma cell lines showed prominent TGase expression, and when the TGase activity was inhibited, the cells became more sensitive to doxorubicin-induced cell death. Thus, TGase II was significantly expressed in mammary cancers from dogs and cats and immunoreactivity of TGase II was similar to that reported in humans beings. The pro-survival effect of TGase II in canine mammary carcinoma cell lines was similar to that previously reported in humans patients.     

Role of Na+ and K+ in enzyme function

Metal complexation is a key mediator or modifier of enzyme structure and function. In addition to divalent and polyvalent metals, group IA metals Na+ and K+ play important and specific roles that assist function of biological macromolecules. We examine the diversity of monovalent cation (M+)-activated enzymes by first comparing coordination in small molecules followed by a discussion of theoretical and practical aspects. Select examples of enzymes that utilize M+ as a cofactor (type I) or allosteric effector (type II) illustrate the structural basis of activation by Na+ and K+, along with unexpected connections with ion transporters. Kinetic expressions are derived for the analysis of type I and type II activation. In conclusion, we address evolutionary implications of Na+ binding in the trypsin-like proteases of vertebrate blood coagulation. From this analysis, M+ complexation has the potential to be an efficient regulator of enzyme catalysis and stability and offers novel strategies for protein engineering to improve enzyme function.