Calcitonin gene-related peptide promotes cellular changes in trigeminal neurons and glia implicated in peripheral and central sensitization

<p>Abstract</p> <p>Background</p> <p>Calcitonin gene-related peptide (CGRP), a neuropeptide released from trigeminal nerves, is implicated in the underlying pathology of temporomandibular joint disorder (TMD). Elevated levels of CGRP in the joint capsule correlate with inflammation and pain. CGRP mediates neurogenic inflammation in peripheral tissues by increasing blood flow, recruiting immune cells, and activating sensory neurons. The goal of this study was to investigate the capability of CGRP to promote peripheral and central sensitization in a model of TMD.</p> <p>Results</p> <p>Temporal changes in protein expression in trigeminal ganglia and spinal trigeminal nucleus were determined by immunohistochemistry following injection of CGRP in the temporomandibular joint (TMJ) capsule of male Sprague-Dawley rats. CGRP stimulated expression of the active forms of the MAP kinases p38 and ERK, and PKA in trigeminal ganglia at 2 and 24 hours. CGRP also caused a sustained increase in the expression of c-Fos neurons in the spinal trigeminal nucleus. In contrast, levels of P2X₃in spinal neurons were only significantly elevated at 2 hours in response to CGRP. In addition, CGRP stimulated expression of GFAP in astrocytes and OX-42 in microglia at 2 and 24 hours post injection.</p> <p>Conclusions</p> <p>Our results demonstrate that an elevated level of CGRP in the joint, which is associated with TMD, stimulate neuronal and glial expression of proteins implicated in the development of peripheral and central sensitization. Based on our findings, we propose that inhibition of CGRP-mediated activation of trigeminal neurons and glial cells with selective non-peptide CGRP receptor antagonists would be beneficial in the treatment of TMD.</p

New technologies for the old: Potential implications of living in later life for travel demand

Assistive technologies for older people, such as personal tracking devices and community alarms, can facilitate living independently for longer. Where and how older people live will affect patterns of travel associated with their lifestyles and needs. They may remain in their own homes, those of relatives or in residential care homes. They may make minimal or extensive use of technologies. As such, assistive technologies represent an example of technological developments and their social uptake outside the field of transport. Such developments may, nevertheless, have an indirect impact on travel demand and one which may be quite substantial. This paper aims, through a series of expert interviews, to examine: (i) to what extent the mobility effects of technological developments (outside transport) are being considered within the transport sector; (ii) how important or relevant it is for such consideration to be given; and (iii) ways in which such impacts can be accounted for in travel demand analysis and policy decisions. What emerges is that such indirect impacts are considered very important but rarely are they examined. The transport experts interviewed noted various ways of increasing the integration between transport and other domains. Several saw more emphasis on these issues in the education of transport professionals as an important starting point. The paper concludes with the case for using scenario planning as a means to emphasise how the living arrangements for older people, facilitated through assistive technologies, could produce distinct and significant consequences for travel demand. © 2013 The Authors

Book reviews

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45933/1/357_2005_Article_BF01195682.pd

Nation-Building Through Compulsory Schooling During the Age of Mass Migration

By the mid-19th century, America was the most educated nation on Earth: significant financial investments in education were being undertaken and the majority of children voluntarily attended public schools. So why did states across America start introducing compulsory schooling laws at this time in history? We provide qualitative and quantitative evidence that states adopted compulsory schooling laws as a nation-building tool to instill civic values to the tens of millions of culturally diverse migrants who arrived during the ‘Age of Mass Migration’ between 1850 and 1914. We show the adoption of state level compulsory schooling laws occurred significantly earlier in states that hosted a subgroup of European migrants with lower exposure to civic values in their home countries. We then use cross-county data to show the same subgroup of European migrants had significantly lower demand for American common schooling pre-compulsion, and so would have been less exposed to the kinds of civic value or discipline instilled by the American education system had compulsory schooling not been passed. By studying the link between mass migration and the endogenous policy responses of American-born voters in receiving states, our analysis provides new micro-foundations for compulsory schooling laws, the legislative bedrock on which all future developments of the American schooling system were built

Using graph theory to analyze biological networks

Understanding complex systems often requires a bottom-up analysis towards a systems biology approach. The need to investigate a system, not only as individual components but as a whole, emerges. This can be done by examining the elementary constituents individually and then how these are connected. The myriad components of a system and their interactions are best characterized as networks and they are mainly represented as graphs where thousands of nodes are connected with thousands of vertices. In this article we demonstrate approaches, models and methods from the graph theory universe and we discuss ways in which they can be used to reveal hidden properties and features of a network. This network profiling combined with knowledge extraction will help us to better understand the biological significance of the system

Genomic investigations of unexplained acute hepatitis in children

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children

A validation study of a variable weighting algorithm for cluster analysis

Ultrametric trees, Hierarchical clustering, Euclidean distances,

A study of standardization of variables in cluster analysis

Standard scores, Cluster analysis,

Measuring the influence of individual data points in a cluster analysis

Hierarchical clustering, Jackknife, Corrected Rand index, Gamma statistic, Clustering stability,