Morphologically unusual feline spinocervical tract neurons

Intracellular horseradish peroxidase studies of spinocervical tract neurons in the cat have demonstrated that they have dendritic arbors primarily confined to laminae III through V. In the present intracellular staining study of this class of neuron we retrieved one cell with its soma in lamina I which arborized in laminae I through III and another cell with a soma in lamina III and a dendritic arbor which extended from lamina I through V. These data indicate therefore that a small proportion of neurons forming the spinocervical tract do not have dendritic arbors that are confined to laminae III through V. These two cells were capable of receiving monosynaptic input from primary afferent fibers innervating mechanical nociceptors and C-fibers.     

The epidemiology of multiple sclerosis in Queensland, Australia

An epidemiological survey of multiple sclerosis (MS) in the State of Queensland was undertaken with its prevalence day being the national census day on June 30th, 1981, 20 years after a regional survey within the State. The relationship between increasing prevalence of MS and increasing south latitude within the State of Queensland which was suggested by the 1961 study was confirmed in the present study. The prevalence rate had increased significantly over the 20-year period between the studies but the State remained a medium frequency zone for MS (prevalence rate between 5 and 29 per 100 000 of population). Although a real increase in disease frequency could not be excluded as a contributing factor to the rise in prevalence, it was most likely due predominantly to an increase in life expectancy amongst the MS population and also in differential migration of a population at a greater risk of developing MS than the indigenous population. The proportions of Australian-born patients who had migrated to Queensland from the higher risk southern regions of Australia or travelled overseas to countries known to be high-risk for MS prior to disease onset, had fallen between the two surveys thus exerting, if anything, a negative influence on the change in prevalence. Analysis of MS prevalence rates amongst migrant populations in Queensland as compared to the more southerly city of Perth in Western Australia, suggested that the risk of acquisition of MS may extend over a wider age range than is generally accepted. Finally, there was an absence of MS cases amongst the Aboriginal population in Queensland but it can only cautiously be concluded from this study that the disease is rare in these peoples.     

Tubers from patients with tuberous sclerosis complex are characterized by changes in microtubule biology through ROCK2 signalling

Most patients with tuberous sclerosis complex (TSC) develop cortical tubers that cause severe neurological disabilities. It has been suggested that defects in neuronal differentiation and/or migration underlie the appearance of tubers. However, the precise molecular alterations remain largely unknown. Here, by combining cytological and immunohistochemical analyses of tubers from nine TSC patients (four of them diagnosed with TSC2 germline mutations), we show that alteration of microtubule biology through ROCK2 signalling contributes to TSC neuropathology. All tubers showed a larger number of binucleated neurons than expected relative to control cortex. An excess of normal and altered cytokinetic figures was also commonly observed. Analysis of centrosomal markers suggested increased microtubule nucleation capacity, which was supported by the analysis of an expression dataset from cortical tubers and control cortex, and subsequently linked to under‐expression of Rho‐associated coiled‐coil containing kinase 2 (ROCK2). Thus, augmented microtubule nucleation capacity was observed in mouse embryonic fibroblasts and human fibroblasts deficient in the Tsc2/TSC2 gene product, tuberin. Consistent with ROCK2 under‐expression, microtubule acetylation was found to be increased with tuberin deficiency; this alteration was abrogated by rapamycin treatment and mimicked by HDAC6 inhibition. Together, the results of this study support the hypothesis that loss of TSC2 expression can alter microtubule organization and dynamics, which, in turn, deregulate cell division and potentially impair neuronal differentiation. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd     

The effects of fornix section on win-stay/lose-shift and win-shift/lose-stay performance in the rat

Two groups of rats were trained in 2-lever operant tasks that required them to follow either a Win-shift/Lose-stay rule, or else a Win-stay/Lose-shift rule. The rats in each testing condition attained a similar level of performance. Once the tasks had been learnt, half of the rats in each testing condition were given fornix lesions. These lesions produced a clear performance impairment at all inter-response retention intervals tested in those rats trained on the Win-shift/Lose-stay task, but impaired performance in rats trained on the Win-stay/Lose-shift condition only when the inter-response interval reached 10 s. The implications of these results for the working memory theory and for the temporal discontiguity theory are discussed.     

The Biomedical Research Hub: a federated platform for patient research data

ObjectiveThe objective was to develop and operate a cloud-based federated system for managing, analyzing, and sharing patient data for research purposes, while allowing each resource sharing patient data to operate their component based upon their own governance rules. The federated system is called the Biomedical Research Hub (BRH).Materials and MethodsThe BRH is a cloud-based federated system built over a core set of software services called framework services. BRH framework services include authentication and authorization, services for generating and assessing findable, accessible, interoperable, and reusable (FAIR) data, and services for importing and exporting bulk clinical data. The BRH includes data resources providing data operated by different entities and workspaces that can access and analyze data from one or more of the data resources in the BRH.ResultsThe BRH contains multiple data commons that in aggregate provide access to over 6 PB of research data from over 400 000 research participants.Discussion and conclusionWith the growing acceptance of using public cloud computing platforms for biomedical research, and the growing use of opaque persistent digital identifiers for datasets, data objects, and other entities, there is now a foundation for systems that federate data from multiple independently operated data resources that expose FAIR application programming interfaces, each using a separate data model. Applications can be built that access data from one or more of the data resources.