Cell-specific deletion of C1qa identifies microglia as the dominant source of C1q in mouse brain

BACKGROUND: The complement cascade not only provides protection from infection but can also mediate destructive inflammation. Complement is also involved in elimination of neuronal synapses which is essential for proper development, but can be detrimental during aging and disease. C1q, required for several of these complement-mediated activities, is present in the neuropil, microglia, and a subset of interneurons in the brain. METHODS: To identify the source(s) of C1q in the brain, the C1qa gene was selectively inactivated in the microglia or Thy-1(+) neurons in both wild type mice and a mouse model of Alzheimer’s disease (AD), and C1q synthesis assessed by immunohistochemistry, QPCR, and western blot analysis. RESULTS: While C1q expression in the brain was unaffected after inactivation of C1qa in Thy-1(+) neurons, the brains of C1qa (FL/FL) :Cx3cr1 (CreERT2) mice in which C1qa was ablated in microglia were devoid of C1q with the exception of limited C1q in subsets of interneurons. Surprisingly, this loss of C1q occurred even in the absence of tamoxifen by 1 month of age, demonstrating that Cre activity is tamoxifen-independent in microglia in Cx3cr1 (CreERT2/WganJ) mice. C1q expression in C1qa (FL/FL) : Cx3cr1 (CreERT2/WganJ) mice continued to decline and remained almost completely absent through aging and in AD model mice. No difference in C1q was detected in the liver or kidney from C1qa (FL/FL) : Cx3cr1 (CreERT2/WganJ) mice relative to controls, and C1qa (FL/FL) : Cx3cr1 (CreERT2/WganJ) mice had minimal, if any, reduction in plasma C1q. CONCLUSIONS: Thus, microglia, but not neurons or peripheral sources, are the dominant source of C1q in the brain. While demonstrating that the Cx3cr1 (CreERT2/WganJ) deleter cannot be used for adult-induced deletion of genes in microglia, the model described here enables further investigation of physiological roles of C1q in the brain and identification of therapeutic targets for the selective control of complement-mediated activities contributing to neurodegenerative disorders. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12974-017-0814-9) contains supplementary material, which is available to authorized users

SOSORT 2012 consensus paper: reducing x-ray exposure in pediatric patients with scoliosis

This 2012 Consensus paper reviews the literature on side effects of x-ray exposure in the pediatric population as it relates to scoliosis evaluation and treatment. Alternative methods of spinal assessment and imaging are reviewed, and strategies for reducing the number of radiographs are developed. Using the Delphi technique, SOSORT members developed consensus statements that describe how often radiographs should be taken in each of the pediatric and adolescent sub-populations

Learning about the opponent in automated bilateral negotiation: a comprehensive survey of opponent modeling techniques

A negotiation between agents is typically an incomplete information game, where the agents initially do not know their opponent’s preferences or strategy. This poses a challenge, as efficient and effective negotiation requires the bidding agent to take the other’s wishes and future behavior into account when deciding on a proposal. Therefore, in order to reach better and earlier agreements, an agent can apply learning techniques to construct a model of the opponent. There is a mature body of research in negotiation that focuses on modeling the opponent, but there exists no recent survey of commonly used opponent modeling techniques. This work aims to advance and integrate knowledge of the field by providing a comprehensive survey of currently existing opponent models in a bilateral negotiation setting. We discuss all possible ways opponent modeling has been used to benefit agents so far, and we introduce a taxonomy of currently existing opponent models based on their underlying learning techniques. We also present techniques to measure the success of opponent models and provide guidelines for deciding on the appropriate performance measures for every opponent model type in our taxonomy

Instrumented measurements of knee laxity: KT-1000 versus navigation

The KT-1000 is widely accepted as a tool for the instrumented measurement of the antero-posterior (AP) tibial translation. The aim of this study is to compare the data obtained with the KT-1000 in ACL deficient knees with the data obtained using a navigation system during "in vivo" ACL reconstruction procedures and to validate the accuracy of the KT-1000. An ACL reconstruction was performed using computer aided surgical navigation (Orthopilot, B-Braun, Aesculap, Tuttlingen, Germany) in 30 patients. AP laxity measurements were obtained for all patients using KT-1000 arthrometer (in a conscious state and under general anaesthesia) and during surgery using the navigation system, always at 30A degrees of knee flexion. The mean AP translation was 14 +/- A 4 and 15.6 +/- A 3.8 mm using the KT-1000 in conscious and under general anaesthesia, respectively (P = 0.02) and 16.1 +/- A 3.7 mm using navigation. Measurements obtained with the KT-1000 under general anaesthesia were no different from those obtained "in vivo" with the navigation system (P = 0.37). In conclusion this study validates the accuracy of the KT-1000 to exactly calculate AP translation of the tibia, in comparison with the more accurate measurements obtained using a navigation system