TGR 5 signalling inhibits the production of pro‐inflammatory cytokines by in vitro differentiated inflammatory and intestinal macrophages in Crohn's disease

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/97471/1/imm12045.pd

Integrated genetic and epigenetic analysis defines novel molecular subgroups in rhabdomyosarcoma.

横紋筋肉腫におけるゲノム・エピゲノム異常の全体図を解明 -横紋筋肉腫を4群に分類-. 京都大学プレスリリース. 2015-07-03.Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma in childhood. Here we studied 60 RMSs using whole-exome/-transcriptome sequencing, copy number (CN) and DNA methylome analyses to unravel the genetic/epigenetic basis of RMS. On the basis of methylation patterns, RMS is clustered into four distinct subtypes, which exhibits remarkable correlation with mutation/CN profiles, histological phenotypes and clinical behaviours. A1 and A2 subtypes, especially A1, largely correspond to alveolar histology with frequent PAX3/7 fusions and alterations in cell cycle regulators. In contrast, mostly showing embryonal histology, both E1 and E2 subtypes are characterized by high frequency of CN alterations and/or allelic imbalances, FGFR4/RAS/AKT pathway mutations and PTEN mutations/methylation and in E2, also by p53 inactivation. Despite the better prognosis of embryonal RMS, patients in the E2 are likely to have a poor prognosis. Our results highlight the close relationships of the methylation status and gene mutations with the biological behaviour in RMS

Hose Bandwidth Allocation Method to Achieve a Minimum Throughput Assurance Service for Provider Provisioned VPNs

We propose a hose bandwidth allocation method to achieve a minimum throughput assurance (MTA) service for the hose model. Although the hose model which has been proposed as a novel VPN service model for provider provisioned virtual private networks (PPVPNs) has been proven to be effective for network resource efficiency and configuration complexity there has been no consideration of a mechanism to assure quality of service (QoS) in the hose model. The basic idea of our method is to gather available bandwidth information from inside a network and use it to divide the available bandwidth into hoses on each bottleneck link. We evaluate and clarify our method through computer simulation runs. The simulation results show that our method can achieve an MTA service in the hose model. We propose a hose bandwidth allocation method to achieve a minimum throughput assurance (MTA) service for the hose model. Although the hose model, which has been proposed as a novel VPN service model for provider provisioned virtual private networks (PPVPNs), has been proven to be effective for network resource efficiency and configuration complexity, there has been no consideration of a mechanism to assure quality of service (QoS) in the hose model. The basic idea of our method is to gather available bandwidth information from inside a network and use it to divide the available bandwidth into hoses on each bottleneck link. We evaluate and clarify our method through computer simulation runs. The simulation results show that our method can achieve an MTA service in the hose model

Elastic and Adaptive Resource Orchestration Architecture on 3-Tier Network Virtualization Model

Network virtualization environments (NVEs) are emerging to meet the increasing diversity of demands by Internet users where a virtual network (VN) can be constructed to accommodate each specific application service. In the future Internet, diverse service providers (SPs) will provide application services on their own VNs running across diverse infrastructure providers (InPs) that provide physical resources in an NVE. To realize both efficient resource utilization and good QoS of each individual service in such environments, SPs should perform adaptive control on network and computational resources in dynamic and competitive resource sharing, instead of explicit and sufficient reservation of physical resources for their VNs. On the other hand, two novel concepts, software-defined networking (SDN) and network function virtualization (NFV), have emerged to facilitate the efficient use of network and computational resources, flexible provisioning, network programmability, unified management, etc., which enable us to implement adaptive resource control. In this paper, therefore, we propose an architectural design of network orchestration for enabling SPs to maintain QoS of their applications aggressively by means of resource control on their VNs efficiently, by introducing virtual network provider (VNP) between InPs and SPs as 3-tier model, and by integrating SDN and NFV functionalities into NVE framework. We define new north-bound interfaces (NBIs) for resource requests, resource upgrades, resource programming, and alert notifications while using the standard OpenFlow interfaces for resource control on users\u27 traffic flows. The feasibility of the proposed architecture is demonstrated through network experiments using a prototype implementation and a sample application service on nation-wide testbed networks, the JGN-X and RISE

β-(1,3)-Glucan derived from induces inflammatory cytokines from macrophages and lamina propria mononuclear cells derived from patients with Crohn's disease

Background/AimsRecent research has highlighted the importance of interactions between commensal fungi and intestinal inflammation. However, there are few studies investigating whether commensal fungi contribute to inflammation in patients with Crohn's disease (CD). The aim of this study is to investigate reveal interactions between commensal fungi and host immune cells in CD.MethodsCD14-positive monocytes were isolated from peripheral blood mononuclear cells from healthy human volunteers and then differentiated in the presence of macrophage colony-stimulating factor (M-CSF) (referred to as M-macrophages, M-Mϕs) or M-CSF and interferon-γ (IFN-γ) (referred to as M-gamma macrophages, Mγ-Mϕs). Cytokine production by these in vitro differentiated macrophages in response to β-(1,3)-glucan was analyzed by flow cytometry. Expression of Dectin-1 was examined using flow cytometry, western blotting, and quantitative reverse transcription-polymerase chain reaction. Cytokine production by in vitro differentiated macrophages in response to β-(1,3)-glucan was measured in the presence of an anti-Dectin-1 receptor antagonist, anti-Syr, or an anti-Fas-1 antibody. Cytokine production by lamina propria mononuclear cells (LPMCs) derived from CD patients in response to β-(1,3)-glucan was also analyzed.ResultsMγ-Mϕs produced a large amount of tumor necrosis factor-α (TNF-α) and interleukin-6 in response to β-(1,3)-glucan. Dectin-1 expression was significantly higher in Mγ-Mϕs than in M-Mϕs. The increase in TNF-α production by Mγ-Mϕs stimulated with glucan was reversed by blocking Dectin-1, Syr or Fas-1. LPMCs derived from CD patients stimulated with β-(1,3)-glucan produced significantly higher amount of TNF-α than LPMCs derived from UC patients.ConclusionsThese results suggest that commensal fungal microbiota may contribute to the pathogenesis of CD by inducing macrophages-derived pro-inflammatory cytokines