The Transcriptional Corepressor NAB2 Inhibits NGF-induced Differentiation of PC12 Cells

The PC12 pheochromocytoma cell line responds to NGF by undergoing growth arrest and proceeding to differentiate toward a neuronal phenotype. Among the early genetic events triggered by NGF in PC12 cells are the rapid activation of the zinc finger transcription factor Egr1/NGFI-A, and a slightly delayed induction of NAB2, a corepressor that inhibits Egr1 transcriptional activity. We found that stably transfected PC12 cells expressing high levels of NAB2 do not differentiate, but rather continue to proliferate in response to NGF. Inhibition of PC12 differentiation by NAB2 overexpression was confirmed using two additional experimental approaches, transient transfection, and adenoviral infection. Early events in the NGF signaling cascade, such as activation of MAP kinase and induction of immediate-early genes, were unaltered in the NAB2-overexpressing PC12 cell lines. However, induction of delayed NGF response genes such as TGF-beta 1 and MMP-3 was inhibited. Furthermore, NAB2 overexpression led to downregulation of p21WAF1, a molecule previously shown to play a pivotal role in the ability of PC12 cells to undergo growth arrest and commit to differentiation in response to NGF. Cotransfection with p21WAF1 restored the ability of NAB2-overexpressing PC12 cells to differentiate in response to NGF

Model-based evaluation of cost-effectiveness of nerve growth factor inhibitors in knee osteoarthritis: impact of drug cost, toxicity, and means of administration

Studies suggest nerve growth factor inhibitors (NGFi) relieve pain but may accelerate disease progression in some patients with osteoarthritis (OA). We sought cost and toxicity thresholds that would make NGFi a cost-effective treatment for moderate-to-severe knee OA

Nuclear receptors in vascular biology

Nuclear receptors sense a wide range of steroids and hormones (estrogens, progesterone, androgens, glucocorticoid, and mineralocorticoid), vitamins (A and D), lipid metabolites, carbohydrates, and xenobiotics. In response to these diverse but critically important mediators, nuclear receptors regulate the homeostatic control of lipids, carbohydrate, cholesterol, and xenobiotic drug metabolism, inflammation, cell differentiation and development, including vascular development. The nuclear receptor family is one of the most important groups of signaling molecules in the body and as such represent some of the most important established and emerging clinical and therapeutic targets. This review will highlight some of the recent trends in nuclear receptor biology related to vascular biology

Distributed multi-user MIMO transmission using real-time sigma-delta-over-fiber for next generation fronthaul interface

To achieve the massive device connectivity and high data rate demanded by 5G, wireless transmission with wider signal bandwidths and higher-order multiple-input multiple-output (MIMO) is inevitable. This work demonstrates a possible function split option for the next generation fronthaul interface (NGFI). The proof-of-concept downlink architecture consists of real-time sigma-delta modulated signal over fiber (SDoF) links in combination with distributed multi-user (MU) MIMO transmission. The setup is fully implemented using off-the-shelf and in-house developed components. A single SDoF link achieves an error vector magnitude (EVM) of 3.14% for a 163.84 MHz-bandwidth 256-QAM OFDM signal (958.64 Mbps) with a carrier frequency around 3.5 GHz transmitted over 100 m OM4 multi-mode fiber at 850 nm using a commercial QSFP module. The centralized architecture of the proposed setup introduces no frequency asynchronism among remote radio units. For most cases, the 2 x 2 MU-MIMO transmission has little performance degradation compared to SISO, 0.8 dB EVM degradation for 40.96 MHz-bandwidth signals and 1.4 dB for 163.84 MHz-bandwidth on average, implying that the wireless spectral efficiency almost doubles by exploiting spatial multiplexing. A 1.4 Gbps data rate (720 Mbps per user, 163.84 MHz-bandwidth, 64-QAM) is reached with an average EVM of 6.66%. The performance shows that this approach is feasible for the high-capacity hot-spot scenario

The Effects of Epigenetics on Stress Response

Despite the vast amount of resources at the disposal of humanity today, the intricacies of human biology are often a mystery. The chemical and biological products of the human genome have been well studied and documented, but many of the chemical and neurological pathways are missing quite a few details. The human stress response is one of the most primal and valuable functions of this code that developed as a self- preservation mechanism (Hans, 1975) to naturally increase the odds of procreation. However, this function is prone to overload, particularly in individuals with certain epigenetic traits instilled by early life events, or even events taking place before their life began. Left unchecked, this overclocked stress response can lead to irate outward behavior with no known cause, and even worse, no known treatments. These irate behaviors can be seen on the experimental level; mice who are not adequately groomed by their mothers expressed an increase glucorticoid receptor (GR) response than mice with adequate grooming (Radtke et al., 2011). In human studies, these GR reactions are responsible for a myriad of mental disorders including suicidal tendencies, psychopathy, and increased aggression. Gene therapy is possible for these epigenetic factors, opening up new possibilities for treatment of mental disorders

Regulation of pituitary MT1 melatonin receptor expression by gonadotrophin-releasing hormone (GnRH) and early growth response factor-1 (Egr-1) : in vivo and in vitro studies

Copyright: © 2014 Bae et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work was funded by the UK Biotechnology and Biological Sciences Research Council (BBSRC; grant BB/F020309/1; http://www.bbsrc.ac.uk/home/home.aspx). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Will SDN be part of 5G?

For many, this is no longer a valid question and the case is considered settled with SDN/NFV (Software Defined Networking/Network Function Virtualization) providing the inevitable innovation enablers solving many outstanding management issues regarding 5G. However, given the monumental task of softwarization of radio access network (RAN) while 5G is just around the corner and some companies have started unveiling their 5G equipment already, the concern is very realistic that we may only see some point solutions involving SDN technology instead of a fully SDN-enabled RAN. This survey paper identifies all important obstacles in the way and looks at the state of the art of the relevant solutions. This survey is different from the previous surveys on SDN-based RAN as it focuses on the salient problems and discusses solutions proposed within and outside SDN literature. Our main focus is on fronthaul, backward compatibility, supposedly disruptive nature of SDN deployment, business cases and monetization of SDN related upgrades, latency of general purpose processors (GPP), and additional security vulnerabilities, softwarization brings along to the RAN. We have also provided a summary of the architectural developments in SDN-based RAN landscape as not all work can be covered under the focused issues. This paper provides a comprehensive survey on the state of the art of SDN-based RAN and clearly points out the gaps in the technology.Comment: 33 pages, 10 figure