NG2 cells response to axonal alteration in the spinal cord white matter in mice with genetic disruption of neurofilament light subunit expression

<p>Abstract</p> <p>Background</p> <p>Chondroitin sulphate proteoglycan (NG2) expressing cells, morphologically characterized by multi-branched processes and small cell bodies, are the 4^thcommonest cell population of non-neuronal cell type in the central nervous system (CNS). They can interact with nodes of Ranvier, receive synaptic input, generate action potential and respond to some pathological stimuli, but the function of the cells is still unclear. We assumed the NG2 cells may play an active role in neuropathogenesis and aimed to determine if NG2 cells could sense and response to the alterations in the axonal contents caused by disruption of neurofilament light subunit (NFL) expression.</p> <p>Results</p> <p>In the early neuropathological development stage, our study showed that the diameter of axons of upper motor neurons of NFL-/- mice decreased significantly while the thickness of their myelin sheath increased remarkably. Although there was an obvious morphological distortion in axons with occasionally partial demyelination, no obvious changes in expression of myelin proteins was detected. Parallel to these changes in the axons and their myelination, the processes of NG2 cells were disconnected from the nodes of Ranvier and extended further, suggesting that these cells in the spinal cord white matter could sense the alteration in axonal contents caused by disruption of NFL expression before astrocytic and microglial activation.</p> <p>Conclusion</p> <p>The structural configuration determined by the NFL gene may be important for maintenance of normal morphology of myelinated axons. The NG2 cells might serve as an early sensor for the delivery of information from impaired neurons to the local environment.</p

Velocity Analysis of a Flow Passing over a Vegetated Slope

A sheet flow or overland flow is simulated by the theory of laminar flow passing over a grassed slope with wood. The flow region is divided into two layers (vegetation layer & soil layer) or three layers (wood layer, vegetation layer & soil layer) according to the water depth. The Navier-Stokes equations are employed to govern the flow in the wood layer, and the Biot's theory of poro-elasticity is applied to delineate the flow in the vegetation and soil layers. These equations are simplified, modified and nondimensionalized under different vegetation situations, and then solved analytically. As a result, the velocity distributions are derived by a semi-analytical approach to understand the flow mechanism.一般坡地上除了草地以外，尚有木本植物，因此模擬植生坡面上之薄層流 (或稱為漫地流)，需同時探討種植木本植物與草本植物之植生坡面，本研究依水深將流場劃分為兩層或三層，分別為植生層、土層兩層，或木本層、植生層和土層三層。木本層之控制方程式是以Navier-Stokes 方程式加上木本植物對水流造成的阻力來描述；植生層與土層之控制方程式則以Biot孔彈性介質理論為基礎，依不同的植生狀態加以修正、無因次化和以半解析的方式針對垂直流速分布進行求解

CXCL-8 Regulates Head and Neck Carcinoma Progression through NOD Signalling Pathway

Head and neck squamous cell carcinoma (HNSCC) ranks sixth among the most common cancers in the world. Interlukin-8 (CXCL-8), a major role in inflammatory response and tumor microenvironment, correlates with tumor progression, metastasis and invasion. We explored CXCL-8 promotes tumor progression in different differentiation HNSCC cells. This project would apply to development on biomarker and target in HNSCC as well as provide a basis of early diagnosis and treatment for clinical. CXCL-8, NOD1 (nucleotide-binding oligomerization domain-containing protein 1) and receptor-interacting protein kinase (RIPK2) levels were detected statistically higher in patient tissue with HNSCC than in non-cancerous matched tissue (NCMT) in the microarray and qRT-PCR study, whereas NOD2 was weakly expressed. Similar results were obtained for CXCL-8, NOD1, NOD2 and RIP2 from RT-PCR and western blotting. High CXCL-8, NOD1 and RIP2 expressions were found on HNSCC patient tissue than that of NCMT, whereas NOD2 was weakly expressed. The analytical results indicate that CXCL-8 is required in NOD 1-mediated signalling pathways in HNSCC

Nanocomposites with Liquid-Like Multiwalled Carbon Nanotubes Dispersed in Epoxy Resin without Solvent Process

Liquid-like multiwall carbon nanotubes (MWNTs) were prepared with as-received carboxylic MWNTs-COOH and poly(ethylene oxide)-block-poly(propylene oxide)-block-poly(ethylene oxide) (PEO-b-PPO-b-PEO) through hydrogen bonding. The sample has liquid-like behavior above 58°C. The MWNTs content is 26.6 wt%. The liquid-like MWNTs nanofluids were incorporated into epoxy matrix with solvent-free process and dispersed well. When the liquid-like MWNTs nanofluids content is up to 1 wt%, the impact toughness of the nanocomposite is 153% higher than the pure epoxy matrix

Immunoproteomic Analysis of Human Serological Antibody Responses to Vaccination with Whole-Cell Pertussis Vaccine (WCV)

BACKGROUND: Pertussis (whooping cough) caused by Bordetella pertussis (B.p), continues to be a serious public health threat. Vaccination is the most economical and effective strategy for preventing and controlling pertussis. However, few systematic investigations of actual human immune responses to pertussis vaccines have been performed. Therefore, we utilized a combination of two-dimensional electrophoresis (2-DE), immunoblotting, and mass spectrometry to reveal the entire antigenic proteome of whole-cell pertussis vaccine (WCV) targeted by the human immune system as a first step toward evaluating the repertoire of human humoral immune responses against WCV. METHODOLOGY/PRINCIPAL FINDINGS: Immunoproteomic profiling of total membrane enriched proteins and extracellular proteins of Chinese WCV strain 58003 identified a total of 30 immunoreactive proteins. Seven are known pertussis antigens including Pertactin, Serum resistance protein, chaperonin GroEL and two OMP porins. Sixteen have been documented to be immunogenic in other pathogens but not in B.p, and the immunogenicity of the last seven proteins was found for the first time. Furthermore, by comparison of the human and murine immunoproteomes of B.p, with the exception of four human immunoreactive proteins that were also reactive with mouse immune sera, a unique group of antigens including more than 20 novel immunoreactive proteins that uniquely reacted with human immune serum was confirmed. CONCLUSIONS/SIGNIFICANCE: This study is the first time that the repertoire of human serum antibody responses against WCV was comprehensively investigated, and a small number of previously unidentified antigens of WCV were also found by means of the classic immunoproteomic strategy. Further research on these newly identified predominant antigens of B.p exclusively against humans will not only remarkably accelerate the development of diagnostic biomarkers and subunit vaccines but also provide detailed insight into human immunity mechanisms against WCV. In particular, this work highlights the heterogeneity of the B.p immunoreactivity patterns of the mouse model and the human host

The Nuclear Chaperone Nucleophosmin Escorts an Epstein-Barr Virus Nuclear Antigen to Establish Transcriptional Cascades for Latent Infection in Human B Cells

Epstein-Barr Virus (EBV) is an oncogenic γ-herpesvirus that capably establishes both latent and lytic modes of infection in host cells and causes malignant diseases in humans. Nuclear antigen 2 (EBNA2)-mediated transcription of both cellular and viral genes is essential for the establishment and maintenance of the EBV latency program in B lymphocytes. Here, we employed a protein affinity pull-down and LC-MS/MS analysis to identify nucleophosmin (NPM1) as one of the cellular proteins bound to EBNA2. Additionally, the specific domains that are responsible for protein-protein interactions were characterized as EBNA2 residues 300 to 360 and the oligomerization domain (OD) of NPM1. As in c-MYC, dramatic NPM1 expression was induced in EBV positively infected B cells after three days of viral infection, and both EBNA2 and EBNALP were implicated in the transactivation of the NPM1 promoter. Depletion of NPM1 with the lentivirus-expressed short-hairpin RNAs (shRNAs) effectively abrogated EBNA2-dependent transcription and transformation outgrowth of lymphoblastoid cells. Notably, the ATP-bound state of NPM1 was required to induce assembly of a protein complex containing EBNA2, RBP-Jκ, and NPM1 by stabilizing the interaction of EBNA2 with RBP-Jκ. In a NPM1-knockdown cell line, we demonstrated that an EBNA2-mediated transcription defect was fully restored by the ectopic expression of NPM1. Our findings highlight the essential role of NPM1 in chaperoning EBNA2 onto the latency-associated membrane protein 1 (LMP1) promoters, which is coordinated with the subsequent activation of transcriptional cascades through RBP-Jκ during EBV infection. These data advance our understanding of EBV pathology and further imply that NPM1 can be exploited as a therapeutic target for EBV-associated diseases

BMI1 and Mel-18 oppositely regulate carcinogenesis and progression of gastric cancer

<p>Abstract</p> <p>Background</p> <p>The <it>BMI1 </it>oncogene is overexpressed in several human malignancies including gastric cancer. In addition to BMI1, mammalian cells also express Mel-18, which is closely related to BMI1. We have reported that Mel-18 functions as a potential tumor suppressor by repressing the expression of BMI1 and consequent downregulation of activated AKT in breast cancer cells. However, the mechanisms of BMI1 overexpression and the role of Mel-18 in other cancers are still not clear. The purpose of this study is to investigate the role of BMI1 and Mel-18 in gastric cancer.</p> <p>Results</p> <p>BMI1 was found to be overexpressed in gastric cancer cell lines and gastric tumors. Overexpression of BMI1 correlated with advanced clinical stage and lymph node metastasis; while the expression of Mel-18 negatively correlated with BMI1. BMI1 but not Mel-18 was found to be an independent prognostic factor. Downregulation of BMI1 by Mel-18 overexpression or knockdown of BMI1 expression in gastric cancer cell lines led to upregulation of p16 (p16INK4a or CDKN2A) in p16 positive cell lines and reduction of phospho-AKT in both p16-positive and p16-negative cell lines. Downregulation of BMI1 was also accompanied by decreased transformed phenotype and migration in both p16- positive and p16-negative gastric cancer cell lines.</p> <p>Conclusions</p> <p>In the context of gastric cancer, <it>BMI1 </it>acts as an oncogene and Mel-18 functions as a tumor suppressor via downregulation of BMI1. Mel-18 and BMI1 may regulate tumorigenesis, cell migration and cancer metastasis via both p16- and AKT-dependent growth regulatory pathways.</p