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Secretion system

Kathrin Fielitz, Kristina Althoff, Katleen De Preter, Julie Nonnekens, Jasmin Ohli, Sandra Elges, Wolfgang Hartmann, Günter Klöppel, Thomas Knösel, Marc Schulte, Ludger Klein-Hitpass, Daniela Beisser, Henning Reis, Annette Eyking, Elke Cario, Johannes H Schulte, Alexander Schramm, Ulrich Schüller
Amplification or overexpression of MYCN is involved in development and maintenance of multiple malignancies. A subset of these tumors originates from neural precursors, including the most aggressive forms of the childhood tumors, neuroblastoma and medulloblastoma. In order to model the spectrum of MYCN-driven neoplasms in mice, we transgenically overexpressed MYCN under the control of the human GFAP-promoter that, among other targets, drives expression in neural progenitor cells. However, LSL-MYCN;hGFAP-Cre double transgenic mice did neither develop neural crest tumors nor tumors of the central nervous system, but presented with neuroendocrine tumors of the pancreas and, less frequently, the pituitary gland...
October 19, 2016: Oncotarget
Yuying Sang, Yaru Wang, Hong Ni, Anne-Claire Cazalé, Yi-Min She, Nemo Peeters, Alberto P Macho
The subversion of plant cellular functions is essential for bacterial pathogens to proliferate in host plants and cause disease. Most bacterial plant pathogens employ a type-III secretion system to inject type-III effector (T3E) proteins inside plant cells, where they contribute to the pathogen-induced alteration of plant physiology. In this work, we found that the Ralstonia solanacearum T3E RipAY suppresses plant immune responses triggered by bacterial elicitors and by the phytohormone salicylic acid. Further biochemical analysis indicated that RipAY associates in planta with thioredoxins from Nicotiana benthamiana and Arabidopsis...
October 21, 2016: Molecular Plant Pathology
Ruben Perez-Carrasco, Pilar Guerrero, James Briscoe, Karen M Page
During tissue development, patterns of gene expression determine the spatial arrangement of cell types. In many cases, gradients of secreted signalling molecules-morphogens-guide this process by controlling downstream transcriptional networks. A mechanism commonly used in these networks to convert the continuous information provided by the gradient into discrete transitions between adjacent cell types is the genetic toggle switch, composed of cross-repressing transcriptional determinants. Previous analyses have emphasised the steady state output of these mechanisms...
October 2016: PLoS Computational Biology
Glenn Yiu, Eric Tieu, Anthony T Nguyen, Brittany Wong, Zeljka Smit-McBride
Purpose: To employ type II clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 endonuclease to suppress ocular angiogenesis by genomic disruption of VEGF-A in human RPE cells. Methods: CRISPR sequences targeting exon 1 of human VEGF-A were computationally identified based on predicted Cas9 on- and off-target probabilities. Single guide RNA (gRNA) cassettes with these target sequences were cloned into lentiviral vectors encoding the Streptococcuspyogenes Cas9 endonuclease (SpCas9) gene...
October 1, 2016: Investigative Ophthalmology & Visual Science
Ali Kermanizadeh, Klaus Villadsen, Ragnhild G Østrem, Knud J Jensen, Peter Møller, Steffen Loft
Utilisation of functionalized liposomes as the means of targeted delivery of therapeutics may enhance specific transport of biologically active drugs to target tissues, while avoiding or reducing undesired side effects. In the present investigation, peptide-conjugated cationic liposomes were constructed with the aim of targeting integrins (i.e. vitronectin and/or fibronectin receptors) on activated endothelial cells. The peptide-conjugated liposomes induced only cytotoxicity at the highest concentration in non-activated or activated endothelial cells, as well as in co-culture of endothelial cells and macrophages...
October 21, 2016: Basic & Clinical Pharmacology & Toxicology
Davod Pashoutan Sarvar, Karim Shamsasenjan, Parvin Akbarzadehlaleh
Mesenchymal stromal/stem cells (MSCs) are involved in tissue homeostasis through direct cell-to-cell interaction, as well as secretion of soluble factors. Exosomes are the sort of soluble biological mediators that obtained from MSCs cultured media in vitro. MSC-derived exosomes (MSC-DEs) which produced under physiological or pathological conditions are central mediators of intercellular communications by conveying proteins, lipids, mRNAs, siRNA, ribosomal RNAs and miRNAs to the neighbor or distant cells. MSC-DEs have been tested in various disease models, and the results have revealed that their functions are similar to those of MSCs...
September 2016: Advanced Pharmaceutical Bulletin
Tobias Wiedemann, Stefan Hofbaur, Eva Loell, Gabriele Rieder
Interleukin-8 (IL-8) is a potent neutrophil-activating chemokine which triggers the infiltration and migration of neutrophils into areas of bacterial infection. Helicobacter pylori-infected patient studies as well as animal models have revealed that H. pylori type I strains carrying an intact cytotoxin-associated gene pathogenicity island (cag-PAI) with a functional type IV secretion system (T4SS) induce IL-8 expression and secretion in gastric mucosa. This gastric mucosal IL-8 expression correlates with severe histological changes due to H...
September 29, 2016: European Journal of Microbiology & Immunology
Gang Li, Mengyu Shen, Shuai Le, Yinling Tan, Ming Li, Xia Zhao, Wei Shen, Yuhui Yang, Jing Wang, Hongbin Zhu, Shu Li, Xiancai Rao, Fuquan Hu, Shuguang Lu
As a third-generation sequencing method, single-molecule real-time (SMRT) technology provides long read length, and it is well suited for re-sequencing projects and de novo assembly. In this study, Pseudomonas aeruginosa PA1 was characterized and re-sequenced using SMRT technology. PA1 was also subjected to genomic, comparative, and pan-genomic analyses. The multi-drug resistant strain PA1 possesses a 6,498,072 bp genome and a sequence type of ST-782. The genome of PA1 was also visualized, and the results revealed the details of general genome annotations, virulence factors, regulatory proteins, secretion system proteins, type II toxin-antitoxin pairs, and genomic islands...
October 20, 2016: Bioscience Reports
Y H You, L H He, X H Peng, L Sun, J Z Zhang
Objective: To learn about the overall genomic characteristics and population structure of Helicobacter pylori isolated in China. Methods: In this study, we used 10 public available genome sequences of H. pylori strains isolated in China, combined with other H. pylori sequences from GenBank, to analyzed the overall genomic characteristics of H. pylori isolated in China. Core genes and strain specific genes were determined for a further function definition. Results: A total of 1 203 core genes were found among all sequenced China H...
October 10, 2016: Zhonghua Liu Xing Bing Xue za Zhi, Zhonghua Liuxingbingxue Zazhi
Kuo-Hsun Chiu, Ling-Hui Wang, Tsung-Ting Tsai, Huan-Yao Lei, Pao-Chi Liao
The secreted proteins of bacteria are usually accompanied by virulence factors, which can cause inflammation and damage host cells. Identifying the secretomes arising from the interactions of bacteria and host cells could, therefore, increase understanding of the mechanisms during initial pathogenesis. The present study used a host-pathogen coculture system of Helicobacter pylori and monocytes (THP-1 cells) to investigate the secreted proteins associated with initial H. pylori pathogenesis. The secreted proteins from the conditioned media from H...
October 20, 2016: Journal of Proteome Research
Xing-Hui Gao, Lu Tian, Jiong Wu, Xiao-Lu Ma, Chun-Yan Zhang, Yan Zhou, Yun-Fan Sun, Bo Hu, Shuang-Jian Qiu, Jian Zhou, Jia Fan, Wei Guo, Xin-Rong Yang
BACKGROUND AND AIM: Myeloid-derived suppressor cells (MDSCs) play an important role in tumor progression. The aim of the present study was to investigate the prognostic value of MDSCs for early recurrence of hepatocellular carcinoma (HCC) patients undergoing curative resection. METHODS: MDSCs were measured by flow cytometry. The correlation between MDSCs and tumor recurrence were analyzed using a cohort of 183 patients who underwent curative resection between February 2014 and July 2015...
October 20, 2016: Hepatology Research: the Official Journal of the Japan Society of Hepatology
Zhu Zeng, Rui Yu, Fanglei Zuo, Bo Zhang, Deju Peng, Huiqin Ma, Shangwu Chen
Exendin-4, a glucagon-like protein-1 (GLP-1) receptor agonist, is an excellent therapeutic peptide drug for type 2 diabetes due to longer lasting biological activity compared to GLP-1. This study explored the feasibility of using probiotic Lactobacillus paracasei as an oral vector for recombinant exendin-4 peptide delivery, an alternative to costly chemical synthesis and inconvenient administration by injection. L. paracasei transformed with a plasmid encoding the exendin-4 gene (L. paracasei L14/pMG76e-exendin-4) with a constitutive promotor was successfully constructed and showed efficient secretion of exendin-4...
2016: PloS One
Daryl C Yang, Jennifer R Deuis, Daniel Dashevsky, James Dobson, Timothy N W Jackson, Andreas Brust, Bing Xie, Ivan Koludarov, Jordan Debono, Iwan Hendrikx, Wayne C Hodgson, Peter Josh, Amanda Nouwens, Gregory J Baillie, Timothy J C Bruxner, Paul F Alewood, Kelvin Kok Peng Lim, Nathaniel Frank, Irina Vetter, Bryan G Fry
Millions of years of evolution have fine-tuned the ability of venom peptides to rapidly incapacitate both prey and potential predators. Toxicofera reptiles are characterized by serous-secreting mandibular or maxillary glands with heightened levels of protein expression. These glands are the core anatomical components of the toxicoferan venom system, which exists in myriad points along an evolutionary continuum. Neofunctionalisation of toxins is facilitated by positive selection at functional hotspots on the ancestral protein and venom proteins have undergone dynamic diversification in helodermatid and varanid lizards as well as advanced snakes...
October 18, 2016: Toxins
Kun Zhong, Yi-Yong Luo, Zheng-Song Wu, Qiang He, Xue-Bin Hu, Qi-Wu Jie, Yan-Ting Li, Shao-Jie Wang
A vertical flow constructed wetland was combined with a biological aerated filter to develop an ecological filter, and to obtain the optimal operating parameters: The hydraulic loading was 1.55 m(3)/(m(2)·d), carbon-nitrogen ratio was 10, and gas-water ratio was 6. The experimental results demonstrated considerable removal efficiency of chemical oxygen demand (COD), ammonia nitrogen (NH4(+)-N), total nitrogen (TN), and total phosphorus (TP) in wastewater by the ecological filter, with average removal rates of 83...
October 2016: Water Science and Technology: a Journal of the International Association on Water Pollution Research
Pakchisa Khonsuphap, Prasit Pavasant, Rizky Aditya Irwandi, Chidchanok Leethanakul, Anjalee Vacharaksa
BACKGROUND: Prostaglandin E2 (PGE2) accumulates in inflamed periodontal tissue and induces the receptor activator of nuclear factor kappa-B ligand (RANKL)-RANK-osteoprotegerin (OPG) signaling associated with bone resorption. Although oral epithelial cells maintain tissue homeostasis, the role of these cells in RANKL regulation remains unknown. METHODS: To mimic inflamed condition, RANKL upregulation in human mandibular osteoblast-like cells (HMOBs) were stimulated with PGE2...
October 20, 2016: Journal of Periodontology
Jingjing Li, Jin Gao, Lei Han, Yinjie Zhang, Wen Guan, Liang Zhou, Yan Yu, Wei Han
Identifying interactions between ligands and transmembrane receptors is crucial for understanding the endocrine system. However, the present approaches for this purpose are still not capable of high-throughput screening. In this report, a membrane-anchored ligand and receptor yeast two-hybrid (MALAR-Y2H) system was established. In the method, an extracellular ligand is linked with an intracellular split-ubiquitin reporter system via a chimeric transmembrane structure. Meanwhile, the prey proteins of transmembrane receptors are fused to the other half of the split-ubiquitin reporter system...
October 20, 2016: Scientific Reports
Shengli Mi, Zhichang Du, Yuanyuan Xu, Zhengjie Wu, Xiang Qian, Min Zhang, Wei Sun
Tumour metastasis is an important reason for cancer death, and cancer cell migration is an important step in the process of tumour metastasis. Studying cancer cell migration is of great significance. Here, we present a novel microfluidic co-culture system and establish mild, moderate and severe cancer models by using HMEpiC and MDA-MB-231 cells to study cancer cell migration and anti-cancer drug screening. Using this device, we achieved high cell viability (over 90%) and a stable analysis of the migration ability of cancer cells...
October 20, 2016: Scientific Reports
Megan Allen, Suhasini Ghosh, Gerard P Ahern, Sonia Villapol, Kathleen A Maguire-Zeiss, Katherine Conant
Matrix metalloproteinases (MMPs) are a family of secreted endopeptidases expressed by neurons and glia. Regulated MMP activity contributes to physiological synaptic plasticity, while dysregulated activity can stimulate injury. Disentangling the role individual MMPs play in synaptic plasticity is difficult due to overlapping structure and function as well as cell-type specific expression. Here, we develop a novel system to investigate the selective overexpression of a single MMP driven by GFAP expressing cells in vivo...
October 20, 2016: Scientific Reports
Vignesh Kandakumar, Vishnu Nagalapuram, Sujaya Menon
Light chain deposition disease (LCDD) is a rare systemic disorder in which monoclonal light chains are abnormally secreted due to clonal proliferation of plasma cells and get deposited in various organs; the kidneys being the common one to be affected leading to renal failure. Advocated therapeutic options include chemotherapy with alkylating agents and steroids, High-Dose Melphalan (HDM) with Autologous Stem Cell Transplantation. Recently, Bortezomib has proven to be a novel therapeutic option in these patients when combined with dexamethasone...
August 2016: Journal of the Association of Physicians of India
Colleen E Dugan, James P Grinias, Sebastian D Parlee, Mahmoud El-Azzouny, Charles R Evans, Robert T Kennedy
Microfluidics is an enabling technology for both cell biology and chemical analysis. We combine these attributes with a microfluidic device for on-line solid-phase extraction (SPE) and mass spectrometry (MS) analysis of secreted metabolites from living cells in culture on the chip. The device was constructed with polydimethylsiloxane (PDMS) and contains a reversibly sealed chamber for perfusing cells. A multilayer design allowed a series of valves to control an on-chip 7.5 μL injection loop downstream of the cell chamber with operation similar to a six-port valve...
October 19, 2016: Analytical and Bioanalytical Chemistry
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