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https://www.readbyqxmd.com/read/28333574/cytosolic-nucleic-acid-sensors-and-innate-immune-regulation
#1
Daisuke Ori, Motoya Murase, Taro Kawai
During viral and bacterial infections, pathogen-derived cytosolic nucleic acids are recognized by the intracellular RNA sensors retinoic acid-inducible gene I and melanoma-differentiated gene 5 and intracellular DNA sensors, including cyclic-di-GMP-AMP synthase, absent in melanoma 2, interferon (IFN)-gamma inducible protein 16, polymerase III, and so on. Binding of intracellular nucleic acids to these sensors activates downstream signaling cascades, resulting in the production of type I IFNs and pro-inflammatory cytokines to induce appropriate systematic immune responses...
March 23, 2017: International Reviews of Immunology
https://www.readbyqxmd.com/read/28333573/new-approaches-for-characterization-of-the-genetic-stability-of-vaccine-cell-lines
#2
Siemon Ng, Lucy Gisonni-Lex, Ali Azizi
The genetic stability of cell lines is a critical analytical attribute required to demonstrate the quality of cells over time. During cell passage, mutations can arise in the genomic DNA, potentially leading to changes in the final vaccine product. The identity and integrity of master cell banks, extended cell banks, complementing cell lines or recombinant cell lines expressing transgenes has to be tested throughout the production process by the vaccine manufacturer. Over the past few years, the traditional methods for evaluation of genetic stability have been replaced with molecular approaches including quantitative PCR, digital PCR and high throughput sequencing...
February 23, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28328921/versatile-modes-of-cellular-regulation-via-cyclic-dinucleotides
#3
REVIEW
Petya Violinova Krasteva, Holger Sondermann
Since the discovery of c-di-GMP almost three decades ago, cyclic dinucleotides (CDNs) have emerged as widely used signaling molecules in most kingdoms of life. The family of second messengers now includes c-di-AMP and distinct versions of mixed cyclic GMP-AMP (cGAMP) compounds. In addition to these nucleotides, a vast number of proteins for the production and turnover of these molecules have been described, as well as effectors that translate the signals into physiological responses. The latter include, but are not limited to, mechanisms for adaptation and survival in prokaryotes, persistence and virulence of bacterial pathogens, and immune responses to viral and bacterial invasion in eukaryotes...
March 22, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28326941/-express-cyclic-gmp-dependent-protein-kinase-i-localized-in-nociceptors-modulates-nociceptive-cortical-neuronal-activity-and-pain-hypersensitivity
#4
Vijayan Gangadharan, Xu Wang, Ceng Luo
No abstract text is available yet for this article.
January 2017: Molecular Pain
https://www.readbyqxmd.com/read/28325767/cohesive-properties-of-the-caulobacter-crescentus-holdfast-adhesin-are-regulated-by-a-novel-c-di-gmp-effector-protein
#5
Kathrin S Sprecher, Isabelle Hug, Jutta Nesper, Eva Potthoff, Mohamed-Ali Mahi, Matteo Sangermani, Volkhard Kaever, Torsten Schwede, Julia Vorholt, Urs Jenal
When encountering surfaces, many bacteria produce adhesins to facilitate their initial attachment and to irreversibly glue themselves to the solid substrate. A central molecule regulating the processes of this motile-sessile transition is the second messenger c-di-GMP, which stimulates the production of a variety of exopolysaccharide adhesins in different bacterial model organisms. In Caulobacter crescentus, c-di-GMP regulates the synthesis of the polar holdfast adhesin during the cell cycle, yet the molecular and cellular details of this control are currently unknown...
March 21, 2017: MBio
https://www.readbyqxmd.com/read/28325558/l-citrulline-ameliorates-cerebral-blood-flow-during-cortical-spreading-depression-in-rats-involvement-of-nitric-oxide-and-prostanoids-mediated-pathway
#6
Yuki Kurauchi, Koichi Mokudai, Asami Mori, Kenji Sakamoto, Tsutomu Nakahara, Masahiko Morita, Ayako Kamimura, Kunio Ishii
l-Citrulline is a potent precursor of l-arginine, and exerts beneficial effect on cardiovascular system via nitric oxide (NO) production. Migraine is one of the most popular neurovascular disorder, and imbalance of cerebral blood flow (CBF) observed in cortical spreading depression (CSD) contributes to the mechanism of migraine aura. Here, we investigated the effect of l-citrulline on cardiovascular changes to KCl-induced CSD. in rats. Intravenous injection of l-citrulline prevented the decrease in CBF, monitored by laser Doppler flowmetry, without affecting mean arterial pressure and heart rate during CSD...
February 17, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28324858/dual-lanthanide-doped-complexes-the-development-of-a-time-resolved-ratiometric-fluorescent-probe-for-anthrax-biomarker-and-a-paper-based-visual-sensor
#7
Qi-Xian Wang, Shi-Fan Xue, Zi-Han Chen, Shi-Hui Ma, Shengqiang Zhang, Guoyue Shi, Min Zhang
In this work, a novel time-resolved ratiometric fluorescent probe based on dual lanthanide (Tb: terbium, and Eu: europium)-doped complexes (Tb/DPA@SiO2-Eu/GMP) has been designed for detecting anthrax biomarker (dipicolinic acid, DPA), a unique and major component of anthrax spores. In such complexes-based probe, Tb/DPA@SiO2 can serve as a stable reference signal with green fluorescence and Eu/GMP act as a sensitive response signal with red fluorescence for ratiometric fluorescent sensing DPA. Additionally, the probe exhibits long fluorescence lifetime, which can significantly reduce the autofluorescence interferences from biological samples by using time-resolved fluorescence measurement...
March 16, 2017: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/28321422/autologous-tenocyte-injection-for-the-treatment-of-chronic-recalcitrant-gluteal-tendinopathy-a-prospective-pilot-study
#8
Thomas A Bucher, Jay R Ebert, Anne Smith, William Breidahl, Michael Fallon, Tao Wang, Ming-Hao Zheng, Gregory C Janes
BACKGROUND: Gluteal tendinopathy is a common cause of lateral hip pain, and existing conservative treatment modalities demonstrate high symptom recurrence rates. Autologous tenocyte injection (ATI) is a promising cell therapy that may be useful for the treatment of gluteal tendinopathy. PURPOSE: To investigate the safety and effectiveness of ATI, specifically in patients with chronic recalcitrant gluteal tendinopathy. STUDY DESIGN: Case series; Level of evidence, 4...
February 2017: Orthopaedic Journal of Sports Medicine
https://www.readbyqxmd.com/read/28321124/combined-inhibition-of-%C3%AE-catenin-and-bcr-abl-synergistically-targets-tyrosine-kinase-inhibitor-resistant-blast-crisis-chronic-myeloid-leukemia-blasts-and-progenitors-in-vitro-and-in-vivo
#9
H Zhou, P Y Mak, H Mu, D H Mak, Z Zeng, J Cortes, Q Liu, M Andreeff, B Z Carter
Tyrosine kinase inhibitor (TKI) resistance and progression to blast crisis (BC), both related to persistent β-catenin activation remain formidable challenges for chronic myeloid leukemia (CML). We observed overexpression of β-catenin in BC-CML stem/progenitor cells, particularly in GMP progenitors, and highest among a novel CD34(+)CD38(+)CD123(hi)Tim-3(hi) subset as determined by CyTOF analysis. Co-culture with mesenchymal stromal cells (MSCs) induced the expression of β-catenin and its target CD44 in CML cells...
March 21, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28320886/optogenetic-module-for-dichromatic-control-of-c-di-gmp-signaling
#10
Min-Hyung Ryu, Anastasia Fomicheva, Oleg V Moskvin, Mark Gomelsky
Many aspects of bacterial physiology and behavior including motility, surface attachment, and cell cycle, are controlled by the c-di-GMP-dependent signaling pathways on the scale of seconds-to-minutes. Interrogation of such processes in real time requires tools for introducing rapid and reversible changes in intracellular c-di-GMP levels. Inducing expression of genes encoding c-di-GMP synthetic (diguanylate cyclases) and degrading (c-di-GMP phosphodiesterase) enzymes by chemicals may not provide adequate temporal control...
March 20, 2017: Journal of Bacteriology
https://www.readbyqxmd.com/read/28320463/hyaluronan-coating-improves-liver-engraftment-of-transplanted-human-biliary-tree-stem-progenitor-cells
#11
Lorenzo Nevi, Guido Carpino, Daniele Costantini, Vincenzo Cardinale, Olga Riccioni, Sabina Di Matteo, Fabio Melandro, Pasquale Bartolomeo Berloco, Lola Reid, Eugenio Gaudio, Domenico Alvaro
BACKGROUND: Cell therapy of liver diseases with human biliary tree stem cells (hBTSCs) is biased by low engraftment efficiency. Coating the hBTSCs with hyaluronans (HAs), the primary constituents of all stem cell niches, could facilitate cell survival, proliferation, and, specifically, liver engraftment given that HAs are cleared selectively by the liver. METHODS: We developed a fast and easy method to coat hBTSCs with HA and assessed the effects of HA-coating on cell properties in vitro and in vivo...
March 20, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28316269/development-of-a-novel-one-step-production-system-for-injectable-liposomes-under-gmp
#12
Ryo Araki, Takashi Matsuzaki, Ayumi Nakamura, Daisaku Nakatani, Shoji Sanada, Hai Ying Fu, Keiji Okuda, Masaki Yamato, Shota Tsuchida, Yasushi Sakata, Tetsuo Minamino
There are few methods available for injectable liposome production under good manufacturing practices (GMP). Injectable liposome production processes under GMP generally consist of liposome formation, size homogenization, organic solvent removal, liposome concentration control and sterilization. However, these complicated and separate processes make it difficult to maintain scalability, reproducibility and sterility. To overcome these limitations, we developed a novel one-step in-line closed liposome production system that integrated all production processes by combining the in-line thermal mixing device with modified counterflow dialysis...
March 20, 2017: Pharmaceutical Development and Technology
https://www.readbyqxmd.com/read/28314590/inflammasome-activation-triggers-caspase-1-mediated-cleavage-of-cgas-to-regulate-responses-to-dna-virus-infection
#13
Yutao Wang, Xiaohan Ning, Pengfei Gao, Shuxian Wu, Mengyin Sha, Mengze Lv, Xiang Zhou, Juyi Gao, Run Fang, Guangxun Meng, Xiaodong Su, Zhengfan Jiang
Viral infection triggers host innate immune responses that result in the production of various cytokines including type I interferons (IFN), activation of inflammasomes, and programmed cell death of the infected cells. Tight control of inflammatory cytokine production is crucial for the triggering of an effective immune response that can resolve the infection without causing host pathology. In examining the inflammatory response of Asc(-/-) and Casp1(-/-) macrophages, we found that deficiency in these molecules resulted in increased IFN production upon DNA virus infection, but not RNA virus challenge...
March 21, 2017: Immunity
https://www.readbyqxmd.com/read/28302626/sting-irf3-triggers-endothelial-inflammation-in-response-to-free-fatty-acid-induced-mitochondrial-damage-in-diet-induced-obesity
#14
Yun Mao, Wei Luo, Lin Zhang, Weiwei Wu, Liangshuai Yuan, Hao Xu, Juhee Song, Keigi Fujiwara, Jun-Ichi Abe, Scott A LeMaire, Xing Li Wang, Ying H Shen
OBJECTIVE: Metabolic stress in obesity induces endothelial inflammation and activation, which initiates adipose tissue inflammation, insulin resistance, and cardiovascular diseases. However, the mechanisms underlying endothelial inflammation induction are not completely understood. Stimulator of interferon genes (STING) is an important molecule in immunity and inflammation. In the present study, we sought to determine the role of STING in palmitic acid-induced endothelial activation/inflammation...
March 16, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28296273/cyclic-di-gmp-signaling-meets-extracellular-polysaccharide-synthesis-in-bacillus-subtilis
#15
Jan Kampf, Jörg Stülke
In order to resist harmful environmental conditions, many bacteria form multicellular aggregates called biofilms. In these biofilms, they protect themselves in a self-produced matrix consisting of extracellular polysaccharides, proteins, and DNA. In many bacteria, biofilm formation is stimulated in the presence of the second messenger cyclic di-GMP. In this issue of Environmental Microbiology Reports, Bedrunka and Graumann have studied matrix production by the proteins encoded in the Bacillus subtilis ydaJKLMN operon...
March 13, 2017: Environmental Microbiology Reports
https://www.readbyqxmd.com/read/28294213/towards-artificial-methanogenesis-biosynthesis-of-the-fe-hydrogenase-cofactor-and-characterization-of-the-semi-synthetic-hydrogenase
#16
Liping Bai, Takashi Fujishiro, Gangfeng Huang, Jürgen Koch, Atsushi Takabayashi, Makio Yokono, Ayumi Tanaka, Tao Xu, Xile Hu, Ulrich Ermler, Seigo Shima
The greenhouse gas and energy carrier methane is produced on Earth mainly by methanogenic archaea. In the hydrogenotrophic methanogenic pathway the reduction of one CO2 to one methane molecule requires four molecules of H2 containing eight electrons. Four of the electrons from two H2 are supplied for reduction of an electron carrier F420, which is catalyzed by F420-reducing [NiFe]-hydrogenase under nickel-sufficient conditions. The same reaction is catalysed under nickel-limiting conditions by [Fe]-hydrogenase coupled with a reaction catalyzed by F420-dependent methylene tetrahydromethanopterin dehydrogenase...
March 15, 2017: Faraday Discussions
https://www.readbyqxmd.com/read/28287600/defined-and-scalable-generation-of-hepatocyte-like-cells-from-human-pluripotent-stem-cells
#17
Yu Wang, Sharmin Alhaque, Kate Cameron, Jose Meseguer-Ripolles, Baltasar Lucendo-Villarin, Hassan Rashidi, David C Hay
Human pluripotent stem cells (hPSCs) possess great value for biomedical research. hPSCs can be scaled and differentiated to all cell types found in the human body. The differentiation of hPSCs to human hepatocyte-like cells (HLCs) has been extensively studied, and efficient differentiation protocols have been established. The combination of extracellular matrix and biological stimuli, including growth factors, cytokines, and small molecules, have made it possible to generate HLCs that resemble primary human hepatocytes...
March 2, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28284763/validation-of-a-two-dimensional-liquid-chromatography-method-for-quality-control-testing-of-pharmaceutical-materials
#18
Samuel H Yang, Jenny Wang, Kelly Zhang
Despite the advantages of 2D-LC, there is currently little to no work in demonstrating the suitability of these 2D-LC methods for use in a quality control (QC) environment for good manufacturing practice (GMP) tests. This lack of information becomes more critical as the availability of commercial 2D-LC instrumentation has significantly increased, and more testing facilities begin to acquire these 2D-LC capabilities. It is increasingly important that the transferability of developed 2D-LC methods be assessed in terms of reproducibility, robustness and performance across different laboratories worldwide...
March 1, 2017: Journal of Chromatography. A
https://www.readbyqxmd.com/read/28284029/shared-function-and-moonlighting-proteins-in-molybdenum-cofactor-biosynthesis
#19
Silke Leimkühler
The biosynthesis of the molybdenum cofactor (Moco) is a highly conserved pathway in bacteria, archaea and eukaryotes. The molybdenum atom in Moco containing enzymes is coordinated to the dithiolene group of a tricyclic pyranopterin monophosphate cofactor. The biosynthesis of Moco can be divided into three conserved steps, with a fourth one present only in bacteria and archaea: 1) formation of cyclic pyranopterin monophosphate, 2) formation of molybdopterin (MPT), 3) insertion of molybdenum into MPT to form Mo-MPT, and 4) additional modification of Mo-MPT in bacteria with the attachment of a GMP or CMP nucleotide, forming the dinucleotide variants of Moco...
March 11, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/28282490/gene-augmentation-therapy-for-a-missense-substitution-in-the-cgmp-binding-domain-of-ovine-cnga3-gene-restores-vision-in-day-blind-sheep
#20
Elisha Gootwine, Mazen Abu-Siam, Alexey Obolensky, Alex Rosov, Hen Honig, Tali Nitzan, Andrey Shirak, Raaya Ezra-Elia, Esther Yamin, Eyal Banin, Edward Averbukh, William W Hauswirth, Ron Ofri, Eyal Seroussi
Purpose: Applying CNGA3 gene augmentation therapy to cure a novel causative mutation underlying achromatopsia (ACHM) in sheep. Methods: Impaired vision that spontaneously appeared in newborn lambs was characterized by behavioral, electroretinographic (ERG), and histologic techniques. Deep-sequencing reads of an affected lamb and an unaffected lamb were compared within conserved genomic regions orthologous to human genes involved in similar visual impairment. Observed nonsynonymous amino acid substitutions were classified by their deleteriousness score...
March 1, 2017: Investigative Ophthalmology & Visual Science
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