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https://www.readbyqxmd.com/read/28641092/nuclear-mechanotransduction-sensing-the-force-from-within
#1
REVIEW
Avathamsa Athirasala, Nivi Hirsch, Amnon Buxboim
The cell nucleus is a hallmark of eukaryotic evolution, where gene expression is regulated and the genome is replicated and repaired. Yet, in addition to complex molecular processes, the nucleus has also evolved to serve physical tasks that utilize its optical and mechanical properties. Nuclear mechanotransduction of externally applied forces and extracellular stiffness is facilitated by the physical connectivity of the extracellular environment, the cytoskeleton and the nucleoskeletal matrix of lamins and chromatin...
June 19, 2017: Current Opinion in Cell Biology
https://www.readbyqxmd.com/read/28641070/elmo-proteins-transduce-g-protein-coupled-receptor-signal-to-control-reorganization-of-actin-cytoskeleton-in-chemotaxis-of-eukaryotic-cells
#2
Xuehua Xu, Tian Jin
Chemotaxis, which is chemoattractant-guided directional cell migration, plays major roles in recruitment of neutrophils, the metastasis of cancer cells, and the development of the model organism Dictyostelium discoideum. These cells share remarkable similarities in the signaling pathways by which they control chemotaxis. They all use a G protein-coupled receptor (GPCR)-mediated signal transduction pathway to sense the chemotactic gradient to guide cell migration. Diverse chemokines activate Rac through conserved GPCR signaling pathways...
June 22, 2017: Small GTPases
https://www.readbyqxmd.com/read/28640953/overview-of-transgenic-mouse-models-of-myeloproliferative-neoplasms-mpns
#3
Andrew Dunbar, Abbas Nazir, Ross Levine
Myeloproliferative neoplasms (MPNs) are a class of hematologic diseases characterized by aberrant proliferation of one or more myeloid lineages and progressive bone marrow fibrosis. In 2005, seminal work by multiple groups identified the JAK2V617F mutation in a significant fraction of MPN patients. Since that time, murine models of JAK2V617F have greatly enhanced the understanding of the role of aberrant JAK-STAT signaling in MPN pathogenesis and have provided an in vivo pre-clinical platform that can be used to develop novel therapies...
June 22, 2017: Current Protocols in Pharmacology
https://www.readbyqxmd.com/read/28640952/label-free-dynamic-mass-redistribution-and-bio-impedance-methods-for-drug-discovery
#4
Manuel Grundmann
Label-free biosensors are increasingly employed in drug discovery. Cell-based biosensors provide valuable insights into the biological consequences of exposing cells and tissues to chemical agents and the underlying molecular mechanisms associated with these effects. Optical biosensors based on the detection of dynamic mass redistribution (DMR) and impedance biosensors using cellular dielectric spectroscopy (CDS) capture changes of the cytoskeleton of living cells in real time. Because signal transduction correlates with changes in cell morphology, DMR and CDS biosensors are exquisitely suited for recording integrated cell responses in an unbiased, yet pathway-specific manner without the use of labels that may interfere with cell function...
June 22, 2017: Current Protocols in Pharmacology
https://www.readbyqxmd.com/read/28640929/modulation-of-tumor-microenvironment-by-chemopreventive-natural-products
#5
REVIEW
Sin-Aye Park, Young-Joon Surh
The tumor microenvironment provides a niche in which cancer cells and their surrounding stromal cells reside and in which their interactions occur. The cross talk between cancer and stromal cells in the tumor microenvironment promotes many biological processes to support cancer cell growth, invasion, angiogenesis, and metastasis. Recently, not only cancer cells but also multiple types of surrounding stromal cells, including endothelial cells, immune cells, and fibroblasts in the tumor microenvironment, have been recognized to be attractive targets for reducing resistance to anticancer therapy and tumor recurrence...
June 22, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/28640891/baculoviral-delivery-of-crispr-cas9-facilitates-efficient-genome-editing-in-human-cells
#6
Sanne Hindriksen, Arne J Bramer, My Anh Truong, Martijn J M Vromans, Jasmin B Post, Ingrid Verlaan-Klink, Hugo J Snippert, Susanne M A Lens, Michael A Hadders
The CRISPR/Cas9 system is a highly effective tool for genome editing. Key to robust genome editing is the efficient delivery of the CRISPR/Cas9 machinery. Viral delivery systems are efficient vehicles for the transduction of foreign genes but commonly used viral vectors suffer from a limited capacity in the genetic information they can carry. Baculovirus however is capable of carrying large exogenous DNA fragments. Here we investigate the use of baculoviral vectors as a delivery vehicle for CRISPR/Cas9 based genome-editing tools...
2017: PloS One
https://www.readbyqxmd.com/read/28640691/the-nesprin-cytoskeleton-interface-probed-directly-on-single-nuclei-is-a-mechanically-rich-system
#7
Daniel A Balikov, Sonia K Brady, Ung Hyun Ko, Jennifer H Shin, Jose M de Pereda, Arnoud Sonnenberg, Hak-Joon Sung, Matthew J Lang
The cytoskeleton provides structure and plays an important role in cellular function such as migration, resisting compression forces, and transport. The cytoskeleton also reacts to physical cues such as fluid shear stress or extracellular matrix remodeling by reorganizing filament associations, most commonly focal adhesions and cell-cell cadherin junctions. These mechanical stimuli can result in genome-level changes, and the physical connection of the cytoskeleton to the nucleus provides an optimal conduit for signal transduction by interfacing with nuclear envelope proteins, called nesprins, within the LINC (linker of the nucleus to the cytoskeleton) complex...
June 22, 2017: Nucleus
https://www.readbyqxmd.com/read/28637716/modulation-of-plasma-metabolite-biomarkers-of-mapk-pathway-with-the-mek-inhibitor-ro4987655-pharmacodynamic-and-predictive-potential-in-metastatic-melanoma
#8
Joo Ern Ang, Akos Pal, Yasmin J Asad, Alan T Henley, Melanie Valenti, Gary Box, Alexis de Haven Brandon, Victoria Revell, Debra J Skene, Miro Venturi, Ruediger Rueger, Valerie Meresse, Suzanne A Eccles, Johann S de Bono, Stanley B Kaye, Paul Workman, Udai Banerji, Florence I Raynaud
<p>MAPK pathway activation is frequently observed in human malignancies, including melanoma, and is associated with sensitivity to MEK inhibition and changes in cellular metabolism. Using quantitative mass spectrometry-based metabolomics, we identified in preclinical models 21 plasma metabolites including amino acids, propionylcarnitine, phosphatidylcholines and sphingomyelins that were significantly altered in two B-RAF mutant melanoma xenografts and that were reversed following a single dose of the potent and selective MEK inhibitor RO4987655...
June 21, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28636944/transduction-of-repetitive-mechanical-stimuli-by-piezo1-and-piezo2-ion-channels
#9
Amanda H Lewis, Alisa F Cui, Malcolm F McDonald, Jörg Grandl
Several cell types experience repetitive mechanical stimuli, including vein endothelial cells during pulsating blood flow, inner ear hair cells upon sound exposure, and skin cells and their innervating dorsal root ganglion (DRG) neurons when sweeping across a textured surface or touching a vibrating object. While mechanosensitive Piezo ion channels have been clearly implicated in sensing static touch, their roles in transducing repetitive stimulations are less clear. Here, we perform electrophysiological recordings of heterologously expressed mouse Piezo1 and Piezo2 responding to repetitive mechanical stimulations...
June 20, 2017: Cell Reports
https://www.readbyqxmd.com/read/28636454/anticancer-potential-of-sanguinarine-for-various-human-malignancies
#10
Iman W Achkar, Fatima Mraiche, Ramzi M Mohammad, Shahab Uddin
Sanguinarine (Sang) - a benzophenanthridine alkaloid extracted from Sanguinaria canadensis - exhibits antioxidant, anti-inflammatory, proapoptotic and growth inhibitory activities on tumor cells of various cancer types as established by in vivo and in vitro studies. Although the underlying mechanism of Sang antitumor activity is yet to be fully elucidated, Sang has displayed multiple biological effects, which remain to suggest its possible use in plant-derived treatments of human malignancies. This review covers the anticancer abilities of Sang including inhibition of aberrantly activated signal transduction pathways, induction of cell death and inhibition of cancer cell proliferation...
June 21, 2017: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/28636424/fluid-shear-stress-regulates-hepg2-cell-migration-though-time-dependent-integrin-signaling-cascade
#11
Hongchi Yu, Yang Shen, Jingsi Jin, Yingying Zhang, Tang Feng, Xiaoheng Liu
Hepatocellular carcinoma (HCC) is a subtype of malignant liver cancer with poor prognosis and limited treatment options. It is noteworthy that mechanical forces in tumor microenvironment play a pivotal role in mediating the behaviors and functions of tumor cells. As an instrumental type of mechanical forces in vivo, fluid shear stress (FSS) has been reported having potent physiologic and pathologic effects on cancer progression. However, the time-dependent mechanochemical transduction in HCC induced by FSS remains unclear...
June 21, 2017: Cell Adhesion & Migration
https://www.readbyqxmd.com/read/28636127/nonmediated-label-free-based-detection-of-cardiovascular-biomarker-in-a-biological-sample
#12
JuKyung Lee, SuRyon Shin, Anna Desalvo, Geonhui Lee, Jeong Yoon Lee, Alessandro Polini, Sukyoung Chae, Hobin Jeong, Jonghan Kim, Haksoo Choi, HeaYeon Lee
Direct electrochemical (EC) monitoring in a cell culture medium without electron transporter as called mediator is attractive topic in vitro organoid based on chip with frequently and long-time monitoring since it can avoid to its disadvantage as stability, toxicity. Here, direct monitoring with nonmediator is demonstrated based on impedance spectroscopy under the culture medium in order to overcome the limitation of mediator. The applicability of EC monitoring is shown by detecting alpha-1-anti trypsin (A1AT) which is known as biomarkers for cardiac damage and is widely chosen in organoid cardiac cell-based chip...
June 21, 2017: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/28635516/concentration-of-uhcl1-in-the-serum-of-children-with-acute-appendicitis-before-and-after-surgery-and-its-correlation-with-crp-and-prealbumin
#13
Ewa Matuszczak, Marzena Tylicka, Wojciech Dębek, Anna Tokarzewicz, Ewa Gorodkiewicz, Adam Hermanowicz
Ubiquitin-mediated protein degradation plays a crucial role in various cellular processes, including signal transduction, cell differentiation, and stress response. Ubiquitin C-terminal hydrolase 1 (UCHL1) is a unique deubiquitinating enzyme that has both hydrolase and ligase activities. The aim of this study was the determination of UCHL1 concentration in serum of children with appendicitis, before and after the surgery. MATERIAL AND METHODS: 42 children with acute appendicitis, who were managed at the Pediatric Surgery Department, between 2013 and 2014, were randomly included into the study (age 9 months up to 14 years, mean age 2...
February 27, 2017: Journal of Investigative Surgery: the Official Journal of the Academy of Surgical Research
https://www.readbyqxmd.com/read/28634758/a-general-double-library-selex-strategy-for-aptamer-selection-using-unmodified-nonimmobilized-targets
#14
Kyung Hyun Lee, Huaqiang Zeng
Aptamer discovery for unmodified nonimmobilized targets has been constantly presenting itself as a significant challenge to the research community. We demonstrate here a novel double library (DL) SELEX strategy and its usefulness and generality toward discovering both ssDNA- and RNA-based aptamers with nanomolar binding affinities toward unmodified targets of both small (e.g., doxycycline) and large (e.g., VEGF165) sizes. The same selection strategy further allows for concurrent selection of an aptamer pair, recognizing discrete epitopes on the same protein, from the same selection cycles for the sandwich aptamer pair-based biosensor development (e...
June 20, 2017: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/28634425/a-transcriptional-regulatory-role-for-the-membrane-type-1-matrix-metalloproteinase-in-carcinogen-induced-inflammasome-gene-expression
#15
Samuel Sheehy, Borhane Annabi
Signal-transducing functions driven by the cytoplasmic domain of membrane type-1 matrix metalloproteinase (MT1-MMP) are believed to regulate many inflammation-associated cancer cell functions including migration, proliferation, and survival. Aside from upregulation of the inflammation biomarker cyclooxygenase-2 (COX-2) expression, MT1-MMP's role in relaying intracellular signals triggered by extracellular pro-inflammatory cues remains poorly understood. Here, we triggered inflammation in HT1080 fibrosarcoma cells with phorbol-12-myristate-13-acetate (PMA), an inducer of COX-2 and of MT1-MMP...
2017: Gene Regulation and Systems Biology
https://www.readbyqxmd.com/read/28634382/expression-of-p301l-htau-in-mouse-mec-induces-hippocampus-dependent-memory-deficit
#16
Xinghua Liu, Kuan Zeng, Mengzhu Li, Qun Wang, Rong Liu, Bin Zhang, Jian-Zhi Wang, Xiji Shu, Xiaochuan Wang
Intracellular accumulation of abnormally phosphorylated tau in different types of neurons is a pathological characteristic of Alzheimer's disease (AD). While tau modification and associated neuronal loss and hypometabolism start in the entorhinal cortex (EC) in early AD patients, the mechanism by which mutant P301L hTau leads to dementia is not fully elucidated. Here, we studied the effects of P301L hTau transduction in the medial EC (MEC) of mice on tau phosphorylation and accumulation, and cognitive deficit...
June 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28634231/hyperactivity-of-the-arabidopsis-cryptochrome-cry1-l407f-mutant-is-caused-by-a-structural-alteration-close-to-the-cry1-atp-binding-sit
#17
Christian Orth, Nils Niemann, Lars Hennig, Lars-Oliver Essen, Alfred Batschauer
Plant cryptochromes (cry) act as UV-A/blue light receptors. The prototype, Arabidopsis thaliana cry1, regulates several light responses during the life cycle, including de-etiolation, and is also involved in regulating flowering time. The cry1 photocycle is initiated by light absorption by its FAD chromophore, which is most likely fully oxidized (FADox) in the dark state and photoreduced to the neutral flavin semiquinone (FADH(o)) in its lit state. Cryptochromes lack the DNA-repair activity of the closely related DNA photolyases, but retain the ability to bind nucleotides such as ATP...
June 20, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28634138/intracellular-and-transdermal-protein-delivery-mediated-by-non-covalent-interactions-with-a-synthetic-guanidine-rich-molecular-carrier
#18
Jungkyun Im, Sanket Das, Dongjun Jeong, Chang-Jin Kim, Hyun-Suk Lim, Ki Hean Kim, Sung-Kee Chung
The impermeability of the cell plasma membrane is one of the major barriers for protein transduction into mammalian cells, and it also limits the use of proteins as therapeutic agents. Protein transduction has usually been achieved based on certain invasive processes or cell penetrating peptides (CPP). Herein we report our study in which a synthetic guanidine-rich molecular carrier is used as a delivery vector for intracellular and transdermal delivery of proteins. First a sorbitol-based molecular carrier having 8 guanidine units (Sor-G8) was synthesized, and then was simply mixed with a cargo protein of varying sizes to form the non-covalent complex of carrier-cargo proteins...
June 17, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28634059/a-pumpkin-polysaccharide-induces-apoptosis-by-inhibiting-the-jak2-stat3-pathway-in-human-hepatoma-hepg2-cells
#19
Weixi Shen, Chunhong Chen, Yuanyuan Guan, Xiaowei Song, Yinghua Jin, Jingfang Wang, Yu Hu, Tao Xin, Qiuying Jiang, Li Zhong
The purpose of this study is to investigate the effect of a purified polysaccharide (PPPF) from pumpkin fruit on the Janus activated kinase (JAK)/signal transducer and activator of transcription (STAT) signaling during apoptotic process. The results showed that PPPF or STAT3 siRNA inhibits the cell growth of HepG2 cells via induction of apoptosis. Moreover, PPPF is able to suppress both constitutive and IL-6-induced phosphorylation of STAT3 (on Tyr705) and subsequent nuclear translocation in cancer cells. Such inhibition is found to be achieved through down-regulation of constitutive phosphorylation of JAK2, but not JAk1, c-Src, ERK1/2, and Akt, which means STAT3 tyrosine phosphorylation in HepG2 cells following PPPF treatment is associated with a reduction in JAK2 activity...
June 17, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28634045/egfr-egfrviii-remodels-the-cytoskeleton-via-epigenetic-silencing-of-ajap1-in-glioma-cells
#20
Chao Yang, Yan-Sheng Li, Qi-Xue Wang, Kai Huang, Jian-Wei Wei, Yun-Fei Wang, Jun-Hu Zhou, Kai-Kai Yi, Kai-Liang Zhang, Bing-Cong Zhou, Cong Liu, Liang Zeng, Chun-Sheng Kang
EGFR amplification and mutations are the most common oncogenic events in GBM. EGFR overexpression correlates with GBM invasion, but the underlying mechanisms are poorly understood. In a previous study, we showed that AJAP1 is involved in regulating F-actin to inhibit the invasive ability of GBM. In addition, in a GBM cell line, the AJAP1 promoter was highly bound by H3K27me3 and, through bioinformatics analysis, we found that AJAP1 expression was negatively correlated with EGFR. In this study, we found that the pathway downstream of EGFR had a higher activation level in GBM cell lines, which led to excessive tumor suppressor silencing...
June 19, 2017: Cancer Letters
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