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https://www.readbyqxmd.com/read/29777705/membrane-proteins-significantly-restrict-exosome-mobility
#1
Mikhail Skliar, Vasiliy S Chernyshev, David M Belnap, German V Sergey, Samer M Al-Hakami, Philip S Bernard, Inge J Stijleman, Rakesh Rachamadugu
Exosomes are membrane nanovesicles implicated in cell-to-cell signaling in which they transfer their molecular cargo from the parent to the recipient cells. This role essentially depends on the exosomes' small size, which is the prerequisite for their rapid migration through the crowded extracellular matrix and into and out of circulation. Here we report much lower exosome mobility than expected from the size of their vesicles, implicate membrane proteins in a substantially impeded rate of migration, and suggest an approach to quantifying the impact...
May 16, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29775585/an-optogenetic-platform-for-real-time-single-cell-interrogation-of-stochastic-transcriptional-regulation
#2
Marc Rullan, Dirk Benzinger, Gregor W Schmidt, Andreas Milias-Argeitis, Mustafa Khammash
Transcription is a highly regulated and inherently stochastic process. The complexity of signal transduction and gene regulation makes it challenging to analyze how the dynamic activity of transcriptional regulators affects stochastic transcription. By combining a fast-acting, photo-regulatable transcription factor with nascent RNA quantification in live cells and an experimental setup for precise spatiotemporal delivery of light inputs, we constructed a platform for the real-time, single-cell interrogation of transcription in Saccharomyces cerevisiae...
May 17, 2018: Molecular Cell
https://www.readbyqxmd.com/read/29775175/hiv-induced-matrix-metalloproteinase-9-activation-through-mitogen-activated-protein-kinase-signalling-promotes-hsv-1-cell-to-cell-spread-in-oral-epithelial-cells
#3
Irna Sufiawati, Sharof M Tugizov
We have shown that cell-free HIV-1 and viral proteins tat and gp120 activate mitogen-activated protein kinases (MAPKs) in tonsil epithelial cells, disrupting their tight and adherens junctions. This causes liberation of the HSV-1 receptor nectin-1 from assembled adherens junctions, leading to promotion of HSV-1 infection and spread. In the present study, we show that HIV-associated activation of MAPK leads to upregulation of transcription factor NF-κB and matrix metalloproteinase-9 (MMP-9). This induces the disruption of tight and adherens junctions, increasing HSV-1 cell-to-cell spread...
May 18, 2018: Journal of General Virology
https://www.readbyqxmd.com/read/29774070/role-of-extracellular-vesicles-in-viral-and-bacterial-infections-pathogenesis-diagnostics-and-therapeutics
#4
REVIEW
Meryl Rodrigues, Jia Fan, Christopher Lyon, Meihua Wan, Ye Hu
Extracellular vesicles (EVs), or exosomes, are nanovesicles of endocytic origin that carry host and pathogen-derived protein, nucleic acid, and lipid cargos. They are secreted by most cell types and play important roles in normal cell-to-cell communications but can also spread pathogen- and host-derived molecules during infections to alter immune responses and pathophysiological processes. New research is beginning to decipher how EVs influence viral and bacterial pathogenesis. In this review, we will describe how EVs influence viral and bacterial pathogenesis by spreading pathogen-derived factors and how they can promote and inhibit the immune response to these pathogens...
2018: Theranostics
https://www.readbyqxmd.com/read/29769580/kv1-3-activity-perturbs-the-homeostatic-properties-of-astrocytes-in-glioma
#5
Alfonso Grimaldi, Giuseppina D'Alessandro, Maria Amalia Di Castro, Clotilde Lauro, Vikrant Singh, Francesca Pagani, Luigi Sforna, Francesca Grassi, Silvia Di Angelantonio, Luigi Catacuzzeno, Heike Wulff, Cristina Limatola, Myriam Catalano
Glial cells actively maintain the homeostasis of brain parenchyma, regulating neuronal excitability and preserving the physiological composition of the extracellular milieu. Under pathological conditions, some functions of glial cells could be compromised, exacerbating the neurotoxic processes. We investigated if the homeostatic activities of astrocytes and microglia could be modulated by the voltage-gated K+ channel Kv1.3. To this end we used in vitro and in vivo systems to model cell-to-cell interactions in tumoral conditions, using a specific inhibitor of Kv1...
May 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29768214/noise-in-the-vertebrate-segmentation-clock-is-boosted-by-time-delays-but-tamed-by-notch-signaling
#6
Sevdenur Keskin, Gnanapackiam S Devakanmalai, Soo Bin Kwon, Ha T Vu, Qiyuan Hong, Yin Yeng Lee, Mohammad Soltani, Abhyudai Singh, Ahmet Ay, Ertuğrul M Özbudak
Taming cell-to-cell variability in gene expression is critical for precise pattern formation during embryonic development. To investigate the source and buffering mechanism of expression variability, we studied a biological clock, the vertebrate segmentation clock, controlling the precise spatiotemporal patterning of the vertebral column. By counting single transcripts of segmentation clock genes in zebrafish, we show that clock genes have low RNA amplitudes and expression variability is primarily driven by gene extrinsic sources, which is suppressed by Notch signaling...
May 15, 2018: Cell Reports
https://www.readbyqxmd.com/read/29767404/carrier-cells-for-delivery-of-oncolytic-measles-virus-into-tumors-determinants-of-efficient-loading
#7
Chun Xu, Mao Xia, Gang Meng, Chunyan Li, Aiqin Jiang, Jiwu Wei
Oncolytic measles virus (OMV) is a promising antitumor agent. However, the presence of anti-measles neutralizing antibodies (NAbs) against the hemagglutinin (H) protein of OMV is a major barrier to the therapeutic application of OMV in clinical practice. In order to overcome this challenge, specific types of cells have been used as carriers for OMV. Differential loading strategies appear to result in different therapeutic outcomes; despite this, only few studies have reported practical ex vivo loading strategies required for effective treatment...
May 16, 2018: Virologica Sinica
https://www.readbyqxmd.com/read/29767267/hdac-inhibitors-trichostatin-a-and-valproic-acid-increase-e%C3%A2-cadherin-and-vimentin-expression-but-inhibit-migration-and-invasion-of-cholangiocarcinoma-cells
#8
Joon Ho Wang, Eun Jeoung Lee, Meiying Ji, Seon Mee Park
The effects of histone deacetylase (HDAC) inhibitors on epithelial-mesenchymal transition (EMT) differ in various cancers. E‑cadherin is a cell‑to‑cell adhesion protein, whereas accumulation of vimentin is related to the development of the spindle shape of the mesenchymal cell phenotype. We investigated the EMT phenotypes of human cholangiocellular carcinoma HuCC‑T1, JCK and SNU‑1079 cell lines. To this end, we measured the expression of E‑cadherin or zonula occludens (ZO)‑1 and vimentin, epithelial and mesenchymal cell markers, respectively, using real‑time reverse transcription‑polymerase chain reaction, western blotting, and immunofluorescence microscopy following treatment with trichostatin A (TSA, 200 nM) or valproic acid (VPA, 0...
May 16, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29765544/comparison-of-infectivity-and-spread-between-hsv-1-and-hsv-2-based-oncolytic-viruses-on-tumor-cells-with-different-receptor-expression-profiles
#9
Xinping Fu, Lihua Tao, Pin-Yi Wang, Timothy P Cripe, Xiaoliu Zhang
Herpes simplex virus (HSV) is one of the many viruses that have been modified or adapted for oncolytic purposes. There are two serotypes of HSV, HSV-1 and HSV-2. The majority of oncolytic HSVs, including T-VEC which has recently been approved by the US Food and Drug Administration (FDA) for clinical use in treating late stage melanoma patients, are derived from HSV-1. Recently, we and others have developed several HSV-2 based oncolytic viruses. During our in vitro characterization of oncolytic viruses developed from both serotypes (Baco-1 from HSV-1 and FusOn-H2 from HSV-2), we noticed there is a subpopulation of cancer cells in which both viruses could infect but only FusOn-H2 could spread from cell to cell on monolayers...
April 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29765007/from-intra-to-extracellular-vesicles-extracellular-vesicles-in-developmental-signalling
#10
REVIEW
Ana-Citlali Gradilla, Eléanor Simon, Gustavo Aguilar, Isabel Guerrero
Signalling from cell-to-cell is fundamental for determining differentiation and patterning. This communication can occur between adjacent and distant cells. Extracellular vesicles (EVs) are membrane-based structures thought to facilitate the long-distance movement of signalling molecules. EVs have recently been found to allow the transport of two major developmental signalling pathways: Hedgehog and Wnt. These signalling molecules undergo crucial post-translational lipid modifications, which anchor them to membranes and impede their free release into the extracellular space...
May 15, 2018: Essays in Biochemistry
https://www.readbyqxmd.com/read/29764944/recon-dependent-inflammation-in-hepatocytes-enhances-listeria-monocytogenes-cell-to-cell-spread
#11
Adelle P McFarland, Thomas P Burke, Alexie A Carletti, Rochelle C Glover, Hannah Tabakh, Matthew D Welch, Joshua J Woodward
The oxidoreductase RECON is a high-affinity cytosolic sensor of bacterium-derived cyclic dinucleotides (CDNs). CDN binding inhibits RECON's enzymatic activity and subsequently promotes inflammation. In this study, we sought to characterize the effects of RECON on the infection cycle of the intracellular bacterium Listeria monocytogenes , which secretes cyclic di-AMP (c-di-AMP) into the cytosol of infected host cells. Here, we report that during infection of RECON-deficient hepatocytes, which exhibit hyperinflammatory responses, L...
May 15, 2018: MBio
https://www.readbyqxmd.com/read/29763730/virtual-screening-of-plant-compounds-and-nonsteroidal-anti-inflammatory-drugs-for-inhibition-of-quorum-sensing-and-biofilm-formation-in-salmonella
#12
Felipe Alves de Almeida, Erika Lorena Giraldo Vargas, Deisy Guimarães Carneiro, Uelinton Manoel Pinto, Maria Cristina Dantas Vanetti
Salmonella belongs to the Enterobacteriaceae family which is widely distributed in the environment due to its adaptive capacity to stress conditions. In addition, Salmonella is able to perform a type of cell-to-cell communication called quorum sensing, which leads to differential gene expression. The quorum sensing system mediated by AI-1, acyl homoserine lactones (AHLs), is incomplete in Salmonella because the luxI homolog gene, which encodes for AI-1 synthase, is missing in the genome. However, a homologue of LuxR, known as SdiA, is present and allows the detection of signaling molecules produced by other species of bacteria, leading to regulation of gene expression, mainly related to virulence and biofilm formation...
May 12, 2018: Microbial Pathogenesis
https://www.readbyqxmd.com/read/29762484/crispr-cas9-mutagenesis-of-ul21-in-multiple-strains-of-herpes-simplex-virus-reveals-differential-requirements-for-pul21-in-viral-replication
#13
Renée L Finnen, Bruce W Banfield
Studies from multiple laboratories using different strains or species of herpes simplex virus (HSV) with deletions in UL21 have yielded conflicting results regarding the necessity of pUL21 in HSV infection. To resolve this discrepancy, we utilized CRISPR/Cas9 mutagenesis to isolate pUL21 deficient viruses in multiple HSV backgrounds, and performed a side-by-side comparison of the cell-to-cell spread and replication phenotypes of these viruses. These analyses confirmed previous studies implicating the involvement of pUL21 in cell-to-cell spread of HSV...
May 15, 2018: Viruses
https://www.readbyqxmd.com/read/29762139/biophysical-constraints-determine-the-selection-of-phenotypic-fluctuations-during-directed-evolution
#14
Hong-Yan Shih, Harry Mickalide, David T Fraebel, Nigel D Goldenfeld, Seppe Kuehn
Phenotypes of individuals in a population of organisms are not fixed. Phenotypic fluctuations, which describe temporal variation of the phenotype of an individual or individual-to-individual variation across a population, are present in populations from microbes to higher animals. Phenotypic fluctuations can provide a basis for adaptation and be the target of selection. Here we present a theoretical and experimental investigation of the fate of phenotypic fluctuations in directed evolution experiments where phenotypes are subject to constraints...
May 15, 2018: Physical Biology
https://www.readbyqxmd.com/read/29761205/cellular-mechanisms-responsible-for-cell-to-cell-spreading-of-prions
#15
REVIEW
Didier Vilette, Josquin Courte, Jean Michel Peyrin, Laurent Coudert, Laurent Schaeffer, Olivier Andréoletti, Pascal Leblanc
Prions are infectious agents that cause fatal neurodegenerative diseases. Current evidence indicates that they are essentially composed of an abnormally folded protein (PrPSc ). These abnormal aggregated PrPSc species multiply in infected cells by recruiting and converting the host PrPC protein into new PrPSc . How prions move from cell to cell and progressively spread across the infected tissue is of crucial importance and may provide experimental opportunity to delay the progression of the disease. In infected cells, different mechanisms have been identified, including release of infectious extracellular vesicles and intercellular transfer of PrPSc -containing organelles through tunneling nanotubes...
May 14, 2018: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29760424/parental-haplotype-specific-single-cell-transcriptomics-reveal-incomplete-epigenetic-reprogramming-in-human-female-germ-cells
#16
Ábel Vértesy, Wibowo Arindrarto, Matthias S Roost, Björn Reinius, Vanessa Torrens-Juaneda, Monika Bialecka, Ioannis Moustakas, Yavuz Ariyurek, Ewart Kuijk, Hailiang Mei, Rickard Sandberg, Alexander van Oudenaarden, Susana M Chuva de Sousa Lopes
In contrast to mouse, human female germ cells develop asynchronously. Germ cells transition to meiosis, erase genomic imprints, and reactivate the X chromosome. It is unknown if these events all appear asynchronously, and how they relate to each other. Here we combine exome sequencing of human fetal and maternal tissues with single-cell RNA-sequencing of five donors. We reconstruct full parental haplotypes and quantify changes in parental allele-specific expression, genome-wide. First we distinguish primordial germ cells (PGC), pre-meiotic, and meiotic transcriptional stages...
May 14, 2018: Nature Communications
https://www.readbyqxmd.com/read/29760292/-targeting-transcellular-transport-of-%C3%AE-synuclein-for-developing-disease-modifying-therapies-for-synucleinopathy
#17
Takafumi Hasegawa
Parkinson's disease (PD) is the second most common neurodegenerative disorder and it is characterized by progressive physical disability along with a variety of non-motor symptoms. Drugs that replenish dopamine can partly alleviate the motor symptoms; however, they do not cure the disease itself. Therefore, there is an urgent need for disease modifying therapies that would delay or prevent neurodegeneration. Increasing evidence suggests that α-synuclein, a key molecule in PD, is secreted into the extracellular environment and can be transported from cell-to-cell, thereby affecting the physiological state of the neighboring cells in a prion-like manner...
May 2018: Brain and Nerve, Shinkei Kenkyū No Shinpo
https://www.readbyqxmd.com/read/29759982/expression-variation-and-covariation-impair-analog-and-enable-binary-signaling-control
#18
Kyle M Kovary, Brooks Taylor, Michael L Zhao, Mary N Teruel
Due to noise in the synthesis and degradation of proteins, the concentrations of individual vertebrate signaling proteins were estimated to vary with a coefficient of variation (CV) of approximately 25% between cells. Such high variation is beneficial for population-level regulation of cell functions but abolishes accurate single-cell signal transmission. Here, we measure cell-to-cell variability of relative protein abundance using quantitative proteomics of individual Xenopus laevis eggs and cultured human cells and show that variation is typically much lower, in the range of 5-15%, compatible with accurate single-cell transmission...
May 14, 2018: Molecular Systems Biology
https://www.readbyqxmd.com/read/29758054/effect-of-fusion-protein-cleavage-site-sequence-on-generation-of-a-genotype-vii-newcastle-disease-virus-vaccine
#19
Vinoth K Manoharan, Berin P Varghese, Anandan Paldurai, Siba K Samal
Newcastle disease (ND) causes severe economic loss to poultry industry worldwide. Frequent outbreaks of ND in commercial chickens vaccinated with live vaccines suggest a need to develop improved vaccines that are genetically matched against circulating Newcastle disease virus (NDV) strains. In this study, the fusion protein cleavage site (FPCS) sequence of NDV strain Banjarmasin/010 (Banj), a genotype VII NDV, was individually modified using primer mutagenesis to those of avian paramyxovirus (APMV) serotypes 2, 7 and 8 and compared with the recombinant Banjarmasin (rBanj) with avirulent NDV LaSota cleavage site (rBanj-LaSota)...
2018: PloS One
https://www.readbyqxmd.com/read/29752311/myeloid-derived-suppressor-cells-impair-b-cell-responses-in-lung-cancer-through-il-7-and-stat5
#20
Yong Wang, Cara C Schafer, Kenneth P Hough, Sultan Tousif, Steven R Duncan, John F Kearney, Selvarangan Ponnazhagan, Hui-Chen Hsu, Jessy S Deshane
Myeloid-derived suppressor cells (MDSCs) are known suppressors of antitumor immunity, affecting amino acid metabolism and T cell function in the tumor microenvironment. However, it is unknown whether MDSCs regulate B cell responses during tumor progression. Using a syngeneic mouse model of lung cancer, we show reduction in percentages and absolute numbers of B cell subsets including pro-, pre-, and mature B cells in the bone marrow (BM) of tumor-bearing mice. The kinetics of this impaired B cell response correlated with the progressive infiltration of MDSCs...
May 11, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
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