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https://www.readbyqxmd.com/read/27923225/integrin-%C3%AE-iib%C3%AE-3-dependent-erk-signaling-is-regulated-by-src-and-rho-kinases-in-both-leu33-and-pro33-polymorphic-isoforms
#1
Khon C Huynh, Thi-Hiep Nguyen, Dinh Chuong Pham, Huong T T Nguyen, Toi Van Vo, Marianna Gyenes, Volker R Stoldt
Platelet integrin αIIbβ3 possesses a Leu/Pro polymorphism at residue 33 (Leu33/HPA-1a or Pro33/HPA-1b). The Pro33 isoform has been suggested to exhibit prothrombotic features. αIIbβ3-expressing CHO (Chinese hamster ovary) cells on immobilized fibrinogen show activation of the MAP kinase family member ERK2, with an enhanced ERK2 activity in Pro33 cells compared to Leu33 cells. In our present work, we examined how the Leu/Pro polymorphism modulates the ERK2 activation stimulated by 2 differently triggered outside-in signalings...
December 7, 2016: Acta Haematologica
https://www.readbyqxmd.com/read/27923070/macrophage-colony-stimulating-factor-derived-from-cd4-t-cells-contributes-to-control-of-a-blood-borne-infection
#2
Mary F Fontana, Gabrielly L de Melo, Chioma Anidi, Rebecca Hamburger, Chris Y Kim, So Youn Lee, Jennifer Pham, Charles C Kim
Dynamic regulation of leukocyte population size and activation state is crucial for an effective immune response. In malaria, Plasmodium parasites elicit robust host expansion of macrophages and monocytes, but the underlying mechanisms remain unclear. Here we show that myeloid expansion during P. chabaudi infection is dependent upon both CD4+ T cells and the cytokine Macrophage Colony Stimulating Factor (MCSF). Single-cell RNA-Seq analysis on antigen-experienced T cells revealed robust expression of Csf1, the gene encoding MCSF, in a sub-population of CD4+ T cells with distinct transcriptional and surface phenotypes...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27923046/mitochondria-and-caspases-tune-nmnat-mediated-stabilization-to-promote-axon-regeneration
#3
Li Chen, Derek M Nye, Michelle C Stone, Alexis T Weiner, Kyle W Gheres, Xin Xiong, Catherine A Collins, Melissa M Rolls
Axon injury can lead to several cell survival responses including increased stability and axon regeneration. Using an accessible Drosophila model system, we investigated the regulation of injury responses and their relationship. Axon injury stabilizes the rest of the cell, including the entire dendrite arbor. After axon injury we found mitochondrial fission in dendrites was upregulated, and that reducing fission increased stabilization or neuroprotection (NP). Thus axon injury seems to both turn on NP, but also dampen it by activating mitochondrial fission...
December 6, 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27923039/natural-variation-in-arabidopsis-cvi-0-accession-reveals-an-important-role-of-mpk12-in-guard-cell-co2-signaling
#4
Liina Jakobson, Lauri Vaahtera, Kadri Tõldsepp, Maris Nuhkat, Cun Wang, Yuh-Shuh Wang, Hanna Hõrak, Ervin Valk, Priit Pechter, Yana Sindarovska, Jing Tang, Chuanlei Xiao, Yang Xu, Ulvi Gerst Talas, Alfonso T García-Sosa, Saijaliisa Kangasjärvi, Uko Maran, Maido Remm, M Rob G Roelfsema, Honghong Hu, Jaakko Kangasjärvi, Mart Loog, Julian I Schroeder, Hannes Kollist, Mikael Brosché
Plant gas exchange is regulated by guard cells that form stomatal pores. Stomatal adjustments are crucial for plant survival; they regulate uptake of CO2 for photosynthesis, loss of water, and entrance of air pollutants such as ozone. We mapped ozone hypersensitivity, more open stomata, and stomatal CO2-insensitivity phenotypes of the Arabidopsis thaliana accession Cvi-0 to a single amino acid substitution in MITOGEN-ACTIVATED PROTEIN (MAP) KINASE 12 (MPK12). In parallel, we showed that stomatal CO2-insensitivity phenotypes of a mutant cis (CO2-insensitive) were caused by a deletion of MPK12...
December 2016: PLoS Biology
https://www.readbyqxmd.com/read/27922937/repurposing-ospemifene-for-potentiating-an-antigen-specific-immune-response
#5
Chiao-Jung Kao, Gregory T Wurz, Yi-Chen Lin, Daniel P Vang, Brian Phong, Michael W DeGregorio
OBJECTIVE: Ospemifene, an estrogen receptor agonist/antagonist approved for the treatment of dyspareunia and vaginal dryness in postmenopausal women, has potential new indications as an immune modulator. The overall objective of the present series of preclinical studies was to evaluate the immunomodulatory activity of ospemifene in combination with a peptide cancer vaccine. METHODS: Immune regulating effects, mechanism of action and structure activity relationships of ospemifene and related compounds were evaluated by examining expression of T-cell activating cytokines in vitro, and antigen-specific immune response and cytotoxic T-lymphocyte activity in vivo...
December 5, 2016: Menopause: the Journal of the North American Menopause Society
https://www.readbyqxmd.com/read/27922761/%C3%AE-6%C3%AE-4-integrin-regulates-the-collective-migration-of-epithelial-cells
#6
Zachary T Colburn, Jonathan C R Jones
α6β4 integrin is localized in a unique punctate distribution at the cell-substratum interface along the leading front of single, front-rear polarized, A549 cells. These puncta are interspersed between focal adhesions and lack association with the actin cytoskeleton. Knockdown of β4 integrin in A549 cells inhibits their directed migration, with knockdown cells exhibiting large focal adhesions and reduced actin dynamics. Despite these changes, the speed of knockdown cells is equivalent to controls cells. Interestingly, in such cells, α6 integrin retains its punctate distribution...
December 6, 2016: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/27922552/novel-use-of-all-trans-retinoic-acid-in-a-model-of-lipopolysaccharide-immunosuppression-to-decrease-the-generation-of-myeloid-derived-suppressor-cells-by-reducing-the-proliferation-of-cd34-precursor-cells
#7
Daiana Martire-Greco, Nahuel Rodriguez-Rodrigues, Luis A Castillo, María Belén Vecchione, Marcelo de Campos-Nebel, Marlina Córdoba Moreno, Roberto Meiss, Mónica Vermeulen, Veronica I Landoni, Gabriela C Fernandez
All-trans-Retinoic Acid (ATRA) is a derivative of vitamin A with anti-proliferative properties. Endotoxin shock and subsequent immunosuppression (IS) by lipopolysaccharide (LPS) stimulates myelopoiesis with expansion of myeloid-derived suppressor cells (MDSC). Since we have previously shown that ATRA reverses the IS state by decreasing functional MDSC, our aim was to investigate if ATRA was able to modulate MDSC generation by regulating myelopoiesis in murine hematopoietic organs. We found that ATRA administration in vivo and in vitro decreased the number of CD34+ precursor cells that were increased in IS mice...
November 25, 2016: Shock
https://www.readbyqxmd.com/read/27922332/effect-of-moderate-and-high-intensity-chronic-exercise-on-the-pancreatic-islet-morphometry-in-healthy-rats-bdnf-receptor-participation
#8
Alberto Jiménez-Maldonado, Adolfo Virgen-Ortiz, Valery Melnikov, Alejandrina Rodríguez-Hernández, Armando Gamboa-Domínguez, Sergio Montero, Jesús Muñiz-Murguía, Mónica Lemus, Elena Roces de Álvarez-Buylla
A B S T R A C T The function and morphology of β-cells is largely dependent on insulin demand. As β-cells cover a bigger cell proportion in pancreas islets, changes of insulin producer cells affect the whole pancreatic islet morphology. Growth factors as the neurotrophins regulate the pancreas physiology, besides; physical exercise increases insulin sensitivity, and further modifies brain derived neurotrophic factor (BDNF) concentration in plasma. The aim of this study was to investigate the effects of chronic exercise (running in a treadmill for eight weeks) intensity on pancreatic islet morphometry in healthy state...
December 6, 2016: Islets
https://www.readbyqxmd.com/read/27922198/dnmt1-modulation-in-chronic-hepatitis-b-patients-and-hypothetic-influence-on-mitochondrial-dna-methylation-status-during-long-term-nucleo-t-side-analogues-therapy
#9
Giordano Madeddu, Silvia Ortu, Giovanni Garrucciu, Ivana Maida, Michela Melis, Alberto Augusto Muredda, Maria Stella Mura, Sergio Babudieri
Inhibition of viral replication is the most important goal in patients with Hepatitis B virus chronic infection (CHB). Currently, five oral nucleo(t)side analogues (NAs), including Lamivudine, Adefovir, Telbivudine, Entecavir and Tenofovir, have been approved for treatment. The widespread use of NAs has also been linked with a progressive growth of unlikely anomaly attributable to mitochondrial dysfunctions, not previously recognized. Here we explore the hypothesis that NAs may cause persistent epigenetic changes during prolonged NAs therapy in CHB patients...
December 6, 2016: Journal of Medical Virology
https://www.readbyqxmd.com/read/27922011/detecting-stoichiometry-of-macromolecular-complexes-in-live-cells-using-fret
#10
Manu Ben-Johny, Daniel N Yue, David T Yue
The stoichiometry of macromolecular interactions is fundamental to cellular signalling yet challenging to detect from living cells. Fluorescence resonance energy transfer (FRET) is a powerful phenomenon for characterizing close-range interactions whereby a donor fluorophore transfers energy to a closely juxtaposed acceptor. Recognizing that FRET measured from the acceptor's perspective reports a related but distinct quantity versus the donor, we utilize the ratiometric comparison of the two to obtain the stoichiometry of a complex...
December 6, 2016: Nature Communications
https://www.readbyqxmd.com/read/27922008/defining-functional-interactions-during-biogenesis-of-epithelial-junctions
#11
J C Erasmus, S Bruche, L Pizarro, N Maimari, T Pogglioli, C Tomlinson, J Lees, I Zalivina, A Wheeler, A Alberts, A Russo, V M M Braga
In spite of extensive recent progress, a comprehensive understanding of how actin cytoskeleton remodelling supports stable junctions remains to be established. Here we design a platform that integrates actin functions with optimized phenotypic clustering and identify new cytoskeletal proteins, their functional hierarchy and pathways that modulate E-cadherin adhesion. Depletion of EEF1A, an actin bundling protein, increases E-cadherin levels at junctions without a corresponding reinforcement of cell-cell contacts...
December 6, 2016: Nature Communications
https://www.readbyqxmd.com/read/27921303/eosinophils-from-eosinophilic-oesophagitis-patients-have-t-cell-suppressive-capacity-and-express-foxp3
#12
C Lingblom, J Wallander, M Ingelsten, H Bergquist, M Bove, R Saalman, A Welin, C Wennerås
Eosinophilic esophagitis (EoE) is an antigen-driven T cell-mediated chronic inflammatory disease where food and environmental antigens are thought to have a role. Human eosinophils express the immunoregulatory protein galectin-10 and have T cell suppressive capacity similar to regulatory T cells (Tregs ). We hypothesized that one function of eosinophils in EoE might be to regulate the T cell-driven inflammation in the oesophagus. This was tested by evaluating the suppressive capacity of eosinophils isolated from the blood of adult EoE patients in a mixed lymphocyte reaction...
November 5, 2016: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/27921272/bcl6-locus-is-hypermethylated-in-angioimmunoblastic-t-cell-lymphoma
#13
Shoko Nishizawa, Mamiko Sakata-Yanagimoto, Keiichiro Hattori, Hideharu Muto, Tran Nguyen, Koji Izutsu, Kenichi Yoshida, Seishi Ogawa, Naoya Nakamura, Shigeru Chiba
BCL6, a master transcription factor for differentiation of follicular helper T (TFH) cells, is highly expressed in angioimmunoblastic T-cell lymphoma (AITL) and peripheral T-cell lymphomas (PTCL) containing tumor cells with TFH features. TET2, encoding an epigenetic regulator, is frequently mutated in AITL/PTCL. We previously reported that Tet2 knockdown mice developed T-cell lymphomas with TFH features. Hypermethylation of the Bcl6 locus followed by BCL6 upregulation was thought to be the key event for lymphoma development in mice...
December 5, 2016: International Journal of Hematology
https://www.readbyqxmd.com/read/27920775/human-papillomavirus-downregulates-the-expression-of-ifitm1-and-ripk3-to-escape-from-ifn%C3%AE-and-tnf%C3%AE-mediated-antiproliferative-effects-and-necroptosis
#14
Wenbo Ma, Bart Tummers, Edith M G van Esch, Renske Goedemans, Cornelis J M Melief, Craig Meyers, Judith M Boer, Sjoerd H van der Burg
The clearance of a high-risk human papillomavirus (hrHPV) infection takes time and requires the local presence of a strong type 1 cytokine T cell response, suggesting that hrHPV has evolved mechanisms to resist this immune attack. Using an unique system for non, newly, and persistent hrHPV infection, we show that hrHPV infection renders keratinocytes (KCs) resistant to the antiproliferative- and necroptosis-inducing effects of IFNγ and TNFα. HrHPV-impaired necroptosis was associated with the upregulation of several methyltransferases, including EZH2, and the downregulation of RIPK3 expression...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27920277/the%C3%A2-diffuse%C3%A2-reduction%C3%A2-of%C3%A2-spleen%C3%A2-density-%C3%A2-an%C3%A2-indicator%C3%A2-of%C3%A2-severe%C3%A2-acute%C3%A2-pancreatitis
#15
Guangdong Shao, Yanmei Zhou, Zengfu Song, Maitao Jiang, Xiaoqian Wang, Xiangren Jin, Bei Sun, Xuewei Bai
BACKGROUND: We observed that acute pancreatitis (AP) was associated with diffuse reduction of spleen density (DROSD) in some patients. Furthermore, the condition of these patients was more serious, and the potential relationship between DROSD and structural and functional injury of the spleen remained unclear. Therefore, we performed a preliminary exploration of these factors. METHODS: We analysed pertinent clinical data for AP patients with normal spleen density (control group) and for those with DROSD (reduction group) at the First Affiliated Hospital of Harbin Medical University (2013...
December 5, 2016: Bioscience Reports
https://www.readbyqxmd.com/read/27920254/casein-kinase-2-is-linked-to-stress-granule-dynamics-through-phosphorylation-of-the-stress-granule-nucleating-protein-g3bp1
#16
Lucas C Reineke, Wei-Chih Tsai, Antrix Jain, Jason T Kaelber, Sung Yun Jung, Richard E Lloyd
Stress granules are large macromolecular aggregates that contain translation initiation complexes and mRNAs. Stress granule formation coincides with translational repression, and stress granules actively signal to mediate cell fate decisions by a) signaling to the translation apparatus to maintain translational repression, b) mount various transcriptional responses including innate immunity, and c) to repress apoptosis. Previous work showed G3BP1 is phosphorylated at serine 149, which regulates G3BP1 oligomerization, stress granule assembly, and RNase activity intrinsic to G3BP1...
December 5, 2016: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/27920151/lin28-is-induced-in-primed-embryonic-stem-cells-and-regulates-let-7-independent-events
#17
Silvia Parisi, Fabiana Passaro, Luigi Russo, Anna Musto, Angelica Navarra, Simona Romano, Giuseppe Petrosino, Tommaso Russo
Lin28 RNA-binding proteins play important roles in pluripotent stem cells, but the regulation of their expression and the mechanisms underlying their functions are still not definitively understood. Here we address the above-mentioned issues in the first steps of mouse embryonic stem cell (ESC) differentiation. We observed that the expression of Lin28 genes is transiently induced soon after the exit of ESCs from the naive ground state and that this induction is due to the Hmga2-dependent engagement of Otx2 with enhancers present at both Lin28 gene loci...
December 5, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27920086/a-role-for-mitotic-bookmarking-of-sox2-in-pluripotency-and-differentiation
#18
Cédric Deluz, Elias T Friman, Daniel Strebinger, Alexander Benke, Mahé Raccaud, Andrea Callegari, Marion Leleu, Suliana Manley, David M Suter
Mitotic bookmarking transcription factors remain bound to chromosomes during mitosis and were proposed to regulate phenotypic maintenance of stem and progenitor cells at the mitosis-to-G1 (M-G1) transition. However, mitotic bookmarking remains largely unexplored in most stem cell types, and its functional relevance for cell fate decisions remains unclear. Here we screened for mitotic chromosome binding within the pluripotency network of embryonic stem (ES) cells and show that SOX2 and OCT4 remain bound to mitotic chromatin through their respective DNA-binding domains...
December 5, 2016: Genes & Development
https://www.readbyqxmd.com/read/27919908/targeting-the-pd-1-pd-l1-axis-in-multiple-myeloma-a-dream-or-a-reality
#19
Jacalyn Rosenblatt, David Avigan
PD-1/PD-L1 pathway is a negative regulator of immune activation that is up-regulated in multiple myeloma and is a critical component of the immunosuppressive tumor microenvironment. Expression is increased in advanced disease and in the presence of bone marrow stromal cells. PD-1/PD-L1 blockade is associated with tumor regression in several malignancies but single agent activity is limited in myeloma patients. Combination therapy involving strategies to expand myeloma specific T cells and T cell activation via PD-1/PD-L1 blockade are currently being explored...
December 5, 2016: Blood
https://www.readbyqxmd.com/read/27919436/complement-in-basic-processes-of-the-cell
#20
Anaïs Jiménez-Reinoso, Ana V Marin, José R Regueiro
The complement system is reemerging in the last few years not only as key element of innate immunity against pathogens, but also as a main regulator of local adaptive responses, affecting dendritic cells as well as T and B lymphocytes. We review data showing that leucocytes are capable of significant autocrine synthesis of complement proteins, and express a large range of complement receptors, which in turn regulate their differentiation and effector functions while cross talking with other innate receptors such as Toll-like receptors...
December 2, 2016: Molecular Immunology
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