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https://www.readbyqxmd.com/read/28820395/chemokine-c-x-c-motif-ligand-1-cxcl1-and-chemokine-c-x-c-motif-ligand-2-cxcl2-modulate-the-activity-of-trpv1-ib4-cultured-rat-dorsal-root-ganglia-neurons-upon-short-term-and-acute-application
#1
A F Deftu, A Filippi, K Shibsaki, R O Gheorghe, M Chiritoiu, V Ristoiu
CXCL1 and CXCL2 are two chemokines with 78% homology of their sequence. CXCL1 was associated with atopic dermatitis, a highly pruritic skin disease, but it is not clear what is its mechanism of action, while for CXCL2 there are no data about an association with itch sensitivity. CXCL1 and CXCL2 can modulate TRPV1 receptors, which are one of the most important downstream effectors for itch sensitivity, upon short-term (4 h) or long-term (24 h) incubation, but the data are incomplete. Therefore, the aims of this study were to better characterize the short-term effects of CXCL1 and CXCL2 on TRPV1(+)/IB4(+) dorsal root ganglia neurons known to include nociceptor and itch-sensitive neurons, and to obtain new data about the acute application (12 min) of the two chemokines on the same population of neurons...
June 2017: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/28820312/architecture-of-the-atg2b-wdr45-complex-and-an-aromatic-y-hf-motif-crucial-for-complex-formation
#2
Jing-Xiang Zheng, Yan Li, Yue-He Ding, Jun-Jie Liu, Mei-Jun Zhang, Meng-Qiu Dong, Hong-Wei Wang, Li Yu
PtdIns3P signaling is critical for dynamic membrane remodeling during autophagosome formation. Proteins in the Atg18/WIPI family are PtdIns3P-binding effectors which can form complexes with proteins in the Atg2 family, and both families are essential for macroautophagy/autophagy. However, little is known about the biophysical properties and biological functions of the Atg2-Atg18/WIPI complex as a whole. Here, we demonstrate that an ortholog of yeast Atg18, mammalian WDR45/WIPI4 has a stronger binding capacity for mammalian ATG2A or ATG2B than the other 3 WIPIs...
August 18, 2017: Autophagy
https://www.readbyqxmd.com/read/28820056/involvement-of-cd24-in-multiple-cancer-related-pathways-makes-it-an-interesting-new-target-for-cancer-therapy
#3
Shirin Eyvazi, Bahram Kazemi, Siavoush Dastmalchi, Mojgan Bandehpour
CD24 (cluster of differentiation 24) is a small heavy glycosylated protein, which is overexpressed in many cancer and some cancer stem cells and is associated with the development, invasion, and metastasis of cancer cells. The exact role of CD24 in these processes is not fully understood, however, in this article, it has been tried to present collection of cancer-related mechanisms attributed to CD24. Based on the literature, CD24 dis-regulates different signaling pathways in various cancer cells, including; Src kinases, STAT3, EGFR, Wnt/β-catenin and MAPK...
August 18, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28819653/targeting-cytokines-in-gvhd-therapy
#4
Sandeep Kumar, Hemn Mohammadpour, Xuefang Cao
Transplantation of donor-derived allogeneic hematopoietic cells causes increased survival in patients suffering from various blood cancers and other hematologic and immunologic diseases. However, this health benefit is limited to certain patients. One major complication is graft-versus-host disease (GVHD) that occurs when donor-derived immune cells recognize host cells/tissues as foreign and perpetrate subsequent destruction. Cytokines are a major class of effector molecules that are involved in GVHD pathogenesis...
2017: Journal of Immunology Research and Therapy
https://www.readbyqxmd.com/read/28819302/generation-and-intracellular-trafficking-of-a-polysialic-acid-carrying-fragment-of-the-neural-cell-adhesion-molecule-ncam-to-the-cell-nucleus
#5
Nina Westphal, Gabriele Loers, David Lutz, Thomas Theis, Ralf Kleene, Melitta Schachner
Polysialic acid (PSA) and its major protein carrier, the neural cell adhesion molecule NCAM, play important roles in many nervous system functions during development and in adulthood. Here, we show that a PSA-carrying NCAM fragment is generated at the plasma membrane by matrix metalloproteases and transferred to the cell nucleus via endosomes and the cytoplasm. Generation and nuclear import of this fragment in cultured cerebellar neurons is induced by a function-triggering NCAM antibody and a peptide comprising the effector domain (ED) of myristoylated alanine-rich C kinase substrate (MARCKS) which interacts with PSA within the plane of the plasma membrane...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28819237/disruption-of-the-plant-specific-cfs1-gene-impairs-autophagosome-turnover-and-triggers-eds1-dependent-cell-death
#6
Arpaporn Sutipatanasomboon, Stefanie Herberth, Ellen G Alwood, Heidrun Häweker, Britta Müller, Mojgan Shahriari, Anke Y Zienert, Birger Marin, Silke Robatzek, Gerrit J K Praefcke, Kathryn R Ayscough, Martin Hülskamp, Swen Schellmann
Cell death, autophagy and endosomal sorting contribute to many physiological, developmental and immunological processes in plants. They are mechanistically interconnected and interdependent, but the molecular basis of their mutual regulation has only begun to emerge in plants. Here, we describe the identification and molecular characterization of CELL DEATH RELATED ENDOSOMAL FYVE/SYLF PROTEIN 1 (CFS1). The CFS1 protein interacts with the ENDOSOMAL SORTING COMPLEX REQUIRED FOR TRANSPORT I (ESCRT-I) component ELCH (ELC) and is localized at ESCRT-I-positive late endosomes likely through its PI3P and actin binding SH3YL1 Ysc84/Lsb4p Lsb3p plant FYVE (SYLF) domain...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28819224/the-role-of-rho-gtpases-and-actin-polymerization-during-macrophage-tunneling-nanotube-biogenesis
#7
Samer J Hanna, Kessler McCoy-Simandle, Veronika Miskolci, Peng Guo, Michael Cammer, Louis Hodgson, Dianne Cox
Macrophage interactions with other cells, either locally or at distances, are imperative in both normal and pathological conditions. While soluble means of communication can transmit signals between different cells, it does not account for all long distance macrophage interactions. Recently described tunneling nanotubes (TNTs) are membranous channels that connect cells together and allow for transfer of signals, vesicles, and organelles. However, very little is known about the mechanism by which these structures are formed...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28819174/interleukin-17-receptor-a-il-17ra-as-a-central-regulator-of-the-protective-immune-response-against-giardia
#8
Oonagh Paerewijck, Brecht Maertens, Leentje Dreesen, Frederik Van Meulder, Iris Peelaers, Dariusz Ratman, Robert W Li, Erik Lubberts, Karolien De Bosscher, Peter Geldhof
The protozoan parasite Giardia is a highly prevalent intestinal pathogen with a wide host range. Data obtained in mice, cattle and humans revealed the importance of IL-17A in the development of a protective immune response against Giardia. The aim of this study was to further unravel the protective effector mechanisms triggered by IL-17A following G. muris infection in mice, by an RNA-sequencing approach. C57BL/6 WT and C57BL/6 IL-17RA KO mice were orally infected with G. muris cysts. Three weeks post infection, intestinal tissue samples were collected for RNA-sequencing, with samples from uninfected C57BL/6 WT and C57BL/6 IL-17RA KO animals serving as negative controls...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28819022/%C3%AE-adrenergic-signaling-in-mice-housed-at-standard-temperatures-suppresses-an-effector-phenotype-in-cd8-t-cells-and-undermines-checkpoint-inhibitor-therapy
#9
Mark J Bucsek, Guanxi Qiao, Cameron R MacDonald, Thejaswini Giridharan, Lauren Evans, Brian Niedzwecki, Haichao Liu, Kathleen M Kokolus, Jason W-L Eng, Michelle N Messmer, Kristopher Attwood, Scott I Abrams, Bonnie L Hylander, Elizabeth A Repasky
The immune context of tumors has significant prognostic value and is predictive of responsiveness to several forms of therapy, including immunotherapy. We report here that CD8(+) T cell frequency and functional orientation within the tumor microenvironment is regulated by β2-adrenergic receptor (β-AR) signaling in host immune cells. We used three strategies - physiologic (manipulation of ambient thermal environment), pharmacologic (β-blockers), and genetic (β2-adrenergic receptor knockout mice) to reduce adrenergic stress signaling in two widely studied preclinical mouse tumor models...
August 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/28818997/ccr2-3-utr-functions-as-a-competing-endogenous-rna-to-inhibit-breast-cancer-metastasis
#10
Jinhang Hu, Xiaoman Li, Xinwei Guo, Qianqian Guo, Chenxi Xiang, Zhiting Zhang, Yingying Xing, Tao Xi, Lufeng Zheng
Diverse RNA transcripts acting as competing endogenous RNAs (ceRNAs) can co-regulate each other's expression by competing for shared microRNAs. CCR2 protein, the receptor of CCL2, is implicated in cancer progression. However, our results showed that higher CCR2 mRNA level was remarkably associated with prolonged survival of breast cancer patients. The conflicting results prompt us to study the non-coding function of CCR2 mRNA. We indicated that CCR2 3'UTR inhibited MDA-MB-231 and MCF-7 cells metastasis by repressing EMT in vitro and suppressed breast cancer metastasis in vivo Mechanistically, CCR2 3'UTR modulated RhoGAP protein STARD13 expression via acting as a STARD13 ceRNA in a microRNA-dependent and protein coding-independent manner...
August 17, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28818668/a-bipolar-role-of-the-transcription-factor-erg-for-cnidarian-germ-layer-formation-and-apical-domain-patterning
#11
Aldine R Amiel, Hereroa Johnston, Taylor Chock, Paul Dahlin, Marta Iglesias, Michael Layden, Eric Röttinger, Mark Q Martindale
Germ layer formation and axial patterning are biological processes that are tightly linked during embryonic development of most metazoans. In addition to canonical WNT, it has been proposed that ERK-MAPK signaling is involved in specifying oral as well as aboral territories in cnidarians. However, the effector and the molecular mechanism underlying latter phenomenon is unknown. By screening for potential effectors of ERK-MAPK signaling in both domains, we identified a member of the ETS family of transcription factors, Nverg that is bi-polarily expressed prior to gastrulation...
August 14, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28818311/characterization-of-the-flow-cytometric-assay-for-ex%C3%A2-vivo-monitoring-of-cytotoxicity-mediated-by-antigen-specific-cytotoxic-t-lymphocytes
#12
Akira Takagi, Yutaka Horiuchi, Masanori Matsui
Several non-radioactive methods have widely been utilized to detect antigen-specific cytotoxic T lymphocyte (CTL) responses instead of the classical (51)Cr-release assay. These methods include intracellular cytokine staining, major histocompatibility complex-class I tetramers, and the CD107a mobilization assay. However, they do not directly measure target-cell death. In contrast, several attempts have been made to develop the flow cytometric CTL (FC-CTL) assay for evaluation of cytotoxicity. However, further improvement is necessary for it to become standardized...
August 14, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28818106/morphoproteomics-e6-e7-in-situ-hybridization-and-biomedical-analytics-define-the-etiopathogenesis-of-hpv-associated-oropharyngeal-carcinoma-and-provide-targeted-therapeutic-options
#13
Robert E Brown, Syed Naqvi, Mary F McGuire, Jamie Buryanek, Ron J Karni
BACKGROUND: Human papillomavirus (HPV) has been identified as an etiopathogenetic factor in oropharyngeal squamous cell carcinoma. The HPV E6 and E7 oncogenes are instrumental in promoting proliferation and blocking differentiation leading to tumorigenesis. Although surgical intervention can remove such tumors, the potential for an etiologic field effect with recurrent disease is real. A downstream effector of E7 oncoprotein, enhancer of zeste homolog 2 (EZH2), is known to promote proliferation and to pose a block in differentiation and in turn, could lead to HPV-induced malignant transformation...
August 17, 2017: Journal of Otolaryngology—Head & Neck Surgery
https://www.readbyqxmd.com/read/28817719/t-cell-expression-of-il-18r-and-dr3-is-essential-for-non-cognate-stimulation-of-th1-cells-and-optimal-clearance-of-intracellular-bacteria
#14
Oanh H Pham, Hope O'Donnell, Aymen Al-Shamkhani, Tobias Kerrinnes, Renée M Tsolis, Stephen J McSorley
Th1 cells can be activated by TCR-independent stimuli, but the importance of this pathway in vivo and the precise mechanisms involved require further investigation. Here, we used a simple model of non-cognate Th1 cell stimulation in Salmonella-infected mice to examine these issues. CD4 Th1 cell expression of both IL-18R and DR3 was required for optimal IFN-γ induction in response to non-cognate stimulation, while IL-15R expression was dispensable. Interestingly, effector Th1 cells generated by immunization rather than live infection had lower non-cognate activity despite comparable IL-18R and DR3 expression...
August 17, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28817232/crystal-structure-of-the-melampsora-lini-effector-avrp-reveals-insights-into-a-possible-nuclear-function-and-recognition-by-the-flax-disease-resistance-protein-p
#15
Xiaoxiao Zhang, Nadya Farah, Laura Rolston, Daniel J Ericsson, Ann-Maree Catanzariti, Maud Bernoux, Thomas Ve, Katerina Bendak, Chunhong Chen, Joel P Mackay, Gregory J Lawrence, Adrienne Hardham, Jeffrey G Ellis, Simon J Williams, Peter N Dodds, David A Jones, Bostjan Kobe
The effector protein AvrP is secreted by the flax rust fungal pathogen (Melampsora lini) and recognized specifically by the flax (Linum usitatissimum) P disease resistance protein, leading to effector-triggered immunity. To investigate the biological function of this effector and mechanisms of specific recognition by the P resistance protein, we determined the crystal structure of AvrP. The structure reveals an elongated zinc-finger-like structure with a novel interleaved zinc-binding topology. The residues responsible for zinc binding are conserved in AvrP effector variants and mutations of these motifs result in loss of P-mediated recognition...
August 17, 2017: Molecular Plant Pathology
https://www.readbyqxmd.com/read/28817192/tssa-the-cap-protein-of-the-type-vi-secretion-system-tail
#16
REVIEW
Abdelrahim Zoued, Eric Durand, Yoann G Santin, Laure Journet, Alain Roussel, Christian Cambillau, Eric Cascales
The Type VI secretion system (T6SS) is a multiprotein and mosaic apparatus that delivers protein effectors into prokaryotic or eukaryotic cells. Recent data on the enteroaggregative Escherichia coli (EAEC) T6SS have provided evidence that the TssA protein is a key component during T6SS biogenesis. The T6SS comprises a trans-envelope complex that docks the baseplate, a cytoplasmic complex that represents the assembly platform for the tail. The T6SS tail is structurally, evolutionarily and functionally similar to the contractile tails of bacteriophages...
August 17, 2017: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
https://www.readbyqxmd.com/read/28817118/altered-marginal-zone-and-innate-like-b-cells-in-aged-senescence-accelerated-samp8-mice-with-defective-igg1-responses
#17
Isabel Cortegano, Mercedes Rodríguez, Isabel Martín, Maria Carmen Prado, Carolina Ruíz, Rafael Hortigüela, Mario Alía, Marçal Vilar, Helena Mira, Eva Cano, Mercedes Domínguez, Belén de Andrés, María Luisa Gaspar
Aging has a strong impact on the activity of the immune system, enhancing susceptibility to pathogens and provoking a predominant pre-inflammatory status, whereas dampening responses to vaccines in humans and mice. Here, we demonstrate a loss of marginal zone B lymphocytes (MZ, CD19(+)CD45R(+)CD21(++)CD23(lo)) and a decrease of naive B cells (CD19(+)IgD(+)), whereas there is an enhancement of a CD19(+)CD45R(lo) innate-like B cell population (B1REL) and the so-called aged B cell compartment (ABC, CD45R(+)CD21(lo)CD23(lo)CD5(-)CD11b(-)) in aged senescence-accelerated (SAMP8) mice but not in aged senescence-resistant (SAMR1) mice...
August 17, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28817117/increased-tumor-infiltrating-cd45ra-ccr7-regulatory-t-cell-subset-with-immunosuppressive-properties-foster-gastric-cancer-progress
#18
Fang-Yuan Mao, Hui Kong, Yong-Liang Zhao, Liu-Sheng Peng, Weisan Chen, Jin-Yu Zhang, Ping Cheng, Ting-Ting Wang, Yi-Pin Lv, Yong-Sheng Teng, Xiao-Long Fu, Yu-Gang Liu, Xiao-Long Wu, Chuan-Jie Hao, Nan You, Ping Luo, Pei-Wu Yu, Quan-Ming Zou, Gang Guo, Yuan Zhuang
Regulatory T cells (Tregs) are major components of tumor-infiltrating immune cells with potent immunosuppressive properties in gastric cancer (GC) microenvironment. However, different subsets of the Tregs and their relevance to GC are unknown. Here, we found that patients with GC showed a significantly higher Tregs infiltration in tumors, and CD45RA(-)CCR7(-) Treg subset constituted most tumor-infiltrating Tregs. Tumor-infiltrating CD45RA(-)CCR7(-) Treg subset with an effector/memory phenotype accumulated in tumors and expressed low level of HLA-DR...
August 17, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28816543/mir-541-5p-regulates-lung-fibrosis-by-targeting-cyclic-nucleotide-phosphodiesterase-1a
#19
Liqin Ren, Chunyan Yang, Yongfeng Dou, Renhui Zhan, Yi Sun, Yan Yu
AIM OF THE STUDY: Idiopathic pulmonary fibrosis (IPF) is a lethal human disease with short survival time and few treatment options. In this study, we aim to demonstrate that cyclic nucleotide phosphodiesterase 1A (PDE1A), a Ca2+/calmodulin-stimulating PDE family member, plays a critical role in the induction of fibrosis and angiogenesis in the lung. MATERIALS AND METHODS: To induce pulmonary damage, adult male SD rats were treated with bleomycin in a dose of 6 mg/kg body weight by a single intratracheal instillation...
August 17, 2017: Experimental Lung Research
https://www.readbyqxmd.com/read/28816089/medusa-s-head-the-complement-system-in-traumatic-brain-and-spinal-cord-injury
#20
Francesco Roselli, Ebru Karasu, Clara Volpe, Markus Huber-Lang
Traumatic brain injury (TBI) and Spinal cord injury (SCI) are critical medical conditions and public health problem for which limited therapeutic options are available. Complement cascade is activated after TBI and SCI and the resulting effects have been investigated in gene-knockout and pharmacological models. Multiple experimental studies support a net detrimental role of C3 and C5 activation in the early stages of TBI and SCI. Less firm experimental evidence suggests that, downstream of C3/C5, effector mechanisms including the generation of MAC and direct damage to membranes and neutrophils infiltration may bring about the direct damage of CNS tissue and the enhancement of neuroinflammation...
August 17, 2017: Journal of Neurotrauma
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