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https://www.readbyqxmd.com/read/28449351/long-term-plasticity-of-corticostriatal-synapses-is-modulated-by-pathway-specific-co-release-of-opioids-through-kappa-opioid-receptors
#1
Sarah L Hawes, Armando G Salinas, David M Lovinger, Kim T Blackwell
Synaptic plasticity in striatum adjusts behaviour adaptively during skill learning, or maladaptively in the case of addiction. Just as dopamine plays a critical role in synaptic plasticity underlying normal skill learning and addiction, endogenous and exogenous opiates also modulate learning and addiction-related striatal plasticity. Though the role of opioid receptors in long-term depression in striatum has been characterized, their effect on long-term potentiation (LTP) remains unknown. In particular, direct pathway (Dopamine D1 Receptor containing; D1R) - spiny projection neurons (SPNs) co-release the opioid neuropeptide dynorphin, which acts at presynaptic kappa opioid receptors (KORs) on dopaminergic afferents and can negatively regulate dopamine release...
April 27, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28448874/regulation-and-roles-of-cd26-dppiv-in-hematopoiesis-and-diseases
#2
REVIEW
Zeynab Aliyari Serej, Abbas Ebrahimi Kalan, Ahmad Mehdipour, Hojjatollah Nozad Charoudeh
Dipeptidyl peptidase IV (DPPIV),(1) on the surface of certain cells, where it is also referred to as CD26, is involved in a vast majority of biological and pathological processes. CD26/DPPIV function contributes to cancer and tumor metastasis as well as inhibition of its expression which alters the expression of immune response-related genes. CD26/DPPIV is a widely distributed multifunctional integral membrane and secreted protein that is defined as early predictive biomarker in HIV, cancer and autoimmunity diseases like diabetes and multiple sclerosis...
April 24, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28448495/dysregulation-of-inf2-mediated-mitochondrial-fission-in-spop-mutated-prostate-cancer
#3
Xiaofeng Jin, Jie Wang, Kun Gao, Pingzhao Zhang, Longfang Yao, Yan Tang, Lisha Tang, Jian Ma, Jiantao Xiao, Enceng Zhang, Jie Zhu, Bin Zhang, Shi-Min Zhao, Yao Li, Shancheng Ren, Haojie Huang, Long Yu, Chenji Wang
Next-generation sequencing of the exome and genome of prostate cancers has identified numerous genetic alternations. SPOP (Speckle-type POZ Protein) was one of the most frequently mutated genes in primary prostate cancer, suggesting SPOP is a potential driver of prostate cancer development and progression. However, how SPOP mutations contribute to prostate cancer pathogenesis remains poorly understood. SPOP acts as an adaptor protein of the CUL3-RBX1 E3 ubiquitin ligase complex that generally recruits substrates for ubiquitination and subsequent degradation...
April 27, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28448128/total-chemical-synthesis-and-folding-of-all-l-and-all-d-variants-of-oncogenic-kras-g12v
#4
Adam Marc Levinson, John H McGee, Andrew G Roberts, Gardner Creech, Ting Wang, Michael T Peterson, Ronald C Hendrickson, Gregory L Verdine, Samuel J Danishefsky
The Ras proteins are essential GTPases involved in the regulation of cell proliferation and survival. Mutated oncogenic forms of Ras alter effector binding and innate GTPase activity, leading to deregulation of downstream signal transduction. Mutated forms of Ras are involved in approximately 30% of human cancers. Despite decades of effort to develop direct Ras inhibitors, Ras has long been considered 'undruggable' due to its high affinity for GTP and its lack of hydrophobic binding pockets. Herein, we report a total chemical synthesis of all-L- and all-D-amino acid biotinylated variants of oncogenic mutant KRas(G12V)...
April 27, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28447750/biological-effects-of-bone-marrow-mesenchymal-stem-cells-on-hepatitis-b-virus-in%C3%A2-vitro
#5
Wei-Ping Zheng, Bo-Ya Zhang, Zhong-Yang Shen, Ming-Li Yin, Yi Cao, Hong-Li Song
The aim of the present study was to explore the effects of co‑culturing bone marrow‑derived mesenchymal stem cells (BM-MSCs) cultured with hepatitis B virus (HBV)‑infected lymphocytes in vitro. BM‑MSCs and lymphocytes from Brown Norway rats were obtained from the bone marrow and spleen, respectively. Rats were divided into the following five experimental groups: Group 1, splenic lymphocytes (SLCs); group 2, HepG2.2.15 cells; group 3, BM‑MSCs + HepG2.2.15 cells; group 4, SLCs + HepG2.2.15 cells; and group 5, SLCs + BM‑MSCs + HepG2...
March 15, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28447721/clinical-significance-of-inflammatory-cytokine-and-chemokine-expression-in-hand-foot-and-mouth-disease
#6
Ping Shao, Xiaoxin Wu, Hongbo Li, Zhigang Wu, Zongxin Yang, Hangping Yao
The present study examined the relationship between cytokine and chemokine expression and the clinical presentation of hand, foot and mouth disease (HFMD), which is currently unclear. The present study involved 28 patients with mild HFMD, 44 patients with severe HFMD and 26 healthy children. Venous blood was tested for cytokine [interleukin (IL)‑4, IL‑12, IL‑18, tumor necrosis factor‑α (TNF‑α), interferon‑γ (IFN‑γ)] and chemokine expression [IL‑8, regulated on activation, normal T cell expressed and secreted (RANTES), monocyte chemoattractant protein‑1 (MCP‑1) and IFN-γ-inducible protein‑10 (IP‑10)]...
March 15, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28447543/human-egf-derived-direct-and-reverse-short-linear-motifs-conformational-dynamics-insight-into-the-receptor-binding-residues
#7
Nurbubu T Moldogazieva, Konstantin V Shaitan, Mikhail Yu Antonov, Innokenty M Mokhosoev, Olga V Levtsova, Аlexander A Terentiev
Short linear motifs (SLiMs) have been recognized to perform diverse functions in a variety of regulatory proteins through the involvement in protein-protein interactions, signal transduction, cell cycle regulation, protein secretion, etc. However, detailed molecular mechanisms underlying their functions including roles of definite amino acid residues remain obscure. In our previous studies, we demonstrated that conformational dynamics of amino acid residues in oligopeptides derived from regulatory proteins such as alpha-fetoprotein (AFP), carcino-embryonic antigen (CEA) and pregnancy specific β1-glycoproteins (PSGs) contributes greatly to their biological activities...
April 27, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/28447025/metabolic-cooperation-and-competition-in-the-tumor-microenvironment-implications-for-therapy
#8
REVIEW
Seema Gupta, Amrita Roy, Bilikere S Dwarakanath
The tumor microenvironment (TME) is an ensemble of non-tumor cells comprising fibroblasts, cells of the immune system, and endothelial cells, besides various soluble secretory factors from all cellular components (including tumor cells). The TME forms a pro-tumorigenic cocoon around the tumor cells where reprogramming of the metabolism occurs in tumor and non-tumor cells that underlies the nature of interactions as well as competitions ensuring steady supply of nutrients and anapleoretic molecules for the tumor cells that fuels its growth even under hypoxic conditions...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28446981/role-of-cxc-group-chemokines-in-lung-cancer-development-and-progression
#9
Artjoms Spaks
BACKGROUND: Clinical and translational research on lung cancer patients undergoing surgical treatment can provide valuable scientific data and unique opportunity to study tumor microenvironment. CXC chemokines, which are members of a big family of cytokines, are undoubtedly involved in tumor growth regulation and metastasizing pathways. For better understanding of CXC chemokine involvement in the process of carcinogenesis we have studied the cohort of early stage non-small cell lung cancer patients undergoing surgery with curative intent...
April 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28446907/regulation-and-molecular-basis-of-environmental-muropeptide-uptake-and-utilization-in-fastidious-oral-anaerobe-tannerella-forsythia
#10
Angela Ruscitto, Kiyonobu Honma, Vamsee M Veeramachineni, Kiyoshi Nishikawa, Graham P Stafford, Ashu Sharma
Tannerella forsythia is a Gram-negative oral anaerobe associated with periodontitis. This bacterium is auxotrophic for the peptidoglycan amino sugar N-acetylmuramic (MurNAc) and likely relies on scavenging peptidoglycan fragments (muropeptides) released by cohabiting bacteria during their cell wall recycling. Many Gram-negative bacteria utilize an inner membrane permease, AmpG, to transport peptidoglycan fragments into their cytoplasm. In the T. forsythia genome, the Tanf_08365 ORF has been identified as a homolog of AmpG permease...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28446880/shifts-in-the-gut-microbiota-composition-due-to-depleted-bone-marrow-beta-adrenergic-signaling-are-associated-with-suppressed-inflammatory-transcriptional-networks-in-the-mouse-colon
#11
Tao Yang, Niousha Ahmari, Jordan T Schmidt, Ty Redler, Rebeca Arocha, Kevin Pacholec, Kacy L Magee, Wendi Malphurs, Jennifer L Owen, Gregory A Krane, Eric Li, Gary P Wang, Thomas W Vickroy, Mohan K Raizada, Christopher J Martyniuk, Jasenka Zubcevic
The brain-gut axis plays a critical role in the regulation of different diseases, many of which are characterized by sympathetic dysregulation. However, a direct link between sympathetic dysregulation and gut dysbiosis remains to be illustrated. Bone marrow (BM)-derived immune cells continuously interact with the gut microbiota to maintain homeostasis in the host. Their function is largely dependent upon the sympathetic nervous system acting via adrenergic receptors present on the BM immune cells. In this study, we utilized a novel chimera mouse that lacks the expression of BM beta1/2 adrenergic receptors (b1/2-ARs) to investigate the role of the sympathetic drive to the BM in gut and microbiota homeostasis...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28446786/how-and-why-do-t-cells-and-their-derived-cytokines-affect-the-injured-and-healthy-brain
#12
REVIEW
Anthony J Filiano, Sachin P Gadani, Jonathan Kipnis
The evolution of adaptive immunity provides enhanced defence against specific pathogens, as well as homeostatic immune surveillance of all tissues. Despite being 'immune privileged', the CNS uses the assistance of the immune system in physiological and pathological states. In this Opinion article, we discuss the influence of adaptive immunity on recovery after CNS injury and on cognitive and social brain function. We further extend a hypothesis that the pro-social effects of interferon-regulated genes were initially exploited by pathogens to increase host-host transmission, and that these genes were later recycled by the host to form part of an immune defence programme...
April 27, 2017: Nature Reviews. Neuroscience
https://www.readbyqxmd.com/read/28446640/ref-1-ape1-as-transcriptional-regulator-and-novel-therapeutic-target-in-pediatric-t-cell-leukemia
#13
Jixin Ding, Melissa L Fishel, April M Reed, Erin McAdams, Magdalena Czader, Angelo A Cardoso, Mark R Kelley
The increasing characterization of childhood acute lymphoblastic leukemia (ALL) has led to the identification of multiple molecular targets, but have yet to translate into more effective targeted therapies, particularly for high-risk, relapsed T-cell ALL. Searching for master regulators controlling multiple signaling pathways in T-ALL, we investigated the multi-functional protein redox factor-1 (Ref-1/APE1), which acts as a signaling "node" by exerting redox regulatory control of transcription factors important in leukemia...
April 26, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28446616/early-immune-responses-are-independent-of-rgc-dysfunction-in-glaucoma-with-complement-component-c3-being-protective
#14
Jeffrey M Harder, Catherine E Braine, Pete A Williams, Xianjun Zhu, Katharine H MacNicoll, Gregory L Sousa, Rebecca A Buchanan, Richard S Smith, Richard T Libby, Gareth R Howell, Simon W M John
Various immune response pathways are altered during early, predegenerative stages of glaucoma; however, whether the early immune responses occur secondarily to or independently of neuronal dysfunction is unclear. To investigate this relationship, we used the Wld(s) allele, which protects from axon dysfunction. We demonstrate that DBA/2J.Wld(s) mice develop high intraocular pressure (IOP) but are protected from retinal ganglion cell (RGC) dysfunction and neuroglial changes that otherwise occur early in DBA/2J glaucoma...
April 26, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28446598/the-histone-variant-h2a-z-promotes-efficient-cotranscriptional-splicing-in-s-cerevisiae
#15
Lauren T Neves, Stephen Douglass, Roberto Spreafico, Srivats Venkataramanan, Tracy L Kress, Tracy L Johnson
In eukaryotes, a dynamic ribonucleic protein machine known as the spliceosome catalyzes the removal of introns from premessenger RNA (pre-mRNA). Recent studies show the processes of RNA synthesis and RNA processing to be spatio-temporally coordinated, indicating that RNA splicing takes place in the context of chromatin. H2A.Z is a highly conserved histone variant of the canonical histone H2A. In Saccharomyces cerevisiae, H2A.Z is deposited into chromatin by the SWR-C complex, is found near the 5' ends of protein-coding genes, and has been implicated in transcription regulation...
April 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/28446591/nfat5-sensitive-orai1-expression-and-store-operated-ca-2-entry-in-megakaryocytes
#16
Itishri Sahu, Lisann Pelzl, Basma Sukkar, Hajar Fakhri, Tamer Al-Maghout, Hang Cao, Stefan Hauser, Ravi Gutti, Meinrad Gawaz, Florian Lang
The transcription factor NFAT5 is up-regulated in several clinical disorders including dehydration. NFAT5-sensitive genes include serum and glucocorticoid-inducible kinase (SGK)-1. The kinase is a powerful regulator of Orai1, a Ca(2+)-channel accomplishing store-operated Ca(2+)-entry (SOCE). Orai1 is stimulated after intracellular store depletion by the Ca(2+) sensors stromal interaction molecule (STIM)-1, or STIM2, or both. In the present study, we explored whether nuclear factor of activated T cell (NFAT)-5 influences Ca(2+)-signaling in megakaryocytes...
April 26, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28446589/antifibrotic-effects-of-cyclosporine-a-on-tgf-%C3%AE-1-treated-lung-fibroblasts-and-lungs-from-bleomycin-treated-mice-role-of-hypoxia-inducible-factor-1%C3%AE
#17
Risa Yamazaki, Yoshitoshi Kasuya, Tetsuo Fujita, Hiroki Umezawa, Madoka Yanagihara, Hiroyuki Nakamura, Ichiro Yoshino, Koichiro Tatsumi, Toshihiko Murayama
Idiopathic pulmonary fibrosis (IPF) is a chronic lung disorder that is characterized by aberrant tissue remodeling and the formation of fibroblastic foci that are composed of fibrogenic myofibroblasts. TGF-β1 is one of the factors that are responsible for fibrosis as it promotes fibroblast to myofibroblast differentiation (FMD) and is associated with up-regulation of α-smooth muscle actin. Therefore, inhibition of FMD may represent an effective strategy for the treatment of IPF. Here, we describe the treatment of human lung fibroblasts (WI-38 and HFL-1 cells) with cyclosporine A (CsA), which reduces TGF-β1-induced FMD via degradation of hypoxia-inducible factor-1α (HIF-1α)...
April 26, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28446226/xenotransplantation-of-interferon-gamma-pretreated-clumps-of-a-human-mesenchymal-stem-cell-extracellular-matrix-complex-induces-mouse-calvarial-bone-regeneration
#18
Kei Takeshita, Souta Motoike, Mikihito Kajiya, Nao Komatsu, Manabu Takewaki, Kazuhisa Ouhara, Tomoyuki Iwata, Katsuhiro Takeda, Noriyoshi Mizuno, Tsuyoshi Fujita, Hidemi Kurihara
BACKGROUND: Three-dimensional cultured clumps of a mesenchymal stem cell (MSC)/extracellular matrix (ECM) complex (C-MSC) consists of cells and self-produced ECM. C-MSC can regulate the cellular function in vitro and induce successful bone regeneration using ECM as a cell scaffold. Potentiating the immunomodulatory capacity of C-MSCs, which can ameliorate the allo-specific immune response, may be helpful in developing beneficial "off-the-shelf" cell therapy for tissue regeneration. It is well reported that interferon (IFN)-γ stimulates the immunosuppressive properties of MSC via upregulation of the immunomodulatory enzyme IDO...
April 26, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28446208/calgizzarin-s100a11-a-novel-inflammatory-mediator-associated-with-disease-activity-of-rheumatoid-arthritis
#19
Lucie Andrés Cerezo, Barbora Šumová, Klára Prajzlerová, David Veigl, Dres Damgaard, Claus Henrik Nielsen, Karel Pavelka, Jiří Vencovský, Ladislav Šenolt
BACKGROUND: Calgizzarin (S100A11) is a member of the S100 protein family that acts in different tumors by regulating a number of biologic functions. Recent data suggest its association with low-grade inflammation in osteoarthritis (OA). The aim of our study is to compare S100A11 expression in the synovial tissues, synovial fluid and serum of patients with rheumatoid arthritis (RA) and osteoarthritis (OA) and to characterize the potential association between S100A11 and disease activity...
April 26, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28445989/tmprss2-erg-gene-fusion-variants-induce-tgf-%C3%AE-signaling-and-epithelial-to-mesenchymal-transition-in-human-prostate-cancer-cells
#20
Leonie Ratz, Mark Laible, Lukasz A Kacprzyk, Stephanie M Wittig-Blaich, Yanis Tolstov, Stefan Duensing, Peter Altevogt, Sabine M Klauck, Holger Sültmann
TMPRSS2:ERG (T/E) gene fusions are present in approximately 50% of all prostate cancer (PCa) cases. The expression of fusion mRNAs from distinct T/E variants is associated with clinicopathological parameters, while the underlying molecular processes remain unclear. We characterized the molecular mechanisms and functional implications caused by doxycycline (Dox)-inducible overexpression of the frequent T/E III and VI fusion variants in LNCaP cells. Induction of T/E expression resulted in increased cellular migratory and invasive potential, and reduced proliferation and accumulation in G1 phase...
April 11, 2017: Oncotarget
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