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https://www.readbyqxmd.com/read/28813597/synthesis-of-4-azido-n-acetylhexosamine-uridine-diphosphate-donors-clickable-glycosaminoglycans
#1
Xing Zhang, Dixy E Green, Victor L Schultz, Lei Lin, Xiaorui Han, Ruitong Wang, Alexander Yaksic, So Young Kim, Paul L DeAngelis, Robert J Linhardt
Unnatural chemically modified, nucleotide sugars, UDP-4-N3-GlcNAc and UDP-4-N3-GalNAc were synthesized for the first time. These unnatural UDP-sugar products were then tested for incorporation into hyaluronan, heparosan or chondroitin using polysaccharide synthases. The UDP-4-N3-GlcNAc served as a chain termination substrate for hyaluronan or heparosan synthases; a single analog was added to the non-reducing end of the sugar chain and no subsequent elongation was detected. Compared to chemical method to introduce azido groups into polysaccharides, this enzymatic technique provided a "green" approach to access regioselectively azide-functionalized GAGs, which would bring better control of the final structure and composition of these macromolecules...
August 16, 2017: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/28805676/inhibitors-of-deubiquitinating-enzymes-block-hiv-1-replication-and-augment-the-presentation-of-gag-derived-mhc-i-epitopes
#2
Christian Setz, Melanie Friedrich, Pia Rauch, Kirsten Fraedrich, Alina Matthaei, Maximilian Traxdorf, Ulrich Schubert
In recent years it has been well established that two major constituent parts of the ubiquitin proteasome system (UPS)-the proteasome holoenzymes and a number of ubiquitin ligases-play a crucial role, not only in virus replication but also in the regulation of the immunogenicity of human immunodeficiency virus type 1 (HIV-1). However, the role in HIV-1 replication of the third major component, the deubiquitinating enzymes (DUBs), has remained largely unknown. In this study, we show that the DUB-inhibitors (DIs) P22077 and PR-619, specific for the DUBs USP7 and USP47, impair Gag processing and thereby reduce the infectivity of released virions without affecting viral protease activity...
August 12, 2017: Viruses
https://www.readbyqxmd.com/read/28804565/thrombospondin-1-inhibits-ossification-of-tissue-engineered-cartilage-constructed-by-adscs
#3
Aiguo Xie, Jixin Xue, Gan Shen, Lanjun Nie
Cartilage tissue engineering provides a new method in the treatment of cartilage defects, and adipose derived stem cells seem to be an ideal seed cell in cartilage tissue engineering because of its characteristics. However, ossification after in vivo implantation of tissue engineered cartilage remains a challenge. Thrombospondin-1 which has been reported to have an inhibitory effect on angiogenesis, may play an important role in inhibiting the ossification of tissue engineered cartilage constructed by adipose derived stem cells...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28803264/hyaluronan-in-the-experimental-injury-of-the-cartilage-biochemical-action-and-protective-effects
#4
REVIEW
Angela Avenoso, Angela D'Ascola, Michele Scuruchi, Giuseppe Mandraffino, Alberto Calatroni, Antonino Saitta, Salvatore Campo, Giuseppe M Campo
INTRODUCTION: Our knowledge of extracellular matrix (ECM) structure and function has increased enormously over the last decade or so. There is evidence demonstrating that ECM provides signals affecting cell adhesion, shape, migration, proliferation, survival, and differentiation. ECM presents many domains that become active after proteolytic cleavage. These active ECM fragments are called matrikines which play different roles; in particular, they may act as potent inflammatory mediators during cartilage injury...
August 12, 2017: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
https://www.readbyqxmd.com/read/28803113/how-a-decreased-fibrillar-interconnectivity-influences-stiffness-and-swelling-properties-during-early-cartilage-degeneration
#5
Mieke Nickien, Ashvin Thambyah, Neil D Broom
OBJECTIVE: The functional coupling between the fibrillar network and the high-swelling proteoglycans largely determines the mechanical properties of the articular cartilage matrix. The objective of this new study was to show specifically how changes in fibrillar interconnectivity arising from early cartilage degeneration influence transverse stiffness and swelling properties at the tissue level. DESIGN: Radial zone transverse layers of cartilage matrix were obtained from intact and mildly degenerate bovine patellae...
August 3, 2017: Journal of the Mechanical Behavior of Biomedical Materials
https://www.readbyqxmd.com/read/28798857/the-role-of-shear-stress-and-altered-tissue-properties-on-endothelial-to-mesenchymal-transformation-and-tumor-endothelial-cell-interaction
#6
Sara G Mina, Peter Huang, Bruce T Murray, Gretchen J Mahler
Tumor development is influenced by stromal cells in aspects including invasion, growth, angiogenesis, and metastasis. Activated fibroblasts are one group of stromal cells involved in cancer metastasis, and one source of activated fibroblasts is endothelial to mesenchymal transformation (EndMT). EndMT begins when the endothelial cells delaminate from the cell monolayer, lose cell-cell contacts, lose endothelial markers such as vascular endothelial-cadherin (VE-cadherin), gain mesenchymal markers like alpha-smooth muscle actin (α-SMA), and acquire mesenchymal cell-like properties...
July 2017: Biomicrofluidics
https://www.readbyqxmd.com/read/28797020/brief-report-selection-of-hiv-1-variants-with-higher-transmission-potential-by-1-tenofovir-gel-microbicide
#7
Nobubelo K Ngandu, Jonathan M Carlson, Denis R Chopera, Nonkululeko Ndabambi, Quarraisha Abdool Karim, Salim Abdool Karim, Carolyn Williamson
BACKGROUND: Women in the CAPRISA 004 trial assigned to use 1% tenofovir (TFV) microbicide gel, who became HIV-1 infected, had higher viral load set-point and slower antibody avidity maturation compared with placebo participants. We investigated whether TFV gel was selected for viruses with altered genetic characteristics. SETTING: The participants of the CAPRISA 004 trial (n = 28 TFV and 43 placebo) were from KwaZulu-Natal Province, South Africa and were infected with HIV-1 subtype C...
September 1, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/28794041/interferon-inducible-cd169-siglec1-attenuates-anti-hiv-1-effects-of-ifn-%C3%AE
#8
Hisashi Akiyama, Nora-Guadalupe Pina Ramirez, Gregory Gibson, Christopher Kline, Simon Watkins, Zandrea Ambrose, Suryaram Gummuluru
A hallmark of HIV-1 infection in vivo is chronic immune activation concomitant with type I interferon (IFN) production. Although type I IFN induces an antiviral state in many cell types, HIV-1 can replicate in vivo via mechanisms that have remained unclear. We have recently identified a type I IFN-inducible protein CD169 as the HIV-1 attachment factor on dendritic cells (DCs) that can mediate robust infection of CD4(+) T cells in trans. Since CD169 expression on macrophages is also induced by type I IFN, we hypothesized that type I IFN-inducible CD169 could facilitate productive HIV-1 infection in myeloid cells in cis and CD4(+) T cells in trans and thus offset antiviral effects of type I IFN...
August 9, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28794032/recombinant-origins-of-pathogenic-and-nonpathogenic-mouse-gammaretroviruses-of-polytropic-host-range
#9
Devinka Bamunusinghe, Qingping Liu, Ronald Plishka, Michael A Dolan, Matthew Skorski, Andrew J Oler, Venkat R K Yedavalli, Alicia Buckler-White, Janet W Hartley, Christine A Kozak
Ecotropic, xenotropic and polytropic mouse leukemia viruses (E-, X-, P-MLVs) exist in mice as infectious viruses and endogenous retroviruses (ERVs) inserted into mouse chromosomes. All 3 MLV subgroups are linked to leukemogenesis, which involves generation of recombinants with polytropic host range. Although P-MLVs are deemed to be the proximal agents of disease induction, few biologically characterized infectious P-MLVs have been sequenced for comparative analysis. We analyzed the complete genomes of 16 naturally occurring infectious P-MLVs, 12 of which were typed for pathogenic potential...
August 9, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28792472/glycosaminoglycan-interactions-with-chemokines-add-complexity-to-a-complex-system
#10
REVIEW
Amanda E I Proudfoot, Zoë Johnson, Pauline Bonvin, Tracy M Handel
Chemokines have two types of interactions that function cooperatively to control cell migration. Chemokine receptors on migrating cells integrate signals initiated upon chemokine binding to promote cell movement. Interactions with glycosaminoglycans (GAGs) localize chemokines on and near cell surfaces and the extracellular matrix to provide direction to the cell movement. The matrix of interacting chemokine-receptor partners has been known for some time, precise signaling and trafficking properties of many chemokine-receptor pairs have been characterized, and recent structural information has revealed atomic level detail on chemokine-receptor recognition and activation...
August 9, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/28791236/interstitial-cystitis-intravesical-therapy
#11
REVIEW
Tanya Ha, Jie Hua Xu
Interstitial cystitis (IC) is a progressive bladder disorder that presents with symptoms of bladder urgency, frequency and pain. The aetiology of the disease remains uncertain, but it is postulated that there is an initial infective insult which damages the glycosaminoglycan (GAG) layer of the bladder urothelium. This defect allows an influx of ions, particularly potassium, which initiates an inflammatory reaction in the bladder wall, which incites the symptoms described above. Treatment initially involves behavioural and oral medication, with second line being intravesical instillation therapy...
July 2017: Translational Andrology and Urology
https://www.readbyqxmd.com/read/28791233/non-surgical-management-of-recurrent-urinary-tract-infections-in-women
#12
REVIEW
Paul A Bergamin, Anthony J Kiosoglous
One in three women will experience a clinically significant urinary tract infection (UTI) by age twenty-four and almost half will have at least one in their lifetime. Recurrent UTIs (rUTIs) are defined as having greater than two infections in a 6-month period, or three infections over twelve months, with complete resolution for at least two weeks. These may be due to relapse from incomplete treatment (persistence) or re-infection (new source). It may be difficult to distinguish between the two, where the same organism is cultured...
July 2017: Translational Andrology and Urology
https://www.readbyqxmd.com/read/28791001/novel-in-vitro-screening-system-based-on-differential-scanning-fluorimetry-to-search-for-small-molecules-against-the-disassembly-or-assembly-of-hiv-1-capsid-protein
#13
Yasuyuki Miyazaki, Naoya Doi, Takaaki Koma, Akio Adachi, Masako Nomaguchi
Varieties of in vitro systems have been used to study biochemical properties of human immunodeficiency virus Gag-capsid protein (HIV Gag-CA). Recently, we have comparatively characterized HIV-1 and HIV-2 Gag-CA proteins using such technology, and have demonstrated that the NaCl-initiated CA-polymerization in vitro and the stability of CA N-terminal domain as judged by differential scanning fluorimetry (DSF) are inversely correlated. In this study, we found that ZnCl2 works as a competent initiator of the in vitro HIV-1 CA-polymerization at much lower concentrations than those of NaCl frequently used for the polymerization initiation...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28783314/deciphering-the-role-of-sulfonated-unit-in-heparin-mimicking-polymer-to-promote-neural-differentiation-of-escs
#14
Jiehua Lei, Yuqi Yuan, Zhonglin Lyu, Mengmeng Wang, Qi Liu, Hongwei Wang, Lin Yuan, Hong Chen
Glycosaminoglycans (GAGs), especially heparin and heparan sulfate (HS) hold great potential for inducing the neural differentiation of embryonic stem cells (ESCs) and have brought new hope for the treatment of neurological diseases. However, the disadvantages of natural heparin/HS, such as difficulty in isolating with a sufficient amount, highly heterogeneous in structure, the risk of immune responses, have limited their further therapeutic applications. Thus, there is a great demand for stable, controllable and well-defined synthetic alternatives of heparin/HS with more effective biological functions...
August 7, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28780538/optimal-dose-of-succinylcholine-for-laryngeal-mask-airway-insertion-systematic-review-meta-analysis-and-metaregression-of-randomised-control-trials
#15
Alan Hsi-Wen Liao, Yu-Cih Lin, Chyi-Huey Bai, Chien-Yu Chen
OBJECTIVES: To evaluate the optimal dose of succinylcholine for laryngeal mask airway (LMA) insertion and all related morbidities. DESIGN: Systematic review, meta-analysis and metaregression of randomised controlled trials (RCTs). DATA SOURCE AND STUDY ELIGIBILITY CRITERIA: A comprehensive search of RCTs in the PubMed, Embase, the Cochrane Library and the ClinicalTrials.gov registry up to July 2016 and articles that evaluated the use of succinylcholine chloride for LMA insertion were included in the analyses...
August 4, 2017: BMJ Open
https://www.readbyqxmd.com/read/28771176/regulation-of-chemokine-function-the-roles-of-gag-binding-and-post-translational-nitration
#16
REVIEW
Sarah Thompson, Beatriz Martínez-Burgo, Krishna Mohan Sepuru, Krishna Rajarathnam, John A Kirby, Neil S Sheerin, Simi Ali
The primary function of chemokines is to direct the migration of leukocytes to the site of injury during inflammation. The effects of chemokines are modulated by several means, including binding to G-protein coupled receptors (GPCRs), binding to glycosaminoglycans (GAGs), and through post-translational modifications (PTMs). GAGs, present on cell surfaces, bind chemokines released in response to injury. Chemokines bind leukocytes via their GPCRs, which directs migration and contributes to local inflammation...
August 3, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28770943/insights-into-the-role-of-3-o-sulfotransferase-in-heparan-sulfate-biosynthesis
#17
Maria Cecília Zorél Meneghetti, Tarsis Gesteira Ferreira, Alexandre Keiji Tashima, Suely F Chavante, Edwin Alexander Yates, Jian Liu, Helena Bonciani Nader, Marcelo A Lima
3-O-Sulfotransferase enzyme (sHS) from Litopenaeus vannamei was cloned and its substrate specificity was investigated against a number of GAG structures, including modified heparin polysaccharides and model oligosaccharides. For the heparin polysaccharides, derived from porcine intestinal mucosa heparin, sulfate groups were incorporated into glucosamine residues containing both N-sulfated and N-acetylated substitution within the regions of the predominant repeating disaccharide, either I-ANS or I-ANAc. However, the resulting polysaccharides did not stabilize antithrombin, which is correlated with anticoagulant activity...
August 16, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28768877/immunodominance-of-adenovirus-derived-cd8-t-cell-epitopes-interferes-with-the-induction-of-transgene-specific-immunity-in-adenovirus-based-immunization
#18
Dominik Schöne, Camilla Patrizia Hrycak, Sonja Windmann, Dennis Lapuente, Ulf Dittmer, Matthias Tenbusch, Wibke Bayer
Adenovirus (Ad)-based immunization is a popular approach in vaccine development, and Ad-based vectors are renowned for their potential to induce strong CD8(+) T cell responses to the encoded transgene. Surprisingly, we found before in the mouse Friend retrovirus (FV) model that Ad-based immunization did not induce CD8(+) T cell responses to the FV Leader-Gag-derived immunodominant epitope GagL85-93 We show now that induction of GagL85-93-specific CD8(+) T cells was highly effective when Leader-Gag was delivered by plasmid DNA immunization, implying a role for Ad-derived epitopes in mediating unresponsiveness...
August 2, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28768854/presence-of-a-shared-5-leader-sequence-in-ancestral-human-and-mammalian-retroviruses-and-its-transduction-into-feline-leukemia-virus
#19
Junna Kawasaki, Maki Kawamura, Yoshiharu Ohsato, Jumpei Ito, Kazuo Nishigaki
Recombination events induce significant genetic changes, and this process can result in virus genetic diversity or in the generation of novel pathogenicity. We discovered a new recombinant feline leukemia virus (FeLV) gag gene harboring an unrelated insertion, termed the "X-region", which was derived from FcERV-gamma4, a feline endogenous gammaretrovirus. The identified FcERV-gamma4 proviruses have lost their coding capability, but some can express their viral RNA in feline tissues. Although the X-region-carrying recombinant FeLVs appeared to be replication-defective viruses, they were detected in 6...
August 2, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28768193/immunogenetic-profiling-for-gastric-cancers-identifies-sulfated-glycosaminoglycans-as-major-and-functional-b-cell-antigens-in-human-malignancies
#20
Hiroto Katoh, Daisuke Komura, Hiroki Konishi, Ryohei Suzuki, Asami Yamamoto, Miwako Kakiuchi, Reiko Sato, Tetsuo Ushiku, Shogo Yamamoto, Kenji Tatsuno, Takashi Oshima, Sachiyo Nomura, Yasuyuki Seto, Masashi Fukayama, Hiroyuki Aburatani, Shumpei Ishikawa
Recent successes in tumor immunotherapies have highlighted the importance of tumor immunity. However, most of the work conducted to date has been on T cell immunity, while the role of B cell immunity in cancer remains more elusive. In this study, immunogenetic repertoire profiling for tumor-infiltrating B and T cells in gastric cancers was carried out to help reveal the architecture of B cell immunity in cancer. Humoral immunity in cancer was shown to involve oligoclonal expansions of tumor-specific and private B cell repertoires...
August 1, 2017: Cell Reports
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