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https://www.readbyqxmd.com/read/29790112/an-automated-high-throughput-method-for-interpreting-the-tandem-mass-spectra-of-glycosaminoglycans
#1
Jiana Duan, I Jonathan Amster
The biological interactions between glycosaminoglycans (GAGs) and other biomolecules are heavily influenced by structural features of the glycan. The structure of GAGs can be assigned using tandem mass spectrometry (MS2 ), but analysis of these data, to date, requires manually interpretation, a slow process that presents a bottleneck to the broader deployment of this approach to solving biologically relevant problems. Automated interpretation remains a challenge, as GAG biosynthesis is not template-driven, and therefore, one cannot predict structures from genomic data, as is done with proteins...
May 22, 2018: Journal of the American Society for Mass Spectrometry
https://www.readbyqxmd.com/read/29788081/proteomic-characterization-of-the-extracellular-matrix-of-human-uterine-fibroids
#2
M Fairuz B Jamaluddin, Pravin Nahar, Pradeep S Tanwar
Uterine leiomyomas (fibroids) are the most common benign tumors that are associated with increased production of extracellular matrix (ECM). The excessive ECM deposition plays a major role in the enlargement and stiffness of these tumors and contributes to clinical symptoms, such as abnormal bleeding and abdominal pain. However, no study so far has explored the global composition of the ECM of fibroids and normal myometrium. In this study, we performed systematic ECM enrichment procedure and comparative proteomic analyses to profile the ECM composition of genetically annotated different size fibroids (small, medium and large) and adjacent normal myometrium (ANM)...
May 16, 2018: Endocrinology
https://www.readbyqxmd.com/read/29785047/rationally-designed-aav2-and-aavrh8r-capsids-provide-improved-transduction-in-the-retina-and-brain
#3
Jennifer A Sullivan, Lisa M Stanek, Michael J Lukason, Jie Bu, Shayla R Osmond, Elizabeth A Barry, Catherine R O'Riordan, Lamya S Shihabuddin, Seng H Cheng, Abraham Scaria
The successful application of adeno-associated virus (AAV) gene delivery vectors as a therapeutic paradigm will require efficient gene delivery to the appropriate cells in affected organs. In this study, we utilized a rational design approach to introduce modifications to the AAV2 and AAVrh8R capsids and the resulting variants were evaluated for transduction activity in the retina and brain. The modifications disrupted either capsid/receptor binding or altered capsid surface charge. Specifically, we mutated AAV2 amino acids R585A and R588A, which are required for binding to its receptor, heparan sulfate proteoglycans, to generate a variant referred to as AAV2-HBKO...
May 22, 2018: Gene Therapy
https://www.readbyqxmd.com/read/29785016/solid-papillary-carcinoma-with-reverse-polarity-of-the-breast-harbors-specific-morphologic-immunohistochemical-and-molecular-profile-in-comparison-with-other-benign-or-malignant-papillary-lesions-of-the-breast-a-comparative-study-of-9-additional-cases
#4
Nadjla Alsadoun, Gaëtan MacGrogan, Caroline Truntzer, Magali Lacroix-Triki, Isabelle Bedgedjian, Marie-Hélène Koeb, Elsy El Alam, Dan Medioni, Michel Parent, Pascal Wuithier, Isabelle Robert, Romain Boidot, Laurent Arnould
Solid papillary carcinoma with reverse polarity is a rare breast cancer of favorable prognosis that can be difficult to diagnose. We report here nine additional cases of this tumor, and we describe its morphologic, immunohistochemical and molecular profile in comparison to other types of papillary and micropapillary lesions of the breast that are intraductal papilloma with usual ductal hyperplasia, encapsulated papillary carcinoma, solid papillary carcinoma and invasive micropapillary carcinoma. We studied nine cases of this special papillary tumor and six of each other types mentioned above...
May 21, 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29783688/isolation-and-composition-analysis-of-bioactive-glycosaminoglycans-from-whelk
#5
Chrow Khurshid, David Alexander Pye
Glycosaminoglycans (GAGs) are found covalently attached to proteins, which create conjugates known as proteoglycans. GAGs have remarkable biological activity as co-receptors for a variety of growth factors, cytokines, and chemokines. The present study identifies the key compositional differences between the GAGs isolated from whelk and mammalian GAGs. This polysaccharide represents a new, previously undescribed GAG with cytotoxic activity on cancer cells. Disaccharides were obtained by sample digestion with heparinases I, II, and III and chondroitinase ABC...
May 18, 2018: Marine Drugs
https://www.readbyqxmd.com/read/29782809/the-effects-of-normal-aging-on-regional-accumulation-of-hyaluronan-and-chondroitin-sulfate-proteoglycans-in-the-mouse-brain
#6
May J Reed, Mamatha Damodarasamy, Jasmine L Pathan, Michelle A Erickson, William A Banks, Robert B Vernon
The brain changes in volume and composition with normal aging. Cellular components of the brain are supported by an extracellular matrix (ECM) comprised largely of hyaluronan (HA) and HA-associated members of the lectican family of chondroitin sulfate proteoglycans (CSPGs). We examined regional differences in microvascular density, neuronal and glial markers, and accumulation of HA and CSPGs in mouse brains during normal aging. The cortex, hippocampus, dentate gyrus, and cerebellum of young (4 months), middle-aged (14 months), and aged (24-26 months) brains were analyzed...
May 1, 2018: Journal of Histochemistry and Cytochemistry: Official Journal of the Histochemistry Society
https://www.readbyqxmd.com/read/29780819/a-comprehensive-review-of-the-pharmacologic-management-of-uterine-leiomyoma
#7
REVIEW
Terrence D Lewis, Minnie Malik, Joy Britten, Angelo Macapagal San Pablo, William H Catherino
Uterine leiomyomata are the most common benign tumors of the gynecologic tract impacting up to 80% of women by 50 years of age. It is well established that these tumors are the leading cause for hysterectomy with an estimated total financial burden greater than $30 billion per year in the United States. However, for the woman who desires future fertility or is a poor surgical candidate, definitive management with hysterectomy is not an optimal management plan. Typical gynecologic symptoms of leiomyoma include infertility, abnormal uterine bleeding (AUB)/heavy menstrual bleeding (HMB) and/or intermenstrual bleeding (IMB) with resulting iron-deficiency anemia, pelvic pressure and pain, urinary incontinence, and dysmenorrhea...
2018: BioMed Research International
https://www.readbyqxmd.com/read/29777959/extracellular-matrix-expression-in-human-pluripotent-stem-cell-derived-retinal-organoids-recapitulates-retinogenesis-in-vivo-and-reveals-an-important-role-for-impg1-and-cd44-in-the-development-of-photoreceptors-and-interphotoreceptor-matrix
#8
Majed Felemban, Birthe Dorgau, Nicola Claire Hunt, Dean Hallam, Darin Zerti, Roman Bauer, Yuchun Ding, Joseph Collin, David Steel, Natalio Krasnogor, Jumana Al-Aama, Susan Lindsay, Carla Mellough, Majlinda Lako
The extracellular matrix (ECM) plays an important role in numerous processes including cellular proliferation, differentiation, migration, maturation, adhesion guidance and axonal growth. To date, there has been no detailed analysis of the ECM distribution during retinal ontogenesis in humans and the functional importance of many ECM components is poorly understood. In this study, the expression of key ECM components in adult mouse and monkey retina, developing and adult human retina and retinal organoids derived from human pluripotent stem cells was studied...
May 16, 2018: Acta Biomaterialia
https://www.readbyqxmd.com/read/29777321/how-changes-in-interconnectivity-affect-the-bulk-properties-of-articular-cartilage-a-fibre-network-study
#9
M A Bilton, A Thambyah, R J Clarke
The remarkable compressive strength of articular cartilage arises from the mechanical interactions between the tension-resisting collagen fibrils and swelling proteoglycan proteins within the tissue. These interactions are facilitated by a significant level of interconnectivity between neighbouring collagen fibrils within the extracellular matrix. A reduction in interconnectivity is suspected to occur during the early stages of osteoarthritic degeneration. However, the relative contribution of these interconnections towards the bulk mechanical properties of articular cartilage has remained an open question...
May 18, 2018: Biomechanics and Modeling in Mechanobiology
https://www.readbyqxmd.com/read/29775732/il4-10-fusion-protein-has-chondroprotective-anti-inflammatory-and-potentially-analgesic-effects-in-the-treatment-of-osteoarthritis
#10
C Steen-Louws, J Popov-Celeketic, S C Mastbergen, K Coeleveld, C E Hack, N Eijkelkamp, M Tryfonidou, S Spruijt, J A G van Roon, F P J G Lafeber
OBJECTIVE: Effective disease-modifying drugs for osteoarthritis (DMOAD) should preferably have chondroprotective, anti-inflammatory, and analgesic activity combined in a single molecule. We developed a fusion protein of IL4 and IL10 (IL4-10 FP), in which the biological activity of both cytokines is preserved. The present study evaluates the chondroprotective, anti-inflammatory, and analgesic activity of IL4-10 FP in in vitro and in vivo models of osteoarthritis. METHODS: Human osteoarthritic cartilage tissue and synovial tissue were cultured with IL4-10 FP...
May 15, 2018: Osteoarthritis and Cartilage
https://www.readbyqxmd.com/read/29775666/the-effect-of-syndecan-4-and-glypican-1-knockdown-on-the-proliferation-and-differentiation-of-turkey-satellite-cells-differing-in-age-and-growth-rates
#11
Sandra G Velleman, Daniel L Clark, Jeffrey R Tonniges
Posthatch skeletal muscle growth requires myogenic satellite cells and the dynamic expression of cell membrane-associated proteins. The membrane associated heparan sulfate proteoglycans, syndecan-4 and glypican-1, link the satellite cell niche to the intracellular environment. Sydnecan-4 and glypican-1 are differentially expressed with age in turkey satellite cells and their over-expression impacts both satellite cell proliferation and differentiation, but their effect on satellite cells from lines with different growth potentials is not known...
May 15, 2018: Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology
https://www.readbyqxmd.com/read/29775609/kruppel-like-factor-4-klf-4-plays-a-crucial-role-in-simvastatin-svt-induced-differentiation-of-rabbit-articular-chondrocytes
#12
Seon-Mi Yu, Song Ja Kim
Simvastatin is a cholesterol-lowing reagent that is derived synthetically from the fermentation of Aspergillus terreus. Recently, SVT has been shown to possess a protective effect of chondrocytes. Kruppel-like factor 4 (KLF-4) is a zinc finger transcription factor that plays crucial roles during the development and maintenance of multiple organs. However, the roles of KLF-4 in chondrocytes have not been well unknown. Here, we investigated whether KLF-4 regulates SVT-caused differentiated phenotype of chondrocytes...
May 15, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29774041/report-on-the-current-inventory-of-the-toolbox-for-plant-cell-wall-analysis-proteinaceous-and-small-molecular-probes
#13
REVIEW
Maja G Rydahl, Aleksander R Hansen, Stjepan K Kračun, Jozef Mravec
Plant cell walls are highly complex structures composed of diverse classes of polysaccharides, proteoglycans, and polyphenolics, which have numerous roles throughout the life of a plant. Significant research efforts aim to understand the biology of this cellular organelle and to facilitate cell-wall-based industrial applications. To accomplish this, researchers need to be provided with a variety of sensitive and specific detection methods for separate cell wall components, and their various molecular characteristics in vitro as well as in situ ...
2018: Frontiers in Plant Science
https://www.readbyqxmd.com/read/29773865/perlecan-a-heparan-sulfate-proteoglycan-regulates-systemic-metabolism-with-dynamic-changes-in-adipose-tissue-and-skeletal-muscle
#14
Yuri Yamashita, Satoshi Nakada, Toshinori Yoshihara, Takeshi Nara, Norihiko Furuya, Takashi Miida, Nobutaka Hattori, Eri Arikawa-Hirasawa
Perlecan (HSPG2), a heparan sulfate proteoglycan, is a component of basement membranes and participates in a variety of biological activities. Here, we show physiological roles of perlecan in both obesity and the onset of metabolic syndrome. The perinatal lethality-rescued perlecan knockout (Hspg2-/- -Tg) mice showed a smaller mass and cell size of white adipose tissues than control (WT-Tg) mice. Abnormal lipid deposition, such as fatty liver, was not detected in the Hspg2-/- -Tg mice, and those mice also consumed more fat as an energy source, likely due to their activated fatty acid oxidation...
May 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29773674/deep-sequencing-of-complex-proteoglycans-a-novel-strategy-for-high-coverage-and-site-specific-identification-of-glycosaminoglycan-linked-peptides
#15
Joshua A Klein, Le Meng, Joseph Zaia
Proteoglycans are distributed in all animal tissues and play critical, multifaceted, physiological roles.  Expressed in a spatially- and temporally-regulated manner, these molecules regulate interactions among growth factors and cell surface receptors and play key roles in basement membranes and other extracellular matrices.  Due to the high degree of glycosylation by glycosaminoglycan (GAG), N-glycan and mucin-type O-glycan classes, the peptide sequence coverage of complex proteoglycans is revealed poorly by standard mass spectrometry-based proteomics methods...
May 17, 2018: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/29772480/proteoglycan-4-regulates-macrophage-function-without-altering-atherosclerotic-lesion-formation-in-a-murine-bone-marrow-specific-deletion-model
#16
Joya E Nahon, Menno Hoekstra, Stefan R Havik, Peter J Van Santbrink, Geesje M Dallinga-Thie, Jan-Albert Kuivenhoven, Janine J Geerling, Miranda Van Eck
BACKGROUND AND AIMS: Proteoglycan 4 (Prg4) has a high structural similarity with the established atherosclerosis-modulating proteoglycan versican, but its role in atherogenesis is still unknown. Therefore, the impact of Prg4 deficiency on macrophage function in vitro and atherosclerosis susceptibility in vivo was investigated. METHODS: The presence and localization of Prg4 was studied in atherosclerotic lesions. Furthermore, the effect of Prg4 deficiency on macrophage foam cell formation, cholesterol efflux and lipopolysaccharide (LPS) response was determined...
May 5, 2018: Atherosclerosis
https://www.readbyqxmd.com/read/29768203/unconventional-secretion-mediates-the-trans-cellular-spreading-of-tau
#17
Taxiarchis Katsinelos, Marcel Zeitler, Eleni Dimou, Andromachi Karakatsani, Hans-Michael Müller, Eliana Nachman, Julia P Steringer, Carmen Ruiz de Almodovar, Walter Nickel, Thomas R Jahn
The progressive deposition of misfolded hyperphosphorylated tau is a pathological hallmark of tauopathies, including Alzheimer's disease. However, the underlying molecular mechanisms governing the intercellular spreading of tau species remain elusive. Here, we show that full-length soluble tau is unconventionally secreted by direct translocation across the plasma membrane. Increased secretion is favored by tau hyperphosphorylation, which provokes microtubule detachment and increases the availability of free protein inside cells...
May 15, 2018: Cell Reports
https://www.readbyqxmd.com/read/29766794/chitosan-coated-c-phycocyanin-liposome-for-extending-the-neuroprotective-time-window-against-ischemic-brain-stroke
#18
Goo Yong Chung, Kyou Hee Shim, Hye Jin Kim, Seul Ki Min, Hwa Sung Shin
The time window for neuroprotection during ischemic brain stroke is short, and hence, development of neuroprotectants is a critical to extend this time window. This study sought to verify if muco-adhesive chitosan coating improves the neuroprotective potential of the pre-proven C-Phycocyanin-pertaining liposome (C-Pc liposome). The use of chitosan-coated liposomes extended the neuroprotective time window by 6 h after reperfusion, and further improved the neuroprotection efficiency of the C-Pc liposome in a rat middle cerebral artery occlusion (MCAO) model...
May 15, 2018: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/29765410/comparison-of-regenerative-tissue-quality-following-matrix-associated-cell-implantation-using-amplified-chondrocytes-compared-to-synovium-derived-stem-cells-in-a-rabbit-model-for-cartilage-lesions
#19
Hagen Schmal, Justyna M Kowal, Moustapha Kassem, Michael Seidenstuecker, Anke Bernstein, Katharina Böttiger, Tanshiyue Xiong, Norbert P Südkamp, Eva J Kubosch
Known problems of the autologous chondrocyte implantation motivate the search for cellular alternatives. The aim of the study was to test the potential of synovium-derived stem cells (SMSC) to regenerate cartilage using a matrix-associated implantation. In an osteochondral defect model of the medial femoral condyle in a rabbit, a collagen membrane was seeded with either culture-expanded allogenic chondrocytes or SMSC and then transplanted into the lesion. A tailored piece synovium served as a control. Rabbit SMSC formed typical cartilage in vitro...
2018: Stem Cells International
https://www.readbyqxmd.com/read/29765073/oncotically-driven-control-over-glycocalyx-dimension-for-cell-surface-engineering-and-protein-binding-in-the-longitudinal-direction
#20
Erika M J Siren, Rafi Chapanian, Iren Constantinescu, Donald E Brooks, Jayachandran N Kizhakkedathu
Here we present a simple technique for re-directing reactions on the cell surface to the outermost region of the glycocalyx. Macromolecular crowding with inert polymers was utilized to reversibly alter the accessibility of glycocalyx proteoglycans toward cell-surface reactive probes allowing for reactivity control in the longitudinal direction ('z'-direction) on the glycocalyx. Studies in HUVECs demonstrated an oncotically driven collapse of the glycocalyx brush structure in the presence of crowders as the mechanism responsible for re-directing reactivity...
May 15, 2018: Scientific Reports
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