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https://www.readbyqxmd.com/read/28813678/therapeutic-antibodies-to-ganglioside-gd2-evolved-from-highly-selective-germline-antibodies
#1
Eric Sterner, Megan L Peach, Marc C Nicklaus, Jeffrey C Gildersleeve
Antibodies play a crucial role in host defense and are indispensable research tools, diagnostics, and therapeutics. Antibody generation involves binding of genomically encoded germline antibodies followed by somatic hypermutation and in vivo selection to obtain antibodies with high affinity and selectivity. Understanding this process is critical for developing monoclonal antibodies, designing effective vaccines, and understanding autoantibody formation. Prior studies have found that antibodies to haptens, peptides, and proteins evolve from polyspecific germline antibodies...
August 15, 2017: Cell Reports
https://www.readbyqxmd.com/read/28810241/molecular-epidemiology-of-charcot-marie-tooth-disease-in-northern-ostrobothnia-finland-a-population-based-study
#2
Maria Marttila, Laura Kytövuori, Seppo Helisalmi, Mika Kallio, Marjo Laitinen, Mikko Hiltunen, Mikko Kärppä, Kari Majamaa
BACKGROUND: Charcot-Marie-Tooth (CMT) disease is the most common hereditary neuromuscular disorder with a population prevalence of 9.7-82.3/100,000. In this study, we have estimated the prevalence of CMT and its subtypes in Finland and examined the frequency of molecular etiologies. METHODS: A population-based survey included adult patients with peripheral neuropathy from the province of Northern Ostrobothnia, Finland. Secondary causes of peripheral polyneuropathy were excluded and patients with clinical and neurophysiological features pertinent with CMT were included...
August 16, 2017: Neuroepidemiology
https://www.readbyqxmd.com/read/28808998/microfluidics-mass-spectrometry-of-protein-carbohydrate-interactions-applications-to-the-development-of-therapeutics-and-biomarker-discovery
#3
Alina D Zamfir
The functional interactions of carbohydrates and their protein receptors are the basis of biological events critical to the evolution of pathological states. Hence, for the past years, such interactions have become the focus of research for the development of therapeutics and discovery of novel glycan biomarkers based on their binding affinity. Due to the high sensitivity, throughput, reproducibility, and capability to ionize minor species in heterogeneous mixtures, microfluidics-mass spectrometry (MS) has recently emerged as a method of choice in protein-glycan interactomics...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28808666/lipidomic-evaluation-of-feline-neurologic-disease-after-aav-gene-therapy
#4
Heather L Gray-Edwards, Xuntian Jiang, Ashley N Randle, Amanda R Taylor, Taylor L Voss, Aime K Johnson, Victoria J McCurdy, Miguel Sena-Esteves, Daniel S Ory, Douglas R Martin
GM1 gangliosidosis is a fatal lysosomal disorder, for which there is no effective treatment. Adeno-associated virus (AAV) gene therapy in GM1 cats has resulted in a greater than 6-fold increase in lifespan, with many cats remaining alive at >5.7 years of age, with minimal clinical signs. Glycolipids are the principal storage product in GM1 gangliosidosis whose pathogenic mechanism is not completely understood. Targeted lipidomics analysis was performed to better define disease mechanisms and identify markers of disease progression for upcoming clinical trials in humans...
September 15, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28800395/using-chemistry-to-target-neuroblastoma
#5
Jeanne N Hansen, Xingguo Li, Y George Zheng, Louis T Lotta, Abhishek Dedhe, Nina F Schor
Neuroblastoma is a cancer of the neural crest almost exclusively seen in childhood. While children with single, small primary tumors are often cured with surgery alone, the 65% of children with neuroblastoma whose disease has metastasized have less than a 50% chance of surviving five years after diagnosis. Innovative pharmacological strategies are critically needed for these children. Efforts to identify novel targets that afford ablation of neuroblastoma with minimal toxicity to normal tissues are underway...
August 11, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28796418/role-of-the-gm1-ganglioside-oligosaccharide-portion-in-the-trka-dependent-neurite-sprouting-in-neuroblastoma-cells
#6
Elena Chiricozzi, Diego Yuri Pomè, Margherita Maggioni, Erika Di Biase, Chiara Parravicini, Luca Palazzolo, Nicoletta Loberto, Ivano Eberini, Sandro Sonnino
GM1 ganglioside (II(3) NeuAc-Gg4 Cer) is known to promote neurite formation in neuroblastoma cells by activating TrkA-MAPK pathway. The molecular mechanism by which GM1 is involved in the neurodifferentiation process is still unknown, however, in vitro and in vivo evidences have suggested that the oligosaccharide portion of this ganglioside could be involved. Here, we report that, similarly to the entire GM1 molecule, its oligosaccharide II(3) NeuAc-Gg4, rather than its ceramide (Cer) portion is responsible for the neurodifferentiation process by augmenting neurite elongation and increasing the neurofilament protein expression in murine neuroblastoma cells, Neuro2a...
August 10, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28789710/transplanted-human-fecal-microbiota-enhanced-guillain-barr%C3%A3-syndrome-autoantibody-responses-after-campylobacter-jejuni-infection-in-c57bl-6-mice
#7
Phillip T Brooks, Kelsey A Brakel, Julia A Bell, Christopher E Bejcek, Trey Gilpin, Jean M Brudvig, Linda S Mansfield
BACKGROUND: Campylobacter jejuni is the leading antecedent infection to the autoimmune neuropathy Guillain-Barré syndrome (GBS), which is accompanied by an autoimmune anti-ganglioside antibody attack on peripheral nerves. Previously, we showed that contrasting immune responses mediate C. jejuni induced colitis and autoimmunity in interleukin-10 (IL-10)-deficient mice, dependent upon the infecting strain. Strains from colitis patients elicited T helper 1 (TH1)-dependent inflammatory responses while strains from GBS patients elicited TH2-dependent autoantibody production...
August 8, 2017: Microbiome
https://www.readbyqxmd.com/read/28761428/monosialoganglioside-1-may-alleviate-neurotoxicity-induced-by-propofol-combined-with-remifentanil-in-neural-stem-cells
#8
Jiang Lu, Xue-Qin Yao, Xin Luo, Yu Wang, Sookja Kim Chung, He-Xin Tang, Chi Wai Cheung, Xian-Yu Wang, Chen Meng, Qing Li
Monosialoganglioside 1 (GM1) is the main ganglioside subtype and has neuroprotective properties in the central nervous system. In this study, we aimed to determine whether GM1 alleviates neurotoxicity induced by moderate and high concentrations of propofol combined with remifentanil in the immature central nervous system. Hippocampal neural stem cells were isolated from newborn Sprague-Dawley rats and treated with remifentanil (5, 10, 20 ng/mL) and propofol (1.0, 2.5, 5.0 μg/mL), and/or GM1 (12.5, 25, 50 μg/mL)...
June 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/28760640/sialidase-neu3-defines-invasive-potential-of-human-glioblastoma-cells-by-regulating-calpain-mediated-proteolysis-of-focal-adhesion-proteins
#9
Kohta Takahashi, Sergei Proshin, Kazunori Yamaguchi, Yoji Yamashita, Ryuichi Katakura, Koji Yamamoto, Hiroshi Shima, Masahiro Hosono, Taeko Miyagi
BACKGROUND: Glioblastoma multiforme is one of the most malignant tumors of the human central nervous system characterized by high degree of invasiveness. Focusing on this invasive nature, we investigated whether ganglioside-specific sialidase NEU3 might be involved, because gangliosides are major components of brain tissues, and cell surface sialic acids, as target residues of sialidase catalysis, are thought to be closely related to cell invasion. METHODS: NEU3 mRNA levels of human glioblastoma specimens were evaluated by quantitative RT-PCR...
July 29, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28754302/immunometabolic-and-lipidomic-markers-associated-with-the-frailty-index-and-quality-of-life-in-aging-hiv-men-on-antiretroviral-therapy
#10
Hui-Ling Yeoh, Allen C Cheng, Catherine L Cherry, Jacquelyn M Weir, Peter J Meikle, Jennifer F Hoy, Suzanne M Crowe, Clovis S Palmer
Chronic immune activation persists despite antiretroviral therapy (ART) in HIV+ individuals and underpins an increased risk of age-related co-morbidities. We assessed the Frailty Index in older HIV+ Australian men on ART. Immunometabolic markers on monocytes and T cells were analyzed using flow cytometry, plasma innate immune activation markers by ELISA, and lipidomic profiling by mass spectrometry. The study population consisted of 80 HIV+ men with a median age of 59 (IQR, 56-65), and most had an undetectable viral load (92%)...
August 2017: EBioMedicine
https://www.readbyqxmd.com/read/28753308/assistance-of-the-c-7-8-picoloyl-moiety-for-directing-the-glycosyl-acceptors-into-the-%C3%AE-orientation-for-the-glycosylation-of-sialyl-donors
#11
Yu-Fa Wu, Yow-Fu Tsai
An efficient α-sialylation method for many primary hydroxyl acceptors that include 6-OH glycosides has been developed. 7,8-Di-O-picoloyl sialyl glycoside was used as the glycosyl donor, and α-glycoconjugation was controlled by using the 7,8-di-O-picoloyl moiety in CH2Cl2. The methodology was successfully applied to the total synthesis of ganglioside Hp-s1 possessing neuritogenic activity.
July 28, 2017: Organic Letters
https://www.readbyqxmd.com/read/28750621/clinical-and-electrophysiological-features-of-post-traumatic-guillain-barr%C3%A3-syndrome
#12
Xiaowen Li, Jinting Xiao, Yanan Ding, Jing Xu, Chuanxia Li, Yating He, Hui Zhai, Bingdi Xie, Junwei Hao
BACKGROUND: Post-traumatic Guillain-Barré syndrome (GBS) is a rarely described potentially life-threatening cause of weakness. We sought to elucidate the clinical features and electrophysiological patterns of post-traumatic GBS as an aid to diagnosis. METHODS: We retrospectively studied six patients diagnosed with post-traumatic GBS between 2014 and 2016 at Tianjin Medical University General Hospital, China. Clinical features, serum analysis, lumbar puncture results, electrophysiological examinations, and prognosis were assessed...
July 27, 2017: BMC Neurology
https://www.readbyqxmd.com/read/28749998/lc-ms-ms-multiplex-analysis-of-lysosphingolipids-in-plasma-and-amniotic-fluid-a-novel-tool-for-the-screening-of-sphingolipidoses-and-niemann-pick-type-c-disease
#13
Magali Pettazzoni, Roseline Froissart, Cécile Pagan, Marie T Vanier, Séverine Ruet, Philippe Latour, Nathalie Guffon, Alain Fouilhoux, Dominique P Germain, Thierry Levade, Christine Vianey-Saban, Monique Piraud, David Cheillan
BACKGROUND: The biological diagnosis of sphingolipidoses currently relies on the measurement of specific enzymatic activities and/or genetic studies. Lysosphingolipids have recently emerged as potential biomarkers of sphingolipidoses and Niemann-Pick type C in plasma. METHODOLOGY: We developed a sensitive and specific method enabling the simultaneous quantification of lysosphingolipids by LC-MS/MS: lysoglobotriaosylceramide for Fabry disease, lysohexosylceramide (i...
2017: PloS One
https://www.readbyqxmd.com/read/28744122/penetration-of-blood-brain-barrier-and-antitumor-activity-and-nerve-repair-in-glioma-by-doxorubicin-loaded-monosialoganglioside-micelles-system
#14
Dan Zou, Wei Wang, Daoxi Lei, Ying Yin, Peng Ren, Jinju Chen, Tieying Yin, Bochu Wang, Guixue Wang, Yazhou Wang
For the treatment of glioma and other central nervous system diseases, one of the biggest challenges is that most therapeutic drugs cannot be delivered to the brain tumor tissue due to the blood-brain barrier (BBB). The goal of this study was to construct a nanodelivery vehicle system with capabilities to overcome the BBB for central nervous system administration. Doxorubicin as a model drug encapsulated in ganglioside GM1 micelles was able to achieve up to 9.33% loading efficiency and 97.05% encapsulation efficiency by orthogonal experimental design...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28734966/development-of-new-ganglioside-probes-and-unraveling-of-raft-domain-structure-by-single-molecule-imaging
#15
REVIEW
Kenichi G N Suzuki, Hiromune Ando, Naoko Komura, Takahiro Fujiwara, Makoto Kiso, Akihiro Kusumi
Gangliosides are involved in a variety of biological roles and are a component of lipid rafts found in cell plasma membranes (PMs). Gangliosides are especially abundant in neuronal PMs and are essential to their physiological functions. However, the dynamic behaviors of gangliosides have not been investigated in living cells due to a lack of fluorescent probes that behave like their parental molecules. We have recently developed, using an entirely chemical method, four new ganglioside probes (GM1, GM2, GM3, and GD1b) that act similarly to their parental molecules in terms of raft partitioning and binding affinity...
July 19, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28720847/the-glycointeractome-of-serogroup-b-neisseria-meningitidis-strain-mc58
#16
Tsitsi D Mubaiwa, Lauren E Hartley-Tassell, Evgeny A Semchenko, Freda E-C Jen, Yogitha N Srikhanta, Christopher J Day, Michael P Jennings, Kate L Seib
Neisseria meningitidis express numerous virulence factors that enable it to interact with diverse microenvironments within the host, during both asymptomatic nasopharyngeal colonization and invasive disease. Many of these interactions involve bacterial or host glycans. In order to characterise the meningococcal glycointeractome, glycan arrays representative of structures found on human cells, were used as a screening tool to investigate host glycans bound by N. meningitidis. Arrays probed with fluorescently labelled wild-type MC58 revealed binding to 223 glycans, including blood group antigens, mucins, gangliosides and glycosaminoglycans...
July 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28714776/tissue-localization-of-glycosphingolipid-accumulation-in-a-gaucher-disease-mouse-brain-by-lc-esi-ms-ms-and-high-resolution-maldi-imaging-mass-spectrometry
#17
E Ellen Jones, Wujuan Zhang, Xueheng Zhao, Cristine Quiason, Stephanie Dale, Sheerin Shahidi-Latham, Gregory A Grabowski, Kenneth D R Setchell, Richard R Drake, Ying Sun
To better understand regional brain glycosphingolipid (GSL) accumulation in Gaucher disease (GD) and its relationship to neuropathology, a feasibility study using mass spectrometry and immunohistochemistry was conducted using brains derived from a GD mouse model (4L/PS/NA) homozygous for a mutant GCase (V394L [4L]) and expressing a prosaposin hypomorphic (PS-NA) transgene. Whole brains from GD and control animals were collected using one hemisphere for MALDI FTICR IMS analysis and the other for quantitation by LC-ESI-MS/MS...
July 1, 2017: SLAS Discovery
https://www.readbyqxmd.com/read/28708322/ganglioside-gm3-suppresses-lipopolysaccharide-induced-inflammatory-responses-in-raw-264-7-macrophage-cells-through-nf-%C3%AE%C2%BAb-ap-1-and-mapks-signaling
#18
Junyoung Park, Choong-Hwan Kwak, Sun-Hyung Ha, Kyung-Min Kwon, Fukushi Abekura, Seung-Hak Cho, Young-Chae Chang, Young-Choon Lee, Ki-Tae Ha, Tae-Wook Chung, Cheorl-Ho Kim
Gangliosides are known to specifically inhibit vascular leukocyte recruitment and consequent interaction with the injured endothelium, the basic inflammatory process. In this study, we have found that the production of nitric oxide (NO), a main regulator of inflammation, is suppressed by GM3 on murine macrophage RAW264.7 cells, when induced by LPS. In addition, GM3 attenuated the increase in cyclooxyenase-2 (COX-2) protein and mRNA levels in lipopolysaccharide (LPS)-activated RAW 264.7 cells in a dose-dependent manner...
July 14, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28701774/inhibition-of-%C3%AE-glucocerebrosidase-activity-preserves-motor-unit-integrity-in-a-mouse-model-of-amyotrophic-lateral-sclerosis
#19
Alexandre Henriques, Mylene Huebecker, Hélène Blasco, Céline Keime, Christian R Andres, Philippe Corcia, David A Priestman, Frances M Platt, Michael Spedding, Jean-Philippe Loeffler
Recent metabolomic reports connect dysregulation of glycosphingolipids, particularly ceramide and glucosylceramide, to neurodegeneration and to motor unit dismantling in amyotrophic lateral sclerosis at late disease stage. We report here altered levels of gangliosides in the cerebrospinal fluid of amyotrophic lateral sclerosis patients in early disease stage. Conduritol B epoxide is an inhibitor of acid beta-glucosidase, and lowers glucosylceramide degradation. Glucosylceramide is the precursor for all of the more complex glycosphingolipids...
July 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28701394/single-particle-detection-of-transcription-following-rotavirus-entry
#20
Eric N Salgado, Srigokul Upadhyayula, Stephen C Harrison
Infectious rotavirus particles are triple-layered, icosahedral assemblies. The outer layer proteins, VP4 (cleaved to VP8* and VP5*) and VP7, surround a transcriptionally competent, double-layer particle (DLP), which they deliver into the cytosol. During entry of rhesus rotavirus, VP8* interacts with cell-surface gangliosides, allowing engulfment into a membrane vesicle by a clathrin-independent process. Escape into the cytosol and outer-layer shedding depend on interaction of a hydrophobic surface on VP5* with the membrane bilayer and on a large-scale conformational change...
July 12, 2017: Journal of Virology
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