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https://www.readbyqxmd.com/read/28921534/exploring-cellular-behaviour-under-transient-gene-expression-and-its-impact-on-mab-productivity-and-fc-glycosylation
#1
Si Nga Sou, Ken Lee, Kalpana Nayyar, Karen M Polizzi, Christopher Sellick, Cleo Kontoravdi
Transient gene expression (TGE) is a methodology employed in bioprocessing for the fast provision of recombinant protein material. Mild hypothermia is often introduced to overcome the low yield typically achieved with TGE and improve specific protein productivity. It is therefore of interest to examine the impact of mild hypothermic temperatures on both the yield and quality of transiently-expressed proteins and the relationship to changes in cellular processes and metabolism. In this study, we focus on the ability of a Chinese hamster ovary cell line to galactosylate a recombinant monoclonal antibody (mAb) product...
September 16, 2017: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/28913702/impaired-fertility-and-motor-function-in-a-zebrafish-model-for-classic-galactosemia
#2
Jo M Vanoevelen, M Estela Rubio-Gozalbo, Britt van Erven, Jörgen Bierau, Xiaoping Huang, Gerard T Berry, Rein Vos, Ana I Coelho
Classic galactosemia is a genetic disorder of galactose metabolism, caused by severe deficiency of galactose-1-phosphate uridylyltransferase (GALT) enzyme activity due to mutations of the GALT gene. Its pathogenesis is still not fully elucidated, and a therapy that prevents chronic impairments is lacking. In order to move research forward, there is a high need for a novel animal model, which allows organ studies throughout development and high-throughput screening of pharmacologic compounds. Here, we describe the generation of a galt knockout zebrafish model and present its phenotypical characterization...
September 14, 2017: Journal of Inherited Metabolic Disease
https://www.readbyqxmd.com/read/28910600/an-acceptor-analogue-of-%C3%AE-1-4-galactosyltransferase-substrate-inhibitor-or-both
#3
Jingqian Jiang, Gerd K Wagner
Many glycosyltransferase inhibitors in the literature are structurally derived from the donor or acceptor substrate of the respective enzyme. A representative example is 2-naphthyl β-d-GlcNAc, a synthetic GlcNAc glycoside that has been reported as a galactosyltransferase inhibitor. This GlcNAc derivative is attractive as a chemical tool compound for biological and biochemical studies because of its reported potency as an inhibitor, and its short and straightforward synthesis from readily available starting materials...
August 31, 2017: Carbohydrate Research
https://www.readbyqxmd.com/read/28882590/targeted-deletion-of-rankl-in-m-cell-inducer-cells-by-the-col6a1-cre-driver
#4
Kazuki Nagashima, Shinichiro Sawa, Takeshi Nitta, Alejandro Prados, Vasiliki Koliaraki, George Kollias, Tomoki Nakashima, Hiroshi Takayanagi
The gut-associated lymphoid tissues (GALTs), including Peyer's patches (PPs), cryptopatches (CPs) and isolated lymphoid follicles (ILFs), establish a host-microbe symbiosis by the promotion of immune reactions against gut microbes. Microfold cell inducer (MCi) cells in GALTs are the recently identified mesenchymal cells that express the cytokine RANKL and initiate bacteria-specific immunoglobulin A (IgA) production via induction of microfold (M) cell differentiation. In the previous study, the Twist2-Cre driver was utilized for gene deletion in mesenchymal cells including MCi cells...
September 5, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28859865/ischemic-stroke-damages-the-intestinal-mucosa-and-induces-alteration-of-the-intestinal-lymphocytes-and-ccl19-mrna-in-rats
#5
Yaning Liu, Shijian Luo, Li Kou, Chaogang Tang, Ruxun Huang, Zhong Pei, Zhendong Li
The immunoreaction has a pivotal effect on ischemic stroke. It has been demonstrated that intestinal lymphocytes infiltrate into the brain and aggravate tissue injury after stroke. However, less attention has been paid to the influence on the intestinal immunology as well as morphology. Here, we utilized a rat permanent middle cerebral artery occlusion (MCAO) model to investigate the influences on intestinal mucosa, lymphocytes of the gut-associated lymphoid tissue (GALT), and the intestinal expression of CCL25 mRNA and CCL19 mRNA of stroke...
August 30, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28851631/strain-specific-helper-t-cell-profile-in-the-gut-associated-lymphoid-tissue
#6
Suzana Stanisavljević, Neda Đedović, Milica Vujičić, Tamara Saksida, Bojan Jevtić, Boško Milovanović, Miljana Momčilović, Đorđe Miljković, Ivana Stojanović
C57BL/6, BALB/c and NOD mice are among the most frequently used strains in autoimmunity research. NOD mice spontaneously develop type 1 diabetes (T1D) and they are prone to induction of experimental autoimmune encephalomyelitis (EAE). Both diseases can be routinely induced in C57BL/6 mice, but not in BALB/c mice. Also, C57BL/6 mice are generally considered T helper (Th)1-biased and BALB/c Th2-biased mice. Having in mind increasingly appreciated role of gut associated lymphoid tissue (GALT) cells in autoimmunity, especially in relation to gut Th17 and regulatory T (Treg) cells, our aim was to determine if there are differences in proportion of CD4(+) T cell populations in mesenteric lymph nodes and Peyer's patches of these mouse strains...
August 26, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28844959/reversal-of-aberrant-pi3k-akt-signaling-by-salubrinal-in-a-galt-deficient-mouse-model
#7
B Balakrishnan, C Nicholas, A Siddiqi, W Chen, E Bales, M Feng, J Johnson, K Lai
Classic Galactosemia is an autosomal recessive disorder caused by deleterious mutations in the GALT gene, which encodes galactose-1 phosphate uridylyltransferase enzyme (GALT: EC 2.7.7.12). Recent studies of primary skin fibroblasts isolated from the GalT-deficient mice demonstrated a slower growth rate, a higher level of endoplasmic reticulum (ER) stress, and down-regulation of the Phosphoinositide 3 kinase/Protein kinase B (PI3K/Akt) signaling pathway. In this study, we compared the expression levels of the PI3K/Akt signaling pathway in normal and GalT-deficient mouse tissues...
August 24, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28832609/distinct-aging-profiles-of-cd8-t-cells-in-blood-versus-gastrointestinal-mucosal-compartments
#8
Jeffrey Dock, Christina M Ramirez, Lance Hultin, Mary Ann Hausner, Patricia Hultin, Julie Elliott, Otto O Yang, Peter A Anton, Beth D Jamieson, Rita B Effros
A hallmark of human immunosenescence is the accumulation of late-differentiated memory CD8+ T cells with features of replicative senescence, such as inability to proliferate, absence of CD28 expression, shortened telomeres, loss of telomerase activity, enhanced activation, and increased secretion of inflammatory cytokines. Importantly, oligoclonal expansions of these cells are associated with increased morbidity and mortality risk in elderly humans. Currently, most information on the adaptive immune system is derived from studies using peripheral blood, which contains approximately only 2% of total body lymphocytes...
2017: PloS One
https://www.readbyqxmd.com/read/28816213/association-of-presenile-cataract-with-galactose-1-phosphate-uridyl-transferase-gene-mutations
#9
Nitin Nema, Ravindra Kumar, Abha Verma, Sonam Verma, Kiran Chaturvedi
BACKGROUND: Presenile cataract is commonly idiopathic in origin. However, patients with presenile cataract could have an underlying genetic abnormality of galactose metabolism. We studied the association, if any, between idiopathic presenile cataract and galactose-1 -phosphate uridyl transferase (GALT) gene mutation. METHODS: We selected 50 patients with idiopathic presenile cataract, <45 years of age, and 50 age- and sex-matched controls for the study. Mutations in the GALT gene were determined by polymerase chain reaction restriction fragment length polymorphism...
March 2017: National Medical Journal of India
https://www.readbyqxmd.com/read/28782046/circulating-loxl2-levels-reflect-severity-of-intestinal-fibrosis-and-galt-cd4-t-lymphocyte-depletion-in-treated-hiv-infection
#10
Sophie Seang, Anoma Somasunderam, Maitreyee Nigalye, Ma Somsouk, Timoty W Schacker, Joyce L Sanchez, Peter W Hunt, Netanya S Utay, Jordan E Lake
BACKGROUND: Incomplete immune reconstitution may occur despite successful antiretroviral therapy (ART). Gut-associated lymphoid tissue (GALT) fibrosis may contribute via local CD4(+) T lymphocyte depletion, intestinal barrier disruption, microbial translocation, and immune activation. METHODS: In a cross-sectional analysis, we measured circulating fibrosis biomarker levels on cryopreserved plasma from adult HIV-infected (HIV+) SCOPE study participants on suppressive ART who also had fibrosis quantification on recto-sigmoid biopsies...
2017: Pathogens & Immunity
https://www.readbyqxmd.com/read/28766043/intestinal-macrophages-in-peyer-s-patches-sacculus-rotundus-and-appendix-of-angora-rabbit
#11
Feyzullah Beyaz, Narin Liman, Emel Ergün, Levent Ergün, Mehmet Özbek
The largest pool of macrophages in the body is harboured by the intestinal mucosa. As the principal phagocytic component of the immune system, macrophages are essential for maintaining mucosal homeostasis as they prevent commensal bacteria from adhering to mucosal epithelial cells. This study provides a RAM11 immunohistochemical and electron microscopic investigation of the existence, localization and distribution of intestinal macrophages in organized gut-associated lymphoid tissue (GALT), including Peyer's patches (PPs), the sacculus rotundus (SR) and the appendix, in the Angora rabbit...
August 2, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28755501/promoter-choice-impacts-the-efficiency-of-plant-glyco-engineering
#12
Somanath Kallolimath, Clemens Gruber, Herta Steinkellner, Alexandra Castilho
Glyco-modulation of therapeutic proteins produced in plants has shown great success. Plant-based expression platforms for tailored human-like N-glycosylation are based on the overexpression of foreign genes. However, drawbacks such as protein miss targeting, interference with endogenous glycosyltransferases or with plant development hamper the widespread use of the technology. Here we describe a technique that facilitates the generation of recombinant proteins with targeted N-glycosylation at high homogeneity...
July 29, 2017: Biotechnology Journal
https://www.readbyqxmd.com/read/28751521/the-third-pathway-of-colorectal-carcinogenesis
#13
REVIEW
Carlos A Rubio, Giacomo Puppa, Giovanni de Petris, Lorand Kis, Peter T Schmidt
AIMS: The majority of the colorectal carcinomas (CRC) arise in a vast mucosal area built with columnar cells and mucus-producing goblet cells. These carcinomas evolve via the conventional (tubular/villous) adenoma-carcinoma pathway, or the serrated adenoma-carcinoma pathway. Much less frequently CRC arise in the gut-associated lymphoid tissue (GALT) mucosal domain via the third pathway of colorectal carcinogenesis. METHODS: All publications on human colorectal GALT carcinomas in the literature were reviewed...
July 27, 2017: Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28725880/role-of-intrinsic-factors-in-the-growth-of-transplanted-organs-following-transplantation
#14
Jigesh A Shah, Tatsu Tanabe, Kazuhiko Yamada
Shortages in the availability of transplantable organs have forced the transplant community to seek alternative methods to increase the supply of available organs. In our recent study following α-1,3-galactocyltransferase knockout (GalT-KO) pig-to-baboon kidney xenotransplantation, we found that certain recipients developed increased serum creatinine, possibly due to the rapid growth of orthotopic pig grafts in smaller baboon recipients. To test our hypothesis, we assessed whether the growth of outbred (Yorkshire) organ transplants (kidney and lung) in miniature swine was regulated by intrinsic (graft) factors...
June 2017: Journal of Immunobiology
https://www.readbyqxmd.com/read/28718185/congenital-pulmonary-lymphangiectasia-a-disorder-not-only-of-fetoneonates
#15
Shi-Min Yuan
Congenital pulmonary lymphangiectasia (CPL) is a rare developmental disorder of the lung, characterized by dilation of pulmonary subpleural, interlobar, perivascular and peribronchial lymphatics. The incidence of CPL among stillborn and neonates was estimated to be <1%. The etiology of CPL is unknown. However, it has been suspected to be of a genetic background. Recent basic studies revealed that it might be caused by the FOXC2, Vegfr-3 and integrin α9β1gene mutations. A clinical diagnosis of CPL can be made much easier in full-term neonates who present with respiratory distress, pleural (especially chylous) effusions with or without generalized edema...
July 2017: Klinische Pädiatrie
https://www.readbyqxmd.com/read/28708466/a-bidirectional-association-between-the-gut-microbiota-and-cns-disease-in-a-biphasic-murine-model-of-multiple-sclerosis
#16
Sara L Colpitts, Eli J Kasper, Abigail Keever, Caleb Liljenberg, Trevor Kirby, Krisztian Magori, Lloyd H Kasper, Javier Ochoa-Repáraz
The gut microbiome plays an important role in the development of inflammatory disease as shown using experimental models of central nervous system (CNS) demyelination. Gut microbes influence the response of regulatory immune cell populations in the gut-associated lymphoid tissue (GALT), which drive protection in acute and chronic experimental autoimmune encephalomyelitis (EAE). Recent observations suggest that communication between the host and the gut microbiome is bidirectional. We hypothesized that the gut microbiota differs between the acute inflammatory and chronic progressive stages of a murine model of secondary-progressive multiple sclerosis (SP-MS)...
July 14, 2017: Gut Microbes
https://www.readbyqxmd.com/read/28697651/mucosal-immune-system-of-the-gastrointestinal-tract-maintaining-balance-between-the-good-and-the-bad
#17
Bani Ahluwalia, Maria K Magnusson, Lena Öhman
The gastrointestinal tract (GI tract) is a unique organ inhabited by a range of commensal microbes, while also being exposed to an overwhelming load of antigens in the form of dietary antigens on a daily basis. The GI tract has dual roles in the body, in that it performs digestion and uptake of nutrients while also carrying out the complex and important task of maintaining immune homeostasis, i.e., keeping the balance between the good and the bad. It is equally important that we protect ourselves from reacting against the good, meaning that we stay tolerant to harmless food, commensal bacteria and self-antigens, as well as react with force against the bad, meaning induction of immune responses against harmful microorganisms...
July 12, 2017: Scandinavian Journal of Gastroenterology
https://www.readbyqxmd.com/read/28656602/rapid-response-team-calls-to-obstetric-patients-in-a-busy-quaternary-maternity-hospital
#18
Timothy M Crozier, Pauline Galt, Stuart J Wilson, Euan M Wallace
AIMS: There is limited published information regarding intensive care unit (ICU) led rapid response team (RRT) calls to obstetric patients. We examined the characteristics of RRT calls to obstetric patients at a tertiary teaching hospital. METHODS: Details of calls to pregnant and postpartum patients between October 2010 and June 2014 were obtained from the hospital RRT database. Each was retrospectively examined for data on patient demographics, call trigger, interventions and outcomes...
June 28, 2017: Australian & New Zealand Journal of Obstetrics & Gynaecology
https://www.readbyqxmd.com/read/28644047/mutational-analysis-of-galt-gene-in-greek-patients-with-galactosaemia-identification-of-two-novel-mutations-and-clinical-evaluation
#19
Kleopatra H Schulpis, Georgia Thodi, Konstantinos Iakovou, Maria Chatzidaki, Yannis Dotsikas, Elina Molou, Olga Triantafylli, Yannis L Loukas
Classical galactosaemia is an inborn error of metabolism due to the deficiency of the enzyme galactose-1-phosphate uridylyltransferase (GALT). The aim of the study was to identify the underlying mutations in Greek patients with GALT deficiency and evaluate their psychomotor and speech development. Patients with GALT deficiency (n = 17) were picked up through neonatal screening. Mutational analysis was conducted via Sanger sequencing, while in silico analysis was used in the cases of novel missense mutations...
June 23, 2017: Scandinavian Journal of Clinical and Laboratory Investigation
https://www.readbyqxmd.com/read/28639977/topical-delivery-of-immunosuppression-to-prolong-xenogeneic-and-allogeneic-split-thickness-skin-graft-survival
#20
Melissa Mastroianni, Zhi Yang Ng, Ritu Goyal, Christopher Mallard, Evan A Farkash, David A Leonard, Alexander Albritton, Kumaran Shanmugarajah, Josef M Kurtz, David H Sachs, Lauren K Macri, Joachim Kohn, Curtis L Cetrulo
Cadaveric skin allograft is the current standard of treatment for temporary coverage of large burn wounds. Porcine xenografts are viable alternatives but undergo α-1,3-galactose (Gal)-mediated hyperacute rejection and are lost by POD 3 because of naturally occurring antibodies to Gal in primate recipients. Using baboons, we previously demonstrated that xenografts from GalT-KO swine (lacking Gal) provided wound coverage comparable with allografts with systemic immunosuppression. In this study, we investigate topical immunosuppression as an alternative to prolong xenograft survival...
June 7, 2017: Journal of Burn Care & Research: Official Publication of the American Burn Association
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