8 results on '"C. Racicot"'
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2. High genetic diversities between isolates of the fish parasite Cryptocaryon irritans (Ciliophora) suggest multiple cryptic species
- Author
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Alycia C. Racicot, Emily J. Foley, Kosuke Zenke, Yen-Ling Song, Hongshu Chi, Hui Gong, Hsin-Yun Lin, Katherine E. Guzzetta, Tomoyoshi Yoshinaga, Che-Huang Tung, Chao-Yin Cheng, Patricia Taik, Hilary M. Gray, and Wei-Jen Chang
- Subjects
0301 basic medicine ,China ,Species complex ,Genetic Speciation ,Taiwan ,Aquaculture ,Subspecies ,03 medical and health sciences ,Japan ,Phylogenetics ,Genetics ,Animals ,Parasite hosting ,Molecular Biology ,Phylogeny ,Ecology, Evolution, Behavior and Systematics ,Hymenostomatida ,Ichthyophthirius multifiliis ,biology ,Cryptocaryon ,Fishes ,Genetic Variation ,Reproductive isolation ,biology.organism_classification ,030104 developmental biology ,GenBank - Abstract
The ciliate protozoan Cryptocaryon irritans parasitizes marine fish and causes lethal white spot disease. Sporadic infections as well as large-scale outbreaks have been reported globally and the parasite's broad host range poses particular threat to the aquaculture and ornamental fish markets. In order to better understand C. irritans' population structure, we sequenced and compared mitochondrial cox-1, SSU rRNA, and ITS-1 sequences from 8 new isolates of C. irritans collected in China, Japan, and Taiwan. We detected two SSU rRNA haplotypes, which differ at three positions, separating the isolates into two main groups (I and II). Cox-1 sequences also support the division into two groups, and the cox-1 divergence between these two groups is unexpectedly high (9.28% for 1582 nucleotide positions). The divergence is much greater than that detected in Ichthyophthirius multifiliis, the ciliate protozoan causing freshwater white spot disease in fish, where intraspecies divergence on cox-1 sequence is only 1.95%. ITS-1 sequences derived from these eight isolates and from all other C. irritans isolates (deposited in the GenBank) not only support the two groups, but further suggest the presence of a third group with even greater sequence divergence. Finally, a small Ka/Ks ratio estimated from cox-1 sequences suggests that this gene in C. irritans remains under strong purifying selection. Taken together, the C. irritans species may consists of many subspecies and/or syngens. Further work is needed to determine if there is reproductive isolation between the groups we have defined.
- Published
- 2017
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3. Upgrade Rate of Atypical Ductal Hyperplasia: Ten Years Experience and Predictive Factors.
- Author
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Gagnon N, Martel E, Cadrin-Chênevert A, Ledoux E, Racicot C, and Villiard R
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- Adult, Aged, Breast surgery, Breast Neoplasms surgery, Carcinoma, Intraductal, Noninfiltrating surgery, Female, Humans, Middle Aged, Retrospective Studies, Biopsy statistics & numerical data, Breast pathology, Breast Neoplasms diagnosis, Carcinoma, Intraductal, Noninfiltrating diagnosis
- Abstract
Background: Atypical ductal hyperplasia (ADH) is a benign epithelial proliferative lesion with histologic features resembling those seen in low grade ductal carcinoma in situ (DCIS). Surgical excision of the biopsy site is the standard management approach. The objective of this study was to determine the upgrade rate from ADH on stereotactic breast biopsies to DCIS or invasive carcinoma (IC) in our institution. We also sought to identify clinical, pathologic and radiologic predictive factors associated with risk of upgrade., Materials and Methods: Clinical charts, mammograms and pathology reports were reviewed for all women with a stereotactic breast biopsy showing ADH and subsequent surgery at our institution between 2008 and 2018. When available, mammograms were re-reviewed by a radiologist for this study., Results: 295 biopsies were analyzed in 290 patients. Mean age was 56 y old. Upgrade rate was 10.5% of which 7.5% were DCIS and 3.1% IC. Mammograms were reviewed by a radiologist in 161 patients from 2013 to 2018. In this subset of patients, the rate of upgrade was 8.7% (4.35% DCIS and 4.35% IC). A statistically significant difference he largest size of the microcalcification clusters on mammogram was observed between the upgraded and the non-upgraded subgroups (14.2 mm versus 8.9 mm, P = 0.03) CONCLUSIONS: The evaluation of the largest size of microcalcification clusters on mammogram as a cut-off feature could be considered to choose between an observational versus a surgical approach. This large series provides contemporary data to assist informed decision making regarding the treatment of our patients., (Copyright © 2021. Published by Elsevier Inc.)
- Published
- 2021
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4. Arabinosylation of recombinant human immunoglobulin-based protein therapeutics.
- Author
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Hossler P, Chumsae C, Racicot C, Ouellette D, Ibraghimov A, Serna D, Mora A, McDermott S, Labkovsky B, Scesney S, Grinnell C, Preston G, Bose S, and Carrillo R
- Subjects
- Animals, Antibodies, Monoclonal chemistry, Antibodies, Monoclonal genetics, Antibody-Dependent Cell Cytotoxicity, CHO Cells, Cricetulus, Glycosylation drug effects, Humans, Immunoglobulin G chemistry, Immunoglobulin G genetics, Recombinant Proteins biosynthesis, Recombinant Proteins chemistry, Recombinant Proteins genetics, Antibodies, Monoclonal biosynthesis, Arabinose pharmacology, Immunoglobulin G blood
- Abstract
Protein glycosylation is arguably the paramount post-translational modification on recombinant glycoproteins, and highly cited in the literature for affecting the physiochemical properties and the efficacy of recombinant glycoprotein therapeutics. Glycosylation of human immunoglobulins follows a reasonably well-understood metabolic pathway, which gives rise to a diverse range of asparagine-linked (N-linked), or serine/threonine-linked (O-linked) glycans. In N-linked glycans, fucose levels have been shown to have an inverse relationship with the degree of antibody-dependent cell-mediated cytotoxicity, and high mannose levels have been implicated in potentially increasing immunogenicity and contributing to less favorable pharmacokinetic profiles. Here, we demonstrate a novel approach to potentially reduce the presence of high-mannose species in recombinant human immunoglobulin preparations, as well as facilitate an approximate 100% replacement of fucosylation with arabinosylation in Chinese hamster ovary cell culture through media supplementation with D-arabinose, an uncommonly used mammalian cell culture sugar substrate. The replacement of fucose with arabinose was very effective and practical to implement, since no cell line engineering or cellular adaptation strategies were required. Arabinosylated recombinant IgGs and the accompanying reduction in high mannose glycans, facilitated a reduction in dendritic cell uptake, increased FcγRIIIa signaling, and significantly increased the levels of ADCC. These aforementioned effects were without any adverse changes to various structural or functional attributes of multiple recombinant human antibodies and a bispecific DVD-Ig. Protein arabinosylation represents an expansion of the N-glycan code in mammalian expressed glycoproteins.
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- 2017
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5. Cell culture media supplementation of infrequently used sugars for the targeted shifting of protein glycosylation profiles.
- Author
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Hossler P, Racicot C, Chumsae C, McDermott S, and Cochran K
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- Animals, CHO Cells, Cricetulus, Glycoproteins genetics, Recombinant Proteins genetics, Culture Media metabolism, Glycoproteins metabolism, Glycosylation, Protein Engineering methods, Recombinant Proteins metabolism, Sugars metabolism
- Abstract
Mammalian cells in culture rely on sources of carbohydrates to supply the energy requirements for proliferation. In addition, carbohydrates provide a large source of the carbon supply for supporting various other metabolic activities, including the intermediates involved in the protein glycosylation pathway. Glucose and galactose, in particular, are commonly used sugars in culture media for these purposes. However, there exists a very large repertoire of other sugars in nature, and many that have been chemically synthesized. These sugars are particularly interesting because they can be utilized by cells in culture in distinct ways. In the present work it has been found that many infrequently used sugars, and the corresponding cellular response towards them as substrates, led to differences in the protein N-glycosylation profile of a recombinant glycoprotein. The selective media supplementation of raffinose, trehalose, turanose, palatinose, melezitose, psicose, lactose, lactulose, and mannose were found to be capable of redirecting N-glycan oligosaccharide profiles. Despite this shifting of protein glycosylation, there were no other adverse changes in culture performance, including both cell growth and cellular productivity over a wide range of supplemented sugar concentrations. The approach presented highlights a potential means towards both the targeted shifting of protein glycosylation profiles and ensuring recombinant protein comparability, which up to this point in time has remained under-appreciated for these under-utilized compounds. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:511-522, 2017., (© 2017 American Institute of Chemical Engineers.)
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- 2017
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6. Development of radio dramas for health communication pilot intervention in Canadian Inuit communities.
- Author
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Racicot-Matta C, Wilcke M, and Egeland GM
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- Adolescent, Adult, Community-Based Participatory Research, Feeding Behavior, Focus Groups, Food Supply, Humans, Nunavut, Pilot Projects, Young Adult, Drama, Health Communication methods, Inuit education, Mass Media, Radio
- Abstract
A mixed-methods approach was used to develop a culturally appropriate health intervention over radio within the Inuit community of Pangnirtung, Nunavut (NU), Canada. The radio dramas were developed, recorded and tested pre-intervention through the use of Participatory Process and informed by the extended elaboration likelihood model (EELM) for education-communication. The radio messages were tested in two focus groups (n = 4 and n = 5) to determine fidelity of the radio dramas to the EELM theory. Focus group feedback identified that revisions needed to be made to two characteristics required of educational programmes by the EELM theorem: first, the quality of the production was improved by adding Inuit youth recorded music and second, the homophily (relatability of characters) of radio dramas was improved by re-recording the dramas with voices of local youth who had been trained in media communication studies. These adjustments would not have been implemented had pre-intervention testing of the radio dramas not taken place and could have reduced effectiveness of the overall intervention. Therefore, it is highly recommended that media tools for health communication/education be tested with the intended target audience before commencement of programmes. Participatory Process was identified to be a powerful tool in the development and sustainability of culturally appropriate community health programming., (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
- Published
- 2016
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7. When Good Intentions Go Awry: Modification of a Recombinant Monoclonal Antibody in Chemically Defined Cell Culture by Xylosone, an Oxidative Product of Ascorbic Acid.
- Author
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Chumsae C, Hossler P, Raharimampionona H, Zhou Y, McDermott S, Racicot C, Radziejewski C, and Zhou ZS
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- Antibodies, Monoclonal chemistry, Ascorbic Acid metabolism, Cell Culture Techniques, Ketoses chemistry, Molecular Structure, Oxidation-Reduction, Recombinant Proteins chemistry, Antibodies, Monoclonal metabolism, Ascorbic Acid chemistry, Ketoses metabolism, Recombinant Proteins metabolism
- Abstract
With the advent of new initiatives to develop chemically defined media, cell culture scientists screen many additives to improve cell growth and productivity. However, the introduction or increase of supplements, typically considered beneficial or protective on their own, to the basal media or feed stream may cause unexpected detrimental consequences to product quality. For instance, because cultured cells are constantly under oxidative stress, ascorbic acid (vitamin C, a potent natural reducing agent) is a common additive to cell culture media. However, as reported herein, a recombinant monoclonal antibody (adalimumab) in cell culture was covalently modified by xylosone (molecular weight 148), an oxidative product of ascorbate. Containing reactive carbonyl groups, xylosone modifies various amines (e.g., the N-termini of the heavy and light chains and susceptible lysines), forming either hemiaminal (+148 Da) or Schiff base (imine, +130 Da) products. Our findings show, for the first time, that ascorbate-derived xylosone can contribute to an increase in molecular heterogeneity, such as acidic species. Our work serves as a reminder that additives to cell culture and their metabolites may become reactive and negatively impact the overall product quality and should be carefully monitored with any changes in cell culture conditions.
- Published
- 2015
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8. Cell culture media supplementation of bioflavonoids for the targeted reduction of acidic species charge variants on recombinant therapeutic proteins.
- Author
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Hossler P, Wang M, McDermott S, Racicot C, Chemfe K, Zhang Y, Chumsae C, and Manuilov A
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- Animals, Bioreactors, CHO Cells, Catechin analogs & derivatives, Cricetinae, Cricetulus, Rutin, Culture Media chemistry, Culture Media metabolism, Flavonoids chemistry, Flavonoids metabolism, Recombinant Proteins chemistry, Recombinant Proteins metabolism
- Abstract
Charge variants in recombinant proteins are an important series of protein modifications, whose potential role on protein stability, activity, immunogenicity, and pharmacokinetics continues to be studied. Monoclonal antibodies in particular have been shown to have a wide range of acidic species variants, including those associated with the addition of covalent modifications as well as the chemical degradation at specific peptide regions on the antibody. These variants play a significant role toward the overall heterogeneity of recombinant therapeutic proteins and are typically monitored during manufacturing to ensure they lie within proven acceptable ranges. In this work, it has been found that the supplementation of members of the bioflavonoid chemical family into mammalian cell culture media was effective toward the reduction of acidic species charge variants on recombinant monoclonal antibodies and dual variable domain immunoglobulins. The demonstrated reduction in acidic species through the use of bioflavonoids facilitates the manufacturing of a less heterogeneous product with potential improvements in antibody structure and function., (© 2015 American Institute of Chemical Engineers.)
- Published
- 2015
- Full Text
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