23 results on '"Bordas M"'
Search Results
2. Pathogenicity of Vibrio alginolyticus for cultured gilt-head sea bream (Sparus aurata L.)
- Author
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Balebona, M. Carmen, Andreu, Manuel J., Bordas, M. Angeles, Zorrilla, Irene, Morinigo, Miguel A., and Borrego, Juan J.
- Subjects
Vibrio ,Marine fishes -- Diseases ,Pathogenic microorganisms -- Research ,Biological sciences - Abstract
The in vivo and in vitro pathogenic actions of whole cells and extracellular products of Vibrio alginolyticus for cultured gilt-head sea bream were studied. The strains were able to fasten to the skin, gills and intestinal mucus of sea bream and to cultured cells of a chinook salmon embryo cell line. The extracellular products were observed to destroy sea bream mucus and tissues. V. alginolyticus was cytotoxic for fish cell lines and deadly for sea bream.
- Published
- 1998
3. Kinetics of adhesion of selected fish-pathogenic Vibrio strains to skin mucus of gilt-head sea bream (Sparus aurata L.)
- Author
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Bordas, M. Angeles, Balebona, M. Carmen, Zorrilla, Irene, Borrego, Juan J., and Morinigo, Miguel A.
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Vibrio -- Research ,Microorganisms -- Adhesion ,Biological sciences - Abstract
The adhesive kinetics of Vibrio strains isolated from diseased gil-head sea bream to superficial skin mucus was investigated by adhesive assay and spectroscopy. Data indicated saturation kinetics for V. anguillarum-like strains, whereas V. alginolyticus showed a proportional adsorption kinetics. Mucus did not have an effect on the adhesive ability of the pathogenic microorganisms, suggesting that there is no relationship between adhesive capability for skin mucus and virulence.
- Published
- 1996
4. On the Malpighian tubes of Orthoptera
- Author
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Bordas, M L and BioStor
- Published
- 1897
5. Chemotaxis of pathogenic Vibrio strains towards mucus surfaces of gilt-head sea bream (Sparus aurata L.)
- Author
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Bordas, M. Angeles, Balebona, M. Carmen, Rodriguqez-Maroto, Jose M., Borrego, Juan J., and Morinigo, Miguel A.
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Vibrio -- Research ,Mucus -- Research ,Chemotaxis -- Research ,Microorganisms -- Effect of temperature on ,Biological sciences - Abstract
Research was conducted to examine the chemotaxis of pathogenic Vibrio strains towards mucus surfaces of gilt-head sea bream Sparus aurata L and to stuy the influence of salinity and temperature on the process. Twenty-two strains of Vibrio anguillarum and Vibrio alginolyticus were isolated from diseased gilt-head sea bream and their abilities to assay were determined following the preparation of raw skin, gill and intestinal mucus. Results indicate that the mucus surfaces are potential portal entries in the fish for V anguillarum and V alginolyticus.
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- 1998
6. Alternative to supply of health services in physical medicine and rehabilitation: From mobile team to home hospitalization
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Duruflé, Aubry, J.F., Bordas, M., Gallien, P., Le Meur, C., and Nicolas, B.
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- 2018
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7. Kinetics of adhesion of selected fish-pathogenic Vibrio strains of skin mucus of gilt-head sea bream (Sparus aurata L.)
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Bordas, M A, primary, Balebona, M C, additional, Zorrilla, I, additional, Borrego, J J, additional, and Moriñigo, M A, additional
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- 1996
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8. Chemotaxis of pathogenic Vibrio strains towards a mucus surfaces of gilt-head sea bream...
- Author
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Balebona, M. Carmen, Borrego, Juan J., Angeles Bordas, M., Rodriguez-Maroto, Jose M., and Moriñigo, Miguel A.
- Subjects
- *
CHEMOTAXIS , *VIBRIO , *MUCUS - Abstract
Presents a study to measure bacterial chemotaxis of pathogenic Vibrio strains towards mucus surfaces of gilt-head sea bream (Sparus aurata L.) Methodology used to conduct study; Indication of findings; Discussion on results.
- Published
- 1998
9. Lipid droplets and small extracellular vesicles: More than two independent entities.
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Genard GC, Tirinato L, Pagliari F, Da Silva J, Giammona A, Alquraish F, Reyes MP, Bordas M, Marafioti MG, Franco SD, Janssen J, Garcia-Calderón D, Hanley R, Nistico C, Fukasawa Y, Müller T, Krijgsveld J, Todaro M, Costanzo FS, Stassi G, Nessling M, Richter K, Maass KK, Liberale C, and Seco J
- Abstract
Despite increasing knowledge about small extracellular vesicle (sEV) composition and functions in cell-cell communication, the mechanism behind their biogenesis remains unclear. Here, we reveal for the first time that sEV biogenesis and release into the microenvironment are tightly connected with another important organelle, Lipid Droplets (LDs). The correlation was observed in several human cancer cell lines as well as patient-derived colorectal cancer stem cells (CR-CSCs). Our results demonstrated that external stimuli such as radiation, pH, hypoxia or lipid-interfering drugs, known to affect the number of LDs/cell, similarly influenced sEV secretion. Importantly, through multiple omics data, at both mRNA and protein levels, we revealed RAB5C as a potential important molecular player behind this organelle connection. Altogether, the potential to fine-tune sEV biogenesis by targeting LDs could significantly impact the amount, cargos and properties of these sEVs, opening new clinical perspectives., Competing Interests: All authors declare no conflict of interest., (© 2024 The Author(s). Journal of Extracellular Biology published by Wiley Periodicals LLC on behalf of International Society for Extracellular Vesicles.)
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- 2024
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10. Red Light Mitigates the Deteriorating Placental Extracellular Matrix in Late Onset of Preeclampsia and Improves the Trophoblast Behavior.
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Griffin J, Krolikowski JG, Kounga K, Struve J, Keszler A, Lindemer B, Bordas M, Broeckel G, Lohr NL, and Weihrauch D
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- Extracellular Matrix metabolism, Female, Humans, Placenta metabolism, Placenta Growth Factor, Placentation, Pregnancy, Pre-Eclampsia metabolism, Trophoblasts metabolism
- Abstract
Preeclampsia is a serious pregnancy disorder which in extreme cases may lead to maternal and fetal injury or death. Preexisting conditions which increase oxidative stress, e.g., hypertension and diabetes, increase the mother's risk to develop preeclampsia. Previously, we established that when the extracellular matrix is exposed to oxidative stress, trophoblast function is impaired, and this may lead to improper placentation. We investigated how the oxidative ECM present in preeclampsia alters the behavior of first trimester extravillous trophoblasts. We demonstrate elevated levels of advanced glycation end products (AGE) and lipid oxidation end product 4-hydroxynonenal in preeclamptic ECM (28%, and 32% increase vs control, respectively) accompanied with 35% and 82% more 3-chlorotyrosine and 3-nitrotyrosine vs control, respectively. Furthermore, we hypothesized that 670 nm phototherapy, which has antioxidant properties, reverses the observed trophoblast dysfunction as depicted in the improved migration and reduction in apoptosis. Since NO is critical for placentation, we examined eNOS activity in preeclamptic placentas compared to healthy ones and found no differences; however, 670 nm light treatment triggered enhanced NO availability presumably by using alternative NO sources. Light exposure decreased apoptosis and restored trophoblast migration to levels in trophoblasts cultured on preeclamptic ECM. Moreover, 670 nm irradiation restored expression of Transforming Growth Factor (TGF β ) and Placental Growth Factor (PLGF) to levels observed in trophoblasts cultured on healthy placental ECM. We conclude the application of 670 nm light can successfully mitigate the damaged placental microenvironment of late onset preeclampsia as depicted by the restored trophoblast behavior., Competing Interests: None of the authors have a conflict of interest., (Copyright © 2022 Jakara Griffin et al.)
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- 2022
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11. An autologous culture model of nodal B-cell lymphoma identifies ex vivo determinants of response to bispecific antibodies.
- Author
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Roider T, Brinkmann BJ, Kim V, Knoll M, Kolb C, Roessner PM, Bordas M, Dreger P, Müller-Tidow C, Huber W, Seiffert M, and Dietrich S
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- Antigens, CD19, Humans, Tumor Microenvironment, Antibodies, Bispecific pharmacology, Lymphoma, B-Cell
- Abstract
Bispecific antibodies (BsAbs) can induce long-term responses in patients with refractory and relapsed B-cell lymphoma. Nevertheless, response rates across patients are heterogeneous, and the factors determining quality and duration of responses are poorly understood. To identify key determinants of response to BsAbs, we established a primary, autologous culture model allowing us to mimic treatment with CD3xCD19 and CD3xCD20 BsAbs within the lymph node microenvironment ex vivo. T cell-mediated killing of lymphoma cells and proliferation of T cells varied significantly among patients but highly correlated between BsAbs targeting CD20 or CD19. Ex vivo response to BsAbs was significantly associated with expansion of T cells and secretion of effector molecules (eg, granzyme B, perforin) but not with expression of T-cell exhaustion (eg, PD1, TIM3) or activation markers (eg, CD25, CD69) or formation of intercellular contacts. In addition, we identified a distinct phenotype of regulatory T cells that was linked to ex vivo response independently from T-cell frequency at baseline. High expression levels of Aiolos (IKZF1), ICOS, and CXCR5 were positively associated with ex vivo response, whereas strong expression of Helios (IKZF2) had an unfavorable impact on ex vivo response to BsAbs. We further showed that lenalidomide, nivolumab, and atezolizumab improved ex vivo response to BsAbs by potentiating T-cell effector functions. In summary, our ex vivo study identified a distinct regulatory T-cell phenotype as a potential contributor to treatment failure of BsAbs and suggests drug combinations of high clinical relevance that could improve the efficacy of BsAbs., (© 2021 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
- Published
- 2021
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12. Optimized Protocol for Isolation of Small Extracellular Vesicles from Human and Murine Lymphoid Tissues.
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Bordas M, Genard G, Ohl S, Nessling M, Richter K, Roider T, Dietrich S, Maaß KK, and Seiffert M
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- Animals, Exosomes genetics, Humans, Lipids chemistry, Mice, Ultracentrifugation, Cell Separation methods, Exosomes chemistry, Extracellular Vesicles chemistry, Lymphoid Tissue chemistry
- Abstract
Small extracellular vesicles (sEVs) are nanoparticles responsible for cell-to-cell communication released by healthy and cancer cells. Different roles have been described for sEVs in physiological and pathological contexts, including acceleration of tissue regeneration, modulation of tumor microenvironment, or premetastatic niche formation, and they are discussed as promising biomarkers for diagnosis and prognosis in body fluids. Although efforts have been made to standardize techniques for isolation and characterization of sEVs, current protocols often result in co-isolation of soluble protein or lipid complexes and of other extracellular vesicles. The risk of contaminated preparations is particularly high when isolating sEVs from tissues. As a consequence, the interpretation of data aiming at understanding the functional role of sEVs remains challenging and inconsistent. Here, we report an optimized protocol for isolation of sEVs from human and murine lymphoid tissues. sEVs from freshly resected human lymph nodes and murine spleens were isolated comparing two different approaches-(1) ultracentrifugation on a sucrose density cushion and (2) combined ultracentrifugation with size-exclusion chromatography. The purity of sEV preparations was analyzed using state-of-the-art techniques, including immunoblots, nanoparticle tracking analysis, and electron microscopy. Our results clearly demonstrate the superiority of size-exclusion chromatography, which resulted in a higher yield and purity of sEVs, and we show that their functionality alters significantly between the two isolation protocols.
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- 2020
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13. Cardiomyocyte-Specific Snrk Prevents Inflammation in the Heart.
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Thirugnanam K, Cossette SM, Lu Q, Chowdhury SR, Harmann LM, Gupta A, Spearman AD, Sonin DL, Bordas M, Kumar SN, Pan AY, Simpson PM, Strande JL, Bishop E, Zou MH, and Ramchandran R
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- Angiotensin II pharmacology, Animals, Cell Line, Fibrosis genetics, Fibrosis metabolism, Fibrosis pathology, Heart drug effects, Heart Failure metabolism, Heart Failure pathology, In Vitro Techniques, Inflammation metabolism, Inflammation pathology, Macrophages metabolism, Macrophages pathology, Mice, Mice, Knockout, Myocardium pathology, Vasoconstrictor Agents pharmacology, Ventricular Dysfunction, Left, Endothelial Cells metabolism, Heart Failure genetics, Inflammation genetics, Myocardium metabolism, Myocytes, Cardiac metabolism, NF-kappa B metabolism, Protein Serine-Threonine Kinases genetics
- Abstract
Background The SNRK (sucrose-nonfermenting-related kinase) enzyme is critical for cardiac function. However, the underlying cause for heart failure observed in Snrk cardiac conditional knockout mouse is unknown. Methods and Results Previously, 6-month adult mice knocked out for Snrk in cardiomyocytes (CMs) displayed left ventricular dysfunction. Here, 4-month adult mice, on angiotensin II (Ang II) infusion, show rapid decline in cardiac systolic function, which leads to heart failure and death in 2 weeks. These mice showed increased expression of nuclear factor κ light chain enhancer of activated B cells (NF-κB), inflammatory signaling proteins, proinflammatory proteins in the heart, and fibrosis. Interestingly, under Ang II infusion, mice knocked out for Snrk in endothelial cells did not show significant systolic or diastolic dysfunction. Although an NF-κB inflammation signaling pathway was increased in Snrk knockout endothelial cells, this did not lead to fibrosis or mortality. In hearts of adult mice knocked out for Snrk in CMs, we also observed NF-κB pathway activation in CMs, and an increased presence of Mac2
+ macrophages was observed in basal and Ang II-infused states. In vitro analysis of Snrk knockdown HL-1 CMs revealed similar upregulation of the NF-κB signaling proteins and proinflammatory proteins that was exacerbated on Ang II treatment. The Ang II-induced NF-κB pathway-mediated proinflammatory effects were mediated in part through protein kinase B or AKT, wherein AKT inhibition restored the proinflammatory signaling protein levels to baseline in Snrk knockdown HL-1 CMs. Conclusions During heart failure, SNRK acts as a cardiomyocyte-specific repressor of cardiac inflammation and fibrosis.- Published
- 2019
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14. Downregulation of TREM-like transcript-1 and collagen receptor α2 subunit, two novel RUNX1-targets, contributes to platelet dysfunction in familial platelet disorder with predisposition to acute myelogenous leukemia.
- Author
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Glembotsky AC, Sliwa D, Bluteau D, Balayn N, Marin Oyarzún CP, Raimbault A, Bordas M, Droin N, Pirozhkova I, Washington V, Goette NP, Marta RF, Favier R, Raslova H, and Heller PG
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- Blood Platelet Disorders blood, Blood Platelets metabolism, Disease Susceptibility, Gene Expression Profiling, Humans, Leukemia, Myeloid, Acute diagnosis, Megakaryocytes metabolism, Mutation, Platelet Aggregation, Platelet Function Tests, Protein Binding, Blood Platelet Disorders genetics, Blood Platelet Disorders metabolism, Core Binding Factor Alpha 2 Subunit metabolism, Gene Expression Regulation, Integrin alpha2 genetics, Leukemia, Myeloid, Acute etiology, Receptors, Immunologic genetics
- Abstract
Germline RUNX1 mutations lead to thrombocytopenia and platelet dysfunction in familial platelet disorder with predisposition to acute myelogenous leukemia (AML). Multiple aspects of platelet function are impaired in these patients, associated with altered expression of genes regulated by RUNX1 We aimed to identify RUNX1 -targets involved in platelet function by combining transcriptome analysis of patient and sh RUNX1 -transduced megakaryocytes (MK). Down-regulated genes included TREM-like transcript (TLT)-1 (TREML1) and the integrin subunit alpha (α)-2 (ITGA2) of collagen receptor α2-beta (β)-1, which are involved in platelet aggregation and adhesion, respectively. RUNX1 binding to regions enriched for H3K27Ac marks was demonstrated for both genes using chromatin immunoprecipitation. Cloning of these regions upstream of the respective promoters in lentivirus allowing mCherry reporter expression showed that RUNX1 positively regulates TREML1 and ITGA2 , and this regulation was abrogated after deletion of RUNX1 sites. TLT-1 content was reduced in patient MK and platelets. A blocking anti-TLT-1 antibody was able to block aggregation of normal but not patient platelets, whereas recombinant soluble TLT-1 potentiated fibrinogen binding to patient platelets, pointing to a role for TLT-1 deficiency in the platelet function defect. Low levels of α2 integrin subunit were demonstrated in patient platelets and MK, coupled with reduced platelet and MK adhesion to collagen, both under static and flow conditions. In conclusion, we show that gene expression profiling of RUNX1 knock-down or mutated MK provides a suitable approach to identify novel RUNX1 targets, among which downregulation of TREML1 and ITGA2 clearly contribute to the platelet phenotype of familial platelet disorder with predisposition to AML., (Copyright© 2019 Ferrata Storti Foundation.)
- Published
- 2019
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15. Non-arteritic anterior ischemic optic neuropathy - Case report.
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Bordas M, Tabacaru B, and Stanca TH
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- Humans, Male, Middle Aged, Visual Acuity, Visual Fields, Optic Disk, Optic Neuropathy, Ischemic diagnosis, Optic Neuropathy, Ischemic therapy
- Abstract
We present a case of Non-Arteritic Anterior Ischemic Optic Neuropathy (NA-AION) with uncertain etiology but a good recovery with a total gain of central visual acuity.
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- 2018
16. Nfix Promotes Survival of Immature Hematopoietic Cells via Regulation of c-Mpl.
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Hall T, Walker M, Ganuza M, Holmfeldt P, Bordas M, Kang G, Bi W, Palmer LE, Finkelstein D, and McKinney-Freeman S
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- Animals, Humans, Mice, Signal Transduction, Hematopoietic Stem Cells metabolism, NFI Transcription Factors metabolism, Receptors, Thrombopoietin metabolism
- Abstract
Hematopoietic stem and progenitor cells (HSPCs) are necessary for life-long blood production and replenishment of the hematopoietic system during stress. We recently reported that nuclear factor I/X (Nfix) promotes HSPC survival post-transplant. Here, we report that ectopic expression of Nfix in primary mouse HSPCs extends their ex vivo culture from about 20 to 40 days. HSPCs overexpressing Nfix display hypersensitivity to supportive cytokines and reduced apoptosis when subjected to cytokine deprivation relative to controls. Ectopic Nfix resulted in elevated levels of c-Mpl transcripts and cell surface protein on primary murine HSPCs as well as increased phosphorylation of STAT5, which is known to be activated down-stream of c-MPL. Blocking c-MPL signaling by removal of thrombopoietin or addition of a c-MPL neutralizing antibody negated the antiapoptotic effect of Nfix overexpression on cultured HSPCs. Furthermore, NFIX was capable of binding to and transcriptionally activating a proximal c-Mpl promoter fragment. In sum, these data suggest that NFIX-mediated upregulation of c-Mpl transcription can protect primitive hematopoietic cells from stress ex vivo. Stem Cells 2018;36:943-950., (© AlphaMed Press 2018.)
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- 2018
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17. SNRK (Sucrose Nonfermenting 1-Related Kinase) Promotes Angiogenesis In Vivo.
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Lu Q, Xie Z, Yan C, Ding Y, Ma Z, Wu S, Qiu Y, Cossette SM, Bordas M, Ramchandran R, and Zou MH
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- Animals, Antigens, CD genetics, Antigens, CD metabolism, Apoptosis, Blood Flow Velocity, Cadherins genetics, Cadherins metabolism, Cell Movement, Cell Proliferation, Cells, Cultured, Disease Models, Animal, Endothelial Cells pathology, Gene Expression Regulation, Enzymologic, Hindlimb, Human Umbilical Vein Endothelial Cells enzymology, Humans, Hypoxia-Inducible Factor 1, alpha Subunit genetics, Hypoxia-Inducible Factor 1, alpha Subunit metabolism, Integrin beta1 genetics, Integrin beta1 metabolism, Ischemia genetics, Ischemia physiopathology, Mice, Inbred C57BL, Mice, Knockout, Promoter Regions, Genetic, Protein Serine-Threonine Kinases deficiency, Protein Serine-Threonine Kinases genetics, Regional Blood Flow, Sp1 Transcription Factor genetics, Sp1 Transcription Factor metabolism, Endothelial Cells enzymology, Ischemia enzymology, Lung blood supply, Muscle, Skeletal blood supply, Neovascularization, Physiologic, Protein Serine-Threonine Kinases metabolism, Retinal Vessels enzymology
- Abstract
Objective: SNRK (sucrose nonfermenting 1-related kinase) is a novel member of the AMPK (adenosine monophosphate-activated protein kinase)-related superfamily that is activated in the process of angiogenesis. Currently, little is known about the function of SNRK in angiogenesis in the physiological and pathological conditions., Approach and Results: In this study, in Snrk global heterozygous knockout mice, retina angiogenesis and neovessel formation after hindlimb ischemia were suppressed. Consistently, mice with endothelial cell (EC)-specific Snrk deletion exhibited impaired retina angiogenesis, and delayed perfusion recovery and exacerbated muscle apoptosis in ischemic hindlimbs, compared with those of littermate wide-type mice. Endothelial SNRK expression was increased in the extremity vessel samples from nonischemic human. In ECs cultured in hypoxic conditions, HIF1α (hypoxia inducible factor 1α) bound to the SNRK promoter to upregulate SNRK expression. In the nuclei of hypoxic ECs, SNRK complexed with SP1 (specificity protein 1), and together, they bound to an SP1-binding motif in the ITGB1 (β1 integrin) promoter, resulting in enhanced ITGB1 expression and promoted EC migration. Furthermore, SNRK or SP1 deficiency in ECs ameliorated hypoxia-induced ITGB1 expression and, consequently, inhibited EC migration and angiogenesis., Conclusions: Taken together, our data have revealed that SNRK/SP1-ITGB1 signaling axis promotes angiogenesis in vivo., (© 2017 American Heart Association, Inc.)
- Published
- 2018
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18. Dual Specificity Phosphatase 5 Is Essential for T Cell Survival.
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Kutty RG, Xin G, Schauder DM, Cossette SM, Bordas M, Cui W, and Ramchandran R
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- Animals, Blotting, Western, CD8-Positive T-Lymphocytes enzymology, CD8-Positive T-Lymphocytes metabolism, CD8-Positive T-Lymphocytes virology, Cell Survival genetics, Cells, Cultured, Dual-Specificity Phosphatases metabolism, Gene Expression Regulation, Enzymologic, Interferon-gamma metabolism, Lymphocytic choriomeningitis virus physiology, Mice, Inbred C57BL, Mice, Knockout, Reverse Transcriptase Polymerase Chain Reaction, T-Lymphocytes enzymology, T-Lymphocytes virology, Tumor Necrosis Factor-alpha metabolism, Apoptosis genetics, Cell Proliferation genetics, Dual-Specificity Phosphatases genetics, T-Lymphocytes metabolism
- Abstract
The mitogen-activated protein kinase (MAPK) pathway regulates many key cellular processes such as differentiation, apoptosis, and survival. The final proteins in this pathway, ERK1/2, are regulated by dual specificity phosphatase 5 (DUSP5). DUSP5 is a nuclear, inducible phosphatase with high affinity and fidelity for ERK1/2. By regulating the final step in the MAPK signaling cascade, DUSP5 exerts strong regulatory control over a central cellular pathway. Like other DUSPs, DUSP5 plays an important role in immune function. In this study, we have utilized new knockout mouse reagents to explore its function further. We demonstrate that global loss of DUSP5 does not result in any gross phenotypic changes. However, loss of DUSP5 affects memory/effector CD8+ T cell populations in response to acute viral infection. Specifically, Dusp5-/- mice have decreased proportions of short-lived effector cells (SLECs) and increased proportions of memory precursor effector cells (MPECs) in response to infection. Further, we show that this phenotype is T cell intrinsic; a bone marrow chimera model restricting loss of DUSP5 to the CD8+ T cell compartment displays a similar phenotype. Dusp5-/- T cells also display increased proliferation, increased apoptosis, and altered metabolic profiles, suggesting that DUSP5 is a pro-survival protein in T cells., Competing Interests: The authors have declared that no competing interests exist.
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- 2016
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19. Nogo-B receptor deficiency causes cerebral vasculature defects during embryonic development in mice.
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Rana U, Liu Z, Kumar SN, Zhao B, Hu W, Bordas M, Cossette S, Szabo S, Foeckler J, Weiler H, Chrzanowska-Wodnicka M, Holtz ML, Misra RP, Salato V, North PE, Ramchandran R, and Miao QR
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- Animals, Female, Mice, Mice, Knockout, Pregnancy, Blood Vessels embryology, Cerebrovascular Circulation, Receptors, Cell Surface genetics
- Abstract
Nogo-B receptor (NgBR) was identified as a receptor specific for Nogo-B. Our previous work has shown that Nogo-B and its receptor (NgBR) are essential for chemotaxis and morphogenesis of endothelial cells in vitro and intersomitic vessel formation via Akt pathway in zebrafish. Here, we further demonstrated the roles of NgBR in regulating vasculature development in mouse embryo and primitive blood vessel formation in embryoid body culture systems, respectively. Our results showed that NgBR homozygous knockout mice are embryonically lethal at E7.5 or earlier, and Tie2Cre-mediated endothelial cell-specific NgBR knockout (NgBR ecKO) mice die at E11.5 and have severe blood vessel assembly defects in embryo. In addition, mutant embryos exhibit dilation of cerebral blood vessel, resulting in thin-walled endothelial caverns. The similar vascular defects also were detected in Cdh5(PAC)-CreERT2 NgBR inducible ecKO mice. Murine NgBR gene-targeting embryonic stem cells (ESC) were generated by homologous recombination approaches. Homozygous knockout of NgBR in ESC results in cell apoptosis. Heterozygous knockout of NgBR does not affect ESC cell survival, but reduces the formation and branching of primitive blood vessels in embryoid body culture systems. Mechanistically, NgBR knockdown not only decreases both Nogo-B and VEGF-stimulated endothelial cell migration by abolishing Akt phosphorylation, but also decreases the expression of CCM1 and CCM2 proteins. Furthermore, we performed immunofluorescence (IF) staining of NgBR in human cerebral cavernous malformation patient tissue sections. The quantitative analysis results showed that NgBR expression levels in CD31 positive endothelial cells is significantly decreased in patient tissue sections. These results suggest that NgBR may be one of important genes coordinating the cerebral vasculature development., (Copyright © 2016 Elsevier Inc. All rights reserved.)
- Published
- 2016
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20. Endothelial Cell Surface Expressed Chemotaxis and Apoptosis Regulator (ECSCR) Regulates Lipolysis in White Adipocytes via the PTEN/AKT Signaling Pathway.
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Kilari S, Cossette S, Pooya S, Bordas M, Huang YW, Ramchandran R, and Wilkinson GA
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- 3T3-L1 Cells, Adipocytes, White cytology, Animals, Apoptosis Regulatory Proteins genetics, Membrane Proteins, Mice, Mice, Knockout, PTEN Phosphohydrolase genetics, Proto-Oncogene Proteins c-akt genetics, Triglycerides genetics, Triglycerides metabolism, Adipocytes, White metabolism, Apoptosis Regulatory Proteins metabolism, Lipolysis physiology, PTEN Phosphohydrolase metabolism, Proto-Oncogene Proteins c-akt metabolism, Signal Transduction physiology
- Abstract
Elevated plasma triglycerides are associated with increased susceptibility to heart disease and stroke, but the mechanisms behind this relationship are unclear. A clearer understanding of gene products which influence plasma triglycerides might help identify new therapeutic targets for these diseases. The Endothelial Cell Surface expressed Chemotaxis and apoptosis Regulator (ECSCR) was initially studied as an endothelial cell marker, but has recently been identified in white adipocytes, the primary storage cell type for triglycerides. Here we confirm ECSCR expression in white adipocytes and show that Ecscr knockout mice show elevated fasting plasma triglycerides. At a cellular level, cultured 3T3-L1 adipocytes silenced for Ecscr show a blunted Akt phosphorylation response. Additionally we show that the phosphatase and tensin homology containing (PTEN) lipid phosphatase association with ECSCR is increased by insulin stimulation. These data suggest a scenario by which ECSCR contributes to control of white adipocyte lipolysis. In this scenario, white adipocytes lacking Ecscr display elevated PTEN activity, thereby reducing AKT activation and impairing insulin-mediated suppression of lipolysis. Collectively, these results suggest that ECSCR plays a critical function in regulating lipolysis in white adipose tissue.
- Published
- 2015
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21. Sucrose non-fermenting related kinase enzyme is essential for cardiac metabolism.
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Cossette SM, Gastonguay AJ, Bao X, Lerch-Gaggl A, Zhong L, Harmann LM, Koceja C, Miao RQ, Vakeel P, Chun C, Li K, Foeckler J, Bordas M, Weiler H, Strande J, Palecek SP, and Ramchandran R
- Abstract
In this study, we have identified a novel member of the AMPK family, namely Sucrose non-fermenting related kinase (Snrk), that is responsible for maintaining cardiac metabolism in mammals. SNRK is expressed in the heart, and brain, and in cell types such as endothelial cells, smooth muscle cells and cardiomyocytes (CMs). Snrk knockout (KO) mice display enlarged hearts, and die at postnatal day 0. Microarray analysis of embryonic day 17.5 Snrk hearts, and blood profile of neonates display defect in lipid metabolic pathways. SNRK knockdown CMs showed altered phospho-acetyl-coA carboxylase and phospho-AMPK levels similar to global and endothelial conditional KO mouse. Finally, adult cardiac conditional KO mouse displays severe cardiac functional defects and lethality. Our results suggest that Snrk is essential for maintaining cardiac metabolic homeostasis, and shows an autonomous role for SNRK during mammalian development., (© 2015. Published by The Company of Biologists Ltd.)
- Published
- 2014
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22. Isolation, selection, and characterization of highly ethanol-tolerant strains of Oenococcus oeni from south Catalonia.
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Bordas M, Araque I, Alegret JO, El Khoury M, Lucas P, Rozès N, Reguant C, and Bordons A
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- Fermentation, France, Genetic Variation, Molecular Sequence Data, Multilocus Sequence Typing, Oenococcus classification, Oenococcus genetics, Phylogeny, Ethanol metabolism, Oenococcus isolation & purification, Oenococcus metabolism, Wine microbiology
- Abstract
Twenty-one strains of Oenococcus oeni were isolated during the malolactic fermentation of wines from south Catalonia. Due to their high ethanol tolerance (14 %, or more), these strains may serve as promising starters. The strains were screened by assays in a wine-like medium and by their co-inoculation in wine, resulting in the selection of well-performing strains, subsequently shown not to produce the main biogenic amines and lacking the genes involved in their synthesis. The genetic diversity of the isolates was studied by multilocus sequence typing (MLST), in which seven housekeeping genes were sequenced. Although the concatenated allelic profile of some strains was the same, the profiles obtained by random amplification of polymorphic DNA together with the variable number of tandem repeats at several loci showed that none of the strains were identical. A phylogenetic tree was constructed based on MLST with the seven genes and clearly showed two phylogroups, in accordance with previous studies. The best-performing strains occurred in members of both subgroups, suggesting that the grouping of housekeeping genes is not directly related to adaptation and ethanol tolerance.
- Published
- 2013
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23. Heparin rescues factor V Leiden-associated placental failure independent of anticoagulation in a murine high-risk pregnancy model.
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An J, Waitara MS, Bordas M, Arumugam V, Hoffmann RG, Petrich BG, Sinha U, North PE, and Sood R
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- Animals, Anticoagulants pharmacology, Anticoagulants therapeutic use, Blood Coagulation genetics, Embryo, Mammalian, Factor V genetics, Female, Heparin pharmacology, Humans, Mice, Mice, Inbred C57BL, Placenta Diseases genetics, Pregnancy, Pregnancy Complications, Hematologic drug therapy, Pregnancy Complications, Hematologic etiology, Pregnancy Complications, Hematologic genetics, Blood Coagulation drug effects, Disease Models, Animal, Factor V physiology, Heparin therapeutic use, Mice, Knockout, Placenta Diseases drug therapy, Placenta Diseases etiology, Pregnancy, High-Risk blood
- Abstract
Low molecular weight heparin (LMWH) is being tested as an experimental drug for improving pregnancy outcome in women with inherited thrombophilia and placenta-mediated pregnancy complications, such as recurrent pregnancy loss. The role of thrombotic processes in these disorders remains unproven, and the issue of antithrombotic prophylaxis is intensely debated. Using a murine model of factor V Leiden-associated placental failure, we show that treatment of the mother with LMWH allows placental development to proceed and affords significant protection from fetal loss. Nonetheless, the therapeutic effect of LMWH is not replicated by anticoagulation; fondaparinux and a direct Xa inhibitor, C921-78, achieve anticoagulation similar to LMWH but produce little or no improvement in pregnancy outcome. Genetic attenuation of maternal platelet aggregation is similarly ineffective. In contrast, even a partial loss of thrombin sensitivity of maternal platelets protects pregnancies. Neonates born from these pregnancies are growth retarded, suggesting that placental function is only partially restored. The placentae are smaller but do not reveal any evidence of thrombosis. Our data demonstrate an anticoagulation-independent role of LMWH in protecting pregnancies and provide evidence against the involvement of thrombotic processes in thrombophilia-associated placental failure. Importantly, thrombin-mediated maternal platelet activation remains central in the mechanism of placental failure.
- Published
- 2013
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