7 results on '"Nunez MG"'
Search Results
2. A dominant function of LynB kinase in preventing autoimmunity.
- Author
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Brian BF 4th, Sauer ML, Greene JT, Senevirathne SE, Lindstedt AJ, Funk OL, Ruis BL, Ramirez LA, Auger JL, Swanson WL, Nunez MG, Moriarity BS, Lowell CA, Binstadt BA, and Freedman TS
- Abstract
Here, we report that the LynB splice variant of the Src-family kinase Lyn exerts a dominant immunosuppressive function in vivo, whereas the LynA isoform is uniquely required to restrain autoimmunity in female mice. We used CRISPR-Cas9 gene editing to constrain lyn splicing and expression, generating single-isoform LynA knockout (LynA
KO ) or LynBKO mice. Autoimmune disease in total LynKO mice is characterized by production of antinuclear antibodies, glomerulonephritis, impaired B cell development, and overabundance of activated B cells and proinflammatory myeloid cells. Expression of LynA or LynB alone uncoupled the developmental phenotype from the autoimmune disease: B cell transitional populations were restored, but myeloid cells and differentiated B cells were dysregulated. These changes were isoform-specific, sexually dimorphic, and distinct from the complete LynKO . Despite the apparent differences in disease etiology and penetrance, loss of either LynA or LynB had the potential to induce severe autoimmune disease with parallels to human systemic lupus erythematosus (SLE).- Published
- 2022
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- View/download PDF
3. Community Interventions to Promote Mental Health and Social Equity.
- Author
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Castillo EG, Ijadi-Maghsoodi R, Shadravan S, Moore E, Mensah MO 3rd, Docherty M, Aguilera Nunez MG, Barcelo N, Goodsmith N, Halpin LE, Morton I, Mango J, Montero AE, Koushkaki SR, Bromley E, Chung B, Jones F, Gabrielian S, Gelberg L, Greenberg JM, Kalofonos I, Kataoka SH, Miranda J, Pincus HA, Zima BT, and Wells KB
- Abstract
(Reprinted with permission from Current Psychiatry Reports (2020) 21: 35)., (Copyright © 2020 by the American Psychiatric Association.)
- Published
- 2020
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- View/download PDF
4. Unique-region phosphorylation targets LynA for rapid degradation, tuning its expression and signaling in myeloid cells.
- Author
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Brian BF 4th, Jolicoeur AS, Guerrero CR, Nunez MG, Sychev ZE, Hegre SA, Sætrom P, Habib N, Drake JM, Schwertfeger KL, and Freedman TS
- Subjects
- Animals, Humans, Jurkat Cells, Mice, Knockout, Phosphorylation, Proteolysis, Proto-Oncogene Proteins c-cbl genetics, Ubiquitin metabolism, src-Family Kinases genetics, Macrophages metabolism, Mast Cells metabolism, Myeloid Cells metabolism, Proto-Oncogene Proteins c-cbl metabolism, src-Family Kinases metabolism
- Abstract
The activity of Src-family kinases (SFKs), which phosphorylate immunoreceptor tyrosine-based activation motifs (ITAMs), is a critical factor regulating myeloid-cell activation. We reported previously that the SFK LynA is uniquely susceptible to rapid ubiquitin-mediated degradation in macrophages, functioning as a rheostat regulating signaling (Freedman et al., 2015). We now report the mechanism by which LynA is preferentially targeted for degradation and how cell specificity is built into the LynA rheostat. Using genetic, biochemical, and quantitative phosphopeptide analyses, we found that the E3 ubiquitin ligase c-Cbl preferentially targets LynA via a phosphorylated tyrosine (Y32) in its unique region. This distinct mode of c-Cbl recognition depresses steady-state expression of LynA in macrophages derived from mice. Mast cells, however, express little c-Cbl and have correspondingly high LynA. Upon activation, mast-cell LynA is not rapidly degraded, and SFK-mediated signaling is amplified relative to macrophages. Cell-specific c-Cbl expression thus builds cell specificity into the LynA checkpoint., Competing Interests: BB, AJ, CG, MN, ZS, SH, PS, NH, JD, KS, TF No competing interests declared, (© 2019, Brian et al.)
- Published
- 2019
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5. Community Engagement and Planning versus Resources for Services for Implementing Depression Quality Improvement: Exploratory Analysis for Black and Latino Adults.
- Author
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Barceló NE, Lopez A, Tang L, Aguilera Nunez MG, Jones F, Miranda J, Chung B, Arevian A, Bonds C, Izquierdo A, Dixon E, and Wells K
- Subjects
- Adult, Black or African American statistics & numerical data, Female, Hispanic or Latino statistics & numerical data, Humans, Male, Mental Health, Middle Aged, Minority Groups psychology, Program Development, Quality Improvement, Quality of Life psychology, Black or African American psychology, Community Mental Health Services methods, Depression ethnology, Depression prevention & control, Hispanic or Latino psychology
- Abstract
Objective: Racial/ethnic minorities experience disparities in depression1 and there is a paucity of evidence-based interventions to improve depression care access and outcomes. Community Partners in Care (CPIC) is a community-partnered study of depression care quality improvement (QI) in under-resourced, urban communities: Community Engagement and Planning (CEP) for multi-sector coalitions, and Resources for Services (RS) for program technical assistance.2 CEP demonstrated benefits for the overall CPIC study population; effects for Black and Latino sub-populations are unknown., Methods: This sub-analysis examines outcomes for 409 Latino and 488 Black (non-Latino) adults recruited from 90 programs who completed baseline or 6-month follow-up. Regression analyses were used to estimate CEP vs RS intervention effects on primary (Mental Health Related Quality of Life [MHRQL], Patient Health Questionnaire-9 [PHQ-9]) and community-prioritized (mental wellness, physical activity, risk for homelessness) outcomes at 6-months., Results: Baseline characteristics did not differ significantly by intervention in either group. In the adjusted analysis for Black adults, CEP resulted in decreased odds of poor MHRQL (OR: .62, 95% CI=.41-.94, P=.028) with a trend for reducing homelessness risk (OR: .60, .35-1.05, P=.69). For Latino adults, CEP resulted in greater probability of mental wellness (OR: 1.81, 1.05-3.13, P=.034) and a trend for increased physical activity (OR: 1.52, .93-2.49, P=.091)., Conclusions: Exploratory analyses of CEP for depression quality improvement suggests significant 6-month benefits in mental health outcomes for Black and Latino participants and trends for improvement in community-prioritized outcomes for both groups. Findings may inform research in multi-sector coalitions to promote equity in depression care., Competing Interests: Competing Interests: None declared.
- Published
- 2019
- Full Text
- View/download PDF
6. Biomarkers of inflammation in infants with cystic fibrosis.
- Author
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Laguna TA, Williams CB, Nunez MG, Welchlin-Bradford C, Moen CE, Reilly CS, and Wendt CH
- Subjects
- Biomarkers metabolism, Bronchoalveolar Lavage Fluid, Child, Preschool, Cohort Studies, Female, Humans, Infant, Infant, Newborn, Inflammation diagnosis, Inflammation metabolism, Longitudinal Studies, Male, Neutrophils metabolism, Prospective Studies, Sputum metabolism, Cystic Fibrosis diagnosis, Cystic Fibrosis metabolism, Neonatal Screening trends
- Abstract
Background: There are urgent needs for clinically relevant biomarkers to identify children with cystic fibrosis (CF) at risk for more progressive lung disease and to serve as outcome measures for clinical trials. Our objective was to investigate three targeted biomarkers in a population of asymptomatic CF infants., Methods: Urine, blood and lung function data were collected for 2 years from clinically stable infants diagnosed with CF by newborn screening. A subset of CF infants had bronchoscopy with lavage performed at 6 months and 1 year. Urine was collected quarterly from healthy control infants. Expectorated sputum and urine were collected quarterly for 2 years from clinically stable CF adults. Desmosine, club cell secretory protein (CCSP) and cathepsin B concentrations were measured and compared. Mixed effects models were used to identify associations between biomarker concentrations and clinical characteristics. Receiver operator characteristic curves were generated to investigate the sensitivity and specificity of the biomarkers., Results: Urinary cathepsin B was significantly higher in CF infants compared to healthy infants (p = 0.005). CF infant airway and urinary cathepsin B concentrations were significantly lower compared to adult CF subjects (p = 0.002 & p = 0.022, respectively). CF infant airway CCSP was significantly higher than adult CF subjects (p < 0.001). There was a significant correlation between CF infant plasma CCSP and BALF CCSP (p = 0.046). BALF CCSP was negatively associated with IL-8 (p = 0.017). There was no correlation between biomarker concentration and FEV
0.5 ., Conclusions: Cathepsin B and CCSP show promise as biomarkers of inflammation in CF infants. Further study is needed.- Published
- 2018
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7. Resiniferatoxin (RTX) causes a uniquely protracted musculoskeletal hyperalgesia in mice by activation of TRPV1 receptors.
- Author
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Abdelhamid RE, Kovács KJ, Honda CN, Nunez MG, and Larson AA
- Subjects
- Animals, Female, Hyperalgesia chemically induced, Mice, Musculoskeletal Pain chemically induced, Pain Measurement drug effects, Diterpenes toxicity, Hyperalgesia metabolism, Musculoskeletal Pain metabolism, Neurotoxins toxicity, Pain Measurement methods, TRPV Cation Channels metabolism
- Abstract
Unlabelled: Inactivation of transient receptor potential vanilloid-1 (TRPV1) receptors is one approach to analgesic drug development. However, TRPV1 receptors exert different effects on each modality of pain. Because muscle pain is clinically important, we compared the effect of TRPV1 ligands on musculoskeletal nociception to that on thermal and tactile nociception. Injected parenterally, capsaicin had no effect on von Frey fiber responses (tactile) but induced a transient hypothermia and hyperalgesia in both the tail flick (thermal) and grip force (musculoskeletal) assays, presumably by its agonistic action at TRPV1 sites. In contrast, resiniferatoxin (RTX) produced a chronic (>58 days) thermal antinociception, consistent with its reported ability to desensitize TRPV1 sites. In the same mice, RTX produced a transient hypothermia (7 hours) and a protracted (28-day) musculoskeletal hyperalgesia in spite of a 35.5% reduction in TRPV1 receptor immunoreactivity in muscle afferents. Once musculoskeletal hyperalgesia subsided, mice were tolerant to the hyperalgesic effects of either capsaicin or RTX whereas tolerance to hypothermia did not develop until after 3 injections. Musculoskeletal hyperalgesia was prevented but not reversed by SB-366791, a TRPV1 antagonist, indicating that TRPV1 receptors initiate but do not maintain hyperalgesia. Injected intrathecally, RTX produced only a brief musculoskeletal hyperalgesia (2 days), after which mice were tolerant to this effect., Perspective: The effect of TRPV1 receptors varies depending on modality and tissue type, such that RTX causes thermal antinociception, musculoskeletal hyperalgesia, and no effect on tactile nociception in healthy mice. Spinal TRPV1 receptors are a potential target for pain relief as they induce only a short musculoskeletal hyperalgesia followed by desensitization., (Copyright © 2013 American Pain Society. Published by Elsevier Inc. All rights reserved.)
- Published
- 2013
- Full Text
- View/download PDF
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