672 results on '"Norris, DM"'
Search Results
2. Phosphatidylserine regulates plasma membrane repair through tetraspanin-enriched macrodomains.
- Author
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Li YE, Norris DM, Xiao FN, Pandzic E, Whan RM, Fok S, Zhou M, Du G, Liu Y, Du X, and Yang H
- Subjects
- Humans, HeLa Cells, Membrane Proteins metabolism, Receptors, Steroid metabolism, Cell Membrane, Phosphatidylserines, Tetraspanins
- Abstract
The integrity of the plasma membrane is critical to cell function and survival. Cells have developed multiple mechanisms to repair damaged plasma membranes. A key process during plasma membrane repair is to limit the size of the damage, which is facilitated by the presence of tetraspanin-enriched rings surrounding damage sites. Here, we identify phosphatidylserine-enriched rings surrounding damaged sites of the plasma membrane, resembling tetraspanin-enriched rings. Importantly, the formation of both the phosphatidylserine- and tetraspanin-enriched rings requires phosphatidylserine and its transfer proteins ORP5 and ORP9. Interestingly, ORP9, but not ORP5, is recruited to the damage sites, suggesting cells acquire phosphatidylserine from multiple sources upon plasma membrane damage. We further demonstrate that ORP9 contributes to efficient plasma membrane repair. Our results thus unveil a role for phosphatidylserine and its transfer proteins in facilitating the formation of tetraspanin-enriched macrodomains and plasma membrane repair., (© 2024 Li et al.)
- Published
- 2024
- Full Text
- View/download PDF
3. Limited oxygen in standard cell culture alters metabolism and function of differentiated cells.
- Author
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Tan J, Virtue S, Norris DM, Conway OJ, Yang M, Bidault G, Gribben C, Lugtu F, Kamzolas I, Krycer JR, Mills RJ, Liang L, Pereira C, Dale M, Shun-Shion AS, Baird HJ, Horscroft JA, Sowton AP, Ma M, Carobbio S, Petsalaki E, Murray AJ, Gershlick DC, Nathan JA, Hudson JE, Vallier L, Fisher-Wellman KH, Frezza C, Vidal-Puig A, and Fazakerley DJ
- Subjects
- Humans, Cell Culture Techniques methods, Animals, Glycolysis, Hepatocytes metabolism, Cell Hypoxia, Mitochondria metabolism, Mice, Hypoxia-Inducible Factor 1, alpha Subunit metabolism, Hypoxia-Inducible Factor 1, alpha Subunit genetics, Cells, Cultured, Glucose metabolism, Macrophages metabolism, Oxygen metabolism, Adipocytes metabolism, Adipocytes cytology, Cell Differentiation
- Abstract
The in vitro oxygen microenvironment profoundly affects the capacity of cell cultures to model physiological and pathophysiological states. Cell culture is often considered to be hyperoxic, but pericellular oxygen levels, which are affected by oxygen diffusivity and consumption, are rarely reported. Here, we provide evidence that several cell types in culture actually experience local hypoxia, with important implications for cell metabolism and function. We focused initially on adipocytes, as adipose tissue hypoxia is frequently observed in obesity and precedes diminished adipocyte function. Under standard conditions, cultured adipocytes are highly glycolytic and exhibit a transcriptional profile indicative of physiological hypoxia. Increasing pericellular oxygen diverted glucose flux toward mitochondria, lowered HIF1α activity, and resulted in widespread transcriptional rewiring. Functionally, adipocytes increased adipokine secretion and sensitivity to insulin and lipolytic stimuli, recapitulating a healthier adipocyte model. The functional benefits of increasing pericellular oxygen were also observed in macrophages, hPSC-derived hepatocytes and cardiac organoids. Our findings demonstrate that oxygen is limiting in many terminally-differentiated cell types, and that considering pericellular oxygen improves the quality, reproducibility and translatability of culture models., (© 2024. The Author(s).)
- Published
- 2024
- Full Text
- View/download PDF
4. Burnout and Moral Injury Among Black Psychiatrists and Other Black Mental Health Professionals.
- Author
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Norris DM and Primm A
- Subjects
- Humans, United States epidemiology, Mental Health, Pandemics, Psychiatrists, Burnout, Psychological, Stress Disorders, Post-Traumatic, Racism
- Abstract
This column discusses burnout and moral injury among Black psychiatrists and other Black mental health professionals and highlights the contribution of racism to these outcomes. In the United States, the COVID-19 pandemic and racial turmoil have revealed stark inequities in health care and social justice, and demand for mental health services has increased. To meet the mental health needs of communities, racism must be recognized as a factor in burnout and moral injury. The authors offer preventive strategies to support the mental health, well-being, and longevity of Black mental health professionals., Competing Interests: The authors report no financial relationships with commercial interests.
- Published
- 2024
- Full Text
- View/download PDF
5. Trafficking regulator of GLUT4-1 (TRARG1) is a GSK3 substrate.
- Author
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Duan, X, Norris, DM, Humphrey, SJ, Yang, P, Cooke, KC, Bultitude, WP, Parker, BL, Conway, OJ, Burchfield, JG, Krycer, JR, Brodsky, FM, James, DE, Fazakerley, DJ, Duan, X, Norris, DM, Humphrey, SJ, Yang, P, Cooke, KC, Bultitude, WP, Parker, BL, Conway, OJ, Burchfield, JG, Krycer, JR, Brodsky, FM, James, DE, and Fazakerley, DJ
- Abstract
Trafficking regulator of GLUT4-1, TRARG1, positively regulates insulin-stimulated GLUT4 trafficking and insulin sensitivity. However, the mechanism(s) by which this occurs remain(s) unclear. Using biochemical and mass spectrometry analyses we found that TRARG1 is dephosphorylated in response to insulin in a PI3K/Akt-dependent manner and is a novel substrate for GSK3. Priming phosphorylation of murine TRARG1 at serine 84 allows for GSK3-directed phosphorylation at serines 72, 76 and 80. A similar pattern of phosphorylation was observed in human TRARG1, suggesting that our findings are translatable to human TRARG1. Pharmacological inhibition of GSK3 increased cell surface GLUT4 in cells stimulated with a submaximal insulin dose, and this was impaired following Trarg1 knockdown, suggesting that TRARG1 acts as a GSK3-mediated regulator in GLUT4 trafficking. These data place TRARG1 within the insulin signaling network and provide insights into how GSK3 regulates GLUT4 trafficking in adipocytes.
- Published
- 2022
6. Genome-wide association study and functional characterization identifies candidate genes for insulin-stimulated glucose uptake.
- Author
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Williamson A, Norris DM, Yin X, Broadaway KA, Moxley AH, Vadlamudi S, Wilson EP, Jackson AU, Ahuja V, Andersen MK, Arzumanyan Z, Bonnycastle LL, Bornstein SR, Bretschneider MP, Buchanan TA, Chang YC, Chuang LM, Chung RH, Clausen TD, Damm P, Delgado GE, de Mello VD, Dupuis J, Dwivedi OP, Erdos MR, Fernandes Silva L, Frayling TM, Gieger C, Goodarzi MO, Guo X, Gustafsson S, Hakaste L, Hammar U, Hatem G, Herrmann S, Højlund K, Horn K, Hsueh WA, Hung YJ, Hwu CM, Jonsson A, Kårhus LL, Kleber ME, Kovacs P, Lakka TA, Lauzon M, Lee IT, Lindgren CM, Lindström J, Linneberg A, Liu CT, Luan J, Aly DM, Mathiesen E, Moissl AP, Morris AP, Narisu N, Perakakis N, Peters A, Prasad RB, Rodionov RN, Roll K, Rundsten CF, Sarnowski C, Savonen K, Scholz M, Sharma S, Stinson SE, Suleman S, Tan J, Taylor KD, Uusitupa M, Vistisen D, Witte DR, Walther R, Wu P, Xiang AH, Zethelius B, Ahlqvist E, Bergman RN, Chen YI, Collins FS, Fall T, Florez JC, Fritsche A, Grallert H, Groop L, Hansen T, Koistinen HA, Komulainen P, Laakso M, Lind L, Loeffler M, März W, Meigs JB, Raffel LJ, Rauramaa R, Rotter JI, Schwarz PEH, Stumvoll M, Sundström J, Tönjes A, Tuomi T, Tuomilehto J, Wagner R, Barroso I, Walker M, Grarup N, Boehnke M, Wareham NJ, Mohlke KL, Wheeler E, O'Rahilly S, Fazakerley DJ, and Langenberg C
- Subjects
- Humans, Insulin genetics, Genome-Wide Association Study, Glucose metabolism, Blood Glucose genetics, Insulin Resistance genetics, Diabetes Mellitus, Type 2 genetics
- Abstract
Distinct tissue-specific mechanisms mediate insulin action in fasting and postprandial states. Previous genetic studies have largely focused on insulin resistance in the fasting state, where hepatic insulin action dominates. Here we studied genetic variants influencing insulin levels measured 2 h after a glucose challenge in >55,000 participants from three ancestry groups. We identified ten new loci (P < 5 × 10
-8 ) not previously associated with postchallenge insulin resistance, eight of which were shown to share their genetic architecture with type 2 diabetes in colocalization analyses. We investigated candidate genes at a subset of associated loci in cultured cells and identified nine candidate genes newly implicated in the expression or trafficking of GLUT4, the key glucose transporter in postprandial glucose uptake in muscle and fat. By focusing on postprandial insulin resistance, we highlighted the mechanisms of action at type 2 diabetes loci that are not adequately captured by studies of fasting glycemic traits., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)- Published
- 2023
- Full Text
- View/download PDF
7. Phosphoproteomics reveals rewiring of the insulin signaling network and multi-nodal defects in insulin resistance.
- Author
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Fazakerley DJ, van Gerwen J, Cooke KC, Duan X, Needham EJ, Díaz-Vegas A, Madsen S, Norris DM, Shun-Shion AS, Krycer JR, Burchfield JG, Yang P, Wade MR, Brozinick JT, James DE, and Humphrey SJ
- Subjects
- Humans, Glycogen Synthase Kinase 3 metabolism, Insulin metabolism, Phosphorylation, Signal Transduction physiology, Proteome metabolism, Diabetes Mellitus, Type 2 metabolism, Insulin Resistance physiology
- Abstract
The failure of metabolic tissues to appropriately respond to insulin ("insulin resistance") is an early marker in the pathogenesis of type 2 diabetes. Protein phosphorylation is central to the adipocyte insulin response, but how adipocyte signaling networks are dysregulated upon insulin resistance is unknown. Here we employ phosphoproteomics to delineate insulin signal transduction in adipocyte cells and adipose tissue. Across a range of insults causing insulin resistance, we observe a marked rewiring of the insulin signaling network. This includes both attenuated insulin-responsive phosphorylation, and the emergence of phosphorylation uniquely insulin-regulated in insulin resistance. Identifying dysregulated phosphosites common to multiple insults reveals subnetworks containing non-canonical regulators of insulin action, such as MARK2/3, and causal drivers of insulin resistance. The presence of several bona fide GSK3 substrates among these phosphosites led us to establish a pipeline for identifying context-specific kinase substrates, revealing widespread dysregulation of GSK3 signaling. Pharmacological inhibition of GSK3 partially reverses insulin resistance in cells and tissue explants. These data highlight that insulin resistance is a multi-nodal signaling defect that includes dysregulated MARK2/3 and GSK3 activity., (© 2023. The Author(s).)
- Published
- 2023
- Full Text
- View/download PDF
8. PI(3)P and DFCP1 regulate the biogenesis of lipid droplets.
- Author
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Lukmantara I, Chen F, Mak HY, Zadoorian A, Du X, Xiao FN, Norris DM, Pandzic E, Whan R, Zhong Q, and Yang H
- Subjects
- Lipid Metabolism, Lipid Droplets metabolism, Phospholipids metabolism
- Abstract
The biogenesis of lipid droplets (LDs), key organelles for cellular lipid storage and homeostasis, remains poorly understood. Seipin is essential to normal LD biogenesis but exactly how it regulates LD initiation remains to be elucidated. Our previous results suggested that seipin may bind anionic phospholipids such as PI(3)P. Here, we investigate whether PI(3)P is functionally linked to seipin and whether PI(3)P can also impact LD biogenesis. In seipin-deficient cells, there were enlarged PI(3)P puncta where its effector, DFCP1, also appeared to congregate. Reducing cellular PI(3)P partially rescued the defective LD initiation caused by seipin deficiency. Increasing PI(3)P impeded the lipidation of nascent LDs. We further demonstrated that DFCP1 localized to LDs and facilitated the efficient lipidation of nascent LDs. However, the normal function and localization of DFCP1 were disrupted when cellular PI(3)P homeostasis was perturbed. Our results thus identify PI(3)P as a novel regulator of LD initiation and suggest that PI(3)P may impact the biogenesis of LDs through DFCP1.
- Published
- 2022
- Full Text
- View/download PDF
9. A high-content endogenous GLUT4 trafficking assay reveals new aspects of adipocyte biology.
- Author
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Diaz-Vegas A, Norris DM, Jall-Rogg S, Cooke KC, Conway OJ, Shun-Shion AS, Duan X, Potter M, van Gerwen J, Baird HJ, Humphrey SJ, James DE, Fazakerley DJ, and Burchfield JG
- Subjects
- Mice, Animals, 3T3-L1 Cells, Insulin metabolism, Glucose Transporter Type 4 genetics, Glucose Transporter Type 4 metabolism, Glucose metabolism, Biology, rab GTP-Binding Proteins metabolism, Adipocytes metabolism
- Abstract
Insulin-induced GLUT4 translocation to the plasma membrane in muscle and adipocytes is crucial for whole-body glucose homeostasis. Currently, GLUT4 trafficking assays rely on overexpression of tagged GLUT4. Here we describe a high-content imaging platform for studying endogenous GLUT4 translocation in intact adipocytes. This method enables high fidelity analysis of GLUT4 responses to specific perturbations, multiplexing of other trafficking proteins and other features including lipid droplet morphology. Using this multiplexed approach we showed that Vps45 and Rab14 are selective regulators of GLUT4, but Trarg1 , Stx6 , Stx16 , Tbc1d4 and Rab10 knockdown affected both GLUT4 and TfR translocation. Thus, GLUT4 and TfR translocation machinery likely have some overlap upon insulin-stimulation. In addition, we identified Kif13A, a Rab10 binding molecular motor, as a novel regulator of GLUT4 traffic. Finally, comparison of endogenous to overexpressed GLUT4 highlights that the endogenous GLUT4 methodology has an enhanced sensitivity to genetic perturbations and emphasises the advantage of studying endogenous protein trafficking for drug discovery and genetic analysis of insulin action in relevant cell types., (© 2022 Diaz-Vegas et al.)
- Published
- 2022
- Full Text
- View/download PDF
10. Trafficking regulator of GLUT4-1 (TRARG1) is a GSK3 substrate.
- Author
-
Duan X, Norris DM, Humphrey SJ, Yang P, Cooke KC, Bultitude WP, Parker BL, Conway OJ, Burchfield JG, Krycer JR, Brodsky FM, James DE, and Fazakerley DJ
- Subjects
- Adipocytes metabolism, Animals, Cell Membrane metabolism, Glucose metabolism, Glucose Transporter Type 4 genetics, Glucose Transporter Type 4 metabolism, Humans, Insulin metabolism, Mice, Phosphorylation, Proto-Oncogene Proteins c-akt genetics, Proto-Oncogene Proteins c-akt metabolism, Serine metabolism, Glycogen Synthase Kinase 3 genetics, Glycogen Synthase Kinase 3 metabolism, Phosphatidylinositol 3-Kinases metabolism
- Abstract
Trafficking regulator of GLUT4-1, TRARG1, positively regulates insulin-stimulated GLUT4 trafficking and insulin sensitivity. However, the mechanism(s) by which this occurs remain(s) unclear. Using biochemical and mass spectrometry analyses we found that TRARG1 is dephosphorylated in response to insulin in a PI3K/Akt-dependent manner and is a novel substrate for GSK3. Priming phosphorylation of murine TRARG1 at serine 84 allows for GSK3-directed phosphorylation at serines 72, 76 and 80. A similar pattern of phosphorylation was observed in human TRARG1, suggesting that our findings are translatable to human TRARG1. Pharmacological inhibition of GSK3 increased cell surface GLUT4 in cells stimulated with a submaximal insulin dose, and this was impaired following Trarg1 knockdown, suggesting that TRARG1 acts as a GSK3-mediated regulator in GLUT4 trafficking. These data place TRARG1 within the insulin signaling network and provide insights into how GSK3 regulates GLUT4 trafficking in adipocytes., (© 2022 The Author(s).)
- Published
- 2022
- Full Text
- View/download PDF
11. Phosphoproteomics reveals conserved exercise-stimulated signaling and AMPK regulation of store-operated calcium entry
- Author
-
Nelson, ME, Parker, BL, Burchfield, JG, Hoffman, NJ, Needham, EJ, Cooke, KC, Naim, T, Sylow, L, Ling, NXY, Francis, D, Norris, DM, Chaudhuri, R, Oakhill, JS, Richter, EA, Lynch, GS, Stockli, J, James, DE, Nelson, ME, Parker, BL, Burchfield, JG, Hoffman, NJ, Needham, EJ, Cooke, KC, Naim, T, Sylow, L, Ling, NXY, Francis, D, Norris, DM, Chaudhuri, R, Oakhill, JS, Richter, EA, Lynch, GS, Stockli, J, and James, DE
- Abstract
Exercise stimulates cellular and physiological adaptations that are associated with widespread health benefits. To uncover conserved protein phosphorylation events underlying this adaptive response, we performed mass spectrometry-based phosphoproteomic analyses of skeletal muscle from two widely used rodent models: treadmill running in mice and in situ muscle contraction in rats. We overlaid these phosphoproteomic signatures with cycling in humans to identify common cross-species phosphosite responses, as well as unique model-specific regulation. We identified > 22,000 phosphosites, revealing orthologous protein phosphorylation and overlapping signaling pathways regulated by exercise. This included two conserved phosphosites on stromal interaction molecule 1 (STIM1), which we validate as AMPK substrates. Furthermore, we demonstrate that AMPK-mediated phosphorylation of STIM1 negatively regulates store-operated calcium entry, and this is beneficial for exercise in Drosophila. This integrated cross-species resource of exercise-regulated signaling in human, mouse, and rat skeletal muscle has uncovered conserved networks and unraveled crosstalk between AMPK and intracellular calcium flux.
- Published
- 2019
12. Global redox proteome and phosphoproteome analysis reveals redox switch in Akt.
- Author
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Su, Z, Burchfield, JG, Yang, P, Humphrey, SJ, Yang, G, Francis, D, Yasmin, S, Shin, S-Y, Norris, DM, Kearney, AL, Astore, MA, Scavuzzo, J, Fisher-Wellman, KH, Wang, Q-P, Parker, BL, Neely, GG, Vafaee, F, Chiu, J, Yeo, R, Hogg, PJ, Fazakerley, DJ, Nguyen, LK, Kuyucak, S, James, DE, Su, Z, Burchfield, JG, Yang, P, Humphrey, SJ, Yang, G, Francis, D, Yasmin, S, Shin, S-Y, Norris, DM, Kearney, AL, Astore, MA, Scavuzzo, J, Fisher-Wellman, KH, Wang, Q-P, Parker, BL, Neely, GG, Vafaee, F, Chiu, J, Yeo, R, Hogg, PJ, Fazakerley, DJ, Nguyen, LK, Kuyucak, S, and James, DE
- Abstract
Protein oxidation sits at the intersection of multiple signalling pathways, yet the magnitude and extent of crosstalk between oxidation and other post-translational modifications remains unclear. Here, we delineate global changes in adipocyte signalling networks following acute oxidative stress and reveal considerable crosstalk between cysteine oxidation and phosphorylation-based signalling. Oxidation of key regulatory kinases, including Akt, mTOR and AMPK influences the fidelity rather than their absolute activation state, highlighting an unappreciated interplay between these modifications. Mechanistic analysis of the redox regulation of Akt identified two cysteine residues in the pleckstrin homology domain (C60 and C77) to be reversibly oxidized. Oxidation at these sites affected Akt recruitment to the plasma membrane by stabilizing the PIP3 binding pocket. Our data provide insights into the interplay between oxidative stress-derived redox signalling and protein phosphorylation networks and serve as a resource for understanding the contribution of cellular oxidation to a range of diseases.
- Published
- 2019
13. Supplemental habitat is reservoir dependent: Identifying optimal planting decision using Bayesian Decision Networks.
- Author
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Norris DM, Colvin ME, Miranda LE, and Lashley MA
- Subjects
- Animals, Bayes Theorem, Environment, Floods, Ecosystem, Fishes
- Abstract
Environmental management often requires making decisions despite system uncertainty. One such example is mudflat mediation in flood control reservoirs. Reservoir mudflats limit development of diverse fish assemblages due to the lack of structural habitat provided by plants. Seeding mudflats with agricultural plants may mimic floodplain wetlands once inundated and provide fish habitat and achieve habitat management objectives. However, planting success is uncertain because of unpredictable water level fluctuations that affect plant survival and growth. Decision support tools can account for uncertainty that influences decision outcomes and reduce the risk in reservoir mudflat planting decisions. We used Bayesian decision networks and sensitivity analyses to quantify uncertainty surrounding mudflat plantings as supplemental fish habitat in four northwest Mississippi reservoirs. When averaged across all uncertainty, planting was the optimal decision only in Enid Lake. Response profiles indicated planting decisions depended on elevation contours within Enid, Sardis, and Grenada reservoirs. No planting was optimal at all elevations for Arkabutla Lake. These results provide a quantified basis for establishing best management practices and identify key system states that influence decision outcomes. The process used in this study to evaluate planting decisions can be applied to any reservoir by modifying reservoir dependent inputs to evaluate planting decisions to provide supplemental fish habitat., (Copyright © 2021 Elsevier Ltd. All rights reserved.)
- Published
- 2022
- Full Text
- View/download PDF
14. Akt phosphorylates insulin receptor substrate to limit PI3K-mediated PIP3 synthesis.
- Author
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Kearney AL, Norris DM, Ghomlaghi M, Kin Lok Wong M, Humphrey SJ, Carroll L, Yang G, Cooke KC, Yang P, Geddes TA, Shin S, Fazakerley DJ, Nguyen LK, James DE, and Burchfield JG
- Subjects
- Animals, Antigens, CD, Cell Membrane metabolism, Computational Biology, Glucose metabolism, Humans, Insulin metabolism, Insulin Receptor Substrate Proteins metabolism, Mechanistic Target of Rapamycin Complex 1, Mice, Phosphorylation, Signal Transduction physiology, Phosphatidylinositol 3-Kinase metabolism, Phosphatidylinositol 3-Kinases metabolism, Proto-Oncogene Proteins c-akt metabolism, Receptor, Insulin metabolism
- Abstract
The phosphoinositide 3-kinase (PI3K)-Akt network is tightly controlled by feedback mechanisms that regulate signal flow and ensure signal fidelity. A rapid overshoot in insulin-stimulated recruitment of Akt to the plasma membrane has previously been reported, which is indicative of negative feedback operating on acute timescales. Here, we show that Akt itself engages this negative feedback by phosphorylating insulin receptor substrate (IRS) 1 and 2 on a number of residues. Phosphorylation results in the depletion of plasma membrane-localised IRS1/2, reducing the pool available for interaction with the insulin receptor. Together these events limit plasma membrane-associated PI3K and phosphatidylinositol (3,4,5)-trisphosphate (PIP3) synthesis. We identified two Akt-dependent phosphorylation sites in IRS2 at S306 (S303 in mouse) and S577 (S573 in mouse) that are key drivers of this negative feedback. These findings establish a novel mechanism by which the kinase Akt acutely controls PIP3 abundance, through post-translational modification of the IRS scaffold., Competing Interests: AK, DN, MG, MK, SH, LC, GY, KC, PY, TG, SS, DF, LN, JB No competing interests declared, DJ Reviewing editor, eLife, (© 2021, Kearney et al.)
- Published
- 2021
- Full Text
- View/download PDF
15. Phosphoproteomics reveals conserved exercise-stimulated signaling and AMPK regulation of store-operated calcium entry.
- Author
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Nelson ME, Parker BL, Burchfield JG, Hoffman NJ, Needham EJ, Cooke KC, Naim T, Sylow L, Ling NX, Francis D, Norris DM, Chaudhuri R, Oakhill JS, Richter EA, Lynch GS, Stöckli J, and James DE
- Published
- 2020
- Full Text
- View/download PDF
16. Phosphoproteomics reveals conserved exercise-stimulated signaling and AMPK regulation of store-operated calcium entry.
- Author
-
Nelson ME, Parker BL, Burchfield JG, Hoffman NJ, Needham EJ, Cooke KC, Naim T, Sylow L, Ling NX, Francis D, Norris DM, Chaudhuri R, Oakhill JS, Richter EA, Lynch GS, Stöckli J, and James DE
- Subjects
- Animals, Calcium Signaling physiology, Drosophila, Female, Humans, Male, Membrane Proteins, Mice, Muscle, Skeletal metabolism, Phosphorylation, Protein Conformation, Rats, Rats, Wistar, Signal Transduction, Stromal Interaction Molecule 1 chemistry, Stromal Interaction Molecule 1 genetics, AMP-Activated Protein Kinases metabolism, Calcium metabolism, Calcium Channels metabolism, Proteomics methods, Stromal Interaction Molecule 1 metabolism
- Abstract
Exercise stimulates cellular and physiological adaptations that are associated with widespread health benefits. To uncover conserved protein phosphorylation events underlying this adaptive response, we performed mass spectrometry-based phosphoproteomic analyses of skeletal muscle from two widely used rodent models: treadmill running in mice and in situ muscle contraction in rats. We overlaid these phosphoproteomic signatures with cycling in humans to identify common cross-species phosphosite responses, as well as unique model-specific regulation. We identified > 22,000 phosphosites, revealing orthologous protein phosphorylation and overlapping signaling pathways regulated by exercise. This included two conserved phosphosites on stromal interaction molecule 1 (STIM1), which we validate as AMPK substrates. Furthermore, we demonstrate that AMPK-mediated phosphorylation of STIM1 negatively regulates store-operated calcium entry, and this is beneficial for exercise in Drosophila. This integrated cross-species resource of exercise-regulated signaling in human, mouse, and rat skeletal muscle has uncovered conserved networks and unraveled crosstalk between AMPK and intracellular calcium flux., (© 2019 The Authors.)
- Published
- 2019
- Full Text
- View/download PDF
17. Global redox proteome and phosphoproteome analysis reveals redox switch in Akt.
- Author
-
Su Z, Burchfield JG, Yang P, Humphrey SJ, Yang G, Francis D, Yasmin S, Shin SY, Norris DM, Kearney AL, Astore MA, Scavuzzo J, Fisher-Wellman KH, Wang QP, Parker BL, Neely GG, Vafaee F, Chiu J, Yeo R, Hogg PJ, Fazakerley DJ, Nguyen LK, Kuyucak S, and James DE
- Subjects
- Adipocytes metabolism, Animals, Cysteine genetics, Cysteine metabolism, Humans, Mice, Oxidation-Reduction, Oxidative Stress, Phosphoproteins chemistry, Phosphoproteins genetics, Phosphorylation, Protein Domains, Proteome chemistry, Proteome genetics, Proteome metabolism, Proteomics, Proto-Oncogene Proteins c-akt chemistry, Proto-Oncogene Proteins c-akt genetics, Signal Transduction, TOR Serine-Threonine Kinases genetics, TOR Serine-Threonine Kinases metabolism, Phosphoproteins metabolism, Proto-Oncogene Proteins c-akt metabolism
- Abstract
Protein oxidation sits at the intersection of multiple signalling pathways, yet the magnitude and extent of crosstalk between oxidation and other post-translational modifications remains unclear. Here, we delineate global changes in adipocyte signalling networks following acute oxidative stress and reveal considerable crosstalk between cysteine oxidation and phosphorylation-based signalling. Oxidation of key regulatory kinases, including Akt, mTOR and AMPK influences the fidelity rather than their absolute activation state, highlighting an unappreciated interplay between these modifications. Mechanistic analysis of the redox regulation of Akt identified two cysteine residues in the pleckstrin homology domain (C60 and C77) to be reversibly oxidized. Oxidation at these sites affected Akt recruitment to the plasma membrane by stabilizing the PIP
3 binding pocket. Our data provide insights into the interplay between oxidative stress-derived redox signalling and protein phosphorylation networks and serve as a resource for understanding the contribution of cellular oxidation to a range of diseases.- Published
- 2019
- Full Text
- View/download PDF
18. Serine 474 phosphorylation is essential for maximal Akt2 kinase activity in adipocytes.
- Author
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Kearney AL, Cooke KC, Norris DM, Zadoorian A, Krycer JR, Fazakerley DJ, Burchfield JG, and James DE
- Subjects
- 3T3-L1 Cells, Adipocytes cytology, Animals, Cell Nucleus metabolism, Forkhead Box Protein O1 metabolism, Glucose metabolism, Glucose Transporter Type 4 metabolism, Heterocyclic Compounds, 3-Ring pharmacology, Insulin pharmacology, Mechanistic Target of Rapamycin Complex 1 metabolism, Mechanistic Target of Rapamycin Complex 2 metabolism, Mice, Mutagenesis, Site-Directed, Phosphorylation drug effects, Protein Biosynthesis drug effects, Proto-Oncogene Proteins c-akt genetics, Tuberous Sclerosis Complex 2 Protein metabolism, Proto-Oncogene Proteins c-akt metabolism, Serine metabolism
- Abstract
The Ser/Thr protein kinase Akt regulates essential biological processes such as cell survival, growth, and metabolism. Upon growth factor stimulation, Akt is phosphorylated at Ser
474 ; however, how this phosphorylation contributes to Akt activation remains controversial. Previous studies, which induced loss of Ser474 phosphorylation by ablating its upstream kinase mTORC2, have implicated Ser474 phosphorylation as a driver of Akt substrate specificity. Here we directly studied the role of Akt2 Ser474 phosphorylation in 3T3-L1 adipocytes by preventing Ser474 phosphorylation without perturbing mTORC2 activity. This was achieved by utilizing a chemical genetics approach, where ectopically expressed S474A Akt2 was engineered with a W80A mutation to confer resistance to the Akt inhibitor MK2206, and thus allow its activation independent of endogenous Akt. We found that insulin-stimulated phosphorylation of four bona fide Akt substrates (TSC2, PRAS40, FOXO1/3a, and AS160) was reduced by ∼50% in the absence of Ser474 phosphorylation. Accordingly, insulin-stimulated mTORC1 activation, protein synthesis, FOXO nuclear exclusion, GLUT4 translocation, and glucose uptake were attenuated upon loss of Ser474 phosphorylation. We propose a model where Ser474 phosphorylation is required for maximal Akt2 kinase activity in adipocytes., (© 2019 Kearney et al.)- Published
- 2019
- Full Text
- View/download PDF
19. New Insights into the Slope and Deep Water Regions of the Southern Grand Banks Area, Offshore Newfoundland, Canada
- Author
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Norris, DM, primary
- Published
- 2016
- Full Text
- View/download PDF
20. Before the Pump.
- Author
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Norris DM and Santoro MM
- Subjects
- Animals, Brain, Cilia, Zebrafish, Zebrafish Proteins
- Published
- 2018
- Full Text
- View/download PDF
21. Comparison of Analysis and Experimental Data for a Unique Crack Arrest Specimen
- Author
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Ayres, DJ, primary, Fabi, RJ, additional, Schonenberg, RY, additional, and Norris, DM, additional
- Published
- 1988
- Full Text
- View/download PDF
22. Applications of Fatigue and Fracture Tolerant Design Concepts in the Nuclear Power Industry
- Author
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Jones, RL, primary, Marston, TU, additional, Tagart, SW, additional, Norris, DM, additional, and Nickell, RE, additional
- Full Text
- View/download PDF
23. A Fracture-Toughness Correlation Based on Charpy Initiation Energy
- Author
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Norris, DM, primary, Reaugh, JE, additional, and Server, WL, additional
- Full Text
- View/download PDF
24. Glucose Transport: Methods for Interrogating GLUT4 Trafficking in Adipocytes.
- Author
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Norris DM, Geddes TA, James DE, Fazakerley DJ, and Burchfield JG
- Subjects
- 3T3-L1 Cells, Animals, Biological Transport, Fluorescent Antibody Technique, Mice, Molecular Imaging, Protein Transport, Adipocytes metabolism, Glucose metabolism, Glucose Transporter Type 4 metabolism
- Abstract
In this chapter we detail methods for the systematic dissection of GLUT4 trafficking. The methods described have been optimized for cultured 3T3-L1 adipocytes, but can be readily adapted to other cell types.
- Published
- 2018
- Full Text
- View/download PDF
25. An improved Akt reporter reveals intra- and inter-cellular heterogeneity and oscillations in signal transduction.
- Author
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Norris DM, Yang P, Krycer JR, Fazakerley DJ, James DE, and Burchfield JG
- Subjects
- 3T3-L1 Cells, Animals, Green Fluorescent Proteins genetics, Green Fluorescent Proteins metabolism, Mice, Molecular Imaging methods, Molecular Imaging standards, Protein Stability, Protein Transport, Recombinant Fusion Proteins genetics, Recombinant Fusion Proteins metabolism, Signal Transduction genetics, Tissue Distribution, Genes, Reporter, Proto-Oncogene Proteins c-akt genetics, Proto-Oncogene Proteins c-akt metabolism
- Abstract
Akt is a key node in a range of signal transduction cascades and play a critical role in diseases such as cancer and diabetes. Fluorescently-tagged Akt reporters have been used to discern Akt localisation, yet it has not been clear how well these tools recapitulate the behaviour of endogenous Akt proteins. Here, we observed that fusion of eGFP to Akt2 impaired both its insulin-stimulated plasma membrane recruitment and its phosphorylation. Endogenous-like responses were restored by replacing eGFP with TagRFP-T. The improved response magnitude and sensitivity afforded by TagRFP-T-Akt2 over eGFP-Akt2 enabled monitoring of signalling outcomes in single cells at physiological doses of insulin with subcellular resolution and revealed two previously unreported features of Akt biology. In 3T3-L1 adipocytes, stimulation with insulin resulted in recruitment of Akt2 to the plasma membrane in a polarised fashion. Additionally, we observed oscillations in plasma membrane localised Akt2 in the presence of insulin with a consistent periodicity of 2 min. Our studies highlight the importance of fluorophore choice when generating reporter constructs and shed light on new Akt signalling responses that may encode complex signalling information.This article has an associated First Person interview with the first author of the paper., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2017. Published by The Company of Biologists Ltd.)
- Published
- 2017
- Full Text
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26. Firearm laws, patients, and the roles of psychiatrists.
- Author
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Norris DM, Price M, Gutheil T, and Reid WH
- Abstract
OBJECTIVE: Persons with mental illness and/or substance abuse are frequently perceived by the public to be dangerous. This has resulted in an increase in state legislation restricting their ability to purchase, possess, register, obtain licensure, retain, and/or carry a firearm of any sort. The purpose of this article is to educate clinicians about the impact of firearms statutes and restrictions for their patients. Many state statutes mandate that treating psychiatrists report such gun possession to state justice or police departments. Psychiatrists may also have a statutory role in an appeals process. METHOD: The firearms statutes of the 50 states, the District of Columbia, and Puerto Rico and the Federal National Firearms Act were surveyed, with particular attention paid to the ability of persons with mental illness and/or alcohol or substance abuse to obtain firearms. The results were tabulated. RESULTS: These statutes are not uniform. They vary in their definition of mental illness, the type and duration of gun restriction, reporting practices, the confidentiality of medical information, and the immunity of clinician reporters and appeals processes. CONCLUSION: Clinicians would be wise to familiarize themselves with the provisions of the relevant statutes in their particular states. This will allow them to identify the consequences to their firearm-possessing patients, understand their own roles and obligations--if any--and better consider potential clinical and ethical issues for particular patients. [ABSTRACT FROM AUTHOR]
- Published
- 2006
- Full Text
- View/download PDF
27. Research issues. King's conceptual system and theory of goal attainment: past, present, and future.
- Author
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Frey MA, Sieloff CL, Norris DM, and Malinski VM
- Abstract
Imogene King is universally recognized as a pioneer of nursing theory development. Her interacting conceptual system for nursing and her theory of goal attainment have been included in every major nursing theory text, are taught to thousands of nursing students, form the basis of nursing education programs, and are implemented in a variety of service settings. [ABSTRACT FROM AUTHOR]
- Published
- 2002
- Full Text
- View/download PDF
28. Evaluation of preprocedural statin loading on clinical outcomes in patients undergoing elective percutaneous coronary intervention.
- Author
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Sinan, Umit Yasar, Meric, Bengisu Keskin, Bursa, Nurbanu, Moumin, Gkiozde, Kaya, Aysem, and Ozkan, Alev Arat
- Published
- 2024
- Full Text
- View/download PDF
29. Exploring the unmapped cysteine redox proteoform landscape.
- Author
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Cobley, James N.
- Subjects
TECHNOLOGICAL innovations ,CYSTEINE ,MASS spectrometry ,DRUG target ,OXIDATION-reduction reaction - Abstract
Cysteine redox proteoforms define the diverse molecular states that proteins with cysteine residues can adopt. A protein with one cysteine residue must adopt one of two binary proteoforms: reduced or oxidized. Their numbers scale: a protein with 10 cysteine residues must assume one of 1,024 proteoforms. Although they play pivotal biological roles, the vast cysteine redox proteoform landscape comprising vast numbers of theoretical proteoforms remains largely uncharted. Progress is hampered by a general underappreciation of cysteine redox proteoforms, their intricate complexity, and the formidable challenges that they pose to existing methods. The present review advances cysteine redox proteoform theory, scrutinizes methodological barriers, and elaborates innovative technologies for detecting unique residue-defined cysteine redox proteoforms. For example, chemistry-enabled hybrid approaches combining the strengths of top-down mass spectrometry (TD-MS) and bottom-up mass spectrometry (BU-MS) for systematically cataloguing cysteine redox proteoforms are delineated. These methods provide the technological means to map uncharted redox terrain. To unravel hidden redox regulatory mechanisms, discover new biomarkers, and pinpoint therapeutic targets by mining the theoretical cysteine redox proteoform space, a community-wide initiative termed the "Human Cysteine Redox Proteoform Project" is proposed. Exploring the cysteine redox proteoform landscape could transform current understanding of redox biology. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
30. Dynamism in practice: parenting within King's framework.
- Author
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Norris DM and Hoyer PJ
- Abstract
A dynamic approach to parenting in a neonatal intensive care unit provides a framework to test King's nursing theory. The framework is based on selected concepts from King's theory of goal attainment and current literature on parenting. The framework stresses the valuational components of human interaction. This article describes an attempt to move neonatal care from medicalization of parenting toward transaction between parents and nurses. [ABSTRACT FROM AUTHOR]
- Published
- 1993
- Full Text
- View/download PDF
31. Statin loading before percutaneous coronary intervention to reduce periprocedural myocardial infarction.
- Author
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Norris DM and Anderson JR
- Subjects
- Angioplasty, Balloon, Coronary adverse effects, Global Health, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors therapeutic use, Incidence, Myocardial Infarction epidemiology, Myocardial Infarction prevention & control, Perioperative Care methods, Retrospective Studies, Time Factors, Angioplasty, Balloon, Coronary methods, Hydroxymethylglutaryl-CoA Reductase Inhibitors administration & dosage, Intraoperative Complications prevention & control, Myocardial Infarction etiology
- Abstract
Periprocedural myocardial infarction (PMI) is a common complication associated with percutaneous coronary intervention (PCI), occurring in approximately 15% to 20% of patients undergoing the procedure. The established diagnostic criteria for PMI is an increase in cardiac biomarkers, specifically creatine kinase-MB levels > 3 times the upper limit of normal. As PMI has been associated with an increased risk of mortality after PCI, investigative efforts have been directed at therapies that can potentially decrease PMI. One such therapy is the use of hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) administered as a loading dose before PCI. Multiple small, randomized, controlled trials have demonstrated significant reductions in the incidence of PMI with statin loading before PCI. The risk reduction was seen in patients with stable and unstable coronary artery disease, as well in statin-naive patients or those on chronic statin therapy. Potential mechanisms for the rapid benefits of statin loading include: anti-inflammatory effects, reversal of endothelial dysfunction, decrease in oxidative stress, and inhibition of the thrombotic system. None of the current studies were of sufficient power or duration to detect benefits on mortality, though a recent meta-analysis did demonstrate a reduction in major adverse cardiovascular events. In addition to long-term effects, several additional questions remain with regard to statin loading, such as statin type, dose, and optimal timing of administration. However, given the current evidence of benefit and the low risk of adverse events, it can be recommended that all patients undergoing PCI be considered for statin loading before the procedure.
- Published
- 2012
- Full Text
- View/download PDF
32. "Certainty" and expert mental health opinions in legal proceedings.
- Author
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Drogin EY, Commons ML, Gutheil TG, Meyer DJ, and Norris DM
- Subjects
- Adult, Aged, Female, Forensic Psychiatry, Humans, Male, Middle Aged, Pilot Projects, Surveys and Questionnaires, Expert Testimony, Mental Health legislation & jurisprudence, Persuasive Communication, Uncertainty
- Abstract
This pilot study addresses the legal and scientific ramifications of the "certainty" expressed by mental health professionals when functioning as expert witnesses in criminal and civil proceedings. The sporadic attention paid to "certainty" in the professional literature has typically taken the form of general policy oriented analyses as opposed to empirical, data-driven investigations. In the current study, 25 doctoral and master's level mental health professionals were provided with 53 different statements. Some statements addressed "certainty" itself in the typical fashion (e.g., "Reasonable Degree of Scientific Certainty," "Reasonable Degree of Medical Certainty," and "Reasonable Degree of Psychological Certainty"). Other statements were confined to specifically legal standards of proof (e.g., "Beyond a Reasonable Doubt," "Preponderance of the Evidence," and "Clear and Convincing"). Additional statements included those that bore at least some direct forensic relevance (e.g., "Based upon All the Data at My Disposal," "In My Medical Opinion," and "In My Clinical Judgment"), as well as those of a non-forensic nature (e.g., "I Would Bet My Life Savings," "On My Word of Honor," and "I Am Personally Convinced"). Ratings were provided on one form as if the participant had uttered the statement, and on another form as if another expert witness had uttered the statement. Overall, participants did not tend to identify traditional legal terms as expressing the highest level of "certainty," and respondents tended to ascribe more "certainty" to the same terms when uttered by themselves as opposed to when uttered by other expert witnesses. Those providing forensic testimony will do well to accommodate the court's traditional requirements while developing and preparing to justify their own notions of just what "certainty" denotes in this context., (Copyright © 2012 Elsevier Ltd. All rights reserved.)
- Published
- 2012
- Full Text
- View/download PDF
33. Mitigating the impact of medication shortages on public health.
- Author
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Skelton Duke M, Chambliss WG, Gardner KN, and Norris DM
- Subjects
- Humans, Pharmaceutical Preparations standards, Professional Role, Public Health, Students, Pharmacy, United States, United States Food and Drug Administration, Drug Industry organization & administration, Pharmaceutical Preparations supply & distribution, Pharmacists organization & administration
- Published
- 2011
- Full Text
- View/download PDF
34. Firearms and mental illness.
- Author
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Norris DM and Price M
- Published
- 2009
35. Firearm laws: a primer for psychiatrists.
- Author
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Price M and Norris DM
- Subjects
- Homicide legislation & jurisprudence, Homicide prevention & control, Humans, Insanity Defense, Mental Disorders psychology, Substance-Related Disorders psychology, Suicide legislation & jurisprudence, United States, Violence prevention & control, Suicide Prevention, Expert Testimony legislation & jurisprudence, Firearms legislation & jurisprudence, Mental Disorders diagnosis, Substance-Related Disorders diagnosis, Violence legislation & jurisprudence
- Abstract
Persons with mental illness or substance abuse have been perceived by the public to pose an increased risk of violence to themselves and others. As a result, federal and state laws have restricted the right of certain categories of persons with mental illness or substance abuse to possess, register, license, retain, or carry a firearm. Clinicians should be familiar with the specific firearm statutes of their own states, which describe the disqualifying mental health/substance abuse history and the role and responsibility of the psychiatrist in the process. State statutes vary widely in terms of the definitions of, and reporting requirements relating to, prohibited persons with mental illness or substance abuse. States also vary in the duration of the prohibition and in the timing of the appeals process. Some of the statutes have specific provisions for the removal of a firearm when a prohibited person is identified. States may maintain a mental health database that is used to determine firearm eligibility and may forward information to the National Instant Criminal Background Check System. The National Instant Criminal Background Check System Improvement Amendments Act of 2007 will likely increase the number of persons identified as belonging to the prohibited class.
- Published
- 2010
- Full Text
- View/download PDF
36. Custodial evaluations of Native American families: implications for forensic psychiatrists.
- Author
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Wills CD and Norris DM
- Subjects
- Adoption, Child, Child Welfare legislation & jurisprudence, Child, Preschool, Expert Testimony, Female, Humans, Male, United States, Family, Forensic Psychiatry, Foster Home Care, Indians, North American
- Abstract
Native American children in the United States have been adopted by non-Indian families at rates that threaten the preservation of their Indian history, traditions, and culture. The Indian Child Welfare Act (ICWA), which established restrictive parameters that govern the placement of Native American children into foster care and adoptive homes, was ratified in an effort to keep American Indian families intact. This article addresses matters of importance to psychiatrists who conduct custody evaluations of Native American children and families. A summary of events that preceded enactment of the ICWA is given, along with guidelines for forensic psychiatrists who conduct foster and adoptive care evaluations of Native American children. We use clinical vignettes to illustrate how the ICWA informs the custody evaluation process as well as approaches to cultural concerns, including biases that forensic evaluators may encounter during these evaluations.
- Published
- 2010
37. Health care fraud: physicians as white collar criminals?
- Author
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Price M and Norris DM
- Subjects
- Drug and Narcotic Control legislation & jurisprudence, Fraud prevention & control, Health Care Reform legislation & jurisprudence, Humans, Insurance Claim Review legislation & jurisprudence, Internet, Medicaid legislation & jurisprudence, Medicare legislation & jurisprudence, Pharmaceutical Services legislation & jurisprudence, Prescription Drugs, United States, Fraud legislation & jurisprudence, Physicians legislation & jurisprudence
- Published
- 2009
38. White-collar crime: corporate and securities and commodities fraud.
- Author
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Price M and Norris DM
- Subjects
- Adult, Ethics, Business, Humans, Male, Middle Aged, Personality Assessment, Prisons legislation & jurisprudence, Public Opinion, Accounting legislation & jurisprudence, Commerce legislation & jurisprudence, Fraud legislation & jurisprudence, Investments legislation & jurisprudence
- Abstract
In this era of increased interest in white-collar crime, forensic psychiatrists are in a key position to study the individual characteristics of offenders. While a comprehensive theory of high-level white-collar crime should consider societal and organizational contributions, there is value in understanding the personal traits that place an individual at high risk for offending. As the impact of the criminal acts of this group has been increasingly felt by larger groups from all socioeconomic strata, there is less willingness by the public to view these crimes as victimless and harmless.
- Published
- 2009
39. Nursing students' perceptions of barriers to addressing patient sexuality concerns.
- Author
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Magnan MA and Norris DM
- Subjects
- Adult, Education, Nursing, Baccalaureate, Education, Professional, Retraining, Female, Health Services Accessibility, Humans, Male, Middle Aged, Needs Assessment, Nurse's Role psychology, Nursing Assessment, Nursing Education Research, Nursing Methodology Research, Patient Education as Topic, Sex Education, Statistics, Nonparametric, Surveys and Questionnaires, Time Management, Attitude of Health Personnel, Clinical Competence standards, Health Knowledge, Attitudes, Practice, Self Efficacy, Sexuality psychology, Students, Nursing psychology
- Abstract
Little is known about nursing students' perceptions of barriers to addressing patient sexuality concerns. The twofold purpose of this study was to identify and describe attitudes and beliefs that might act as barriers to addressing patient sexuality concerns and to determine the extent to which these attitudes and beliefs are influenced by personal factors such as age, gender, and education. The Sexuality Attitudes and Beliefs Survey was used to assess students (N = 341) enrolled in either a traditional or accelerated second-degree baccalaureate program. Important barriers to addressing patient sexuality concerns reported by the majority of the students included not making time to address the concerns (67.9%) and believing that patients do not expect nurses to address the concerns (66.4%). Findings also revealed that accelerated second-degree students were more restrictive in their attitudes toward addressing patient sexuality concerns, compared with traditional students. Results of this study have implications for BSN program development and evaluation.
- Published
- 2008
- Full Text
- View/download PDF
40. National Instant Criminal Background Check Improvement Act: implications for persons with mental illness.
- Author
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Price M and Norris DM
- Subjects
- Databases, Factual, Domestic Violence legislation & jurisprudence, Domestic Violence prevention & control, Homicide legislation & jurisprudence, Homicide prevention & control, Humans, Mental Disorders psychology, Substance-Related Disorders psychology, Suicide legislation & jurisprudence, United States, Suicide Prevention, Commitment of Mentally Ill legislation & jurisprudence, Crime legislation & jurisprudence, Dangerous Behavior, Firearms legislation & jurisprudence, Insanity Defense, Mental Disorders diagnosis, Substance-Related Disorders diagnosis
- Abstract
The National Instant Criminal Background Check Improvement Act has serious implications for persons with mental illness with regard to the ability to purchase firearms. Federally prohibited persons include those who have been adjudicated as mentally defective, or have been committed to a mental institution, or are unlawful users of or are addicted to a controlled substance. The legislation was intended to expand the reporting practices of states by providing significant financial incentives and disincentives for releasing all relevant records, including those contained within mental health databases, to the National Instant Criminal Background Check System (NICS). As of April 2007, only 22 states were voluntarily submitting records from mental health databases to the NICS. The legislation was introduced following the Virginia Tech tragedy, when public opinion favored tightening control over access to firearms of persons with mental illness.
- Published
- 2008
41. A medical malpractice tribunal experience.
- Author
-
Norris DM
- Subjects
- United States, Insurance, Liability economics, Malpractice legislation & jurisprudence
- Published
- 2007
42. Guanine-Rich RNA Sequence Binding Factor 1 Deficiency Promotes Colorectal Cancer Progression by Regulating PI3K/AKT Signaling Pathway.
- Author
-
Huang, Jingzhan, Liu, Jialong, Lan, Jin, Sun, Jingbo, Zhou, Kun, Deng, Yunyao, Liang, Li, Liu, Lixin, and Liu, Xiaolong
- Subjects
PI3K/AKT pathway ,NUCLEOTIDE sequence ,CELLULAR signal transduction ,COLORECTAL cancer ,CANCER invasiveness - Abstract
Background: Guanine-rich RNA sequence binding factor 1 (GRSF1), part of the RNA-binding protein family, is now attracting interest due to its potential association with the progression of a variety of human cancers. The precise contribution and molecular mechanism of GRSF1 to colorectal cancer (CRC) progression, however, have yet to be clarified. Methods: Immunohistochemistry and Western Blot analysis was carried out to detect the expression of GRSF1 in CRC at both mRNA and protein levels and its subsequent effects on prognosis. A series of functional tests were performed to understand its influence on proliferation, migration, and invasion of CRC cells. Results: The universal downregulation of GRSF1 in CRC was identified, indicating a correlation with poor prognosis. Our functional studies unveiled that the elimination of GRSF1 enhances tumour activities such as proliferation, migration, and invasion of CRC cells, while GRSF1 overexpression curtailed these abilities. Conclusion: Notably, we uncovered that GRSF1 insufficiency modulates the PI3K/Akt signaling pathway and Ras activation in CRC. Therefore, our data suggest GRSF1 operates as a tumor suppressor gene in CRC and may offer promise as a potential biomarker and novel therapeutic target in CRC management. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
43. Short–Term Preconditioning with Insulin and Glucose Efficiently Protected the Kidney Against Ischemia-Reperfusion Injury via the P-AKT-Bax-Caspase-3 Signaling Pathway in Mice.
- Author
-
Sun, Liwei, Bing, Hailong, Zhang, Chenxi, Lin, Lin, Lian, Hongkai, Chu, Qinjun, and Jin, Xiaogao
- Published
- 2024
- Full Text
- View/download PDF
44. Epigenetics of the non-coding RNA nc886 across blood, adipose tissue and skeletal muscle in offspring exposed to diabetes in pregnancy.
- Author
-
Hjort, Line, Bredgaard, Sandra Stokholm, Manitta, Eleonora, Marques, Irene, Sørensen, Anja Elaine, Martino, David, Grunnet, Louise Groth, Kelstrup, Louise, Houshmand-Oeregaard, Azadeh, Clausen, Tine Dalsgaard, Mathiesen, Elisabeth Reinhardt, Olsen, Sjurdur Frodi, Saffery, Richard, Barrès, Romain, Damm, Peter, Vaag, Allan Arthur, and Dalgaard, Louise Torp
- Subjects
GESTATIONAL diabetes ,NON-coding RNA ,GENE expression ,SKELETAL muscle ,TYPE 1 diabetes ,ADIPOSE tissues ,ADIPOSE tissue physiology ,MUSCLE mass - Abstract
Background: Diabetes in pregnancy is associated with increased risk of long-term metabolic disease in the offspring, potentially mediated by in utero epigenetic variation. Previously, we identified multiple differentially methylated single CpG sites in offspring of women with gestational diabetes mellitus (GDM), but whether stretches of differentially methylated regions (DMRs) can also be identified in adolescent GDM offspring is unknown. Here, we investigate which DNA regions in adolescent offspring are differentially methylated in blood by exposure to diabetes in pregnancy. The secondary aim was to characterize the RNA expression of the identified DMR, which contained the nc886 non-coding RNA. Methods: To identify DMRs, we employed the bump hunter method in samples from young (9–16 yr, n = 92) offspring of women with GDM (O-GDM) and control offspring (n = 94). Validation by pyrosequencing was performed in an adult offspring cohort (age 28–33 years) consisting of O-GDM (n = 82), offspring exposed to maternal type 1 diabetes (O-T1D, n = 67) and control offspring (O-BP, n = 57). RNA-expression was measured using RT-qPCR in subcutaneous adipose tissue and skeletal muscle. Results: One significant DMR represented by 10 CpGs with a bimodal methylation pattern was identified, located in the nc886/VTRNA2-1 non-coding RNA gene. Low methylation status across all CpGs of the nc886 in the young offspring was associated with maternal GDM. While low methylation degree in adult offspring in blood, adipose tissue, and skeletal muscle was not associated with maternal GDM, adipose tissue nc886 expression was increased in O-GDM compared to O-BP, but not in O-T1D. In addition, adipose tissue nc886 expression levels were positively associated with maternal pre-pregnancy BMI (p = 0.006), but not with the offspring's own adiposity. Conclusions: Our results highlight that nc886 is a metastable epiallele, whose methylation in young offspring is negatively correlated with maternal obesity and GDM status. The physiological effect of nc886 may be more important in adipose tissue than in skeletal muscle. Further research should aim to investigate how nc886 regulation in adipose tissue by exposure to GDM may contribute to development of metabolic disease. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
45. Ageing-dependent thiol oxidation reveals early oxidation of proteins with core proteostasis functions.
- Author
-
Jonak, Katarzyna, Suppanz, Ida, Bender, Julian, Chacinska, Agnieszka, Warscheid, Bettina, and Topf, Ulrike
- Published
- 2024
- Full Text
- View/download PDF
46. Effectiveness of extracorporeal shockwave treatment in 353 patients with chronic plantar fasciitis.
- Author
-
Norris DM, Eickmeier KM, and Werber BR
- Subjects
- Humans, Mobility Limitation, Pain Measurement, Surveys and Questionnaires, Treatment Outcome, Fasciitis, Plantar therapy, High-Energy Shock Waves
- Abstract
A 16-question post-treatment survey was sent to 874 patients after extracorporeal shockwave treatment for chronic plantar fasciitis. Of the 377 surveys returned, 353 were used for analysis. These patients were treated by 169 physicians in 19 states using either electrohydraulic or electromagnetic extracorporeal shockwave equipment. Seventy-six percent of the patients underwent treatment after having had continued pain for a year or longer. Seventy percent of patients who rated their pretreatment pain level as severe (score >or= 8 on a scale from 1 to 10) experienced sharp declines in pain, with a sharp decline considered to be a difference in pain level before and after treatment of 3 or more. In addition, 66% of patients who rated their pretreatment immobility as severe (score >or= 8 on a scale from 1 to 10) experienced sharp declines in immobility. Of the patients who underwent extracorporeal shockwave treatment, 69% indicated that they would recommend this procedure to someone in a similar situation. If extracorporeal shockwave treatment were not available, 62% of patients indicated that they would have undergone open or invasive surgery, and 41% indicated that they would have continued with additional physician office visits.
- Published
- 2005
- Full Text
- View/download PDF
47. Harassment and intimidation of forensic psychiatrists: an update.
- Author
-
Norris DM and Gutheil TG
- Subjects
- Humans, Professional-Patient Relations, United States, Violence classification, Coercion, Expert Testimony, Forensic Psychiatry, Occupational Exposure
- Published
- 2003
- Full Text
- View/download PDF
48. This couldn't happen to me: boundary problems and sexual misconduct in the psychotherapy relationship.
- Author
-
Norris DM, Gutheil TG, and Strasburger LH
- Subjects
- Confidentiality, Humans, Personal Space, Professional Role, Psychotherapeutic Processes, Psychotherapy education, Psychotherapy methods, Psychotherapy standards, Risk Factors, Self Disclosure, Sex Offenses psychology, Ethics, Clinical, Mental Disorders therapy, Professional Misconduct, Professional-Patient Relations, Psychotherapy ethics
- Abstract
Drawing on their own consultative experience illustrated by case vignettes and with support from the professional literature, the authors discuss the perennial problematic issue of boundary violations and sexual misconduct, aiming at an audience of both experienced and novice clinicians. The authors review the difference between boundary crossings and boundary violations and stress the therapist's responsibility to maintain boundaries. Therapist risk factors for violations include the therapist's own life crises, a tendency to idealize a "special" patient or an inability to set limits, and denial about the possibility of boundary problems. Factors exacerbating patient vulnerability, such as overdependence on the therapist, seeking therapy to find an intense relationship or even "true love," and the acceptance by childhood abuse victims of an abusive therapy relationship, are discussed. Consultation and education-for students and for clinicians at all levels of experience-and effective supervision are reviewed as approaches to boundary problems.
- Published
- 2003
- Full Text
- View/download PDF
49. Forensic consultation and the clergy sexual abuse crisis.
- Author
-
Norris DM
- Subjects
- Child, Child Abuse, Sexual legislation & jurisprudence, Clergy legislation & jurisprudence, Humans, Male, United States, Catholicism, Child Abuse, Sexual psychology, Clergy psychology, Forensic Psychiatry, Referral and Consultation
- Published
- 2003
50. King's conceptual system and theory of goal attainment: past, present, and future.
- Author
-
Frey MA, Sieloff CL, and Norris DM
- Subjects
- History, 20th Century, Program Development, Education, Nursing history, Nursing Theory
- Abstract
Imogene King is universally recognized as a pioneer of nursing theory development. Her interacting conceptual system for nursing and her theory of goal attainment have been included in every major nursing theory text, are taught to thousands of nursing students, form the basis of nursing education programs, and are implemented in a variety of service settings.
- Published
- 2002
- Full Text
- View/download PDF
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