2,962 research outputs found
Dysregulated Erythroid Mg2+ Efflux in Type 2 Diabetes
CEECIND/01053/2017
UIDB/04647/2020
UIDP/04647/2020Hyperglycemia is associated with decreased Mg2+ content in red blood cells (RBC), but mechanisms remain unclear. We characterized the regulation of Mg2+ efflux by glucose in ex vivo human RBC. We observed that hemoglobin A1C (HbA1C) values correlated with Na+-dependent Mg2+ efflux (Na+/Mg2+ exchange) and inversely correlated with cellular Mg content. Treatment of cells with 50 mM D-glucose, but not with sorbitol, lowered total cellular Mg (2.2 ± 0.1 to 2.0 ± 0.1 mM, p < 0.01) and enhanced Na+/Mg2+ exchange activity [0.60 ± 0.09 to 1.12 ± 0.09 mmol/1013 cell × h (flux units, FU), p < 0.05]. In contrast, incubation with selective Src family kinase inhibitors PP2 or SU6656 reduced glucose-stimulated exchange activation (p < 0.01). Na+/Mg2+ exchange activity was also higher in RBC from individuals with type 2 diabetes (T2D, 1.19 ± 0.13 FU) than from non-diabetic individuals (0.58 ± 0.05 FU, p < 0.01). Increased Na+/Mg2+ exchange activity in RBC from T2D subjects was associated with lower intracellular Mg content. Similarly increased exchange activity was evident in RBC from the diabetic db/db mouse model as compared to its non-diabetic control (p < 0.03). Extracellular exposure of intact RBC from T2D subjects to recombinant peptidyl-N-glycosidase F (PNGase F) reduced Na+/Mg2+ exchange activity from 0.98 ± 0.14 to 0.59 ± 0.13 FU (p < 0.05) and increased baseline intracellular Mg content (1.8 ± 0.1 mM) to normal values (2.1 ± 0.1 mM, p < 0.05). These data suggest that the reduced RBC Mg content of T2D RBC reflects enhanced RBC Na+/Mg2+ exchange subject to regulation by Src family kinases and by the N-glycosylation state of one or more membrane proteins. The data extend our understanding of dysregulated RBC Mg2+ homeostasis in T2D.publishersversionpublishe
k cl co transport plays an important role in normal and β thalassemic erythropoiesis
Background and Objectives Cell volume changes are hallmarks of both cell maturation and apoptosis, and are paralleled by modulation of membrane ion transport pathways. We evaluated the possible role of K-Cl co-transport (KCC) in both normal and β-thalassemic erythropoiesis in vitro . Design and Methods We studied the effects of the KCC inhibitor, DIOA, on cell proliferation and differentiation, on expression of KCC mRNA and polypeptides, and on expression of cell cycle and apoptosis genes in in vitro liquid-cultures of CD34+ cells from normal and β-thalassemic subjects. Results β-thalassemic erythroid precursors showed increased abundance of KCC1-3 mRNA and of KCC polypeptides in late erythropoiesis. DIOA markedly modified the composition of normal erythroid precursors, promoting differentiation and arrest at the polychromatic erythroblast stage and resulting in a precursor distribution profile similar to that of untreated β-thalassemic cells. DIOA up-regulated cyclin-D mRNA levels in late erythropoiesis in both cell models, paralleling changes in the percentage of S-phase-cells. Caspase-3 activity in late erythropoiesis declined to similar degrees in both cell models. DIOA did not modify caspase-3 or -8 mRNA levels. Interpretation and Conclusions Ineffective erythropoiesis of in vitro cultured β-thalassemic cells is likely related to impaired cell maturation. KCC activity appears to contribute to erythroid cell growth during late erythropoiesis
Using a Targeted OSCE Station to Measure Unprofessional Behavior
Standardized patients are widely used in medical education but their use to assess professionalism is limited. With grant support from the Edward J. Stemmler, MD Medical Education Research Fund (“Stemmler Fund”) of the National Board of Medical Examiners (NBME), the usefulness of standardized patients (SPs) in the assessment of professional behavior was investigated. A targeted professionalism OSCE station featuring a values conflict was written. A professionalism instrument was developed and subsequently revised during the course of the study, with the final version containing various components of American Board of Internal Medicine (ABIM) core set of eight professionalism attributes and several other scales in recent medical research.
Presented at the Ottawa Conference, 2006
Stratifying quotient stacks and moduli stacks
Recent results in geometric invariant theory (GIT) for non-reductive linear
algebraic group actions allow us to stratify quotient stacks of the form [X/H],
where X is a projective scheme and H is a linear algebraic group with
internally graded unipotent radical acting linearly on X, in such a way that
each stratum [S/H] has a geometric quotient S/H. This leads to stratifications
of moduli stacks (for example, sheaves over a projective scheme) such that each
stratum has a coarse moduli space.Comment: 25 pages, submitted to the Proceedings of the Abel Symposium 201
Who I Am: The Meaning of Early Adolescents’ Most Valued Activities and Relationships, and Implications for Self-Concept Research
Self-concept research in early adolescence typically measures young people’s self-perceptions of competence in specific, adult-defined domains. However, studies have rarely explored young people’s own views of valued self-concept factors and their meanings. For two major self domains, the active and the social self, this mixed-methods study identified factors valued most by 526 young people from socioeconomically diverse backgrounds in Ireland (10-12 years), and explored the meanings associated with these in a stratified subsample (n = 99). Findings indicate that self-concept scales for early adolescence omit active and social self factors and meanings valued by young people, raising questions about content validity of scales in these domains. Findings also suggest scales may under-represent girls’ active and social selves; focus too much on some school-based competencies; and, in omitting intrinsically salient self domains and meanings, may focus more on contingent (extrinsic) rather than true (intrinsic) self-esteem
“A Faustian bargain?” Public voices on forensic DNA technologies and the National DNA Database
This article draws on the idea of the ‘forensic imaginary’ (Williams 2010) to explore UK public perspectives on the place, role and significance of forensic DNA technologies, both independent of and in relation to other genetic applications. Using correspondents’ replies to the Spring 2006 Mass Observation Directive ‘Genes, Genetics and Cloning’, the analysis focuses on continuities and tensions in their discursive repertoires. The argument examines (a) the ways in which knowledge is made sense of in these accounts, and (b) the discrepancy between an appreciation of the benefits of using DNA identification techniques in police work and a more critical attitude towards a wider national DNA database. The conclusion reflects on the need for a wider scope in research on public understandings of science, which looks beyond targeted consultations and specific publics, and provides more textured data to document collective views on the development and governance of forensic DNA technologies
Quantum Interference Effects in Electronic Transport through Nanotube Contacts
Quantum interference has dramatic effects on electronic transport through
nanotube contacts. In optimal configuration the intertube conductance can
approach that of a perfect nanotube (). The maximum conductance
increases rapidly with the contact length up to 10 nm, beyond which it exhibits
long wavelength oscillations. This is attributed to the resonant cavity-like
interference phenomena in the contact region. For two concentric nanotubes
symmetry breaking reduces the maximum intertube conductance from to
. The phenomena discussed here can serve as a foundation for building
nanotube electronic circuits and high speed nanoscale electromechanical
devices
Observation of confined current ribbon in JET plasmas
we report the identification of a localised current structure inside the JET
plasma. It is a field aligned closed helical ribbon, carrying current in the
same direction as the background current profile (co-current), rotating
toroidally with the ion velocity (co-rotating). It appears to be located at a
flat spot in the plasma pressure profile, at the top of the pedestal. The
structure appears spontaneously in low density, high rotation plasmas, and can
last up to 1.4 s, a time comparable to a local resistive time. It considerably
delays the appearance of the first ELM.Comment: 10 pages, 6 figure
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