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Cristian A. Droppelmann Brian A. Keller Danae Campos-Melo Kathryn Volkening Michael J. Strong 《Neurobiology of aging》2013
Amyotrophic lateral sclerosis (ALS) is an adult-onset progressive disorder of unknown etiology characterized by the selective degeneration of motor neurons. Recent evidence supports the hypothesis that alterations in RNA metabolism in motor neurons can explain the development of protein inclusions, including neurofilamentous aggregates, observed in this pathology. In mice, p190RhoGEF, a guanine nucleotide exchange factor, is involved in neurofilament protein aggregation in an RNA-triggered transgenic model of motor neuron disease. Here, we observed that rho guanine nucleotide exchange factor (RGNEF), the human homologue of p190RhoGEF, binds low molecular weight neurofilament mRNA and affects its stability via 3′ untranslated region destabilization. We observed that the overexpression of RGNEF in a stable cell line significantly decreased the level of low molecular weight neurofilament protein. Furthermore, we observed RGNEF cytoplasmic inclusions in ALS spinal motor neurons that colocalized with ubiquitin, p62/sequestosome-1, and TAR (trans-active regulatory) DNA-binding protein 43 (TDP-43). Our results provide further evidence that RNA metabolism pathways are integral to ALS pathology. This is also the first described link between ALS and an RNA binding protein with aggregate formation that is also a central cell signaling pathway molecule. 相似文献
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Lisa E. Rasbach Ashley E. Atkins Kerry M. Milaszewski Joyce Keady Lisa M. Schmidt Lisa K. Volkening Lori M. Laffel 《Journal of diabetes science and technology》2014,8(3):494-497
Glycemic control remains suboptimal in youth with type 1 diabetes. Retrospective continuous glucose monitoring (CGM) has demonstrated utility in fine-tuning diabetes management by detecting postprandial hyperglycemia and hypoglycemia. In this study, we explored the process of 3-day masked CGM use, subsequent treatment recommendations, and impact on A1c in a clinic-based sample of youth with type 1 diabetes. Over 2 years, 122 youth were referred for masked CGM. Patients/families completed a diary of blood glucose levels, insulin doses, food intake, and exercise during CGM use. A1c was assessed pre- and 2-3 months post-CGM. Treatment recommendations were formulated using data from CGM reports and diaries. Mean age was 14.3 ± 3.9 years, diabetes duration was 7.5 ± 4.7 years, and A1c was 8.5 ± 1.1% (69 ± 12 mmol/mol); 61% were pump-treated. Patients received an average of 3.1 ± 1.1 treatment recommendations following review of the CGM report. Most (80%) received reinforcement of the importance of preprandial bolusing; 37% received a recommendation regarding advanced insulin management (use of combination boluses/attend to active insulin). Receipt of the latter recommendation was related to A1c improvement ≥0.5% (OR: 4.0, P < .001). Masked CGM offers opportunities to guide advanced insulin management (by injection or pump), which may yield A1c improvements in youth with type 1 diabetes. 相似文献
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The Blood Glucose Monitoring Communication questionnaire: an instrument to measure affect specific to blood glucose monitoring 总被引:4,自引:0,他引:4
OBJECTIVE: The aim of this study was to present the psychometric properties of a new tool for evaluating affective response to blood glucose monitoring (BGM) in youths with type 1 diabetes and their parents. RESEARCH DESIGN AND METHODS: Study participants included 153 youths with type 1 diabetes and their parents. Each youth and parent completed the Blood Glucose Monitoring Communication (BGMC) questionnaire, Diabetes Family Conflict Scale, and Pediatric Quality of Life Inventory. Statistical analyses evaluated the psychometric properties of the BGMC questionnaires and their association with glycemic outcomes. RESULTS: Youth and parent BGMC questionnaires had acceptable internal consistency (youth, alpha = 0.77; parent, alpha = 0.82) and 1-year test-retest reliability (youth, r = 0.60; parent, r = 0.80). Higher BGMC questionnaire scores (indicating more negative affect) showed a strong association with higher levels of diabetes-specific family conflict (youth, r = 0.33; parent, r = 0.44) and poorer health-related psychosocial quality of life (youth, r = -0.50; parent, r = -0.42). Higher BGMC questionnaire scores were also associated with poorer glycemic control (youth, r = 0.28; parent, r = 0.20), even when the effects of diabetes-specific family conflict and psychosocial quality of life were controlled. Youths with BGMC questionnaire scores in the upper quartile had A1c values 1 percentage point higher (9.1%) than youths with scores in the lowest quartile (8.0%). CONCLUSIONS: The BGMC questionnaires have strong psychometric properties and are convenient measures of affect specific to BGM. Further, BGM affect is associated with glycemic outcomes and may provide a unique contribution to factors associated with glycemic control in youths. 相似文献
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Ge WW Volkening K Leystra-Lantz C Jaffe H Strong MJ 《Molecular and cellular neurosciences》2007,34(1):80-87
We have previously reported that altered stability of low molecular weight neurofilament (NFL) mRNA in lumbar spinal cord homogenates in amyotrophic lateral sclerosis (ALS) is associated with altered expression of trans-acting 3' UTR mRNA binding proteins. We have identified two hexanucleotide motifs as the main cis elements and, using LC/MS/MS of peptide digests of NFL 3' UTR interacting proteins from human spinal cord, observed that 14-3-3 proteins interact with these motifs. 14-3-3 beta, zeta, tau, gamma, and eta isoforms were found to be expressed in human spinal cord. Each isoform was expressed in vitro and shown to interact with NFL 3' UTR mRNA. Mutation of one or both motifs resulted in decreased 14-3-3 interaction, changes in predicted mRNA structure or alteration in stability of the mRNA. These data show a novel interaction for 14-3-3 with NFL mRNA, and suggests that 14-3-3 may play a role in regulating NFL mRNA stability. 相似文献
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Mehta SN Volkening LK Anderson BJ Nansel T Weissberg-Benchell J Wysocki T Laffel LM;Family Management of Childhood Diabetes Study Steering Committee 《Diabetes care》2008,31(7):1318-1320
OBJECTIVE—To investigate the association between dietary adherence and glycemic control among youth with type 1 diabetes.RESEARCH DESIGN AND METHODS—We conducted a cross-sectional analysis of 119 youth aged 9–14 years (mean ± SD 12.1 ± 1.6 years) with diabetes duration ≥1 year (5.4 ± 3.1 years). Dietary adherence was assessed using the Diabetes Self-Management Profile diet domain. Higher score defined greater dietary adherence. Glycemic control was determined by A1C.RESULTS—Dietary adherence score was inversely correlated with A1C (r = −0.36, P < 0.0001). In a multivariate model (R2 = 0.34, P < 0.0001), dietary adherence (P = 0.004), pump use (P = 0.03), and caregiver education (P = 0.01) were associated with A1C. A1C of youth in the lowest (9.0%) tertile of diet score was higher than A1C of youth in the middle (8.1%, P = 0.004) and upper (8.4%, P = 0.06) tertiles. Dietary adherence uniquely explained 8% of the variance in A1C in the model.CONCLUSIONS—Greater dietary adherence was associated with lower A1C among youth with type 1 diabetes.Data for youth with type 1 diabetes demonstrate a gap between attained glycemic control and age-specific goals (1–3). With intensive insulin therapy, dietary behaviors become central to optimizing glycemic control. Studies have shown that greater dietary adherence improves glycemic control among adults with type 1 diabetes (4,5). In this study, we investigated the relationship between dietary adherence and glycemic control in youth with type 1 diabetes. 相似文献
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Jessica T. Markowitz Lisa K. Volkening Deborah A. Butler Lori M. B. Laffel 《Journal of diabetes science and technology》2015,9(5):1080-1085