Distinct regulation of glucose transport and GLUT1/GLUT3 transporters by glucose deprivation and IGF-I in chromaffin cells

AbstractEffects of prolonged metabolic (glucose deprivation) and hormonal [insulin-like growth factor I (IGF-I)] challenge on regulation of glucose transporter (GLUT) expression, glucose transport rate and possible signaling pathways involved were studied in the neuroendocrine chromaffin cell. The results show that bovine chromaffin cells express both GLUT1 and GLUT3. Glucose deprivation and IGF-I activation led to an elevation of GLUT1 and GLUT3 mRNA, the strongest effect being that of IGF-I on GLUT3 mRNA. Both types of stimulus increased the GLUT1 protein content in a cycloheximide (CHX)-sensitive manner, and the glucose transport rate was elevated by 3- to 4-fold after 48 h under both experimental conditions. IGF-I-induced glucose uptake was totally suppressed by CHX. In contrast, only ∼50% of transport activation in glucose-deprived cells was sensitive to the protein synthesis inhibitor. Specific inhibitors of mTOR/FRAP and p38 MAPK each partially blocked IGF-I-stimulated glucose transport, but had no effect on transport rate in glucose-deprived cells. The results are consistent with IGF-I-activated transport being completely dependent on new GLUT protein synthesis while the enhanced transport in glucose-deprived cells was partially achieved independent of new synthesis of proteins, suggesting a mechanism relying on preexisting transporters

Effectiveness of the International Child Development Programme: Results from a randomized controlled trial

This study aimed to evaluate the effectiveness of the International Child Development Programme (ICDP), a group-based parenting programme used internationally and implemented nationally in Norway. We used a cluster randomized controlled trial in which 81 groups were randomly assigned to either the intervention or waitlist control condition after the baseline data collection. A total of 590 parents completed at least one of three questionnaires (administrated before and after ICDP and 4 months after completing the intervention). Primary outcomes included parental self-efficacy, parental emotion sensitivity and positive involvement with their child. Secondary outcomes included parents' perceptions of their relationship with the child, child-rearing conflicts and the child's psychosocial health. We found significant effects favouring the intervention arm following the intervention and at follow-up on two primary outcomes (parental self-efficacy and emotion sensitivity). For the secondary outcomes, we found a significant reduction in child-rearing conflict at the 4-month follow-up, increased closeness to the child, reduced child internalizing difficulties and increased prosocial behaviour immediately following the intervention. However, ICDP seems to have limited effects on parent-reported changes in children. We conclude that ICDP as a universal preventive programme offered to parents in groups can be effective in strengthening parental self-efficacy and improving parental emotion sensitivity.publishedVersio

A Rare Functional Noncoding Variant at the GWAS-Implicated MIR137/MIR2682 Locus Might Confer Risk to Schizophrenia and Bipolar Disorder

Schizophrenia (SZ) genome-wide association studies (GWASs) have identified common risk variants in >100 susceptibility loci; however, the contribution of rare variants at these loci remains largely unexplored. One of the strongly associated loci spans MIR137 (miR137) and MIR2682 (miR2682), two microRNA genes important for neuronal function. We sequenced ∼6.9 kb MIR137/MIR2682 and upstream regulatory sequences in 2,610 SZ cases and 2,611 controls of European ancestry. We identified 133 rare variants with minor allele frequency (MAF) <0.5%. The rare variant burden in promoters and enhancers, but not insulators, was associated with SZ (p = 0.021 for MAF < 0.5%, p = 0.003 for MAF < 0.1%). A rare enhancer SNP, 1:g.98515539A>T, presented exclusively in 11 SZ cases (nominal p = 4.8 × 10−4). We further identified its risk allele T in 2 of 2,434 additional SZ cases, 11 of 4,339 bipolar (BP) cases, and 3 of 3,572 SZ/BP study controls and 1,688 population controls; yielding combined p values of 0.0007, 0.0013, and 0.0001 for SZ, BP, and SZ/BP, respectively. The risk allele T of 1:g.98515539A>T reduced enhancer activity of its flanking sequence by >50% in human neuroblastoma cells, predicting lower expression of MIR137/MIR2682. Both empirical and computational analyses showed weaker transcription factor (YY1) binding by the risk allele. Chromatin conformation capture (3C) assay further indicated that 1:g.98515539A>T influenced MIR137/MIR2682, but not the nearby DPYD or LOC729987. Our results suggest that rare noncoding risk variants are associated with SZ and BP at MIR137/MIR2682 locus, with risk alleles decreasing MIR137/MIR2682 expression

HPV DNA testing improves CIN2+ risk stratification and detection of CIN2+ in delayed triage of ASCUS and LSIL. A population-based follow-up study from Western Norway

In Norway, Pap smears with atypical squamous cells of uncertain significance (ASCUS) and low-grade squamous intraepithelial lesions (LSIL) are triaged after 6 months. The aim of the study was to evaluate effects of implementing human papillomavirus (HPV) test (2005) in delayed triage of ASCUS and LSIL in a cohort of women from Western Norway. After a survey of 119,469 cervical Pap smears during 2005–2007, a total of 1055 women with an index ASCUS or LSIL were included in the study and followed up for 3–6 years with respect to progression into cervical intraepithelial neoplasia grade 2 or worse (CIN2+). Overall sensitivity for detection of CIN2+ with HPV testing and cytology was 96% and 72%, respectively. The sensitivity for detection of CIN2+ was not affected by age, but the specificity of the HPV test increased with age. Thus, for the age groups 50 years, the specificity of a positive HPV test to detect CIN2+ was 47%, 71%, and 82%, respectively. Positive predictive values for CIN2+ in women with positive cytology, positive HPV test, negative cytology, negative HPV test, or negative HPV and cytology tests were 52%, 41%, 8%, 1.5%, and 0.4%, respectively. HPV testing resulted in a net 22% increased detection of CIN2+. Fifty-six percent of CIN2+ was detected at an earlier time point with HPV testing in triage. Implementation of HPV testing in delayed triage of ASCUS and LSIL improved the stratification of CIN2+ risk and increased CIN2+ detection and at an earlier time point than with triage by cytology alon

Modern Business ; An Introduction to Principles and Problems

x, 417 p. ; 23 cm

A variable-pulse and square-wave generator /

Work performed at the Iowa State College."AECU-561"Includes bibliographic references.Mode of access: Internet

Elliptical structure of phospholipid bilayer nanodiscs encapsulated by scaffold proteins:casting the roles of the lipids and the protein

Phospholipid bilayers host and support the function of membrane proteins and may be stabilized in disk-like nano structures allowing for unprecedented solution studies of assembly, structure and function of membrane proteins. Based on small-angle neutron scattering in combination with variable temperature studies of synchrotron small-angle x-ray scattering on nanodiscs(1) in solution we show that the fundamental nanodisc unit, consisting of a lipid bilayer surrounded by amphiphilic scaffold proteins, posses intrinsically an elliptical shape. The temperature dependence of the curvature of the nanodiscs prepared with two different phospholipid types (DLPC and POPC) shows that it is the scaffold protein that determines the overall elliptical shape and that the nanodiscs become more circular with increasing temperature. Our data also show that the hydrophobic bilayer thickness is to a large extent dictated by the scaffolding protein and adjusted to minimize the hydrophobic mismatch between protein and phospholipid. Our conclusions result from a new comprehensive and molecular based model of the nanodisc structure and the use of this to analyze the experimental scattering profile from nanodiscs. The model paves the way for future detailed structural studies of functional membrane proteins encapsulated in nanodiscs