| 1. |
- Birney, Ewan, et al.
(författare)
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Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
- 2007
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 447:7146, s. 799-816
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Tidskriftsartikel (refereegranskat)abstract
- We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.
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| 2. |
- Hemmingsson, Erik, et al.
(författare)
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No apparent progress in bioelectrical impedance accuracy : validation against metabolic risk and DXA.
- 2009
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Ingår i: Obesity. - : Wiley. - 1930-7381 .- 1930-739X. ; 17:1, s. 183-7
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Tidskriftsartikel (refereegranskat)abstract
- Bioelectrical impedance (BIA) is quick, easy, and safe when quantifying fat and lean tissue. New BIA models (Tanita BC-418 MA, abbreviated BIA(8)) can perform segmental body composition analysis, e.g., estimate %trunkal fatness (%TF). It is not known, however, whether new BIA models can detect metabolic risk factors (MRFs) better than older models (Tanita TBF-300, abbreviated BIA(4)). We therefore tested the correlation between MRF and percentage whole-body fat (%BF) from BIA(4) and BIA(8) and compared these with the correlation between MRF and dual-energy X-ray absorptiometry (DXA, used as gold standard), BMI and waist circumference (WC). The sample consisted of 136 abdominally obese (WC >or= 88 cm), middle-aged (30-60 years) women. MRF included fasting blood glucose and insulin; high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides; high sensitive C-reactive protein, plasminogen activator inhibitor-1 (PAI-1), and fibrinogen; and alanine transaminase (ALT) liver enzyme. We found that similar to DXA, but in contrast to BMI, neither %BF BIA(4) nor %BF BIA(8) correlated with blood lipids or ALT. In the segmental analysis of %TF, BIA(8) only correlated with inflammatory markers, but not insulin, blood lipids, or ALT liver enzyme (in contrast to WC and %TF DXA). %TF DXA was associated with homeostatic model assessment insulin resistance (HOMA-IR) independently of WC (P = 0.03), whereas %TF BIA(8) was not (P = 0.53). Receiver-operating characteristic (ROC) curves confirmed that %TF BIA(8) did not differ from chance in the detection of insulin resistance (P = 0.26). BIA estimates of fatness were, at best, weakly correlated with obesity-related risk factors in abdominally obese women, even the new eight-electrode model. Our data support the continued use of WC and BMI.
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| 3. |
- Mårtensson, Ulrika, et al.
(författare)
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Deletion of the G protein-coupled receptor 30 impairs glucose tolerance, reduces bone growth, increases blood pressure, and eliminates estradiol-stimulated insulin release in female mice.
- 2009
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Ingår i: Endocrinology. - : The Endocrine Society. - 1945-7170 .- 0013-7227. ; 150:2, s. 687-98
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Tidskriftsartikel (refereegranskat)abstract
- In vitro studies suggest that the G protein-coupled receptor (GPR) 30 is a functional estrogen receptor. However, the physiological role of GPR30 in vivo is unknown, and it remains to be determined whether GPR30 is an estrogen receptor also in vivo. To this end, we studied the effects of disrupting the GPR30 gene in female and male mice. Female GPR30((-/-)) mice had hyperglycemia and impaired glucose tolerance, reduced body growth, increased blood pressure, and reduced serum IGF-I levels. The reduced growth correlated with a proportional decrease in skeletal development. The elevated blood pressure was associated with an increased vascular resistance manifested as an increased media to lumen ratio of the resistance arteries. The hyperglycemia and impaired glucose tolerance in vivo were associated with decreased insulin expression and release in vivo and in vitro in isolated pancreatic islets. GPR30 is expressed in islets, and GPR30 deletion abolished estradiol-stimulated insulin release both in vivo in ovariectomized adult mice and in vitro in isolated islets. Our findings show that GPR30 is important for several metabolic functions in female mice, including estradiol-stimulated insulin release.
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| 4. |
- Neovius, Martin, et al.
(författare)
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Assessment of change in body fat percentage with DXA and eight-electrode BIA in centrally obese women.
- 2007
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Ingår i: Medicine & Science in Sports & Exercise. - : Ovid Technologies (Wolters Kluwer Health). - 0195-9131 .- 1530-0315. ; 39:12, s. 2199-203
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To compare estimates of change in percent body fat (Delta%BF) between DXA and BIA8 in abdominally obese women.METHODS: Six-month longitudinal study of 106 women (baseline: age 48.2 +/- 7.6 yr; BMI 30.4 +/- 2.9 kg.m; %BFDXA 45.8 +/- 3.6%) participating in an exercise-oriented behavior-change program (walking and bicycling). Fatness was measured by DXA and Tanita BC-418 (BIA8). Agreement between methods was assessed, and regression analysis was used to find predictors of the deviation between methods for estimating changes in fat mass percentage.RESULTS: The methods differed significantly, both at baseline and follow-up (-5.0 and -4.4%BF, respectively; both P < 0.001). The mean Delta%BF was -1.1 +/- 2.5%BFDXA and -0.5 +/- 2.2%BFBIA8 (mean difference between methods 0.6 +/- 1.8%BF; P < 0.001; 95% limits of agreement -3.0 to 4.2%BF), with a range of -14.8 to 3.3%BFDXA and -9.4 to 3.5%BFBIA8. Approximately 49% of the variation in the difference between methods was explained by variations in age (beta = -0.05; P = 0.006), DeltaBMI (beta = 0.98; P < 0.001), and Delta%BFDXA (beta = -0.71; P < 0.001), indicating that the larger the change, the greater the discrepancy between methods.CONCLUSION: The difference between methods regarding Delta%BF was statistically significant, but it was of small magnitude. However, with increasing Delta%BF, increasing discrepancies were observed, implying that the BIA equipment may have limited validity for detecting larger fat losses. Both clinicians and researchers may benefit from awareness of this potential limitation.
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| 5. |
- Neovius, Martin, et al.
(författare)
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Bioelectrical impedance underestimates total and truncal fatness in abdominally obese women.
- 2006
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Ingår i: Obesity. - : Wiley. - 1930-7381 .- 1930-739X. ; 14:10, s. 1731-8
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To compare estimates of total and truncal fatness from eight-electrode bioelectrical impedance analysis equipment (BIA(8)) with those from DXA in centrally obese women. The secondary aim was to examine BMI and waist circumference (WC) as proxy measures for percentage total body fat (%TBF) and truncal body fat percentage (tr%BF).RESEARCH METHODS AND PROCEDURES: This was a cross-sectional study of 136 women (age, 48.1 +/- 7.7 years; BMI, 30.4 +/- 2.9 kg/m(2); %TBF(DXA), 46.0 +/- 3.7%; WC, 104 +/- 8 cm). Fatness was measured by DXA and Tanita BC-418 equipment (Tanita Corp., Tokyo, Japan). Agreement among methods was assessed by Bland-Altman plots, and regression analysis was used to evaluate anthropometric measures as proxies for total and abdominal fatness.RESULTS: The percentage of overweight subjects was 41.9%, whereas 55.9% of the subjects were obese, as defined by BMI, and all subjects had a WC exceeding the World Health Organization cut-off point for abdominal obesity. Compared with DXA, the BIA(8) equipment significantly underestimated total %BF (-5.0; -3.6 to -8.5 [mean; 95% confidence interval]), fat mass (-3.6; -3.9 to -3.2), and tr%BF (-8.5; -9.1 to -7.9). The discrepancies between the methods increased with increasing adiposity for both %TBF and tr%BF (both p < 0.001). Variation in BMI explained 28% of the variation in %TBF(DXA) and 51% of %TBF(BIA8). Using WC as a proxy for truncal adiposity, it explained only 18% of tr%BF(DXA) variance and 27% of tr%BF(BIA8) variance. The corresponding figures for truncal fat mass were 49% and 35%, respectively. No significant age effects were observed in any of the regressions.DISCUSSION: BIA(8) underestimated both total and truncal fatness, compared with DXA, with higher dispersion for tr%BF than %TBF. The discrepancies increased with degree of adiposity, suggesting that the accuracy of BIA is negatively affected by obesity.
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| 6. |
- Staender, Sonja, et al.
(författare)
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Clinical classification of itch: a position paper of the international forum for the study of itch
- 2007
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Ingår i: Acta Dermato-Venereologica. - : Medical Journals Sweden AB. - 1651-2057 .- 0001-5555. ; 87:4, s. 291-294
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Tidskriftsartikel (refereegranskat)abstract
- Chronic itch is a common and distressing symptom that arises from a variety of skin conditions and systemic diseases. Despite this, there is no clinically based classification of pruritic diseases to assist in the diagnosis and cost-effective medical care of patients with pruritus. The proposed classification focuses on clinical signs and distinguishes between diseases with and without primary or secondary skin lesions. Three groups of conditions are proposed: pruritus on diseased (inflamed) skin (group I), pruritus on non-diseased (non-inflamed) skin (group II), and pruritus presenting with severe chronic secondary scratch lesions, such as prurigo nodularis (group III). The next part classifies the underlying diseases according to different categories: dermatological diseases, systemic diseases including diseases of pregnancy and drug-induced pruritus, neurological and psychiatric diseases. In some patients more than one cause may account for pruritus (category "mixed") while in others no underlying disease can be identified (category "others"). This is the first version of a clinical classification worked out by the members of the International Forum for the Study of Itch. It is intended to serve as a diagnostic route for better evaluation of patients with chronic pruritus and aims to improve patients' care.
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| 7. |
- Turner, Martin R, et al.
(författare)
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Volumetric cortical loss in sporadic and familial amyotrophic lateral sclerosis.
- 2007
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Ingår i: Amyotrophic lateral sclerosis : official publication of the World Federation of Neurology Research Group on Motor Neuron Diseases. - : Informa UK Limited. - 1471-180X. ; 8:6, s. 343-7
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Tidskriftsartikel (refereegranskat)abstract
- Patients homozygous for the D90A mutation of the SOD1 gene (homD90A) demonstrate markedly slower progression of disease than those patients with sporadic ALS (SALS). PET studies have demonstrated a different cortical vulnerability in the two groups, reflected also in neurophysiological studies showing reduced cortical excitability in homD90A. Voxel-based morphometric analysis of magnetic resonance images (MRIs) enables the detection of regional differences in grey matter volume, and can be used to localize cortical atrophy in vivo. In this study, segmented, spatially normalized, modulated and smoothed grey matter portions of the MRIs from 23 SALS and seven homD90A patients with similar disability, were compared with those from 28 healthy control subjects. The SALS group showed bilateral areas of atrophy mainly confined to motor and pre-motor cortices. Cortical changes in the homD90A group were more pronounced within the frontal lobes when both were compared with healthy controls. This study provides further evidence for a different pattern of cortical neuronal vulnerability in homD90A versus SALS patients that may provide insight as to their slower rate of disease progression.
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