| 1. |
- van de Pol, L. A., et al.
(författare)
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White matter hyperintensities and medial temporal lobe atrophy in clinical subtypes of mild cognitive impairment: the DESCRIPA study
- 2009
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Ingår i: Journal of Neurology, Neurosurgery and Psychiatry. - : BMJ. - 1468-330X .- 0022-3050. ; 80:10, s. 1069-1074
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Tidskriftsartikel (refereegranskat)abstract
- Background: Clinical subtypes of mild cognitive impairment (MCI) may represent different underlying aetiologies. Methods: This European, multicentre, memory clinic based study (DESCRIPA) of non-demented subjects investigated whether MCI subtypes have different brain correlates on MRI and whether the relation between subtypes and brain pathology is modified by age. Using visual rating scales, medial temporal lobe atrophy (MTA) (0-4) and white matter hyperintensities (WMH) (0-30) were assessed. Results: Severity of MTA differed between MCI subtypes (p < 0.001), increasing from a mean of 0.8 (SD 0.7) in subjective complaints (n = 77) to 1.3 (0.8) in non-amnestic MCI (n = 93), and from 1.4 (0.9) in single domain amnestic MCI (n = 70) to 1.7 (0.9) in multiple domain amnestic MCI (n = 89). The association between MCI subtype and MTA was modified by age and mainly present in subjects >70 years of age. Severity of WMH did not differ between MCI subtypes (p = 0.21). However, the combination of MTA and WMH differed between MCI subtypes (p = 0.02) Conclusion: We conclude that MCI subtypes may have different brain substrates, especially in older subjects. Isolated MTA was mainly associated with amnestic MCI subtypes, suggesting AD as the underlying cause. In non-amnestic MCI, the relatively higher prevalence of MTA in combination with WMH may suggest a different pathophysiological origin.
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| 2. |
- Wortman, J. R., et al.
(författare)
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The 2008 update of the Aspergillus nidulans genome annotation: A community effort
- 2009
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Ingår i: Fungal Genetics and Biology. - : Elsevier BV. - 1096-0937 .- 1087-1845. ; 46, s. S2-S13
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Tidskriftsartikel (refereegranskat)abstract
- The identification and annotation of protein-coding genes is one of the primary goals of whole-genome sequencing projects, and the accuracy of predicting the primary protein products of gene expression is vital to the interpretation of the available data and the design of downstream functional applications. Nevertheless, the comprehensive annotation of eukaryotic genomes remains a considerable challenge. Many genomes submitted to public databases, including those of major model organisms, contain significant numbers of wrong and incomplete gene predictions. We present a community-based reannotation of the Aspergillus nidulans genome with the primary goal of increasing the number and quality of protein functional assignments through the careful review of experts in the field of fungal biology. (C) 2009 Elsevier Inc. All rights reserved.
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| 3. |
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| 4. |
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| 5. |
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| 6. |
- Visser, P. J., et al.
(författare)
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Development of screening guidelines and clinical criteria for predementia Alzheimer's disease
- 2008
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Ingår i: Neuroepidemiology. - : S. Karger AG. - 1423-0208 .- 0251-5350. ; 30:4, s. 254-265
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Tidskriftsartikel (refereegranskat)abstract
- Background: There is an urgent need to identify subjects with Alzheimer's disease (AD) in the predementia phase, but validated diagnostic approaches are currently lacking. In this paper, we present the background, design and methods of a study, which aims to develop clinical criteria for predementia AD. We also present baseline characteristics of the subjects included. The study was part of the multicentre DESCRIPA project, which is being conducted within the network of the European Alzheimer's Disease Consortium. Methods: Clinical criteria will be based on a prospective cohort study of non-demented subjects older than 55 years and referred to a memory clinic. At baseline, a number of markers and risk factors for AD were collected, including demographic variables, measures of performance in activities of daily living, cognitive, neuroimaging and genetic markers, and serum and cerebrospinal fluid markers. Subjects will be reassessed annually for 2 - 3 years, and we will evaluate which combination of variables best predicts AD-type dementia at follow-up. Results: Between 2003 and 2005, 881 subjects were included from 20 memory clinics. Subjects were on average 70.3 years old, and had 10.4 years of education. The average score on the Mini-Mental State Examination was 27.4.
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| 7. |
- Visser, W Edward, et al.
(författare)
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Novel pathogenic mechanism suggested by ex vivo analysis of MCT8 (SLC16A2) mutations
- 2009
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Ingår i: Human Mutation. - : Hindawi Limited. - 1059-7794 .- 1098-1004. ; 30:1, s. 29-38
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Tidskriftsartikel (refereegranskat)abstract
- Monocarboxylate transporter 8 (MCT8; approved symbol SLC16A2) facilitates cellular uptake and efflux of 3,3',5-triiodothyronine (T3). Mutations in MCT8 arc associated with severe psychomotor retardation, high serum T3 and low 3,3',5'-triiodothyronine (rT3) levels. Here we report three novel MCT8 mutations. Two subjects with the F501 del mutation have mild psychomotor retardation with slightly elevated T3 and normal rT3 levels. T3 uptake was mildly affected in F501del fibroblasts and strongly decreased in fibroblasts from other MCT8 patients, while T3 efflux was always strongly reduced. Moreover, type 3 deiodinase activity was highly elevated in F501del fibroblasts, whereas it was reduced in fibroblasts from other MCT8 patients, probably reflecting parallel variation in cellular T3 content. Additionally, T3 responsive genes were markedly upregulated by T3 treatment in F501del fibroblasts but not in fibroblasts with other MCT8 mutations. In conclusion, mutations in MCT8 result in a decreased T3 uptake in skin fibroblasts. The much milder clinical phenotype of patients with the F501 del mutation may be correlated with the relatively small decrease in T3 uptake combined with an even greater decrease in T3 efflux. If fibroblasts are representative of central neurons, abnormal brain development associated with MCT8 mutations may be the consequence of either decreased or increased intracellular T3 concentrations.
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| 8. |
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| 9. |
- Baezner, H, et al.
(författare)
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Association of gait and balance disorders with age-related white matter changes: the LADIS study.
- 2008
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Ingår i: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 1526-632X .- 0028-3878. ; 70:12, s. 935-42
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: In the Leukoaraiosis and Disability (LADIS) Study, 11 European centers are evaluating the role of age-related white matter changes (ARWMC) as an independent determinant of the transition to disability in the elderly (65 to 84 years). We aimed at determining the influence of ARWMC on different objective measures of gait and balance. METHODS: Six hundred thirty-nine nondisabled individuals were prospectively enrolled and are being followed-up for 3 years. Subjects are graded in three standardized categories of ARWMC (mild, moderate, and severe) according to central MRI reading. Quantitative tests of gait and balance include the Short Physical Performance Battery (SPPB; range: 0 [poor] to 12 [normal]), a timed 8-m walk, and a timed single leg stance test. RESULTS: In cross-sectional analysis, deficiencies in gait and balance performance were correlated with the severity of ARWMC (SPPB: 10.2 +/- 2.1 in the mild, 9.9 +/- 2.0 in the moderate, 8.9 +/- 2.6 in the severe group; p < 0.001). Walking speed correlated with the severity of ARWMC (1.24 +/- 0.28 m/second in the mild, 1.18 +/- 0.32 m/second in the moderate, and 1.09 +/- 0.31 m/second in the severe group; p < 0.001). Balance was best in individuals with mild ARWMC (single leg stance time: 18.9 +/- 10.8 seconds) compared with moderate and severe ARWMC (16.4 +/- 10.8 and 13.6 +/- 11.2 seconds) (p < 0.001). Physically inactive individuals had a higher risk of a pathologic SPPB score (moderate vs mild ARWMC: odds ratio 1.60, 95% CI 1.02 to 2.52; severe vs mild ARWMC: odds ratio 1.75, 95% CI 1.09 to 2.80). CONCLUSIONS: Our findings support a strong association between the severity of age-related white matter changes and the severity of gait and motor compromise. Physical activity might have the potential to reduce the risk of limitations in mobility.
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| 10. |
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| 11. |
- Blahak, C, et al.
(författare)
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Deep frontal and periventricular age related white matter changes but not basal ganglia and infratentorial hyperintensities are associated with falls: cross sectional results from the LADIS study.
- 2009
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Ingår i: Journal of neurology, neurosurgery, and psychiatry. - : BMJ. - 1468-330X .- 0022-3050. ; 80:6, s. 608-13
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Global age related white matter changes (ARWMC) are associated with progressive gait disturbances and falls, hypothesised to result from interruptions of cortico-subcortical circuits controlling balance, posture and locomotion. METHODS: The location of ARWMC in a large cohort of elderly non-disabled individuals with reported falls was analysed, using the cross sectional data of the Leukoaraiosis and Disability (LADIS) study. Detailed anatomical distributions of ARWMC assessed by MRI studies were analysed with respect to falls and balance performance. RESULTS: The severity of global ARWMC was significantly associated with a history of falls in the year prior to study inclusion (22.2% in the mild, 31.6% in the moderate and 37.3% in the severe ARWMC group according to the Fazekas scale; p = 0.002). Analysing the anatomical distribution of ARWMC, using the semiquantitative Scheltens scale, in multivariate analysis, periventricular (p = 0.006) and frontal deep (p = 0.033) ARWMC were independently associated with falls. Furthermore, logistic regression identified frontal deep (p = 0.003) ARWMC, but not basal ganglia and infratentorial hyperintensities, as significantly associated with balance disturbances. CONCLUSION: The association of frontal and periventricular ARWMC with falls supports the hypothesis that interruption of frontal subcortical motor circuits lead to balance disturbances and hence to an increased risk for falls in ARWMC.
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| 12. |
- Both, C., et al.
(författare)
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Pied Flycatchers Ficedula hypoleuca travelling from Africa to breed in Europe: differential effects of winter and migration conditions on breeding date
- 2006
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Ingår i: ARDEA. - 0373-2266 .- 2213-1175. ; 94:3, s. 511-525
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Tidskriftsartikel (refereegranskat)abstract
- In most bird species there is only a short time window available for optimal breeding due to variation in ecological conditions in a seasonal environment. Long-distance migrants must travel before they start breeding, and conditions at the wintering grounds and during migration may affect travelling speed and hence arrival and breeding dates. These effects are to a large extent determined by climate variables such as rainfall and temperature, and need to be identified to predict how well species can adapt to climate change. In this paper we analyse effects of vegetation growth on the wintering grounds and sites en route on the annual timing of breeding of 17 populations of Pied Flycatchers Ficedula hypoleuca studied between 1982–2000. Timing of breeding was largely correlated with local spring temperatures, supplemented by striking effects of African vegetation and NAO. Populations differed in the effects of vegetation growth on the wintering grounds, and on their northern African staging grounds, as well as ecological conditions in Europe as measured by the winter NAO. In general, early breeding populations (low altitude, western European populations) bred earlier in years with more vegetation in the Northern Sahel zone, as well as in Northern Africa. In contrast, late breeding populations (high altitude and northern and eastern populations) advanced their breeding dates when circumstances in Europe were more advanced (high NAO). Thus, timing of breeding in most Pied Flycatcher populations not only depends upon local circumstances, but also on conditions encountered during travelling, and these effects differ across populations dependent on the timing of travelling and breeding.
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| 13. |
- Coutinho, P. M., et al.
(författare)
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Post-genomic insights into the plant polysaccharide degradation potential of Aspergillus nidulans and comparison to Aspergillus niger and Aspergillus oryzae
- 2009
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Ingår i: Fungal Genetics and Biology. - : Elsevier BV. - 1096-0937 .- 1087-1845. ; 46:Suppl 1, s. S161-S169
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Tidskriftsartikel (refereegranskat)abstract
- The plant polysaccharide degradative potential of Aspergillus nidulans was analysed in detail and compared to that of Aspergillus niger and Aspergillus oryzae using a combination of bioinformatics, physiology and transcriptomics. Manual verification indicated that 28.4% of the A. nidulans ORFs analysed in this study do not contain a secretion signal, of which 40% may be secreted through a non-classical method. While significant differences were found between the species in the numbers of ORFs assigned to the relevant CAZy families, no significant difference was observed in growth on polysaccharides. Growth differences were observed between the Aspergilli and Podospora anserina, which has a more different genomic potential for polysaccharide degradation, suggesting that large genomic differences are required to cause growth differences oil polysaccharides, Differences were also detected between the Aspergilli in the presence Of putative regulatory sequences in the promoters of the ORFs Of this Study and correlation of the presence Of putative XlnR binding sites to induction by xylose was detected for A. niger. These data demonstrate differences at genome content, Substrate specificity of the enzymes and gene regulation in these three Aspergilli, which likely reflect their individual adaptation to their natural biotope. (C) 2008 Elsevier Inc. All rights reserved.
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| 14. |
- Farbru, E, et al.
(författare)
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EFNS guideline on diagnosis and management of post-polio syndrome. Report of an EFNS task force
- 2006
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Ingår i: European Journal of Neurology. - : Wiley. - 1351-5101 .- 1468-1331. ; 13:8, s. 795-801
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Tidskriftsartikel (refereegranskat)abstract
- Post-polio syndrome (PPS) is characterized by new or increased muscular weakness, atrophy, muscle pain and fatigue several years after acute polio. The aim of the article is to prepare diagnostic criteria for PPS, and to evaluate the existing evidence for therapeutic interventions. The Medline, EMBASE and ISI databases were searched. Consensus in the group was reached after discussion by e-mail. We recommend Halstead's definition of PPS from 1991 as diagnostic criteria. Supervised, aerobic muscular training, both isokinetic and isometric, is a safe and effective way to prevent further decline for patients with moderate weakness (Level B). Muscular training can also improve muscular fatigue, muscle weakness and pain. Training in a warm climate and non-swimming water exercises are particularly useful (Level B). Respiratory muscle training can improve pulmonary function. Recognition of respiratory impairment and early introduction of non-invasive ventilatory aids prevent or delay further respiratory decline and the need for invasive respiratory aid (Level C). Group training, regular follow-up and patient education are useful for the patients’ mental status and well-being. Weight loss, adjustment and introduction of properly fitted assistive devices should be considered (good practice points). A small number of controlled studies of potential-specific treatments for PPS have been completed, but no definitive therapeutic effect has been reported for the agents evaluated (pyridostigmine, corticosteroids, amantadine). Future randomized trials should particularly address the treatment of pain, which is commonly reported by PPS patients. There is also a need for studies evaluating the long-term effects of muscular training.
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| 15. |
- Horváth, Beatrix M, et al.
(författare)
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EBP1 regulates organ size through cell growth and proliferation in plants.
- 2006
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Ingår i: EMBO Journal. - : Wiley. - 0261-4189 .- 1460-2075. ; 25:20, s. 4909-20
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Tidskriftsartikel (refereegranskat)abstract
- Plant organ size shows remarkable uniformity within species indicating strong endogenous control. We have identified a plant growth regulatory gene, functionally and structurally homologous to human EBP1. Plant EBP1 levels are tightly regulated; gene expression is highest in developing organs and correlates with genes involved in ribosome biogenesis and function. EBP1 protein is stabilised by auxin. Elevating or decreasing EBP1 levels in transgenic plants results in a dose-dependent increase or reduction in organ growth, respectively. During early stages of organ development, EBP1 promotes cell proliferation, influences cell-size threshold for division and shortens the period of meristematic activity. In postmitotic cells, it enhances cell expansion. EBP1 is required for expression of cell cycle genes; CyclinD3;1, ribonucleotide reductase 2 and the cyclin-dependent kinase B1;1. The regulation of these genes by EBP1 is dose and auxin dependent and might rely on the effect of EBP1 to reduce RBR1 protein level. We argue that EBP1 is a conserved, dose-dependent regulator of cell growth that is connected to meristematic competence and cell proliferation via regulation of RBR1 level.
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| 16. |
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| 17. |
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| 18. |
- Miranda, B, et al.
(författare)
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Self-perceived memory impairment and cognitive performance in an elderly independent population with age-related white matter changes.
- 2008
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Ingår i: Journal of neurology, neurosurgery, and psychiatry. - : BMJ. - 1468-330X .- 0022-3050. ; 79:8, s. 869-73
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To determine whether self-perceived memory impairment is associated with the severity of white matter changes (WMC) and is related to cognitive impairment. METHODS: Data were drawn from the multinational Leukoaraiosis and Disability Study (LADIS), which investigates the impact of WMC on global functioning. WMC severity was rated using the Fazekas scale. Medial temporal lobe atrophy (MTA) was scored visually and mean values were calculated. The neuropsychological battery consisted of the Mini-Mental State Examination, a modified version of the VADAS-Cog, Trail making and Stroop tests. A question about self-perceived memory impairment was used as a measure for presence of memory complaints. Cognitive performance was analysed test-by-test and in three main domains: memory, executive functions and speed/motor control. The Geriatric Depression Scale (GDS) was used as a measure of depressive symptoms. RESULTS: Six hundred and thirty-eight subjects were included in this study. No association was found between memory complaints and the severity of WMC. Subjects with memory complaints (n = 399) had a higher GDS score [t((637)) = -7.15; p<0.02] and performed worse on almost all cognitive tests and on the three cognitive domains. Multiple linear regression showed that the worse performance on the memory domain was associated with memory complaints independently of depressive symptoms, WMC severity and MTA (R(2) = 0.183; F = 17.09, beta = -0.126; p<0.05). CONCLUSION: In a sample of non-disabled elderly subjects with WMC, self-perceived memory impairment is significantly associated with objective memory impairment independently of the WMC severity, depressive symptoms and MTA.
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| 19. |
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| 20. |
- Reynish, E, et al.
(författare)
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The ICTUS Study: A Prospective longitudinal observational study of 1,380 AD patients in Europe. Study design and baseline characteristics of the cohort
- 2007
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Ingår i: Neuroepidemiology. - : S. Karger AG. - 1423-0208 .- 0251-5350. ; 29:1-2, s. 29-38
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Tidskriftsartikel (refereegranskat)abstract
- The long-term objective of the ICTUS study is to identify milestones in Alzheimer’s disease (AD) progression and to develop a model to predict disease course in individual AD patients in Europe. The secondary objectives are to describe the patterns of prescribing, and the socioeconomic impact of AD in Europe. Between 2003 and 2005 1,380 patients with probable AD were recruited in specialised (secondary care) clinics in 12 European countries. Their mean age was 76 years and they had a mean of 8.0 ± (SD) 4.6 years of education. Thirty-five percent were male. The mean MMSE score was 20.4 ± (SD) 4.0. Forty-three percent had very mild dementia (CDR 0.5) and 44% had mild dementia (CDR 1). All patients completed baseline evaluation and biannual follow-up is ongoing. The goals of the current study are to describe the specific methods for recruitment in this crosscultural setting and the characteristics of the inception ICTUS cohort, including clinical features, co-morbidity, neuropsychological performance, neuropsychiatric symptoms, functional impairment and social burden.
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| 21. |
- Visser, R., et al.
(författare)
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The photodissociation and chemistry of CO isotopologues: applications to interstellar clouds and circumstellar disks
- 2009
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Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 503, s. 323 - 343
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Tidskriftsartikel (refereegranskat)abstract
- Aims. Photodissociation by UV light is an important destruction mechanism for carbon monoxide (CO) in many astrophysical environments, ranging from interstellar clouds to protoplanetary disks. The aim of this work is to gain a better understanding of the depth dependence and isotope-selective nature of this process.Methods. We present a photodissociation model based on recent spectroscopic data from the literature, which allows us to compute depth-dependent and isotope-selective photodissociation rates at higher accuracy than in previous work. The model includes self-shielding, mutual shielding and shielding by atomic and molecular hydrogen, and it is the first such model to include the rare isotopologues C17O and 13C17O. We couple it to a simple chemical network to analyse CO abundances in diffuse and translucent clouds, photon-dominated regions, and circumstellar disks.Results. The photodissociation rate in the unattenuated interstellar radiation field is 2.6 $\times$ 10-10 s-1, 30% higher than currently adopted values. Increasing the excitation temperature or the Doppler width can reduce the photodissociation rates and the isotopic selectivity by as much as a factor of three for temperatures above 100 K. The model reproduces column densities observed towards diffuse clouds and PDRs, and it offers an explanation for both the enhanced and the reduced N(12CO)/N(13CO) ratios seen in diffuse clouds. The photodissociation of C17O and 13C17O shows almost exactly the same depth dependence as that of C18O and 13C18O, respectively, so 17O and 18O are equally fractionated with respect to 16O. This supports the recent hypothesis that CO photodissociation in the solar nebula is responsible for the anomalous 17O and 18O abundances in meteorites. Grain growth in circumstellar disks can enhance the N(12CO)/N(C17O) and N(12CO)/N(C18O) ratios by a factor of ten relative to the initial isotopic abundances.
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| 22. |
- Vujovic, M, et al.
(författare)
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Interference of a mutant thyroid hormone receptor alpha1 with hepatic glucose metabolism
- 2009
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Ingår i: Endocrinology. - : The Endocrine Society. - 1945-7170 .- 0013-7227. ; 150:6, s. 2940-2947
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Tidskriftsartikel (refereegranskat)abstract
- Mice expressing the mutant thyroid hormone receptor TRα1R384C, which has a 10-fold reduced affinity to the ligand T3, exhibit hypermetabolism due to an overactivation of the sympathetic nervous system. To define the consequences in the liver, we analyzed hepatic metabolism and the regulation of liver genes in the mutant mice. Our results showed that hepatic phosphoenolpyruvate-carboxykinase was up-regulated and pyruvate kinase mRNA down-regulated, contrary to what observed after T3 treatment. In contrast, mice expressing a mutant TRα1L400R specifically in the liver did not show a dysregulation of these genes; however, when the TRα1L400R was expressed ubiquitously, the hepatic phenotype differed from TRα1R384C animals, suggesting that the localization of the mutation plays an important role for its consequences on glucose metabolism. Furthermore, we observed that glycogen stores were completely depleted in TRα1R384C animals, despite increased gluconeogenesis and decreased glycolysis. Exposure of the mutant mice to high maternal levels of thyroid hormone during fetal development leads to a normal liver phenotype in the adult. Our results show how genetic and maternal factors interact to determine the metabolic setpoint of the offspring and indicate an important role for maternal thyroid hormone in the susceptibility to metabolic disorders in adulthood.
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