| 1. |
- Anderson, Beverley H., et al.
(författare)
-
Mutations in CTC1, encoding conserved telomere maintenance component 1, cause Coats plus
- 2012
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:3, s. 338-342
-
Tidskriftsartikel (refereegranskat)abstract
- Coats plus is a highly pleiotropic disorder particularly affecting the eye, brain, bone and gastrointestinal tract. Here, we show that Coats plus results from mutations in CTC1, encoding conserved telomere maintenance component 1, a member of the mammalian homolog of the yeast heterotrimeric CST telomeric capping complex. Consistent with the observation of shortened telomeres in an Arabidopsis CTC1 mutant and the phenotypic overlap of Coats plus with the telomeric maintenance disorders comprising dyskeratosis congenita, we observed shortened telomeres in three individuals with Coats plus and an increase in spontaneous gamma H2AX-positive cells in cell lines derived from two affected individuals. CTC1 is also a subunit of the alpha-accessory factor (AAF) complex, stimulating the activity of DNA polymerase-alpha primase, the only enzyme known to initiate DNA replication in eukaryotic cells. Thus, CTC1 may have a function in DNA metabolism that is necessary for but not specific to telomeric integrity.
|
|
| 2. |
- Kranendijk, Martijn, et al.
(författare)
-
IDH2 Mutations in Patients with D-2-Hydroxyglutaric Aciduria.
- 2010
-
Ingår i: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 330:6002
-
Tidskriftsartikel (refereegranskat)abstract
- Heterozygous somatic mutations in the genes encoding isocitrate dehydrogenase- 1 and -2 (IDH1 and IDH2) were recently discovered in human neoplastic disorders. These mutations disable the enzymes' normal ability to convert isocitrate to 2-ketoglutarate (2-KG) and confer on the enzymes a new function: the ability to convert 2-KG to d-2-hydroxyglutarate (D-2-HG). We have detected heterozygous germline mutations in IDH2 that alter enzyme residue R140 in 15 unrelated patients with d-2-hydroxyglutaric aciduria (D-2-HGA), a rare neurometabolic disorder characterized by supraphysiological levels of D-2-HG. These findings provide additional impetus for investigating the role of D-2-HG in the pathophysiology of metabolic disease and cancer.
|
|
| 3. |
- Strandberg, G., et al.
(författare)
-
Regional climate model simulations for Europe at 6 k and 0.2 k yr BP: sensitivity to changes in anthropogenic deforestation.
- 2013
-
Ingår i: Climate of the Past Discussions. - : Copernicus GmbH. - 1814-9340 .- 1814-9359. ; 9:5, s. 5785-5836
-
Tidskriftsartikel (refereegranskat)abstract
- This study aims to evaluate the direct effects of anthropogenic deforestation on simulated climate at two contrasting periods in the Holocene, ~6 k BP and ~0.2 k BP in Europe. We apply RCA3, a regional climate model with 50 km spatial resolution, for both time periods, considering three alternative descriptions of the past vegetation: (i) potential natural vegetation (V) simulated by the dynamic vegetation model LPJ-GUESS, (ii) potential vegetation with anthropogenic land cover (deforestation) as simulated by the HYDE model (V + H), and (iii) potential vegetation with anthropogenic land cover as simulated by the KK model (V + K). The KK model estimates are closer to a set of pollen-based reconstructions of vegetation cover than the HYDE model estimates. The climate-model results show that the simulated effects of deforestation depend on both local/regional climate and vegetation characteristics. At ~6 k BP the extent of simulated deforestation in Europe is generally small, but there are areas where deforestation is large enough to produce significant differences in summer temperatures of 0.5–1 °C. At ~0.2 k BP, simulated deforestation is much more extensive than previously assumed, in particular according to the KK model. This leads to significant temperature differences in large parts of Europe in both winter and summer. In winter, deforestation leads to lower temperatures because of the differences in albedo between forested and unforested areas, particularly in the snow-covered regions. In summer, deforestation leads to higher temperatures in central and eastern Europe since evapotranspiration from unforested areas is lower than from forests. Summer evaporation is already limited in the southernmost parts of Europe under potential vegetation conditions and, therefore, cannot become much lower. Accordingly, the albedo effect dominates also in summer, which implies that deforestation causes a decrease in temperatures. Differences in summer temperature due to deforestation range from −1 °C in south-western Europe to +1 °C in eastern Europe. The choice of anthropogenic land cover estimate has a significant influence on the simulated climate, but uncertainties in palaeoclimate proxy data for the two time periods do not allow for a thorough comparison with climate model results.
|
|
| 4. |
- Gaillard, Marie-José, 1953-, et al.
(författare)
-
Holocene land-cover reconstructions for studies on land cover-climate feedbacks
- 2010
-
Ingår i: Climate of the Past. - : Copernicus GmbH. - 1814-9324 .- 1814-9332. ; 6, s. 483-499
-
Tidskriftsartikel (refereegranskat)abstract
- The major objectives of this paper are: (1) to review the pros and cons of the scenarios of past anthropogenic land cover change (ALCC) developed during the last ten years, (2) to discuss issues related to pollen-based reconstruction of the past land-cover and introduce a new method, REVEALS (Regional Estimates of VEgetation Abundance from Large Sites), to infer long-term records of past land-cover from pollen data, (3) to present a new project (LANDCLIM: LAND cover – CLIMate interactions in NW Europe during the Holocene) currently underway, and show preliminary results of REVEALS reconstructions of the regional land-cover in the Czech Republic for five selected time windows of the Holocene, and (4) to discuss the implications and future directions in climate and vegetation/land-cover modeling, and in the assessment of the effects of human-induced changes in land-cover on the regional climate through altered feedbacks. The existing ALCC scenarios show large discrepancies between them, and few cover time periods older than AD 800. When these scenarios are used to assess the impact of human land-use on climate, contrasting results are obtained. It emphasizes the need for methods such as the REVEALS model-based land-cover reconstructions. They might help to fine-tune descriptions of past land-cover and lead to a better understanding of how long-term changes in ALCC might have influenced climate. The REVEALS model is demonstrated to provide better estimates of the regional vegetation/landcover changes than the traditional use of pollen percentages. This will achieve a robust assessment of land cover at regional- to continental-spatial scale throughout the Holocene. We present maps of REVEALS estimates for the percentage cover of 10 plant functional types (PFTs) at 200 BP and 6000 BP, and of the two open-land PFTs “grassland” and “agricultural land” at five time-windows from 6000 BP to recent time. The LANDCLIM results are expected to provide crucial data to reassess ALCC estimates for a better understanding of the land suface-atmosphere interactions.
|
|
| 5. |
- Livingston, John H, et al.
(författare)
-
Leukoencephalopathy with Calcifications and Cysts : A Purely Neurological Disorder Distinct from Coats Plus
- 2014
-
Ingår i: Neuropediatrics. - : Georg Thieme Verlag KG. - 0174-304X .- 1439-1899. ; 45:3, s. 175-182
-
Tidskriftsartikel (refereegranskat)abstract
- Objective With the identification of mutations in the conserved telomere maintenance component 1 (CTC1) gene as the cause of Coats plus (CP) disease, it has become evident that leukoencephalopathy with calcifications and cysts (LCC) is a distinct genetic entity. Patients and Methods A total of 15 patients with LCC were identified from our database of patients with intracranial calcification. The clinical and radiological features are described. Results The median age (range) at presentation was 10 months (range, 2 days-54 years). Of the 15 patients, 9 presented with epileptic seizures, 5 with motor abnormalities, and 1 with developmental delay. Motor abnormalities developed in 14 patients and cognitive problems in 13 patients. Dense calcification occurred in the basal ganglia, thalami, dentate nucleus, brain stem, deep gyri, deep white matter, and in a pericystic distribution. Diffuse leukoencephalopathy was present in all patients, and it was usually symmetrical involving periventricular, deep, and sometimes subcortical, regions. Cysts developed in the basal ganglia, thalamus, deep white matter, cerebellum, or brain stem. In unaffected areas, normal myelination was present. No patient demonstrated cerebral atrophy. Conclusion LCC shares the neuroradiological features of CP. However, LCC is a purely neurological disorder distinguished genetically by the absence of mutations in CTC1. The molecular cause(s) of LCC has (have) not yet been determined.
|
|
| 6. |
- Strandberg, Gustav, et al.
(författare)
-
Regional climate model simulations for Europe at 6 and 0.2 k BP : sensitivity to changes in anthropogenic deforestation
- 2014
-
Ingår i: Climate of the Past. - : Copernicus GmbH. - 1814-9324 .- 1814-9332. ; 10:2, s. 661-680
-
Tidskriftsartikel (refereegranskat)abstract
- This study aims to evaluate the direct effects of anthropogenic deforestation on simulated climate at two contrasting periods in the Holocene, similar to 6 and similar to 0.2 k BP in Europe. We apply We apply the Rossby Centre regional climate model RCA3, a regional climate model with 50 km spatial resolution, for both time periods, considering three alternative descriptions of the past vegetation: (i) potential natural vegetation (V) simulated by the dynamic vegetation model LPJ-GUESS, (ii) potential vegetation with anthropogenic land use (deforestation) from the HYDE3.1 (History Database of the Global Environment) scenario (V + H3.1), and (iii) potential vegetation with anthropogenic land use from the KK10 scenario (V + KK10). The climate model results show that the simulated effects of deforestation depend on both local/regional climate and vegetation characteristics. At similar to 6 k BP the extent of simulated deforestation in Europe is generally small, but there are areas where deforestation is large enough to produce significant differences in summer temperatures of 0.5-1 degrees C. At similar to 0.2 k BP, extensive deforestation, particularly according to the KK10 model, leads to significant temperature differences in large parts of Europe in both winter and summer. In winter, deforestation leads to lower temperatures because of the differences in albedo between forested and unforested areas, particularly in the snow-covered regions. In summer, deforestation leads to higher temperatures in central and eastern Europe because evapotranspiration from unforested areas is lower than from forests. Summer evaporation is already limited in the southernmost parts of Europe under potential vegetation conditions and, therefore, cannot become much lower. Accordingly, the albedo effect dominates in southern Europe also in summer, which implies that deforestation causes a decrease in temperatures. Differences in summer temperature due to deforestation range from -1 degrees C in south-western Europe to +1 degrees C in eastern Europe. The choice of anthropogenic land-cover scenario has a significant influence on the simulated climate, but uncertainties in palaeoclimate proxy data for the two time periods do not allow for a definitive discrimination among climate model results.
|
|
