| 1. |
|
|
| 2. |
|
|
| 3. |
- Navin, N, et al.
(författare)
-
Inferring tumor progression from genomic heterogeneity
- 2010
-
Ingår i: Genome research. - : Cold Spring Harbor Laboratory. - 1549-5469 .- 1088-9051. ; 20:1, s. 68-80
-
Tidskriftsartikel (refereegranskat)abstract
- Cancer progression in humans is difficult to infer because we do not routinely sample patients at multiple stages of their disease. However, heterogeneous breast tumors provide a unique opportunity to study human tumor progression because they still contain evidence of early and intermediate subpopulations in the form of the phylogenetic relationships. We have developed a method we call Sector-Ploidy-Profiling (SPP) to study the clonal composition of breast tumors. SPP involves macro-dissecting tumors, flow-sorting genomic subpopulations by DNA content, and profiling genomes using comparative genomic hybridization (CGH). Breast carcinomas display two classes of genomic structural variation: (1) monogenomic and (2) polygenomic. Monogenomic tumors appear to contain a single major clonal subpopulation with a highly stable chromosome structure. Polygenomic tumors contain multiple clonal tumor subpopulations, which may occupy the same sectors, or separate anatomic locations. In polygenomic tumors, we show that heterogeneity can be ascribed to a few clonal subpopulations, rather than a series of gradual intermediates. By comparing multiple subpopulations from different anatomic locations, we have inferred pathways of cancer progression and the organization of tumor growth.
|
|
| 4. |
- van Egmond, L. T., et al.
(författare)
-
Acute sleep loss increases CNS health biomarkers and compromises the ability to stay awake in a sex-and weight-specific manner
- 2022
-
Ingår i: Translational Psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 12:1
-
Tidskriftsartikel (refereegranskat)abstract
- Night shift work impairs vigilance performance, reduces the ability to stay awake, and compromises brain health. To investigate if the magnitude of these adverse night shift work effects differs between sexes and weight groups, 47 men and women with either normal weight or obesity participated in one night of sleep and one night of total sleep loss. During the night of sleep loss, participants' subjective sleepiness, vigilance performance, and ability to stay awake during 2-min quiet wake with eyes closed were repeatedly assessed. In addition, blood was collected in the morning after sleep loss and sleep to measure central nervous system (CNS) health biomarkers. Our analysis showed that women were sleepier during the night of sleep loss (P < 0.05) and spent more time in microsleep during quiet wake testing (P < 0.05). Finally, higher blood levels of neurofilament light chain, a biomarker of axonal damage, were found among women in the morning after sleep loss (P < 0.002). Compared with normal-weight subjects, those with obesity were more prone to fall asleep during quiet wake (P < 0.05) and exhibited higher blood levels of the CNS health biomarker pTau181 following sleep loss (P = 0.001). Finally, no differences in vigilance performance were noted between the sex and weight groups. Our findings suggest that the ability to stay awake during and the CNS health biomarker response to night shift work may differ between sexes and weight groups. Follow-up studies must confirm our findings under more long-term night shift work conditions.
|
|
| 5. |
- Ujvári, G.a , Varga, A.b , Ramos, F.C.c , Kovács, J.b , Németh, T.d e , Stevens, T.f g
(författare)
-
Evaluating the use of clay mineralogy, Sr-Nd isotopes and zircon U-Pb ages in tracking dust provenance : An example from loess of the Carpathian Basin
- 2012
-
Ingår i: Chemical Geology. ; 304-305, s. 83-96
-
Tidskriftsartikel (refereegranskat)abstract
- Multiple competing hypotheses have been proposed to explain the source of loess dust in the Carpathian Basin yet none has been demonstrated. Here bulk and grain-size differentiated Nd and Sr isotopic and bulk and clay mineralogical compositions, together with detrital zircon ages and morphologies from loess along the Danube in the Carpathian Basin are used to demonstrate that no single method is capable of unequivocally isolating sources, yet combined, they allow for discriminating likely provenance. Zircon ages indicate multiple sources for Carpathian Basin loess, restricting the use of bulk or grain-size differentiation methods. Ambiguities are further highlighted by the fact that the Sr-Nd isotopic composition of Greenland dust is very similar to Carpathian loess. This match demonstrates that such methods are not always capable of unequivocally excluding unlikely potential source areas and implies that current hypotheses regarding the origin of Greenland dust require further evaluation. Sr isotopes are also limited by high dolomite contents of loess, while palygorskite is of questionable utility as a Saharan dust indicator due to its rapid weathering under typical Carpathian climates. In terms of specific Carpathian loess sources, alluvial fans of the Danube River likely contribute, but detrital zircon ages and morphologies suggest that a proportion directly originates from eroded uplands and local rocks throughout the basin, while detrital dolomite implies local, primary sources such as the Transdanubian Range. An upper limit of 5-10% is placed on the North African contribution to fine dust in loess of the mid-Carpathian Basin based on mineralogy and grain size. Overall, results suggest that the single grain (zircon) approach is likely the most diagnostic method to identify sources in loess studies, although to solve complex provenance issues, simultaneous consideration of the isotopic characteristics of more than one heavy (or light) mineral is required. © 2012 Elsevier B.V.
|
|
