| 1. |
- Chigrinova, Ekaterina, et al.
(författare)
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Two main genetic pathways lead to the transformation of chronic lymphocytic leukemia to Richter syndrome
- 2013
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 122:15, s. 2673-2682
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Tidskriftsartikel (refereegranskat)abstract
- Richter syndrome (RS) occurs in up to 15% of patients with chronic lymphocytic leukemia (CLL). Although RS, usually represented by the histologic transformation to a diffuse large B-cell lymphoma (DLBCL), is associated with a very poor outcome, especially when clonally related to the preexisting CLL, the mechanisms leading to RS have not been clarified. To better understand the pathogenesis of RS, we analyzed a series of cases including 59 RS, 28 CLL phase of RS, 315 CLL, and 127 de novo DLBCL. RS demonstrated a genomic complexity intermediate between CLL and DLBCL. Cell-cycle deregulation via inactivation of TP53 and of CDKN2A was a main mechanism in the histologic transformation from CLL phase, being present in approximately one half of the cases, and affected the outcome of the RS patients. A second major subgroup was characterized by the presence of trisomy 12 and comprised one third of the cases. Although RS shared some of the lesions seen in de novo DLBCL, its genomic profile was clearly separate. The CLL phase preceding RS had not a generalized increase in genomic complexity compared with untransformed CLL, but it presented clear differences in the frequency of specific genetic lesions.
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| 2. |
- Edgar, Graham J., et al.
(författare)
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Global conservation outcomes depend on marine protected areas with five key features
- 2014
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 506:7487, s. 216-
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Tidskriftsartikel (refereegranskat)abstract
- In line with global targets agreed under the Convention on Biological Diversity, the number of marine protected areas (MPAs) is increasing rapidly, yet socio-economic benefits generated by MPAs remain difficult to predict and under debate(1,2). MPAs often fail to reach their full potential as a consequence of factors such as illegal harvesting, regulations that legally allow detrimental harvesting, or emigration of animals outside boundaries because of continuous habitat or inadequate size of reserve(3-5). Here we show that the conservation benefits of 87 MPAs investigated worldwide increase exponentially with the accumulation of five key features: no take, well enforced, old (>10 years), large (>100 km(2)), and isolated by deep water or sand. Using effective MPAs with four or five key features as an unfished standard, comparisons of underwater survey data from effective MPAs with predictions based on survey data from fished coasts indicate that total fish biomass has declined about two-thirds from historical baselines as a result of fishing. Effective MPAs also had twice as many large (>250 mm total length) fish species per transect, five times more large fish biomass, and fourteen times more shark biomass than fished areas. Most (59%) of the MPAs studied had only one or two key features and were not ecologically distinguishable from fished sites. Our results show that global conservation targets based on area alone will not optimize protection of marine biodiversity. More emphasis is needed on better MPA design, durable management and compliance to ensure that MPAs achieve their desired conservation value.
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| 3. |
- Baeyens, Luc, et al.
(författare)
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Transient cytokine treatment induces acinar cell reprogramming and regenerates functional beta cell mass in diabetic mice
- 2014
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Ingår i: Nature Biotechnology. - : Springer Science and Business Media LLC. - 1087-0156 .- 1546-1696. ; 32:1, s. 76-83
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Tidskriftsartikel (refereegranskat)abstract
- Reprogramming of pancreatic exocrine cells into cells resembling beta cells may provide a strategy for treating diabetes. Here we show that transient administration of epidermal growth factor and ciliary neurotrophic factor to adult mice with chronic hyperglycemia efficiently stimulates the conversion of terminally differentiated acinar cells to beta-like cells. Newly generated beta-like cells are epigenetically reprogrammed, functional and glucose responsive, and they reinstate normal glycemic control for up to 248 d. The regenerative process depends on Stat3 signaling and requires a threshold number of Neurogenin 3 (Ngn3)-expressing acinar cells. In contrast to previous work demonstrating in vivo conversion of acinar cells to beta-like cells by viral delivery of exogenous transcription factors, our approach achieves acinar-to-beta-cell reprogramming through transient cytokine exposure rather than genetic modification.
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| 4. |
- Estrader, M., et al.
(författare)
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Robust antiferromagnetic coupling in hard-soft bi-magnetic core/shell nanoparticles
- 2013
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- The growing miniaturization demand of magnetic devices is fuelling the recent interest in bi-magnetic nanoparticles as ultimate small components. One of the main goals has been to reproduce practical magnetic properties observed so far in layered systems. In this context, although useful effects such as exchange bias or spring magnets have been demonstrated in core/shell nanoparticles, other interesting key properties for devices remain elusive. Here we show a robust antiferromagnetic (AFM) coupling in core/shell nanoparticles which, in turn, leads to the foremost elucidation of positive exchange bias in bi-magnetic hard-soft systems and the remarkable regulation of the resonance field and amplitude. The AFM coupling in iron oxide-manganese oxide based, soft/hard and hard/soft, core/shell nanoparticles is demonstrated by magnetometry, ferromagnetic resonance and X-ray magnetic circular dichroism. Monte Carlo simulations prove the consistency of the AFM coupling. This unique coupling could give rise to more advanced applications of bi-magnetic core/shell nanoparticles.
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| 5. |
- Gomez, German E., et al.
(författare)
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Two Sets of Metal Organic Frameworks along the Lanthanide Series Constructed by 2,3-Dimethylsuccinate: Structures, Topologies, and Strong Emission without Ligand Sensitization
- 2013
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Ingår i: Crystal Growth & Design. - : American Chemical Society (ACS). - 1528-7483 .- 1528-7505. ; 13:12, s. 5249-5260
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Tidskriftsartikel (refereegranskat)abstract
- Reactions in aqueous solution under hydrothermal conditions between (+/-)-2,3-dimethylsuccinic acid and lanthanide chlorides lead to two different isostructural types with chemical formulas [Ln(2)(C6H8O4)(3)(H2O)(2)] Ln(III) = Pr-Eu (except Pm) (Type I, compounds 1-4) and [Ln(2)(C6H8O4)(3)] Ln(III) = Tb-Yb (except Tm) (Type II, compounds 5-9). The crystal structure has been solved for the Pr (1)-, Sm (3)-, and Ho (7)-containing compounds by means of single-crystal XRD methods, whereas powder XRD Rietveld refinement was used for the rest of the MOFs. Compounds 1-4 crystallize in the triclinic space group P (1) over bar, whereas compounds 5-9 belong to the tetragonal space group P(4)2(1)2. Type I and II compounds are 3D frameworks consisting of chains of [LnO(8)(H2O)] or [LnO(8)] polyhedra, respectively, linked by dimethylsuccinate anions, giving rise to (IO2)-O-1 connectivity. All the compounds were characterized by X-ray diffraction, variable-temperature Fourier transform infrared spectroscopy, and thermal analysis. An exhaustive topological study was performed in comparison with other related compounds. The photoluminescent (PL) properties for compounds 3, 4, and 5 have been also explored, indicating that a metal-centered luminescent process takes place.
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| 6. |
- Lanner, Fredrik, et al.
(författare)
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Hypoxia-Induced Arterial Differentiation Requires Adrenomedullin and Notch Signaling
- 2013
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Ingår i: Stem Cells and Development. - : Mary Ann Liebert Inc. - 1547-3287 .- 1557-8534. ; 22:9, s. 1360-1369
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Tidskriftsartikel (refereegranskat)abstract
- Hypoxia (low oxygen) and Notch signaling are 2 important regulators of vascular development, but how they interact in controlling the choice between arterial and venous fates for endothelial cells during vasculogenesis is less well understood. In this report, we show that hypoxia and Notch signaling intersect in promotion of arterial differentiation. Hypoxia upregulated expression of the Notch ligand Dll4 and increased Notch signaling in a process requiring the vasoactive hormone adrenomedullin. Notch signaling also upregulated Dll4 expression, leading to a positive feedback loop sustaining Dll4 expression and Notch signaling. In addition, hypoxia-mediated upregulation of the arterial marker genes Depp, connexin40 (Gja5), Cxcr4, and Hey1 required Notch signaling. In conclusion, the data reveal an intricate interaction between hypoxia and Notch signaling in the control of endothelial cell differentiation, including a hypoxia/adrenomedullin/Dll4 axis that initiates Notch signaling and a requirement for Notch signaling to effectuate hypoxia-mediated induction of the arterial differentiation program.
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| 7. |
- Stuart-Smith, Rick D., et al.
(författare)
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Integrating abundance and functional traits reveals new global hotspots of fish diversity
- 2013
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 501:7468, s. 539-
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Tidskriftsartikel (refereegranskat)abstract
- Species richness has dominated our view of global biodiversity patterns for centuries(1,2). The dominance of this paradigm is reflected in the focus by ecologists and conservation managers on richness and associated occurrence-based measures for understanding drivers of broad-scale diversity patterns and as a biological basis for management(3,4). However, this is changing rapidly, as it is now recognized that not only the number of species but the species present, their phenotypes and the number of individuals of each species are critical in determining the nature and strength of the relationships between species diversity and a range of ecological functions (such as biomass production and nutrient cycling)(5). Integrating these measures should provide a more relevant representation of global biodiversity patterns in terms of ecological functions than that provided by simple species counts. Here we provide comparisons of a traditional global biodiversity distribution measure based on richness with metrics that incorporate species abundances and functional traits. We use data from standardized quantitative surveys of 2,473 marine reef fish species at 1,844 sites, spanning 133 degrees of latitude from all ocean basins, to identify new diversity hotspots in some temperate regions and the tropical eastern Pacific Ocean. These relate to high diversity of functional traits amongst individuals in the community (calculated using Rao's Q(6)), and differ from previously reported patterns in functional diversity and richness for terrestrial animals, which emphasize species-rich tropical regions only(7,8). There is a global trend for greater evenness in the number of individuals of each species, across the reef fish species observed at sites ('community evenness'), at higher latitudes. This contributes to the distribution of functional diversity hotspots and contrasts with well-known latitudinal gradients in richness(2,4). Our findings suggest that the contribution of species diversity to a range of ecosystem functions varies over large scales, and imply that in tropical regions, which have higher numbers of species, each species contributes proportionally less to community-level ecological processes on average than species in temperate regions. Metrics of ecological function usefully complement metrics of species diversity in conservation management, including when identifying planning priorities and when tracking changes to biodiversity values.
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| 8. |
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