1. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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2. |
- Ma, Tao, et al.
(författare)
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Genomic insights into salt adaptation in a desert poplar
- 2013
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 4, s. 2797-
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Tidskriftsartikel (refereegranskat)abstract
- Despite the high economic and ecological importance of forests, our knowledge of the genomic evolution of trees under salt stress remains very limited. Here we report the genome sequence of the desert poplar, Populus euphratica, which exhibits high tolerance to salt stress. Its genome is very similar and collinear to that of the closely related mesophytic congener, P. trichocarpa. However, we find that several gene families likely to be involved in tolerance to salt stress contain significantly more gene copies within the P. euphratica lineage. Furthermore, genes showing evidence of positive selection are significantly enriched in functional categories related to salt stress. Some of these genes, and others within the same categories, are significantly upregulated under salt stress relative to their expression in another salt-sensitive poplar. Our results provide an important background for understanding tree adaptation to salt stress and facilitating the genetic improvement of cultivated poplars for saline soils.
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3. |
- Du, Yaoyao, et al.
(författare)
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Cartilage Oligomeric Matrix Protein Inhibits Vascular Smooth Muscle Calcification by Interacting With Bone Morphogenetic Protein-2.
- 2011
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Ingår i: Circulation Research. - 1524-4571. ; 108, s. 79-917
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Tidskriftsartikel (refereegranskat)abstract
- Rationale: Vascular calcification is a significant contributor to cardiovascular morbidity and mortality. We recently reported that cartilage oligomeric matrix protein (COMP) is pivotal for maintaining the homeostasis of vascular smooth muscle cells (VSMCs). Whether COMP affects the process of vascular calcification is unknown. Objective: We aimed to test whether COMP modulates vascular calcification. Methods and Results: VSMC calcification in vitro was induced by calcifying media containing high inorganic phosphate or calcium. In vivo medial vessel calcification was induced in rats by 5/6 nephrectomy with a high-phosphate diet or by periadventitial application of CaCl(2) to the abdominal aorta. COMP protein level was markedly reduced in both calcified VSMCs and arteries. COMP deficiency remarkably exacerbated VSMC calcification, whereas ectopic expression of COMP greatly reduced calcification. Furthermore, COMP knockdown facilitated osteogenic markers expression by VSMCs even in the absence of calcifying media. By contrast, COMP overexpression significantly inhibited high phosphate- or high calcium-induced VSMC osteochondrogenic transition. Induction of osteogenic marker expression by COMP silencing was reversed by a soluble form of bone morphogenetic protein (BMP)-2 receptor IA, which suggests a BMP-2-dependent mechanism. Our data revealed that COMP bound directly to BMP-2 through the C terminus, inhibited BMP-2 receptor binding, and blocked BMP-2 osteogenic signaling, indicating COMP inhibits osteochondrogenic transition of VSMCs at least partially through inhibiting BMP-2. Conclusions: Our data strongly suggest that COMP is a novel inhibitor of vascular calcification. The imbalance between the effects of COMP and BMP-2 may provide new insights into the pathophysiology of vascular calcification.
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4. |
- Tang, Feng, et al.
(författare)
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Eoandromeda and the origin of Ctenophora.
- 2011
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Ingår i: Evolution & Development. - 1520-541X .- 1525-142X. ; 13:5, s. 408-414
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Tidskriftsartikel (refereegranskat)abstract
- The Ediacaran fossil Eoandromeda octobrachiata had a high conical body with eight arms in helicospiral arrangement along the flanks. The arms carried transverse bands proposed to be homologous to ctenophore ctenes (comb plates). Eoandromeda is interpreted as an early stem-group ctenophore, characterized by the synapomorphies ctenes, comb rows, and octoradial symmetry but lacking crown-group synapomorphies such as tentacles, statoliths, polar fields, and biradial symmetry. It probably had a pelagic mode of life. The early appearance in the fossil record of octoradial ctenophores is most consistent with the Planulozoa hypothesis (Ctenophora is the sister group of Cnidaria + Bilateria) of metazoan phylogeny.
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6. |
- Yan, J. Y., et al.
(författare)
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Growth of metamorphic InGaP layers on GaAs substrates
- 2013
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Ingår i: Journal of Crystal Growth. - : Elsevier BV. - 0022-0248. ; 378, s. 141-144
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Tidskriftsartikel (refereegranskat)abstract
- We report on the growth of InGaP metamorphic layer by gas source molecular-beam epitaxy. After optimization of the growth temperatures of the compositionally graded InGaP layer and the indium content in the top metamorphic InGaP layer, almost fully relaxed metamorphic layer was obtained with surface roughness of only about 2.17 nm. Strong photoluminescence signals were measured from both InGaAs quantum well and InAs quantum dots embedded in the metamorphic layer, indicating that the top metamorphic layer had low density of threading dislocations. (c) 2013 Elsevier B.V. All rights reserved.
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8. |
- Zhao, Wei, et al.
(författare)
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Weak Crossability Barrier but Strong Juvenile Selection Supports Ecological Speciation of the Hybrid Pine Pinus Densata on the Tibetan Plateau
- 2014
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Ingår i: Evolution. - : John Wiley & Sons. - 0014-3820 .- 1558-5646. ; 68:11, s. 3120-3133
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Tidskriftsartikel (refereegranskat)abstract
- Determining how a new hybrid lineage can achieve reproductive isolation is a key to understanding the process and mechanisms of homoploid hybrid speciation. Here, we evaluated the degree and nature of reproductive isolation between the ecologically successful hybrid species Pinus densata and its parental species P. tabuliformis and P. yunnanensis. We performed interspecific crosses among the three species to assess their crossability. We then conducted reciprocal transplantation experiments to evaluate their fitness differentiation, and to examine how natural populations representing different directions of introgression differ in adaptation. The crossing experiments revealed weak genetic barriers among the species. The transplantation trials showed manifest evidence of local adaptation as the three species all performed best in their native habitats. Pinus densata populations from the western edge of its distribution have evolved a strong local adaptation to the specific habitat in that range; populations representing different directions of introgressants with the two parental species all showed fitness disadvantages in this P. densata habitat. These observations illustrate that premating isolation through selection against immigrants from other habitat types or postzygotic isolation through selection against backcrosses between the three species is strong. Thus, ecological selection in combination with endogenous components and geographic isolation has likely played a significant role in the speciation of P. densata.
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9. |
- Bodin, Olle, et al.
(författare)
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LES of the Exhaust Flow in a Heavy-Duty Engine
- 2014
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Ingår i: Oil & gas science and technology. - : EDP Sciences. - 1294-4475 .- 1953-8189. ; 69:1, s. 177-188
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Tidskriftsartikel (refereegranskat)abstract
- The flow in the exhaust port and the exhaust manifold of a heavy-duty Diesel engine has been studied using the Large Eddy Simulation approach. Some of the flow characteristics in these components are: flow unsteadiness and separation combined with significant geometry-induced secondary flow motion. Detailed analysis of these features may add understanding which can be used to decrease the flow losses and increase the eciency of downstream components such as turbochargers and EGR coolers. Few LES studies of the flow in these components have been conducted in the past and this, together with the complexity of the flow are the motivations for this work. This paper shows that in the exhaust port, even global parameters like total pressure losses are handled better by LES than RANS. Flow structures of the type that afect both turbine performance and EGR cooler efficiency are generated in the manifold and these are found to vary significantly during the exhaust pulse. This paper also clearly illustrates the need to make coupled simulations in order to handle the complicated boundary conditions of these gas exchange components.
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10. |
- Choi, Murim, et al.
(författare)
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K+ Channel Mutations in Adrenal Aldosterone-Producing Adenomas and Hereditary Hypertension
- 2011
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 331:6018, s. 768-772
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Tidskriftsartikel (refereegranskat)abstract
- Endocrine tumors such as aldosterone-producing adrenal adenomas (APAs), a cause of severe hypertension, feature constitutive hormone production and unrestrained cell proliferation; the mechanisms linking these events are unknown. We identify two recurrent somatic mutations in and near the selectivity filter of the potassium (K+) channel KCNJ5 that are present in 8 of 22 human APAs studied. Both produce increased sodium (Na+) conductance and cell depolarization, which in adrenal glomerulosa cells produces calcium (Ca2+) entry, the signal for aldosterone production and cell proliferation. Similarly, we identify an inherited KCNJ5 mutation that produces increased Na+ conductance in a Mendelian form of severe aldosteronism and massive bilateral adrenal hyperplasia. These findings explain pathogenesis in a subset of patients with severe hypertension and implicate loss of K+ channel selectivity in constitutive cell proliferation and hormone production.
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