| 1. |
- Klionsky, Daniel J., et al.
(author)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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In: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Research review (peer-reviewed)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. |
- van der Harst, Pim, et al.
(author)
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Seventy-five genetic loci influencing the human red blood cell
- 2012
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 492:7429, s. 369-375
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Journal article (peer-reviewed)abstract
- Anaemia is a chief determinant of global ill health, contributing to cognitive impairment, growth retardation and impaired physical capacity. To understand further the genetic factors influencing red blood cells, we carried out a genome-wide association study of haemoglobin concentration and related parameters in up to 135,367 individuals. Here we identify 75 independent genetic loci associated with one or more red blood cell phenotypes at P < 10(-8), which together explain 4-9% of the phenotypic variance per trait. Using expression quantitative trait loci and bioinformatic strategies, we identify 121 candidate genes enriched in functions relevant to red blood cell biology. The candidate genes are expressed preferentially in red blood cell precursors, and 43 have haematopoietic phenotypes in Mus musculus or Drosophila melanogaster. Through open-chromatin and coding-variant analyses we identify potential causal genetic variants at 41 loci. Our findings provide extensive new insights into genetic mechanisms and biological pathways controlling red blood cell formation and function.
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| 3. |
- Yu, Changxun, et al.
(author)
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Effect of weathering on abundance and release of potentially toxic elements in soils developed on Lower Cambrian black shales, P. R. China
- 2012
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In: Environmental Geochemistry and Health. - : Springer. - 0269-4042 .- 1573-2983. ; 34:3, s. 375-390
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Journal article (peer-reviewed)abstract
- This paper examines the geochemical features of 8 soil profiles developed on metalliferous black shales distributed in the central parts of the South China black shale horizon. The concentrations of 21 trace elements and 8 major elements were determined using ICP-MS and XRF, respectively, and weathering intensity (W) was calculated according to a new technique recently proposed in the literature. The data showed that the black shale soils inherited a heterogeneous geochemical character from their parent materials. A partial least square regression model and EFbedrock (enrichment factor normalized to underlying bedrock) indicated that W was not a major control in the redistribution of trace metals. Barium, Sn, Cu, V, and U tended to be leached in the upper soil horizons and trapped by Al and Fe oxides, whereas Sb, Cd, and Mo with negative EF values across the whole profiles may have been leached out during the first stage of pedogenesis (mainly weathering of black shale). Compared with the Chinese average soils, the soils were strongly enriched in the potentially toxic metals Mo, Cd, Sb, Sn, U, V, Cu, and Ba, among which the 5 first listed were enriched to the highest degrees. Elevated concentrations of these toxic metals can have a long-term negative effect on human health, in particular, the soils in mining areas dominated by strongly acidic conditions. As a whole, the black shale soils have much in common with acid sulfate soils. Therefore, black shale soils together with acid sulfate soils deserve more attention in the context of metal exposure and human health.
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| 4. |
- Deng, Min, et al.
(author)
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Genome-wide association analyses in Han Chinese identify two new susceptibility loci for amyotrophic lateral sclerosis
- 2013
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In: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 45:6, s. 697-
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Journal article (peer-reviewed)abstract
- To identify susceptibility genes for amyotrophic lateral sclerosis (ALS), we conducted a genome-wide association study (GWAS) in 506 individuals with sporadic ALS and 1,859 controls of Han Chinese ancestry. Ninety top SNPs suggested by the current GWAS and 6 SNPs identified by previous GWAS were analyzed in an independent cohort of 706 individuals with ALS and 1,777 controls of Han Chinese ancestry. We discovered two new susceptibility loci for ALS at 1q32 (CAMK1G, rs6703183, P-combined = 2.92 x 10(-8), odds ratio (OR) = 1.31) and 22p11 (CABIN1 and SUSD2, rs8141797, P-combined = 2.35 x 10(-9), OR = 1.52). These two loci explain 12.48% of the overall variance in disease risk in the Han Chinese population. We found no association evidence for the previously reported loci in the Han Chinese population, suggesting genetic heterogeneity of disease susceptibility for ALS between ancestry groups. Our study identifies two new susceptibility loci and suggests new pathogenic mechanisms of ALS.
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| 5. |
- Du, Jian, et al.
(author)
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Antiproliferative effect of alpinetin in BxPC-3 pancreatic cancer cells
- 2012
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In: International Journal of Molecular Medicine. - : Spandidos Publications. - 1107-3756 .- 1791-244X. ; 29:4, s. 607-612
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Journal article (peer-reviewed)abstract
- Alpinetin is a novel plant flavonoid derived from Alpinia katsumadai Hayata, found to possess strong anticancer effects. However, the antitumor effect of alpinetin on pancreatic cancer cells and the detailed mechanism remain unclear. The aim of this study was to investigate alpinetin's beneficial effect on pancreatic cancer and the possible molecular mechanism involved. Pancreatic cancer cell lines were treated with alpinetin at various doses and for different times, and the effect of alpinetin on cell growth inhibition, apoptosis and the cell cycle was determined. The expression of Bcl-2, Bcl-xL, XIAP and Bax, the activity of caspases and the levels of cytochrome c released were measured. The results showed that alpinetin inhibited the viability of three pancreatic cancer cell lines and induced apoptosis of BxPC-3 cells in a dose- and time-dependent manner. This was accompanied by regulation of the expression of Bcl-2, Bcl-xL, Bax and XIAP. Furthermore, alpinetin treatment led to the release of cytochrome c and activation of caspases-3, -8 and -9 proteins. Taken together, our studies indicate that alpinetin inhibited the proliferation of pancreatic cancer cells possibly through the regulation of the Bcl-2 family and XIAP expression, release of cytochrome c and the activation of caspases. Alpinetin may serve as a potential agent for the development of pancreatic cancer cell therapies.
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| 6. |
- Du, Yaoyao, et al.
(author)
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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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In: Circulation Research. - 1524-4571. ; 108, s. 79-917
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Journal article (peer-reviewed)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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| 7. |
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| 8. |
- Lu, Fangchao, et al.
(author)
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Enhanced Anisotropic Effective g Factors of an Al10.25Ga0.75N/GaN Heterostructure Based Quantum Point Contact
- 2013
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In: Nano Letters. - : American Chemical Society (ACS). - 1530-6992 .- 1530-6984. ; 13:10, s. 4654-4658
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Journal article (peer-reviewed)abstract
- Gate-defined quantum point contacts (QPCs) were fabricated with Al0.25Ga0.75N/GaN heterostructures grown by metal organic chemical Vapor deposition (MOCVD). In the transport study of the Zeeman effect, greatly enhanced effective g factors (g*).were obtained. The in-plane g* is found to be 5.5 +/- 0.6, 4.8 0.4, and 4.2 0.4 for the first to the third subband, respectively. Similarly, the out-of-plane g* is 8.3 0.6, 6.7 0.7, and 5.1 0.7. Increasing g* with the population of odd-numbered spin-splitted subbands are obtabed at 14 T. This portion of increase is assumed to arise from the exchange interaction in one-dimensional systems. A careful analysis shows that not only the exchange interaction but the spin orbit interaction (SOI) in the strongly confined QPC contribunts to the enhancement and anisotropy of g* in different subbands. An approach to distinguish the respective contributions from the SOI and exchange interaction is therefore proposed.
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| 9. |
- Morosan, D. E., et al.
(author)
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LOFAR tied-array imaging of Type III solar radio bursts
- 2014
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 568, s. articl no. A67-
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Journal article (peer-reviewed)abstract
- Context. The Sun is an active source of radio emission which is often associated with energetic phenomena such as solar flares and coronal mass ejections (CMEs). At low radio frequencies (
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| 10. |
- Peng, Bo, et al.
(author)
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Geochemistry of major and trace elements and Pb-Sr isotopes of a weathering profile developed on the Lower Cambrian black shales in central Hunan, China
- 2014
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In: Applied Geochemistry. - : Elsevier BV. - 0883-2927 .- 1872-9134. ; 51, s. 191-203
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Journal article (peer-reviewed)abstract
- This paper reports a geochemical study on the major and trace elements and Pb-Sr isotopes of a weathering profile developed in the Lower Cambrian black shales in central Hunan (China). Six weathering horizons were identified and sampled vertically throughout the profile. The chemical composition of the profile consists of variable concentrations of the major elements Fe2O3, FeO, MnO, MgO, CaO, Na2O, and P2O5 and of less variable concentrations of SiO2, TiO2, Al2O3, and K2O. The chemical change caused by weathering is estimated by mass-balance calculations, and the results show that the element mobility is characterised by substantial loss of SiO2, FeO, CaO, K2O, Na2O, LOI, Cr, V, Ba, Cs, Rb, Sr, U, and Th, and moderate loss of Al2O3, MgO, Fe2O3, Ni, Cu, Pb, Tl, Sn, Sc, Ge and REE (Y). The high field strength elements TiO2, Sn, Sc, U, Ga, Ge, Zr, Hf, Nb, and Ta were immobile during weathering. The chemical changes and the Pb-Sr isotopic data suggest that four types of chemical reactions occurred: the oxidation of sulphide minerals (e.g., pyrite) and organic carbon (OS), the dissolution of less resistant clinochlore-Ia, calcite, and P-bearing minerals (DL), the dissolution of detrital albite and microcline (DA), and the transformation of clay (TC) minerals (e.g., muscovite and illite-smectite). These chemical reactions then led to two stages of geochemical processes, an early stage of chemical differentiation and a later stage of chemical homogenisation. The chemical differentiation dominated by the OS, DL, and DA reactions, led to the leaching of mobile elements (e.g., MgO, Na2O, K2O, P2O5, Sr, and REE) and the redistribution of some less mobile elements (e.g., SiO2 and Al2O3). In contrast, the chemical homogenisation, which was caused by TC reactions, led to the leaching of both mobile and less mobile elements from the system and ultimately transformed the weathered black shales into soil. Soils derived from black shales in South China might result from the above two geochemical processes. (C) 2014 Elsevier Ltd. All rights reserved.
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