| 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. |
- Wei, Ting, et al.
(författare)
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Developed and developing world responsibilities for historical climate change and CO2 mitigation
- 2012
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 109:32, s. 12911-12915
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Tidskriftsartikel (refereegranskat)abstract
- At the United Nations Framework Convention on Climate Change Conference in Cancun, in November 2010, the Heads of State reached an agreement on the aim of limiting the global temperature rise to 2 degrees C relative to preindustrial levels. They recognized that long-term future warming is primarily constrained by cumulative anthropogenic greenhouse gas emissions, that deep cuts in global emissions are required, and that action based on equity must be taken to meet this objective. However, negotiations on emission reduction among countries are increasingly fraught with difficulty, partly because of arguments about the responsibility for the ongoing temperature rise. Simulations with two earth-system models (NCAR/CESM and BNU-ESM) demonstrate that developed countries had contributed about 60-80%, developing countries about 20-40%, to the global temperature rise, upper ocean warming, and sea-ice reduction by 2005. Enacting pledges made at Cancun with continuation to 2100 leads to a reduction in global temperature rise relative to business as usual with a 1/3-2/3 (CESM 33-67%, BNU-ESM 35-65%) contribution from developed and developing countries, respectively. To prevent a temperature rise by 2 degrees C or more in 2100, it is necessary to fill the gap with more ambitious mitigation efforts.
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| 3. |
- Cho, Yoon Shin, et al.
(författare)
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Meta-analysis of genome-wide association studies identifies eight new loci for type 2 diabetes in east Asians.
- 2012
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:1
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Tidskriftsartikel (refereegranskat)abstract
- We conducted a three-stage genetic study to identify susceptibility loci for type 2 diabetes (T2D) in east Asian populations. We followed our stage 1 meta-analysis of eight T2D genome-wide association studies (6,952 cases with T2D and 11,865 controls) with a stage 2 in silico replication analysis (5,843 cases and 4,574 controls) and a stage 3 de novo replication analysis (12,284 cases and 13,172 controls). The combined analysis identified eight new T2D loci reaching genome-wide significance, which mapped in or near GLIS3, PEPD, FITM2-R3HDML-HNF4A, KCNK16, MAEA, GCC1-PAX4, PSMD6 and ZFAND3. GLIS3, which is involved in pancreatic beta cell development and insulin gene expression, is known for its association with fasting glucose levels. The evidence of an association with T2D for PEPD and HNF4A has been shown in previous studies. KCNK16 may regulate glucose-dependent insulin secretion in the pancreas. These findings, derived from an east Asian population, provide new perspectives on the etiology of T2D.
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| 4. |
- Hua, Kuo-Tai, et al.
(författare)
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N-α-acetyltransferase 10 protein suppresses cancer cell metastasis by binding PIX proteins and inhibiting Cdc42/Rac1 activity
- 2011
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Ingår i: Cancer Cell. - : Cell Press. - 1535-6108 .- 1878-3686. ; 19:2, s. 218-231
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Tidskriftsartikel (refereegranskat)abstract
- N-α-acetyltransferase 10 protein, Naa10p, is an N-acetyltransferase known to be involved in cell cycle control. We found that Naa10p was expressed lower in varieties of malignancies with lymph node metastasis compared with non-lymph node metastasis. Higher Naa10p expression correlates the survival of lung cancer patients. Naa10p significantly suppressed migration, tumor growth, and metastasis independent of its enzymatic activity. Instead, Naa10p binds to the GIT-binding domain of PIX, thereby preventing the formation of the GIT-PIX-Paxillin complex, resulting in reduced intrinsic Cdc42/Rac1 activity and decreased cell migration. Forced expression of PIX in Naa10-transfected tumor cells restored the migration and metastasis ability. We suggest that Naa10p functions as a tumor metastasis suppressor by disrupting the migratory complex, PIX-GIT- Paxillin, in cancer cells.
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| 5. |
- Tang, Ting-Ting, et al.
(författare)
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Impaired thymic export and apoptosis contribute to regulatory T-cell defects in patients with chronic heart failure.
- 2011
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203 .- 1932-6203. ; 6:9, s. e24272-
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Tidskriftsartikel (refereegranskat)abstract
- Animal studies suggest that regulatory T (T(reg)) cells play a beneficial role in ventricular remodeling and our previous data have demonstrated defects of T(reg) cells in patients with chronic heart failure (CHF). However, the mechanisms behind T(reg-)cell defects remained unknown. We here sought to elucidate the mechanism of T(reg-)cell defects in CHF patients.
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| 6. |
- Andersson, Martin, et al.
(författare)
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Modeling Validation and Simulation of an Anode Supported SOFC including Mass and Heat Transport, Fluid Flow and Chemical Reactions
- 2011
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Ingår i: ASME 2011 9th International Conference on Fuel Cell Science, Engineering and Technology. Collocated with ASME 2011 5th International Conference on Energy Sustainability, FUELCELL 2011. - 9780791854693 ; , s. 317-327
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Konferensbidrag (refereegranskat)abstract
- Fuel cells are electrochemical devices that directly transform chemical energy into electricity, which are promising for future energy systems, since they are energy efficient and, when hydrogen is used as fuel, there are no direct emissions of greenhouse gases. The cell performance depends strongly on the material characteristics, the operating conditions and the chemical reactions that occur inside the cell. The chemical- And electrochemical reaction rates depend on temperature, material structure, catalytic activity, degradation and the partial pressures for the different species components. There is a lack of information, within the open literature, concerning the fundamentals behind these reactions. Experimental as well as modeling studies are needed to reduce this gap. In this study experimental data collected from an intermediate temperature standard SOFC with H2/H2O in the fuel stream are used to validate a previously developed computational fluid dynamics model based on the finite element method. The developed model is based on the governing equations of heat and mass transport and fluid flow, which are solved together with kinetic expressions for internal reforming reactions of hydrocarbon fuels and electrochemistry. This model is further updated to describe the experimental environment concerning cell design. Discussion on available active area for electrochemical reactions and average ionic transport distance from the anodic- to the cathodic three-phase boundary (TPB) are presented. The fuel inlet mole fractions are changed for the validated model to simulate a H2/H2O mixture and 30 % pre-reformed natural gas.
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| 7. |
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| 8. |
- Shen, Yang-mei, et al.
(författare)
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Novel gene hBiot2 is an independent prognostic factor in colorectal cancer patients
- 2012
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Ingår i: Oncology Reports. - : Spandidos Publications. - 1021-335X .- 1791-2431. ; 27:2, s. 376-382
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Tidskriftsartikel (refereegranskat)abstract
- The present study investigated the expression of the novel gene hBiot2 in colorectal cancer (CRC) and its relationships with clinicopathological variables in CRC patients. The expression of hBiot2 in 163 primary CRCs together with the corresponding normal mucosa, 36 liver metastases and 5 colon cancer cell lines was examined using real-time PCR. In situ hybridization (ISH) was performed to evaluate the localization of hBiot2 expression in CRC and normal mucosa. hBiot2 expression at the RNA level was localized in the nucleus of tumor cells and normal epithelial cells. The mean expression of hBiot2 in the CRCs (243.571 +/- 564.569) was higher compared to the normal mucosa (107.252 +/- 413.635, Pandlt;0.0001) and liver metastasis samples (42.002 +/- 40.809, P=0.0002). hBiot2 expression was increased from stages I + II to III (P=0.047), and no difference in the expression was found in stages III and IV (P=0.452). A high value of hBiot2 was associated with a poorer prognosis compared with a low value independently of gender, age, tumor site, stage and differentiation (P=0.007, RR 7.519, 95% Cl 1.729-32.704). Liver metastasis, smaller tumors, non-local recurrence and primary liver surgery alone were associated with a higher value of hBiot2 compared to larger tumors, local recurrence and repeated liver surgery (P=0.003, 0.044 and 0.026, respectively). An inverse relationship was found between hBiot2 expression and the metastatic potential of the colon cancer cell lines. Thus, increased expression of hBiot2 may be an early and interim event in the development of CRC. A higher expression of hBiot2 in primary CRC patients independently indicates a poorer prognosis.
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| 9. |
- Wang, Thanh, 1979-, et al.
(författare)
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The in vitro estrogenic activities of polyfluorinated iodine alkanes
- 2012
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Ingår i: Journal of Environmental Health Perspectives. - USA : National Institute of Environmental Health Sciences (NIEHS). - 0091-6765 .- 1552-9924. ; 120:1, s. 119-125
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Polyfluorinated iodine alkanes (PFIs) are important intermediates in the synthesis of organic fluoride products. Recently, PFIs have been detected in fluoropolymers as residual raw materials, as well as in the ambient environment.OBJECTIVES: High production volumes and potential environmental releases of PFIs might become a concern, but the exposure risk and toxicity of these chemicals are still unclear. In this study, we investigated the potential estrogenic effects of PFIs.METHODS: We studied the estrogenic effects of fluorinated iodine alkanes (FIAs), fluorinated telomer iodides (FTIs), and fluorinated diiodine alkanes (FDIAs) using the E-screen and MVLN assays and the evaluation of estrogen-responsive genes in MCF-7 cells.RESULTS: FIAs have an iodine atom at one end of the perfluorinated carbon chain. 1-Iodoperfluorohexane (PFHxI) and 1-iodoperfluorooctane (PFOI) promoted the proliferation of MCF-7 cells, induced luciferase activity in MVLN cells, and up-regulated the expression of TFF1 and EGR3. In these assays, other FIAs gave negative responses. FDIAs have an iodine atom at each end of the perfluorinated carbon chain, and all the FDIAs showed estrogenic effects. The estrogenic potencies of FIAs and FDIAs correlate well with the carbon chain length of the chemicals. The optimum chain length for estrogenic effects is six carbons, and then eight and four carbons. All FTIs have a single iodine atom at the end of a partially fluorinated carbon chain. None of the FTIs showed estrogenic effects in the tests.CONCLUSIONS: The estrogenic effects of PFIs are dependent on the structural features of iodine substitution and chain length. This research will be helpful in further understanding the estrogenic effects of perfluorinated compounds.
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| 10. |
- Wu, Ming-Chung, et al.
(författare)
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Photocatalytic activity of nitrogen-doped TiO2-based nanowires : a photo-assisted Kelvin probe force microscopy study
- 2013
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Ingår i: Journal of nanoparticle research. - : Springer. - 1388-0764 .- 1572-896X. ; 16:1, s. Article Number: UNSP 2143-
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Tidskriftsartikel (refereegranskat)abstract
- In this study, a set of nitrogen-doped TiO2-based nanomaterials demonstrating photocatalytic activity was developed by combining the efforts of lattice doping and metal nanoparticle decoration and tested for photo-degradation of methylene blue dye by applying solar simulator irradiation. The surface potential shifts of these TiO2-based photocatalytic nanomaterials measured by Kelvin probe force microscope have been used to study the degree of electron generation of the photocatalysts after irradiation and were well correlated with the photocatalytic activity. The nitrogen-doped TiO2 nanowires decorated with Pt nanoparticles can induce obvious electron accumulation and result in a large shift of surface potential. The analysis shows a clear correlation between the surface potential shift and the photodegradation activity. Furthermore, a thorough comparative photocatalytic activity study combined with X-ray photoelectron spectroscopy analysis of the materials-doped with nitrogen under various conditions-reveals that the photocatalytic efficiency of the catalysts is maintained even if the lattice doping is leached e.g., by thermal treatments after doping. By monitoring the surface potential shifts of various TiO2-based photocatalysts by photo-assisted Kelvin probe force microscopy, we obtain a useful tool for developing novel materials with high photocatalytic activity.
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| 11. |
- Yi, Wei, et al.
(författare)
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Paracrine regulation of growth factor signaling by shed leucine-rich repeats and immunoglobulin-like domains 1
- 2011
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Ingår i: Experimental Cell Research. - New York : Academic Press. - 0014-4827 .- 1090-2422. ; 317:4, s. 504-512
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Tidskriftsartikel (refereegranskat)abstract
- Leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) is a recently discovered negative regulator of growth factor signaling. The LRIG1 integral membrane protein has been demonstrated to regulate various oncogenic receptor tyrosine kinases, including epidermal growth factor (EGF) receptor (EGFR), by cell-autonomous mechanisms. Here, we investigated whether LRIG1 ectodomains were shed, and if LRIG1 could regulate cell proliferation and EGF signaling in a paracrine manner. Cells constitutively shed LRIG1 ectodomains in vitro, and shedding was modulated by known regulators of metalloproteases, including the ADAM17 specific inhibitor TAPI-2. Furthermore, shedding was enhanced by ectopic expression of Adam17. LRIG1 ectodomains appeared to be shed in vivo, as well, as demonstrated by immunoblotting of mouse and human tissue lysates. Ectopic expression of LRIG1 in lymphocytes suppressed EGF signaling in co-cultured fibroblastoid cells, demonstrating that shed LRIG1 ectodomains can function in a paracrine fashion. Purified LRIG1 ectodomains suppressed EGF signaling without any apparent downregulation of EGFR levels. Taken together, the results show that the LRIG1 ectodomain can be proteolytically shed and can function as a non-cell-autonomous regulator of growth factor signaling. Thus, LRIG1 or its ectodomain could have therapeutic potential in the treatment of growth factor receptor-dependent cancers.
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| 12. |
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| 13. |
- Zanchetti, Alberto, et al.
(författare)
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Blood pressure and low-density lipoprotein-cholesterol lowering for prevention of strokes and cognitive decline: a review of available trial evidence.
- 2014
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Ingår i: Journal of Hypertension. - 1473-5598. ; 32:9, s. 1741-1750
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Forskningsöversikt (refereegranskat)abstract
- It is well established by a large number of randomized controlled trials that lowering blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) by drugs are powerful means to reduce stroke incidence, but the optimal BP and LDL-C levels to be achieved are largely uncertain. Concerning BP targets, two hypotheses are being confronted: first, the lower the BP, the better the treatment outcome, and second, the hypothesis that too low BP values are accompanied by a lower benefit and even higher risk. It is also unknown whether BP lowering and LDL-C lowering have additive beneficial effects for the primary and secondary prevention of stroke, and whether these treatments can prevent cognitive decline after stroke.
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| 14. |
- Zhao, Ning-Wei, et al.
(författare)
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Characterization and sequence identification of angiotensin II by a novel method involving ultra-fast liquid chromatography assay coupled with matrix-assisted laser desorption/ionization quadrupole ion trap time-of-flight five tandem mass spectrometry analysis
- 2010
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Ingår i: European journal of mass spectrometry. - : SAGE Publications. - 1469-0667 .- 1751-6838. ; 16:6, s. 663-671
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Tidskriftsartikel (refereegranskat)abstract
- High-throughput proteomics aims to investigate dynamically changing proteins expressed by a full organism, specific tissue or cellular compartment under certain conditions. High-sensitivity mass spectrometry has gradually become a significant tool for characterizing peptides. Here, we analyzed angiotensin II using ultra-fast liquid chromatography (UFLC) coupled with matrix-assisted laser desoprtion/ionization time-of-flight mass spectrometry (MALDI-ToF MS5). First, we applied UFLC in isolating and collecting the angiotensin II, and then Axima-Resonance (MALDI-QIT-ToF MS5) was adopted, which enables collision-induced dissociation-MS5 analysis for fine structural characterization of angiotensin II. Resultant MS, MS2, MS3 and MS4 spectra of interested [M+H](+) ions selected as precursor ions yielded detailed information about the sites of fragmentation as well as the amino acid sequence for angiotensin II; meanwhile, the average deviation between theoretical mass and actually measured mass from MS to MS5 spectra was only 0.32 Da. It indicated that Axima-Resonance was capable of analysing the peptide sequence accurately and providing the corresponding fragmentation information thoroughly, thus suggesting a potential strategy involving UFLC assay coupled with MALDI-QIT-ToF MS5 analysis for high-throughput proteomics studies in the future.
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