| 1. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes
- 2008
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Ingår i: Autophagy. - : Landes Bioscience. - 1554-8627 .- 1554-8635. ; 4:2, s. 151-175
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Forskningsöversikt (refereegranskat)abstract
- Research in autophagy continues to accelerate,1 and as a result many new scientists are entering the field. Accordingly, it is important to establish a standard set of criteria for monitoring macroautophagy in different organisms. Recent reviews have described the range of assays that have been used for this purpose.2,3 There are many useful and convenient methods that can be used to monitor macroautophagy in yeast, but relatively few in other model systems, and there is much confusion regarding acceptable methods to measure macroautophagy in higher eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers of autophagosomes versus those that measure flux through the autophagy pathway; thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from fully functional autophagy that includes delivery to, and degradation within, lysosomes (in most higher eukaryotes) or the vacuole (in plants and fungi). Here, we present a set of guidelines for the selection and interpretation of the methods that can be used by investigators who are attempting to examine macroautophagy and related processes, as well as by reviewers who need to provide realistic and reasonable critiques of papers that investigate these processes. This set of guidelines is 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 verify an autophagic response.
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| 2. |
- Guo, Xiao-Hua, et al.
(författare)
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Advanced glycation end products induce actin rearrangement and subsequent hyperpermeability of endothelial cells
- 2006
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Ingår i: APMIS : acta pathologica, microbiologica, et immunologica Scandinavica. - : Wiley. - 1600-0463 .- 0903-4641. ; 114:12, s. 874-883
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Tidskriftsartikel (refereegranskat)abstract
- This study aimed to determine the effects of advanced glycation end products (AGEs) on endothelial cytoskeleton morphology and permeability, and to detect the underlying signaling mechanisms involved in these responses. Cultured endothelial cells (ECs) were exposed to AGE-modified human serum albumin (AGE-HSA), and EC cytoskeletal changes were evaluated by observing fluorescence of F-actin following ligation with labeled antibodies. Endothelial permeability was detected by measuring the flux of TRITC-albumin across the EC monolayers. To explore the signaling pathways behind AGE-induced EC alteration, ECs were treated with either soluble anti-AGE receptor (RAGE) IgG, or the MAPK inhibitors PD98059 and SB203580 before AGE-HSA administration. To further elucidate possible involvement of the ERK and p38 pathways in AGE-induced EC changes, adenovirus-carried recombinant constitutive dominant-negative forms of upstream ERK and p38 kinases, namely MEK1(A) and MKK6b(A), were pre-infected into ECs 24 h prior to AGE-HSA exposure. AGE-HSA induced actin cytoskeleton rearrangement, as well as EC hyperpermeability, in a dose and time-dependent manner. The effects were attenuated in cells pretreated with anti-RAGE IgG, PD98059 or SB203580, respectively. EC pre-infection with MEK1(A) and MKK6b(A) also alleviated the effect of AGEs. Furthermore, adenovirus-mediated administration of activated forms of either MEK1 or MKK6b alone induced rearrangement of F-actin and hyperpermeability. The results indicate that ERK and p38 MAPK play important roles in the mediation of AGE-induced EC barrier dysfunction associated with morphological changes of the F-actin.
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| 3. |
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| 4. |
- Liu, X, et al.
(författare)
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Autoantigen-pulsed dendritic cells constitute a beneficial cytokine and growth factor network in ameliorating experimental allergic encephalomyelitis
- 2005
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Ingår i: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1352-4585 .- 1477-0970. ; 11:4, s. 381-389
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Tidskriftsartikel (refereegranskat)abstract
- Injection of myelin basic protein (MBP)-pulsed dendritic cells (DC) into healthy rats, as we reported before and observed in this study, did not induce clinical experimental allergic encephalomyelitis (EAE), but effectively protected the rats from subsequent EAE induction. The mechanisms by which MBP-pulsed DC mediate immune protection are not completely understood. In the present study, we mainly explored the dynamic change of cytokine and growth factor mRNA expression in spinal cords after subcutaneous injection of MBP-pulsed and unpulsed DC. The expression of interleukin (IL)-1, interferon-g and tumour necrosis factor-a as well as programmed death ligand (PDL)-1, PDL-2, signal transducer and activator of transcription (STAT)4, STAT6, matrix metalloproteinase (MMP)-9 and tissue inhibitor of metalloproteinases (TIMP)-2 was increased on day 0 postimmunization (p.i.). The increase of IL-12 expression was observed on day 7 p.i., while the increase of IL-10 expression mainly occurred on day 14 p.i. Except downregulation of insulin-like growth factor-1, the expression of brain-derived neurotrophic factor, ciliary neurotrophic factor, fibroblast growth factor (FGF)-2 and platelet-derived growth factor (PDGF)-B/C as well as nerve growth factor receptor (NGF-R), FGF receptor, PDGF-R-a and b was elevated on day 0 p.i., while the increase of TIMP and NGF was observed on days 0 and 7 p.i. There were no significant differences on MMP-2, spinal cord-derived growth factor and PDGF-A mRNA expression. In line with the suppression of EAE induced by MBP-pulsed DC, the dynamic change of cytokines and growth factors in spinal cords should constitute a beneficial microenvironment against EAE.
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| 5. |
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| 6. |
- Rutqvist, Jonny, et al.
(författare)
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A multiple-code simulation study of the long-term EDZ evolution of geological nuclear waste repositories
- 2009
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Ingår i: Environmental Geology. - : Springer Science and Business Media LLC. - 0943-0105 .- 1432-0495. ; 57:6, s. 1313-1324
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Tidskriftsartikel (refereegranskat)abstract
- This simulation study shows how widely different model approaches can be adapted to model the evolution of the excavation disturbed zone (EDZ) around a heated nuclear waste emplacement drift in fractured rock. The study includes modeling of coupled thermal-hydrological-mechanical (THM) processes, with simplified consideration of chemical coupling in terms of time-dependent strength degradation or subcritical crack growth. The different model approaches applied in this study include boundary element, finite element, finite difference, particle mechanics, and elasto-plastic cellular automata methods. The simulation results indicate that thermally induced differential stresses near the top of the emplacement drift may cause progressive failure and permeability changes during the first 100 years (i.e., after emplacement and drift closure). Moreover, the results indicate that time-dependent mechanical changes may play only a small role during the first 100 years of increasing temperature and thermal stress, whereas such time-dependency is insignificant after peak temperature, because of decreasing thermal stress.
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| 7. |
- Su, Min, et al.
(författare)
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Temporal trends of esophageal cancer during 1995-2004 in Nanao Island, an extremely high-risk area in China
- 2007
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Ingår i: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 1573-7284 .- 0393-2990. ; 22:1, s. 43-48
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of our study was to investigate the temporal malignant tumor incidence rates among the 70,000 residents at the relatively isolated Nanao Island in South China Sea. The data on all malignant tumor cases from Nanao Cancer Registry during 1995-2004 were coded, computerized, and analyzed using the software SPSS10.0. The tumor incident cases, crude incident rate, age-standardized incidence rate, their sex distribution and temporal trend were assessed. A total of 1450 new cancer cases (990 males and 460 females) were identified. The annual average age-standardized incidence rate (ASR) of malignant tumors was 208.18/100,000. The age-standardized incidence rate of the ten leading cancers in both sexes combined per 100,000 population were 74.47 for esophageal cancer (EC), 34.81 for cardiac cancer (CC), 25.66 for liver cancer, 26.01 for lung cancer, 18.52 for stomach cancer, 4.45 for nasopharyngeal cancer, 3.91 for breast cancer, 2.53 for colon/rectum cancer, 2.45 for bladder cancer and 1.92 for pancreatic cancer. These ten types of cancers make up to 93% of all cancer cases, with EC and CC being the most prevalent and making up 52% of the total cases. The incidence rates of esophagus, liver, lung, breast, nasopharyngeal, and colon/rectum cancers showed increasing trends during the period from 1995 to 2004 in Nanao Island. Astounding the EC ASR were 72-150/100,000 among male and 26-64/100,000 among female in Nanao Island during 1995-2004. The EC incidence rate in Nanao population is among the highest across the world, which suggests that there are potential genetic and/or environmental factors affecting this particular population.
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| 10. |
- Zhu, WH, et al.
(författare)
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A putative mechanism on remission of multiple sclerosis during pregnancy: estrogen-induced indoleamine 2,3-dioxygenase by dendritic cells
- 2007
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Ingår i: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1352-4585 .- 1477-0970. ; 13:1, s. 33-40
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Tidskriftsartikel (refereegranskat)abstract
- The basis for the reduced relapse rate of multiple sclerosis (MS) during pregnancy remains unexplained but, if defined, could create novel treatment options. Estrogen constitutes one candidate molecule, but the mechanism by which estrogen may affect MS during pregnancy is unclear. In this study, we used monocyte-derived dendritic cells (DCs) from MS patients to explore the estrogen (17-b-estradiol)-related pathway of immune modulation. Estrogen induced the expression of indoleamine 2,3-dioxygenase (IDO) on DCs, limiting T-cell proliferation and both Th1 and Th2 cytokine production. The suppression of T-cell proliferation mediated by estrogenexposed DCs was partly abolished by the IDO-inhibitor, 1-methyl-dl-tryptophan, indicating that estrogen-exposed DCs induced IDO-dependent T-cell suppression. Our data support the hypothesis that the change in the clinical course of MS observed in pregnancy may be related to the estrogen DC-IDO axis, which could represent a novel target for MS therapy.
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