| 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. |
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| 3. |
- Fan, C-W, et al.
(författare)
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Cancer-initiating cells derived from human rectal adenocarcinoma tissues carry mesenchymal phenotypes and resist drug therapies
- 2013
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Ingår i: Cell Death and Disease. - : Nature Publishing Group: Open Access Journals - Option B / Nature Publishing Group. - 2041-4889 .- 2041-4889. ; 4, s. e828-
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Tidskriftsartikel (refereegranskat)abstract
- Accumulating evidence indicates that cancer-initiating cells (CICs) are responsible for cancer initiation, relapse, and metastasis. Colorectal carcinoma (CRC) is typically classified into proximal colon, distal colon, and rectal cancer. The gradual changes in CRC molecular features within the bowel may have considerable implications in colon and rectal CICs. Unfortunately, limited information is available on CICs derived from rectal cancer, although colon CICs have been described. Here we identified rectal CICs (R-CICs) that possess differentiation potential in tumors derived from patients with rectal adenocarcinoma. The R-CICs carried both CD44 and CD54 surface markers, while R-CICs and their immediate progenies carried potential epithelial–mesenchymal transition characteristics. These R-CICs generated tumors similar to their tumor of origin when injected into immunodeficient mice, differentiated into rectal epithelial cells in vitro, and were capable of self-renewal both in vitro and in vivo. More importantly, subpopulations of R-CICs resisted both 5-fluorouracil/calcium folinate/oxaliplatin (FolFox) and cetuximab treatment, which are the most common therapeutic regimens used for patients with advanced or metastatic rectal cancer. Thus, the identification, expansion, and properties of R-CICs provide an ideal cellular model to further investigate tumor progression and determine therapeutic resistance in these patients.
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| 4. |
- Shen, X-G, et al.
(författare)
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Downregulation of caspase-9 is a frequent event in patients with stage II colorectal cancer and correlates with poor clinical outcome
- 2010
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Ingår i: COLORECTAL DISEASE. - : Blackwell Publishing Ltd. - 1462-8910. ; 12:12, s. 1213-1218
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Tidskriftsartikel (refereegranskat)abstract
- Objective To evaluate the clinical significance of caspase-9 mRNA expression and investigate its prognostic value in stage II colorectal cancer. Method Quantitative real-time RT-PCR was used to analyse caspase-9 mRNA expression in cancer tissue and corresponding normal mucosa from 120 patients. Results Compared with normal mucosa, the expression of caspase-9 mRNA was found to be downregulated in cancer tissue (P = 0.001). Poorly differentiated cancer showed lower mRNA expression than cancer with greater differentiation (P = 0.031). The Kaplan-Meier survival analysis demonstrated that patients with downregulated caspase-9 showed a worse overall survival (P = 0.012) and disease-free survival (P = 0.022). Coxs proportional hazards regression model confirmed that expression of caspase-9 was the strongest prognostic factor in stage II colorectal cancer. Conclusion The mRNA expression of caspase-9 can be used as an independent prognostic factor for patients with stage II colorectal cancer.
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| 5. |
- Johansson, Maria E, 1977, et al.
(författare)
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Innate immune receptor NOD2 promotes vascular inflammation and formation of lipid-rich necrotic cores in hypercholesterolemic mice
- 2014
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Ingår i: European Journal of Immunology. - : Wiley. - 0014-2980 .- 1521-4141. ; 44:10, s. 3081-3092
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Tidskriftsartikel (refereegranskat)abstract
- Atherosclerosis is an inflammatory disease associated with the activation of innate immune TLRs and nucleotide-binding oligomerization domain-containing protein (NOD)like receptor pathways. However, the function of most innate immune receptors in atherosclerosis remains unclear. Here, we show that NOD2 is a crucial innate immune receptor influencing vascular inflammation and atherosclerosis severity. 10-week stimulation with muramyl dipeptide (MDP), the NOD2 cognate ligand, aggravated atherosclerosis, as indicated by the augmented lesion burden, increased vascular inflammation and enlarged lipid-rich necrotic cores in Ldlr(-/-) mice. Myeloid-specific ablation of NOD2, but not its downstream kinase, receptor-interacting serine/threonine-protein kinase 2, restrained the expansion of the lipid-rich necrotic core in Ldlr(-/-) chimeric mice. In vitro stimulation of macrophages with MDP enhanced the uptake of oxidized low-density lipoprotein and impaired cholesterol efflux in concordance with upregulation of scavenger receptor A1/2 and downregulation of ATP-binding cassette transporter A1. Ex vivo stimulation of human carotid plaques with MDP led to increased activation of inflammatory signaling pathways p38 MAPK and NF-kappa B-mediated release of proinflammatory cytokines. Altogether, this study suggests that NOD2 contributes to the expansion of the lipid-rich necrotic core and promotes vascular inflammation in atherosclerosis.
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| 6. |
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| 7. |
- Li, C.W., et al.
(författare)
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Phonon Self-Energy and Origin of Anomalous Neutron Scattering Spectra in SnTe and PbTe Thermoelectrics
- 2014
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Ingår i: Physical Review Letters. - : American Physical Society. - 0031-9007 .- 1079-7114. ; 112:17, s. 175501-
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Tidskriftsartikel (refereegranskat)abstract
- The anharmonic lattice dynamics of rock-salt thermoelectric compounds SnTe and PbTe are investigated with inelastic neutron scattering (INS) and first-principles calculations. The experiments show that, surprisingly, although SnTe is closer to the ferroelectric instability, phonon spectra in PbTe exhibit a more anharmonic character. This behavior is reproduced in first-principles calculations of the temperature-dependent phonon self-energy. Our simulations reveal how the nesting of phonon dispersions induces prominent features in the self-energy, which account for the measured INS spectra and their temperature dependence. We establish that the phase space for three-phonon scattering processes, combined with the proximity to the lattice instability, is the mechanism determining the complex spectrum of the transverse-optic ferroelectric mode.
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| 8. |
- Li, N, et al.
(författare)
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Localized amorphism after high-strain-rate deformation in TWIP steel
- 2011
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Ingår i: Acta Materialia. - : Elsevier. - 1359-6454 .- 1873-2453. ; 59:16, s. 6369-6377
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Tidskriftsartikel (refereegranskat)abstract
- The microstructural features of shear localization, generated by a high-strain-rate deformation (similar to 10(5) s(-1)), of a twinning-induced plasticity (TWIP) steel containing about 17.5 wt.% Mn were well characterized by means of optical microscopy, transmission electron microscopy and electron backscatter diffraction. The high deformation rate was obtained by a ballistic impact penetration test on the TWIP steel sheet. In addition to the deformation twins observed as the main microstructural characterization in the matrix, some shear bands consisting of complex microstructures were also evidenced in the highly deformed area. Inside the shear band, there exist a large region of amorphous phase and a smooth transition zone that also contains nanocrystalline phases. The grain size decreases gradually in the transition zone, changing from a coarse scale (andgt;100 nm) to a fine scale (andlt;10 nm) adjacent to the amorphous region. The coexistence of the amorphous state and the fine-scaled nanocrystalline phase clearly suggests that melting inside the shear bands occurred, which is corroborated by calculations showing a very high rise in temperature due to localized plastic deformation and extremely rapid cooling by heat dissipation into the specimen.
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| 9. |
- Li, N, et al.
(författare)
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Synchrotron X-Ray Diffraction Study of Texture Evolution in 904L Stainless Steel under Dynamic Shock Compression
- 2011
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Ingår i: METALLURGICAL AND MATERIALS TRANSACTIONS A-PHYSICAL METALLURGY AND MATERIALS SCIENCE. - : Springer Science Business Media. - 1073-5623. ; 42A:1, s. 81-88
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Tidskriftsartikel (refereegranskat)abstract
- The influence of strain rate on development of deformation texture under a dynamic shock compression of a 904L stainless steel was quantitatively investigated using synchrotron X-ray diffraction and crystallographic orientation distribution function (ODF) analysis. The Split-Hopkinson Pressure Bar (SHPB) technique was used to generate a high strain rate of andgt; 10(3) s(-1) for preparing the deformed samples. Starting with an almost random texture in a solution treatment condition, the deformed material developed several typical texture components, such as Goss texture and Brass texture. Compared to the texture components displayed in the state of quasi-static compression deformation, it was found that the high-speed deformation generated much weaker texture components. In combination with the change in microstructures observed by electron backscattering diffraction (EBSD) and the transmission electron microscopy (TEM) technique, the high-energy X-ray diffraction provides a powerful tool for characterizing the strain-rate dependence of grain rotation at each stage of deformation. The deformation heterogeneity evident in our experiment can be explained by a transition of deformation mechanism from the dislocation/twin-dominated mode to a shear-band-dominated one with increasing strain rate.
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