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- 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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- Kristanl, Matej, et al.
(författare)
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The Seventh Visual Object Tracking VOT2019 Challenge Results
- 2019
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Ingår i: 2019 IEEE/CVF INTERNATIONAL CONFERENCE ON COMPUTER VISION WORKSHOPS (ICCVW). - : IEEE COMPUTER SOC. - 9781728150239 ; , s. 2206-2241
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Konferensbidrag (refereegranskat)abstract
- The Visual Object Tracking challenge VOT2019 is the seventh annual tracker benchmarking activity organized by the VOT initiative. Results of 81 trackers are presented; many are state-of-the-art trackers published at major computer vision conferences or in journals in the recent years. The evaluation included the standard VOT and other popular methodologies for short-term tracking analysis as well as the standard VOT methodology for long-term tracking analysis. The VOT2019 challenge was composed of five challenges focusing on different tracking domains: (i) VOT-ST2019 challenge focused on short-term tracking in RGB, (ii) VOT-RT2019 challenge focused on "real-time" short-term tracking in RGB, (iii) VOT-LT2019 focused on long-term tracking namely coping with target disappearance and reappearance. Two new challenges have been introduced: (iv) VOT-RGBT2019 challenge focused on short-term tracking in RGB and thermal imagery and (v) VOT-RGBD2019 challenge focused on long-term tracking in RGB and depth imagery. The VOT-ST2019, VOT-RT2019 and VOT-LT2019 datasets were refreshed while new datasets were introduced for VOT-RGBT2019 and VOT-RGBD2019. The VOT toolkit has been updated to support both standard short-term, long-term tracking and tracking with multi-channel imagery. Performance of the tested trackers typically by far exceeds standard baselines. The source code for most of the trackers is publicly available from the VOT page. The dataset, the evaluation kit and the results are publicly available at the challenge website(1).
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| 5. |
- Bruhn, Sören, et al.
(författare)
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A Generally Applicable Translational Strategy Identifies S100A4 as a Candidate Gene in Allergy
- 2014
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Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6234 .- 1946-6242. ; 6:218
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Tidskriftsartikel (refereegranskat)abstract
- The identification of diagnostic markers and therapeutic candidate genes in common diseases is complicated by the involvement of thousands of genes. We hypothesized that genes co-regulated with a key gene in allergy, IL13, would form a module that could help to identify candidate genes. We identified a T helper 2 (T(H)2) cell module by small interfering RNA-mediated knockdown of 25 putative IL13-regulating transcription factors followed by expression profiling. The module contained candidate genes whose diagnostic potential was supported by clinical studies. Functional studies of human TH2 cells as well as mouse models of allergy showed that deletion of one of the genes, S100A4, resulted in decreased signs of allergy including TH2 cell activation, humoral immunity, and infiltration of effector cells. Specifically, dendritic cells required S100A4 for activating T cells. Treatment with an anti-S100A4 antibody resulted in decreased signs of allergy in the mouse model as well as in allergen-challenged T cells from allergic patients. This strategy, which may be generally applicable to complex diseases, identified and validated an important diagnostic and therapeutic candidate gene in allergy.
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- Cao, S., et al.
(författare)
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Hierachically Structured Hollow Silica Spheres for High Efficiency Immobilization of Enzymes
- 2013
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Ingår i: Advanced Functional Materials. - : Wiley. - 1616-301X .- 1616-3028. ; 23:17, s. 2162-2167
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Tidskriftsartikel (refereegranskat)abstract
- In this work, the first example of a hierarchically structured hollow silica system is reported without any chemical modification to the enzyme involved in the process. The leaching of the physically adsorbed enzyme is substantially restrained in comparison to pure hollow silica supports. The hierarchical architecture is composed of the ordered hollow silica spheres with a shell-in-shell structure. This rationally integrated architecture, which serves as the host for glucose oxidase immobilization, displays many significant advantages, including increases in mechanical stability, enzyme loading, and bioactivity, and a decrease in enzyme leaching compared to existing pure hollow silica matrices. This facilitates further multifarious applications for enhanced enzyme immobilization, biosensors, and biocatalysis.
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| 7. |
- Fan, Chuan-Wen, et al.
(författare)
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Expression profile, molecular functions, and prognostic significance of miRNAs in primary colorectal cancer stem cells
- 2021
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Ingår i: Aging. - : Impact Journals LLC. - 1945-4589 .- 1945-4589. ; 13:8, s. 12067-12085
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Tidskriftsartikel (refereegranskat)abstract
- MicroRNAs (miRNAs) are known to drive the pathogenesis of colorectal cancer (CRC) via the regulation of cancer stem cells (CSCs). We studied the miRNA expression profile of primary CSCs isolated from patients with CRC (pCRCSCs). Compared to pCRCSC-derived differentiated cells, 98 differentially expressed miRNAs were identified in pCRCSCs. Target genes encoding pCRCSC-related miRNAs were identified using a combination of miRNA target databases and miRNA-mRNA regulatory networks from the same patient. The pCRCSC-related miRNA target genes were associated with pathways contributing to malignant phenotypes, including I-kappa B kinase/NF-kappa B signaling, signal transduction by p53 class mediator, Ras signaling, and cGMP-PKG signaling. The pCRCSC-related miRNA expression signature was independently associated with poor overall survival in both the training and validation cohorts. We have thus identified several pCRCSC-related miRNAs with oncogenic potential that could serve as prognostic biomarkers for CRC.
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| 8. |
- Ji, Guomin, et al.
(författare)
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Enhanced rectifying performance by asymmetrical gate voltage for BDC20 molecular devices
- 2014
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Ingår i: RSC Advances. - : Royal Society of Chemistry. - 2046-2069. ; 4:32, s. 16537-16544
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Tidskriftsartikel (refereegranskat)abstract
- By applying the asymmetrical gate voltage on the 1,4-bis (fullero[c]pyrrolidin-1-yl) benzene BDC20 molecule, we investigate theoretically its electronic transport properties using the density functional theory and nonequilibrium Greens function formalism for a unimolecule device with metal electrodes. Interestingly, the rectifying characteristic with very high rectification ratio, 91.7 and 24.0, can be obtained when the gate voltage is asymmetrically applied on the BDC20 molecular device. The rectification direction can be tuned by the different gate voltage applying regions. The rectification behavior is understood in terms of the evolution of the transmission spectrum and projected density of states spectrum with applied bias combined with molecular projected self-consistent Hamiltonian states analyses. Our finding implies that to realize and greatly promote rectifying performance of the BDC20 molecule the variable gate voltage applying position might be a key
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| 9. |
- Jiang, S., et al.
(författare)
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Micromechanical behavior of multilayered Ti/Nb composites processed by accumulative roll bonding : An in-situ synchrotron X-ray diffraction investigation
- 2021
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Ingår i: Acta Materialia. - Oxford, United Kingdom : Elsevier. - 1359-6454 .- 1873-2453. ; 205
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Tidskriftsartikel (refereegranskat)abstract
- Heterophase interfaces play a crucial role in deformation microstructures and thus govern mechanical properties of multilayered composites. Here, we fabricated Ti/Nb multilayers by accumulative roll bonding (ARB) where shear bands became predominant with increasing rolling cycles. To explore correlation between micromechanical behavior and mechanical properties of the composites with various lamellar morphologies, in-situ high-energy X-ray diffraction tensile tests were performed. The results quantitatively reveal that the rapid strengthening of the composites with increasing ARB cycles mainly originates from the Nb layers strengthened by dislocations, grain boundaries and heterophase interfaces, and the {211} grains mostly contribute to the global strain hardening. The softer Ti grains also extend global strain hardening to a wide range and postpone necking. Furthermore, complete stress state analysis show that in the presence of extensive shear bands, significant load partitioning between the neighboring metals leads to triaxial stresses in each constituent and dislocations tend to slip along the shear direction. This promotes dislocation multiplication and motion, which is conducive to overall strength enhancement while maintaining a satisfactory ductility. These findings elucidate the effect of strong constraints of the interfaces on mechanical properties, which provides a fundamental understanding of load partitioning and strengthening mechanisms of the multilayers processed by multiple ARB cycles.
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| 10. |
- Lee, Chunsik, et al.
(författare)
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VEGF-B prevents excessive angiogenesis by inhibiting FGF2/FGFR1 pathway
- 2023
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Ingår i: SIGNAL TRANSDUCTION AND TARGETED THERAPY. - : SPRINGERNATURE. - 2095-9907 .- 2059-3635. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Although VEGF-B was discovered as a VEGF-A homolog a long time ago, the angiogenic effect of VEGF-B remains poorly understood with limited and diverse findings from different groups. Notwithstanding, drugs that inhibit VEGF-B together with other VEGF family members are being used to treat patients with various neovascular diseases. It is therefore critical to have a better understanding of the angiogenic effect of VEGF-B and the underlying mechanisms. Using comprehensive in vitro and in vivo methods and models, we reveal here for the first time an unexpected and surprising function of VEGF-B as an endogenous inhibitor of angiogenesis by inhibiting the FGF2/FGFR1 pathway when the latter is abundantly expressed. Mechanistically, we unveil that VEGF-B binds to FGFR1, induces FGFR1/VEGFR1 complex formation, and suppresses FGF2-induced Erk activation, and inhibits FGF2-driven angiogenesis and tumor growth. Our work uncovers a previously unrecognized novel function of VEGF-B in tethering the FGF2/FGFR1 pathway. Given the anti-angiogenic nature of VEGF-B under conditions of high FGF2/FGFR1 levels, caution is warranted when modulating VEGF-B activity to treat neovascular diseases.
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