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| 2. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 3. |
- 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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| 4. |
- Zhao, Li-Juan, et al.
(författare)
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Lysine demethylase LSD1 delivered via small extracellular vesicles promotes gastric cancer cell stemness
- 2021
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Ingår i: EMBO Reports. - : EMBO. - 1469-221X .- 1469-3178. ; 22:8
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Tidskriftsartikel (refereegranskat)abstract
- Several studies have examined the functions of nucleic acids in small extracellular vesicles (sEVs). However, much less is known about the protein cargos of sEVs and their functions in recipient cells. This study demonstrates the presence of lysine-specific demethylase 1 (LSD1), which is the first identified histone demethylase, in the culture medium of gastric cancer cells. We show that sEVs derived from gastric cancer cells and the plasma of patients with gastric cancer harbor LSD1. The shuttling of LSD1-containing sEVs from donor cells to recipient gastric cancer cells promotes cancer cell stemness by positively regulating the expression of Nanog, OCT4, SOX2, and CD44. Additionally, sEV-delivered LSD1 suppresses oxaliplatin response of recipient cells in vitro and in vivo, whereas LSD1-depleted sEVs do not. Taken together, we demonstrate that LSD1-loaded sEVs can promote stemness and chemoresistance to oxaliplatin. These findings suggest that the LSD1 content of sEV could serve as a biomarker to predict oxaliplatin response in gastric cancer patients.
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| 5. |
- Kärkäs, Markus D., et al.
(författare)
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Metal-Ligand Cooperation in Single-Site Ruthenium Water Oxidation Catalysts : A Combined Experimental and Quantum Chemical Approach
- 2018
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Ingår i: Inorganic Chemistry. - : American Chemical Society (ACS). - 0020-1669 .- 1520-510X. ; 57:17, s. 10881-10895
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Tidskriftsartikel (refereegranskat)abstract
- Catalysts for oxidation of water to molecular oxygen are essential in solar-driven water splitting. In order to develop more efficient catalysts for this oxidatively demanding reaction, it is vital to have mechanistic insight in order to understand how the catalysts operate. Herein, we report the mechanistic details associated with the two Ru catalysts 1 and 2. Insight into the mechanistic landscape of water oxidation catalyzed by the two single-site Ru catalysts was revealed by the use of a combination of experimental techniques and quantum chemical calculations. On the basis of the obtained results, detailed mechanisms for oxidation of water by complexes 1 and 2 are proposed. Although the two complexes are structurally related, two deviating mechanistic scenarios are proposed with metal-ligand cooperation being an important feature in both processes. The proposed mechanistic platforms provide insight for the activation of water or related small molecules through nontraditional and previously unexplored routes.
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| 6. |
- Li, Ying-Ying, et al.
(författare)
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Mechanism of Water Oxidation Catalyzed by a Mononuclear Manganese Complex
- 2017
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Ingår i: ChemSusChem. - : Wiley. - 1864-5631 .- 1864-564X. ; 10:5, s. 903-911
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Tidskriftsartikel (refereegranskat)abstract
- The design and synthesis of biomimetic Mn complexes to catalyze oxygen evolution is a very appealing goal because water oxidation in nature employs a Mn complex. Recently, the mononuclear Mn complex [LMnII(H2O)(2)](2+) [1, L=Py2N(tBu)(2), Py= pyridyl] was reported to catalyze water oxidation electro-chemically at an applied potential of 1.23 V at pH 12.2 in aqueous solution. Density functional calculations were performed to elucidate the mechanism of water oxidation promoted by this catalyst. The calculations showed that 1 can lose two protons and one electron readily to produce [LMnIII(OH)(2)](+) (2), which then undergoes two sequential proton-coupled electron-transfer processes to afford [(LMnOO)-O-V](+) (4). The O-O bond formation can occur through direct coupling of the two oxido ligands or through nucleophilic attack of water. These two mechanisms have similar barriers of approximately 17 kcal mol(-1). The further oxidation of 4 to generate [(LMnO)-O-VI-O](2+) (5), which enables O-O bond formation, has a much higher barrier. In addition, ligand degradation by C-H activation has a similar barrier to that for the O-O bond formation, and this explains the relatively low turnover number of this catalyst.
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| 7. |
- Li, Ying-Ying, et al.
(författare)
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Quantum Chemical Study of the Mechanism of Water Oxidation Catalyzed by a Heterotrinuclear Ru2Mn Complex
- 2019
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Ingår i: ChemSusChem. - : Wiley. - 1864-5631 .- 1864-564X. ; 12:5, s. 1101-1110
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Tidskriftsartikel (refereegranskat)abstract
- The heterotrinuclear complex A {[Ru-II(H2O)(tpy)](2)(mu-[Mn-II(H2O)(2)(bpp)(2)])}(4+) [tpy=2,2 ':6 ',2 ''-terpyridine, bpp=3,5-bis(2-pyridyl)pyrazolate] was found to catalyze water oxidation both electrochemically and photochemically with [Ru(bpy)(3)](3+) (bpy=2,2 '-bipyridine) as the photosensitizer and Na2S2O8 as the electron acceptor in neutral phosphate buffer. The mechanism of water oxidation catalyzed by this unprecedented trinuclear complex was studied by density functional calculations. The calculations showed that a series of oxidation and deprotonation events take place from A, leading to the formation of complex 1 (formal oxidation state of Ru1(IV)Mn(III)Ru2(III)), which is the starting species for the catalytic cycle. Three sequential oxidations of 1 result in the generation of the catalytically competing species 4 (formal oxidation state of Ru1(IV)Mn(V)Ru2(IV)), which triggers the O-O bond formation. The direct coupling of two adjacent oxo ligands bound to Ru and Mn leads to the production of a superoxide intermediate Int1. This step was calculated to have a barrier of 7.2 kcal mol(-1) at the B3LYP*-D3 level. Subsequent O-2 release from Int1 turns out to be quite facile. Other possible pathways were found to be much less favorable, including water nucleophilic attack, the coupling of an oxo and a hydroxide, and the direct coupling pathway at a lower oxidation state ((RuMnRuIV)-Mn-IV-Ru-IV).
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| 8. |
- Yu, Wenjin, et al.
(författare)
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Deep Learning-Based Classification of Cancer Cell in Leptomeningeal Metastasis on Cytomorphologic Features of Cerebrospinal Fluid
- 2022
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Ingår i: Frontiers in Oncology. - : Frontiers Media SA. - 2234-943X. ; 12, s. 1-11
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Tidskriftsartikel (refereegranskat)abstract
- Background: It is a critical challenge to diagnose leptomeningeal metastasis (LM), given its technical difficulty and the lack of typical symptoms. The existing gold standard of diagnosing LM is to use positive cerebrospinal fluid (CSF) cytology, which consumes significantly more time to classify cells under a microscope.Objective: This study aims to establish a deep learning model to classify cancer cells in CSF, thus facilitating doctors to achieve an accurate and fast diagnosis of LM in an early stage.Method: The cerebrospinal fluid laboratory of Xijing Hospital provides 53,255 cells from 90 LM patients in the research. We used two deep convolutional neural networks (CNN) models to classify cells in the CSF. A five-way cell classification model (CNN1) consists of lymphocytes, monocytes, neutrophils, erythrocytes, and cancer cells. A four-way cancer cell classification model (CNN2) consists of lung cancer cells, gastric cancer cells, breast cancer cells, and pancreatic cancer cells. Here, the CNN models were constructed by Resnet-inception-V2. We evaluated the performance of the proposed models on two external datasets and compared them with the results from 42 doctors of various levels of experience in the human-machine tests. Furthermore, we develop a computer-aided diagnosis (CAD) software to generate cytology diagnosis reports in the research rapidly.Results: With respect to the validation set, the mean average precision (mAP) of CNN1 is over 95% and that of CNN2 is close to 80%. Hence, the proposed deep learning model effectively classifies cells in CSF to facilitate the screening of cancer cells. In the human-machine tests, the accuracy of CNN1 is similar to the results from experts, with higher accuracy than doctors in other levels. Moreover, the overall accuracy of CNN2 is 10% higher than that of experts, with a time consumption of only one-third of that consumed by an expert. Using the CAD software saves 90% working time of cytologists.Conclusion: A deep learning method has been developed to assist the LM diagnosis with high accuracy and low time consumption effectively. Thanks to labeled data and step-by-step training, our proposed method can successfully classify cancer cells in the CSF to assist LM diagnosis early. In addition, this unique research can predict cancer’s primary source of LM, which relies on cytomorphologic features without immunohistochemistry. Our results show that deep learning can be widely used in medical images to classify cerebrospinal fluid cells. For complex cancer classification tasks, the accuracy of the proposed method is significantly higher than that of specialist doctors, and its performance is better than that of junior doctors and interns. The application of CNNs and CAD software may ultimately aid in expediting the diagnosis and overcoming the shortage of experienced cytologists, thereby facilitating earlier treatment and improving the prognosis of LM.
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| 9. |
- Antfolk, Christian, et al.
(författare)
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Exploring the conditions for PhD-students to develop abilities to independently formulate research questions
- 2015
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Rapport (populärvet., debatt m.m.)abstract
- Developing an ability to independently formulate research questions is an important goal in doctoral education. During a seminar in the “Docent course”, accredited by Genombrottet at Lund University, the authors behind this paper ended up in a discussion on the actual conditions for developing such ability. During the discussions, the authors, based on their own experiences, identified several conditions that could hamper the PhD-students’ abilities to develop the skills required to independently formulate research questions. Examples of such conditions were: involvement in projects where objectives and deliverables already were stated by a funder, a lack of discussions with supervisors early in the PhD-process, and/or a lack of proper training. The authors also discussed if working with a compilation thesis automatically lead to contrived overall research questions, which resulted primarily as an afterthought at a very late stage in the process.
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