| 1. |
- Klionsky, Daniel J., et al.
(författare)
-
Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
-
Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
-
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.
|
|
| 2. |
-
- 2019
-
Tidskriftsartikel (refereegranskat)
|
|
| 3. |
- Almet, Axel A., et al.
(författare)
-
A Roadmap for a Consensus Human Skin Cell Atlas and Single-Cell Data Standardization
- 2023
-
Ingår i: Journal of Investigative Dermatology. - : Elsevier. - 0022-202X .- 1523-1747. ; 143:9, s. 1667-1677
-
Forskningsöversikt (refereegranskat)abstract
- Single-cell technologies have become essential to driving discovery in both basic and translational investigative dermatology. Despite the multitude of available datasets, a central reference atlas of normal human skin, which can serve as a reference resource for skin cell types, cell states, and their molecular signatures, is still lacking. For any such atlas to receive broad acceptance, participation by many investigators during atlas construction is an essential prerequisite. As part of the Human Cell Atlas project, we have assembled a Skin Biological Network to build a consensus Human Skin Cell Atlas and outline a roadmap toward that goal. We define the drivers of skin diversity to be considered when selecting sequencing datasets for the atlas and list practical hurdles during skin sampling that can result in data gaps and impede comprehensive representation and technical considerations for tissue processing and computational analysis, the accounting for which should minimize biases in cell type enrichments and exclusions and decrease batch effects. By outlining our goals for Atlas 1.0, we discuss how it will uncover new aspects of skin biology.
|
|
| 4. |
- Hu, Li-Peng, et al.
(författare)
-
Terbinafine prevents colorectal cancer growth by inducing dNTP starvation and reducing immune suppression
- 2022
-
Ingår i: Molecular Therapy. - : Elsevier BV. - 1525-0024 .- 1525-0016. ; 30:10, s. 3284-3299
-
Tidskriftsartikel (refereegranskat)abstract
- Existing evidence indicates that gut fungal dysbiosis might play a key role in the pathogenesis of colorectal cancer (CRC). We sought to explore whether reversing the fungal dysbiosis by terbinafine, an approved antifungal drug, might inhibit the development of CRC. A population-based study from Sweden identified a total of 185 patients who received terbinafine after their CRC diagnosis and found that they had a decreased risk of death (hazard ratio=0.50) and metastasis (hazard ratio=0.44) compared with patients without terbinafine administration. In multiple mouse models of CRC, administration of terbinafine decreased the fungal load, the fungus-induced myeloid-derived suppressor cell (MDSC) expansion, and the tumor burden. Fecal microbiota transplantation from mice without terbinafine treatment reversed MDSC infiltration and partially restored tumor proliferation. Mechanistically, terbinafine directly impaired tumor cell proliferation by reducing the ratio of nicotinamide adenine dinucleotide phosphate (NADP+) to reduced form of nicotinamide adenine dinucleotide phosphate (NADPH), suppressing the activity of glucose-6-phosphate dehydrogenase (G6PD), resulting in nucleotide synthesis disruption, deoxyribonucleotide (dNTP) starvation and cell cycle arrest. Collectively, terbinafine can inhibit CRC by reversing fungal dysbiosis, suppressing tumor cell proliferation, inhibiting fungus-induced MDSC infiltration, and restoring antitumor immune response.
|
|
| 5. |
- Lei, Shiwen, et al.
(författare)
-
A CFAR Adaptive Subspace Detector Based on a Single Observation in System-Dependent Clutter Background
- 2014
-
Ingår i: IEEE Transactions on Signal Processing. - 1053-587X. ; 62:20, s. 5260-5269
-
Tidskriftsartikel (refereegranskat)abstract
- In this paper, the problem of detecting target in system-dependent clutter (SDC) background with a single observation from the test cell is researched. Classical detectors, such as the generalized likelihood ratio detectors (GLRDs) and the adaptive matched filters (AMFs), etc., usually deal with the clutter and the noise as a whole. The low rank detectors (LRDs) make use of the low rank property of the clutter to improve the detection performance. However, the performance of LRDs degrades when the signal is not orthogonal with respect to (w.r.t.) the clutter. In this paper, an adaptive subspace detector for SDC (SDC-ASD) background which deals with the clutter and the noise separately is proposed. The SDC-ASD designs the test statistic by replacing the signal and the clutter covariance matrix with their maximum likelihood estimations (MLEs). Its theoretical false alarm probability and detection probability are analytically deduced. Analytical results show that the test statistic has the form of non-central distribution. Besides, it is shown that the SDC-ASD has constant false alarm rate (CFAR) performance w.r.t. the clutter and the noise. Numerical experiments are provided to validate the detection performance of the SDC-ASD in dealing with the target detection in SDC background.
|
|
| 6. |
- Lei, Shiwen, et al.
(författare)
-
Adaptive polarimetric detection method for target in partially homogeneous background
- 2015
-
Ingår i: Signal Processing. - : Elsevier BV. - 0165-1684. ; 106, s. 301-311
-
Tidskriftsartikel (refereegranskat)abstract
- In this paper,the problem of enhancing the detection performance of detector for target in partially homogeneous background is addressed. ased on a general measurement model, a new constant false alarm rate (CFAR) adaptive matched detector (AMD) is proposed through a two-step design procedure. The detection performance of the AMD is theoretically analyzed. Then, the correctness of the analytical results and the effectiveness of the AMD are validated through numerical experiments and IPIX radar data. To further improve the detection performance of AMD, optimal polarimetric waveform design is approached. The waveform is designed by optimally selecting the transmitted polarization that maximizes a non-central parameter of the detection probability. Numerical experiments are provided to validate the performance improvement by comparing the optimal AMD with the optimal adaptive subspace detector(ASD) and the fixed AMDs. Comparison results show that a gain of 1–5 dB is obtained by the optimal AMD.
|
|
| 7. |
- Nie, Huizhen, et al.
(författare)
-
The short isoform of PRLR suppresses the pentose phosphate pathway and nucleotide synthesis through the NEK9-Hippo axis in pancreatic cancer
- 2021
-
Ingår i: Theranostics. - : Ivyspring International Publisher. - 1838-7640. ; 11:8, s. 3898-3915
-
Tidskriftsartikel (refereegranskat)abstract
- Prolactin binding to the prolactin receptor exerts pleiotropic biological effects in vertebrates. The prolactin receptor (PRLR) has multiple isoforms due to alternative splicing. The biological roles and related signaling of the long isoform (PRLR-LF) have been fully elucidated. However, little is known about the short isoform (PRLR-SF), particularly in cancer development and metabolic reprogramming, a core hallmark of cancer. Here, we reveal the role and underlying mechanism of PRLR-SF in pancreatic ductal adenocarcinoma (PDAC). Methods: A human PDAC tissue array was used to investigate the clinical relevance of PRLR in PDAC. The in vivo implications of PRLR-SF in PDAC were examined in a subcutaneous xenograft model and an orthotopic xenograft model. Immunohistochemistry was performed on tumor tissue obtained from genetically engineered KPC (KrasG12D/+; Trp53R172H/+; Pdx1-Cre) mice with spontaneous tumors. 13C-labeled metabolite measures, LC-MS, EdU incorporation assays and seahorse analyses were used to identify the effects of PRLR-SF on the pentose phosphate pathway and glycolysis. We identified the molecular mechanisms by immunofluorescence, coimmunoprecipitation, proximity ligation assays, chromatin immunoprecipitation and promoter luciferase activity. Public databases (TCGA, GEO and GTEx) were used to analyze the expression and survival correlations of the related genes. Results: We demonstrated that PRLR-SF is predominantly expressed in spontaneously forming pancreatic tumors of genetically engineered KPC mice and human PDAC cell lines. PRLR-SF inhibits the proliferation of PDAC cells (AsPC-1 and BxPC-3) in vitro and tumor growth in vivo. We showed that PRLR-SF reduces the expression of genes in the pentose phosphate pathway (PPP) and nucleotide biosynthesis by activating Hippo signaling. TEAD1, a downstream transcription factor of Hippo signaling, directly regulates the expression of G6PD and TKT, which are PPP rate-limiting enzymes. Moreover, NEK9 directly interacts with PRLR-SF and is the intermediator between PRLR and the Hippo pathway. The PRLR expression level is negatively correlated with overall survival and TNM stage in PDAC patients. Additionally, pregnancy and lactation increase the ratio of PRLR-SF:PRLR-LF in the pancreas of wild-type mice and subcutaneous PDAC xenograft tumors. Conclusion: Our characterization of the relationship between PRLR-SF signaling, the NEK9-Hippo pathway, PPP and nucleotide synthesis explains a mechanism for the correlation between PRLR-SF and metabolic reprogramming in PDAC progression. Strategies to alter this pathway might be developed for the treatment or prevention of pancreatic cancer.
|
|
| 8. |
- Nie, Zhicheng, et al.
(författare)
-
Tailoring the d-band center by intermetallic charge-transfer manipulation in bimetal alloy nanoparticle confined in N-doped carbon nanobox for efficient rechargeable Zn-air battery
- 2023
-
Ingår i: Chemical Engineering Journal. - : Elsevier. - 1385-8947 .- 1873-3212. ; 463
-
Tidskriftsartikel (refereegranskat)abstract
- In this effort, the electronic-structure modulation strategy through nano-alloying was rationally designed to fabricate Fe-Ni alloy particles embedded in an N-doped carbon nanobox. The as-developed catalyst outperformed the commercialized noble-metal benchmarks with a decent half-wave potential of 0.891 V for ORR and a small overpotential of 325 mV at 10 mA/cm2 for OER both in 0.1 M KOH solution. Beyond that, a highly-efficient regenerative Zn-air battery was also successfully constructed, evidenced by a small potential gap of 0.664 V (between Ej=10 and E1/2), a high specific capacity of 763 mAh/g, a large peak power density of 270 mW/cm2, and robust stability. Ultraviolet photoelectron spectroscopy and theoretical simulation confirmed that the alloying of Ni into Fe could well manipulate the electronic structure, leading to favorable intermetallic charge-transfer and then downshifting the d-band center of Fe adsorption sites, all of which help to significantly lower the reaction barriers of the involved intermediates during the electrocatalytic ORR/OER processes.
|
|
| 9. |
- Xu, Jie, et al.
(författare)
-
UV-B-induced molecular mechanisms of stress physiology responses in the major northern Chinese conifer Pinus tabuliformis Carr
- 2021
-
Ingår i: Tree Physiology. - : Oxford University Press. - 0829-318X .- 1758-4469. ; 41:7, s. 1247-1263
-
Tidskriftsartikel (refereegranskat)abstract
- During their lifetimes, plants are exposed to different abiotic stress factors eliciting various physiological responses and triggering important defense processes. For UV-B radiation responses in forest trees, the genetics and molecular regulation remain to be elucidated. Here, we exposed Pinus tabuliformis Carr., a major conifer from northern China, to short-term high-intensity UV-B and employed a systems biology approach to characterize the early physiological processes and the hierarchical gene regulation, which revealed a temporal transition from primary to secondary metabolism, the buildup of enhanced antioxidant capacity and stress-signaling activation. Our findings showed that photosynthesis and biosynthesis of photosynthetic pigments were inhibited, while flavonoids and their related derivates biosynthesis, as well as glutathione and glutathione S-transferase mediated antioxidant processes, were enhanced. Likewise, stress-related phytohormones (jasmonic acid, salicylic acid and ethylene), kinase and reactive oxygen species signal transduction pathways were activated. Biological processes regulated by auxin and karrikin were, for the first time, found to be involved in plant defense against UV-B by promoting the biosynthesis of flavonoids and the improvement of antioxidant capacity in our research system. Our work evaluated the physiological and transcriptome perturbations in a conifer's response to UV-B, and generally, highlighted the necessity of a systems biology approach in addressing plant stress biology.
|
|
| 10. |
|
|
