180 results on '"Yumei Wu"'
Search Results
2. On-Chip Ultralow-Threshold Tunable CdSSe Nanobelt Lasers Excited by the Emission of Linked ZnO Nanowire
- Author
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Jing Lyu, Yunsong Yin, Denan Kong, Chunyu Zhao, Xinyu Zhang, An Li, Wen Yi, Yumei Wu, Xianshuang Wang, and Ruibin Liu
- Subjects
General Materials Science ,Physical and Theoretical Chemistry - Published
- 2023
3. A Lysosome-Targeted Near-Infrared Fluorescent Probe with Excellent Water Solubility for Surgery Navigation in Breast Cancer
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Yumei Wu, Zhengjun Chen, Dan Shen, Zhiquan He, Jiajia Lv, Hongyu Li, Mingyan Yang, Jun Tan, Jianrong Yuan, Jie Gao, and Zeli Yuan
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General Chemical Engineering ,General Chemistry - Published
- 2023
4. Blend with the Sea Surface Temperature from Different Satellites and Their Comparison in the Southeast Pacific Ocean
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Yumei Wu, Fenghua Tang, Yang Dai, Fei Wang, Yongchuang Shi, and Shengmao Zhang
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Ocean Engineering ,Oceanography - Published
- 2023
5. Regulation of <scp>CD18</scp> stability by <scp>SIGIRR</scp> ‐modulated ubiquitination: new insights into the relationship between innate immune response and acute lung injury
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Feng Tian, Jie Lei, Yunfeng Ni, Daixing Zhong, Nianlin Xie, Jun Ma, Haiqiang Wang, Shaokui Si, Yumei Wu, and Tao Jiang
- Subjects
Cell Biology ,Molecular Biology ,Biochemistry - Abstract
Inappropriate accumulation of alveolar macrophages (AMs) and subsequent excessive production of immune responses play critical roles in the pathogenesis of acute lung injury (ALI), but the core negative regulators governing innate signaling in AMs are ill defined. We have previously shown that single immunoglobin IL-1 receptor-related protein (SIGIRR), a negative regulator of IL-1 receptor and Toll-like receptor signaling, inhibits lipopolysaccharide (LPS)-induced inflammatory responses in AMs. To address the biological relevance of SIGIRR in vivo, we generated a murine ALI model via intratracheal instillation of LPS. Intriguingly, SIGIRR expression was observed to be decreased in resident and recruited macrophages during ALI. This decrease was associated with parallel induction in CD18 protein levels in LPS-challenged lung tissues. Through intranasal injection of SIGIRR lentiviral particles studies, we showed that overexpression of SIGIRR attenuated recruitment of macrophages and neutrophils, decreased production of inflammatory cytokines and ameliorated pathological changes in lungs. Whilst exploring the basis for this phenotype, SIGIRR was found to be coexpressed with CD18 in AMs, and SIGIRR potentiated the instability of CD18 protein via enhancement of its ubiquitination and proteasome degradation. Conversely, by using CD18
- Published
- 2022
6. ACL stump and ACL femoral landmarks are equally reliable in ACL reconstruction for assisting ACL femoral tunnel positioning
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Weijie Liu, Yumei Wu, Xiaopeng Wang, Shida Kuang, Chao Su, Yilin Xiong, Hang Tang, Yifan Xiao, and Shuguang Gao
- Subjects
Orthopedics and Sports Medicine ,Surgery - Abstract
This study aimed to comparatively evaluate the accuracy of femoral tunnel positioning after anatomic single-bundle anterior cruciate ligament (ACL) reconstruction performed with the remnant preservation (RP) technique versus the non-remnant preservation (NRP) technique.A retrospective review of 145 patients who underwent ACL reconstruction from May 2020 to May 2022 were performed in this single-surgeon study. A total of 120 patients met the inclusion criteria and were allocated into two groups according to the surgical technique (i.e. RP group and NRP group). The relative location of the femoral tunnel in the lateral condyle was evaluated as a percentage using a standardized grid system on the three-dimensional computed tomography (3D-CT) image. The accuracy and precision of the RP group were assessed based on published anatomical data in direct comparison with the NRP group.According to the surgical procedure, 57 of the 120 patients included were allocated into the RP group, and 63 into the NRP group. Significant differences were observed between the two groups in terms of tunnel position (posterior-to-distal (PD): 28.4 ± 5.4% (RP) vs. 31.8 ± 5.3% (NRP); P = 0.01), (anterior-to-posterior (AP): 32.6 ± 7.7% (RP) vs. 38.8 ± 7.7% (NRP); P = 0.00), while no significant differences were found in terms of the accuracy (8.6% (RP) vs. 8.9% (NRP); n.s) and precision (4.4% (RP) vs. 5.6% (NRP); n.s) of femoral tunnel positioning between the two groups.From this single-surgeon study, it was concluded that there were no differences in the creation of ACL femoral tunnel between the RP technique and the non-remnant preserving technique. Meanwhile, the RP technique would not sacrifice the ideal position of the femoral tunnel and is able to retain the possible benefits of the ACL stump.Level III.
- Published
- 2022
7. Development of Humanized ACE2 Mouse and Rat Models for COVID-19 Research
- Author
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Hongmei Jiang, Emma Hyddmark, Jianqiu Xiao, Sara Gordon, Angela Bartels, Yumei Wu, Joe Warren, Lauren Klaskala, Andrew Brown, Michael Garratt, Helmut Ehall, and Guojun Zhao
- Published
- 2023
8. ATG9 vesicles comprise the seed membrane of mammalian autophagosomes
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Taryn J. Olivas, Yumei Wu, Shenliang Yu, Lin Luan, Peter Choi, Emily D. Guinn, Shanta Nag, Pietro V. De Camilli, Kallol Gupta, and Thomas J. Melia
- Subjects
Cell Biology - Abstract
As the autophagosome forms, its membrane surface area expands rapidly, while its volume is kept low. Protein-mediated transfer of lipids from another organelle to the autophagosome likely drives this expansion, but as these lipids are only introduced into the cytoplasmic-facing leaflet of the organelle, full membrane growth also requires lipid scramblase activity. ATG9 harbors scramblase activity and is essential to autophagosome formation; however, whether ATG9 is integrated into mammalian autophagosomes remains unclear. Here we show that in the absence of lipid transport, ATG9 vesicles are already competent to collect proteins found on mature autophagosomes, including LC3-II. Further, we use styrene–maleic acid lipid particles to reveal the nanoscale organization of protein on LC3-II membranes; ATG9 and LC3-II are each fully integrated into expanding autophagosomes. The ratios of these two proteins at different stages of maturation demonstrate that ATG9 proteins are not continuously integrated, but rather are present on the seed vesicles only and become diluted in the expanding autophagosome membrane.
- Published
- 2023
9. Analysis of prognostic value of lactate metabolism-related genes in ovarian cancer based on bioinformatics
- Author
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Jinrui Sun, Yingying Xu, Ping Liu, and Yumei Wu
- Abstract
Background Recent studies have provided evidence supporting the functional role and mechanism of lactate in suppressing anticancer immunity. However, there is no systematic analysis of lactate metabolism-related genes (LMRGs) and ovarian cancer (OV) prognosis.Results Six genes (CCL18, CCND1, MXRA5, NRBP2, OLFML2B and THY1) were selected as prognostic genes and a prognostic model was utilized. Kaplan-Meier (K-M) and Receiver Operating Characteristic (ROC) analyses were further performed and indicated that the prognostic model was effective. Subsequently, the neoplasm_cancer_status and RiskScore were determined as independent prognostic factors, and a nomogram was established with relatively accurate forecasting ability. Additionally, 2 types of immune cells (Central memory CD8 T cell and Immature B cell), 4 types of immune functions (APC co inhibition, DCs, Tfh and Th1 cells), 9 immune checkpoints (BTLA, CTLA4, IDO1, LAG3, VTCN1, CXCL10, CXCL9, IFNG, CD27) and tumor immune dysfunction and exclusion (TIDE) scores were significantly different between risk groups. The expression of 6 genes were verified by quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) and the expression of 6 genes were higher in the high-grade serous carcinoma (HGSC) samples.Conclusion A prognostic model related to lactate metabolism was established for OV based on six genes (CCL18, CCND1, MXRA5, NRBP2, OLFML2B and THY1) that could provide new insights into therapy.
- Published
- 2023
10. The association between fatty liver index and onset of diabetes: secondary analysis of a population-based cohort study
- Author
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Yanqiong Zhu, Haofei Hu, Yumei Wu, Yinhua Rao, Qixiang Li, Xuehui Duan, Guopeng Yao, Hekun Yin, and Ziyi Luo
- Subjects
Public Health, Environmental and Occupational Health - Abstract
Background According to research, the fatty liver index (FLI) is associated with diabetes. However, few studies have been conducted to investigate the relationship between FLI and diabetes risk from various perspectives. This study comprehensively investigated the relationship between FLI and incident diabetes in a large Japanese population. Methods This retrospective cohort study included 14,280 participants from Murakami Memorial Hospital in Japan from 2004 to 2015. The independent and dependent variables are FLI and risk of type 2 diabetes mellitus (T2DM), respectively. To examine the link between FLI and incident T2DM, Cox proportional-hazards regression was employed. In addition, we performed a number of sensitivity studies to guarantee the validity of the results. Moreover, we conducted subgroup analyses. Results After adjusting covariates, the results showed that FLI was positively associated with the risk of T2DM (HR = 1.019, 95%CI: 1.012, 1.025). Additionally, the sensitivity analysis showed how reliable the outcomes were. And a stronger association between FLI and incident T2DM was observed in the regular exercisers (HR = 1.036, 95%CI: 1.019–1.053, P P Conclusion FLI is positively associated with incident T2DM.
- Published
- 2023
11. Pharmacological Activation of GPR55 Improved Cognitive Impairment Induced by Lipopolysaccharide in Mice
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Xin Wang, XiaoTong Xiang, Jie Hu, YuMei Wu, YueYue Li, ShiYu Jin, and Xian Wu
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Cannabinoid Receptor Agonists ,Lipopolysaccharides ,Mice, Inbred ICR ,Caspase 3 ,Superoxide Dismutase ,NF-kappa B ,General Medicine ,Hippocampus ,Mice ,Cellular and Molecular Neuroscience ,Proto-Oncogene Proteins c-bcl-2 ,Animals ,Cytokines ,Cognitive Dysfunction ,Microglia ,Maze Learning ,Receptors, Cannabinoid ,bcl-2-Associated X Protein - Abstract
Our previous research found that activation of GPR55 can alleviate cognitive impairment induced by amyloid-beta 1-42 (Aβ
- Published
- 2022
12. Association of waist circumference with all-cause and cardiovascular mortality in diabetes from NHANES 2003-2014
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Tian Tian, Yang Geng, Xuehui Li, Xueli Sun, Yan Liu, Changjun Pei, Xin Wang, Ling Cao, Hui Chen, Hengzhong Zhang, Yumei Wu, and Bin Song
- Abstract
Background In diabetes mellitus (DM), the relationship between waist circumference (WC) and mortality is scarce. Herein, we explored all-cause and cardiovascular mortality relationships with the baseline WC among individuals with DM. Methods US adults with DM (2256 women and 2427 men) from NHANES 2003–2014 who had WC measurement at the baseline were included. The national death index was employed to obtain their survival data from the enrollment till 2015. The mortality risk was calculated using multivariable Cox proportional hazards models, smooth curve fitting, and threshold effect analysis. Results Among a total of 4683 participants with diabetes, 346 women and 482 men died during the median follow-up of 5.7 and 5.4 years, respectively. With all-cause and cardiovascular mortality, WC exhibited a U-shaped association among females and a J-shaped trend among males. The adjusted hazard ratios (HRs) along with 95% confidence intervals (CIs) for all-cause mortality given WC values below and above 107.0 cm were 0.98 (0.96–0.98) and 1.03 (1.01–1.05), respectively, among women, and those below and above 89.5 cm were 0.91 (0.87–0.96) and 1.04 (1.02–1.05), respectively, among men. Conclusions WC presented a U-shaped relationship among women, and a J-shaped relation among men regarding all-cause and cardiovascular mortality among US adults with DM from NHANES.
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- 2023
13. Hydrodynamic simulation and experiment of depth adjustable beam trawl for Antarctic krill
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Ruilin He, Hanfeng Zheng, Shuo Ma, Yumei Wu, Shenglong Yang, Yang Dai, and Yongjin Wang
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Mechanics of Materials ,Mechanical Engineering ,Ocean Engineering ,Oceanography - Published
- 2023
14. Synaptic vesicle proteins and ATG9A self-organize in distinct vesicle phases within synapsin condensates
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Daehun Park, Yumei Wu, Xinbo Wang, Swetha Gowrishankar, Aaron Baublis, and Pietro De Camilli
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Multidisciplinary ,General Physics and Astronomy ,General Chemistry ,General Biochemistry, Genetics and Molecular Biology - Abstract
Ectopic expression in fibroblasts of synapsin 1 and synaptophysin is sufficient to generate condensates of vesicles highly reminiscent of synaptic vesicle (SV) clusters and with liquid-like properties. Here we show that unlike synaptophysin, other major integral SV membrane proteins fail to form condensates with synapsin, but co-assemble into the clusters formed by synaptophysin and synapsin in this ectopic expression system. Another vesicle membrane protein, ATG9A, undergoes activity-dependent exo-endocytosis at synapses, raising questions about the relation of ATG9A traffic to the traffic of SVs. We find that both in fibroblasts and in nerve terminals ATG9A does not co-assemble into synaptophysin-positive vesicle condensates but localizes on a distinct class of vesicles that also assembles with synapsin but into a distinct phase. Our findings suggest that ATG9A undergoes differential sorting relative to SV proteins and also point to a dual role of synapsin in controlling clustering at synapses of SVs and ATG9A vesicles.
- Published
- 2023
15. Multi-Source Feature Mapping Via Spectral Embedding for Heterogeneous Defect Prediction
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Jingxiu Yao, Bin Liu, Yumei Wu, and Hao Yu
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- 2023
16. Parametrial involvement and decreased survival of women with FIGO stage IIIC1 cervical cancer
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Hong Chang, Ming Wang, Yang Liu, and Yumei Wu
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Oncology ,Obstetrics and Gynecology ,General Medicine - Published
- 2023
17. A Comparative Study of Animal Metaphors in Cantonese and English Nursery Rhymes
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Yumei WU
- Abstract
Animal metaphors are commonly seen in daily language and often appears in nursery rhymes. With the Great Chain of Being as the theoretical framework, this study deeply analyzes and compares the animal metaphors in 896 Cantonese and English nursery rhymes from the cognitive linguistic perspective by classifying them and interpreting their formed images. It is found that the number of animal metaphors in Cantonese nursery rhymes is much higher than that in English nursery rhymes for Cantonese is a dialect of the Chinese language, which belongs to imagery languages. Besides, although in some way animal metaphors in Cantonese and English nursery rhymes are similar from the perspective of their educational functions, due to the cultural differences between the Cantonese-English ethnic groups, animal metaphors in Cantonese and English nursery rhymes present the cultural characteristics of Cantonese and English respectively in terms of the source domains, their metaphorical connotation and mappings. This study may provide some reference for the translation and inheritance of Cantonese and English nursery rhymes, helping to pass down and communicate the local culture, so as to realize the purposes of creating and spreading nursery rhymes.
- Published
- 2022
18. Helicobacter pylori infection affects the human gastric microbiome, as revealed by metagenomic sequencing
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Daoming Wang, Tongda Zhang, Yueqi Lu, Changzheng Wang, Yumei Wu, Jiandong Li, Ye Tao, Le Deng, Xiaoyin Zhang, and Jinmin Ma
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Helicobacter pylori ,Gastritis ,Microbiota ,Humans ,General Biochemistry, Genetics and Molecular Biology ,Gastrointestinal Microbiome ,Helicobacter Infections - Abstract
Helicobacter pylori infection is a prevalent infectious disease, associated with many gastric diseases, including gastritis, gastric ulcer, and gastric cancer. To reveal the characteristics of the gastric microbiome in patients infected with H. pylori, we performed metagenomic shotgun sequencing of stomach swab samples from 96 patients and then conducted metagenomic association analyses between alterations in the gastric microbiome and H. pylori infection status. The overall composition of the gastric microbiota in H. pylori-infected individuals was distinctly different from the negative controls; H. pylori became the dominant species after colonizing the human stomach and significantly decreased the α-diversity of the gastric community (P 0.05, Wilcoxon rank-sum test). We also identified 6 HPI-associated microbial species (FDR 0.05, Wilcoxon rank-sum test): Stenotrophomonas maltophilia, Stenotrophomonas unclassified, Chryseobacterium unclassified, Pedobacter unclassified, Variovorax unclassified, and Pseudomonas stutzeri. Furthermore, 55 gastric microbial pathways were enriched in the H. pylori-positive group, whereas only 2 pathways were more abundant in the H. pylori-negative group: dTDP-L-rhamnose biosynthesis and tetrapyrrole biosynthesis (FDR 0.05, Wilcoxon rank-sum test). Gastritis was not associated with non-H. pylori species in the stomach (P 0.05, Wilcoxon rank-sum test). This study revealed alterations in gastric microbial taxa and function associated with HPI in the Chinese population, which provides an insight into gastric microbial interactions and their potential role in the pathological process of gastric diseases.
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- 2022
19. Latest Research Progress of the Pathogenesis of Depression and Its Status of TCM Treatment
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Hesheng Zheng and Yumei Wu
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- 2022
20. The Role of IL-2, IL-4, IL-10 and IFN-γ Cytokines Expression in the Microenvironment of Cervical Intraepithelial Neoplasia
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Yu Cai, Jianjun Zhai, Yumei Wu, Rui Chen, and Xingyue Tian
- Subjects
Cultural Studies ,History ,Literature and Literary Theory - Published
- 2022
21. 3D printed microfluidics-based droplet generation for single cell encapsulation and optical imaging
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Zequan Lin, Wencong Zhang, Ting Liu, Shanhang Luo, Yumei Wu, Yeqian Liu, Yiya Qiu, Jing Song, Jiale Chen, and Meiai Lin
- Published
- 2022
22. Author response for 'Regulation of <scp>CD18</scp> stability by <scp>SIGIRR</scp> ‐modulated ubiquitination: New insights into the relationship between innate immune response and acute lung injury'
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null Feng Tian, null Jie Lei, null Yunfeng Ni, null Daixing Zhong, null Nianlin Xie, null Jun Ma, null Haiqiang Wang, null Shaokui Si, null Yumei Wu, and null Tao Jiang
- Published
- 2022
23. Proximity proteomics of synaptopodin provides insight into the molecular composition of the spine apparatus of dendritic spines
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Hanieh Falahati, Yumei Wu, Vanessa Feuerer, Hans-Georg Simon, and Pietro De Camilli
- Subjects
Proteomics ,Multidisciplinary ,Dendritic Spines ,Microfilament Proteins ,Endoplasmic Reticulum ,Hippocampus - Abstract
The spine apparatus is a specialized compartment of the neuronal smooth endoplasmic reticulum (ER) located in a subset of dendritic spines. It consists of stacks of ER cisterns that are interconnected by an unknown dense matrix and are continuous with each other and with the ER of the dendritic shaft. While this organelle was first observed over 60 y ago, its molecular organization remains a mystery. Here, we performed in vivo proximity proteomics to gain some insight into its molecular components. To do so, we used the only known spine apparatus–specific protein, synaptopodin, to target a biotinylating enzyme to this organelle. We validated the specific localization in dendritic spines of a small subset of proteins identified by this approach, and we further showed their colocalization with synaptopodin when expressed in nonneuronal cells. One such protein is Pdlim7, an actin binding protein not previously identified in spines. Pdlim7, which we found to interact with synaptopodin through multiple domains, also colocalizes with synaptopodin on the cisternal organelle, a peculiar stack of ER cisterns resembling the spine apparatus and found at axon initial segments of a subset of neurons. Moreover, Pdlim7 has an expression pattern similar to that of synaptopodin in the brain, highlighting a functional partnership between the two proteins. The components of the spine apparatus identified in this work will help elucidate mechanisms in the biogenesis and maintenance of this enigmatic structure with implications for the function of dendritic spines in physiology and disease.
- Published
- 2022
24. A partnership between the lipid scramblase XK and the lipid transfer protein VPS13A at the plasma membrane
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Andrés Guillén-Samander, Yumei Wu, S. Sebastian Pineda, Francisco J. García, Julia N. Eisen, Marianna Leonzino, Berrak Ugur, Manolis Kellis, Myriam Heiman, and Pietro De Camilli
- Subjects
Multidisciplinary ,Cell Membrane ,Vesicular Transport Proteins ,Humans ,Carrier Proteins ,Endoplasmic Reticulum ,Lipids ,Neuroacanthocytosis - Abstract
Chorea-acanthocytosis (ChAc) and McLeod syndrome are diseases with shared clinical manifestations caused by mutations in VPS13A and XK, respectively. Key features of these conditions are the degeneration of caudate neurons and the presence of abnormally shaped erythrocytes. XK belongs to a family of plasma membrane (PM) lipid scramblases whose action results in exposure of PtdSer at the cell surface. VPS13A is an endoplasmic reticulum (ER)-anchored lipid transfer protein with a putative role in the transport of lipids at contacts of the ER with other membranes. Recently VPS13A and XK were reported to interact by still unknown mechanisms. So far, however, there is no evidence for a colocalization of the two proteins at contacts of the ER with the PM, where XK resides, as VPS13A was shown to be localized at contacts between the ER and either mitochondria or lipid droplets. Here we show that VPS13A can also localize at ER–PM contacts via the binding of its PH domain to a cytosolic loop of XK, that such interaction is regulated by an intramolecular interaction within XK, and that both VPS13A and XK are highly expressed in the caudate neurons. Binding of the PH domain of VPS13A to XK is competitive with its binding to intracellular membranes that mediate other tethering functions of VPS13A. Our findings support a model according to which VPS13A-dependent lipid transfer between the ER and the PM is coupled to lipid scrambling within the PM. They raise the possibility that defective cell surface exposure of PtdSer may be responsible for neurodegeneration.
- Published
- 2022
25. ATG9 vesicles comprise the seed membrane of mammalian autophagosomes
- Author
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Taryn J. Olivas, Yumei Wu, Shenliang Yu, Lin Luan, Peter Choi, Shanta Nag, Pietro De Camilli, Kallol Gupta, and Thomas J. Melia
- Abstract
During autophagosome biogenesis, the incorporation of transmembrane proteins into the expanding phagophore is not readily observed. In addition, the membrane surface area of the organelle expands rapidly, while the volume of the autophagosome is kept low. Several recent studies have suggested a model of membrane expansion that explains how these attributes are maintained. The autophagosome expands predominantly through the direct protein-mediated transfer of lipids through the lipid transfer protein ATG2. As these lipids are only introduced into the cytoplasmic-facing leaflet of the expanding phagophore, full membrane growth also requires lipid scramblase activity. ATG9 has been demonstrated to harbor scramblase activity and is essential to autophagosome formation, however if and when it is integrated into mammalian autophagosomes remains unclear. Here we show that in the absence of lipid transport, ATG9 vesicles are already fully competent to collect proteins normally found on mature autophagosomes, including LC3-II. Further, through the novel use of styrene-maleic acid lipid particles as a nanoscale interrogation of protein organization on intact membranes, we show that ATG9 is fully integrated in the same membranes as LC3-II, even on maturing autophagosomes. The ratios of these two proteins at different stages of maturation demonstrate that ATG9 proteins are not continuously integrated, but rather are present on the seed vesicles only and become diluted in the rapidly expanding autophagosome membrane. Thus, ATG9 vesicles are the seed membrane from which mammalian autophagosomes form.
- Published
- 2022
26. Membrane remodeling properties of the Parkinson’s disease protein LRRK2
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Xinbo Wang, Yumei Wu, Shujun Cai, Jinghua Ge, Lin Shao, and Pietro De Camilli
- Abstract
Mutations in Leucine-rich repeat kinase 2 (LRRK2) are responsible for late-onset autosomal dominant Parkinson’s disease (PD). LRRK2 has been implicated in a wide range of physiological processes including membrane repair in the endolysosomal system. Here, we report that purified LRRK2 directly binds acidic lipid bilayers in a cell-free system and can deform them into narrow tubules in a guanylnucleotide-dependent but ATP-independent way. Moreover, we found that LRRK2 shows preferential assembly on highly curved lipid nanotubes relative to spherical liposomes. We suggest that an interplay between the membrane remodeling and signaling properties of LRRK2 may be key to its physiological function. LRRK2, via its kinase activity, may achieve its signaling role at sites where membrane remodeling occurs.
- Published
- 2022
27. In situ architecture of the lipid transport protein VPS13C at ER-lysosome membrane contacts
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Shujun Cai, Yumei Wu, Andrés Guillén-Samander, William Hancock-Cerutti, Jun Liu, and Pietro De Camilli
- Subjects
Multidisciplinary ,Cell Membrane ,Cryoelectron Microscopy ,Humans ,Proteins ,ATP-Binding Cassette Transporters ,Biological Transport ,Endoplasmic Reticulum ,Lipid Metabolism ,Lysosomes ,Bacterial Outer Membrane Proteins ,HeLa Cells - Abstract
VPS13 is a eukaryotic lipid transport protein localized at membrane contact sites. Previous studies suggested that it may transfer lipids between adjacent bilayers by a bridge-like mechanism. Direct evidence for this hypothesis from a full-length structure and from electron microscopy (EM) studies in situ is still missing, however. Here, we have capitalized on AlphaFold predictions to complement the structural information already available about VPS13 and to generate a full-length model of human VPS13C, the Parkinson’s disease–linked VPS13 paralog localized at contacts between the endoplasmic reticulum (ER) and endo/lysosomes. Such a model predicts an ∼30-nm rod with a hydrophobic groove that extends throughout its length. We further investigated whether such a structure can be observed in situ at ER–endo/lysosome contacts. To this aim, we combined genetic approaches with cryo-focused ion beam (cryo-FIB) milling and cryo–electron tomography (cryo-ET) to examine HeLa cells overexpressing this protein (either full length or with an internal truncation) along with VAP, its anchoring binding partner at the ER. Using these methods, we identified rod-like densities that span the space separating the two adjacent membranes and that match the predicted structures of either full-length VPS13C or its shorter truncated mutant, thus providing in situ evidence for a bridge model of VPS13 in lipid transport.
- Published
- 2022
28. Measurement and control of system resilience recovery by path planning based on improved genetic algorithm
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Dongsheng Wang, Yumei Wu, Zhengwei Yu, Zhen Li, Chenxu Sun, and Zhaobin Wang
- Subjects
education.field_of_study ,Mathematical optimization ,Control and Optimization ,Control engineering systems. Automatic machinery (General) ,Computer science ,Applied Mathematics ,Population ,Control (management) ,Field (computer science) ,TJ212-225 ,Genetic algorithm ,T1-995 ,Slow convergence ,Motion planning ,education ,Resilience (network) ,Instrumentation ,Technology (General) ,Randomness - Abstract
Aiming at the problems of basic genetic algorithm in the field of path planning to system resilience recovery such as excessive randomness of initial population, slow convergence, low efficiency of evolution operator, and poor population diversity, this paper uses quotient model to measure resilience, uses overall task importance to measure system performance, and proposes an improved genetic algorithm on initial population and evolutionary operation. Improved genetic algorithm (IHGA) proposes a new greedy model that considers system node tasks importance, travel time, and maintenance time, which uses greedy ideas to generate partial high-quality initial population. And a new operator is also designed as intra-group head-to-head mutation operator (IHMO) to control the evolution to be more determinate and less ineffectively random. The simulation results in three cases show that the IHGA overcomes the defects and can better effectively recover system resilience with comparison to basic genetic algorithm (BGA) and multi-chromosome genetic algorithm (MCGA). Specially, it has obviously better optimal solution, convergence, and stability, especially in the harsh conditions as shorter repair time, more and unbalanced demands for spare parts, which shows the IHGA has great value to deal with measurement and control of system resilience recovery in practice.
- Published
- 2021
29. Synaptic vesicle proteins and ATG9A self-organize in distinct vesicle phases within synapsin condensates
- Author
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Daehun Park, Yumei Wu, Aaron Baublis, and Pietro De Camilli
- Abstract
Ectopic expression in fibroblasts of synapsin 1 and synaptophysin is sufficient to generate condensates of vesicles highly reminiscent of synaptic vesicle (SV) clusters and with liquid-like properties. We show that unlike synaptophysin, other major integral SV membrane proteins fail to form condensates with synapsin, but coassemble into the clusters formed by synaptophysin and synapsin in this ectopic expression system. Another vesicle membrane protein, ATG9A, undergoes activity-dependent exo-endocytosis at synapses, raising questions about the relation of ATG9A traffic to the traffic of SVs. We have found that both in fibroblasts and in nerve terminals ATG9A does not coassemble into synaptophysin-positive vesicle condensates but localizes on a distinct class of vesicles that also assembles with synapsin but into a distinct phase. Our findings suggest that ATG9A undergoes differential sorting relative to SV proteins and also point to a dual role of synapsin in controlling clustering at synapses of SVs and ATG9A vesicles.
- Published
- 2022
30. SHIP164 is a Chorein Motif Lipid Transfer Protein that Controls Endosome‐Golgi Membrane Traffic
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Michael G. Hanna, Patreece H. Suen, Yumei Wu, Karin M. Reinisch, and Pietro De Camilli
- Subjects
Intracellular Signaling Peptides and Proteins ,Genetics ,Golgi Apparatus ,Endosomes ,Intracellular Membranes ,Cell Biology ,Carrier Proteins ,Lipids ,Molecular Biology ,Biochemistry ,Biotechnology - Abstract
Cellular membranes differ in protein and lipid composition as well as in the protein–lipid ratio. Thus, progression of membranous organelles along traffic routes requires mechanisms to control bilayer lipid chemistry and their abundance relative to proteins. The recent structural and functional characterization of VPS13-family proteins has suggested a mechanism through which lipids can be transferred in bulk from one membrane to another at membrane contact sites, and thus independently of vesicular traffic. Here, we show that SHIP164 (UHRF1BP1L) shares structural and lipid transfer properties with these proteins and is localized on a subpopulation of vesicle clusters in the early endocytic pathway whose membrane cargo includes the cation-independent mannose-6-phosphate receptor (MPR). Loss of SHIP164 disrupts retrograde traffic of these organelles to the Golgi complex. Our findings raise the possibility that bulk transfer of lipids to endocytic membranes may play a role in their traffic.
- Published
- 2022
31. ATG9 Vesicles Are Incorporated Into Nascent Autophagosome Membranes
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Taryn J. Olivas, Shenliang Yu, Yumei Wu, Lin Luan, Peter Choi, Kallol Gupta, Pietro De Camilli, and Thomas J. Melia
- Subjects
Genetics ,Molecular Biology ,Biochemistry ,Biotechnology - Published
- 2022
32. Development of humanized ACE2 mouse and rat models for COVID‐19 research
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Hongmei Jiang, Emma M. V. Hyddmark, Sara Gordon, Angela Bartels, Yumei Wu, Joe Warren, Andrew Brown, Michael Garrett, Helmut Ehall, and Guojun Zhao
- Subjects
Genetics ,Molecular Biology ,Biochemistry ,Biotechnology - Published
- 2022
33. Spatial-Temporal Change of Phytoplankton Biomass in the East China Sea with MODIS Data
- Author
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Xiaoyan Dang, Yumei Wu, Liangmin Huang, Xuesen Cui, Haopeng Zhu, Lin Wang, Tianfei Cheng, and Shenglong Yang
- Subjects
geography ,geography.geographical_feature_category ,Red tide ,Ocean Engineering ,Estuary ,04 agricultural and veterinary sciences ,Oceanography ,Algal bloom ,Phytoplankton biomass ,Phytoplankton ,040102 fisheries ,0401 agriculture, forestry, and fisheries ,Environmental science ,Temporal change ,Bloom ,China sea - Abstract
A ten-year chlorophyll-a concentration dataset from Moderate Resolution Imaging Spectro-radiometer (MODIS) were used to analyze the variation of phytoplankton biomass and its potential relation with climate in the East China Sea. The result indicated that the phytoplankton biomass generally had a regular pattern every year, and phytoplankton bloom mainly occurred between May and July. The highest phytoplankton biomass appeared near the Yangtze River Estuary. The lowest phytoplankton biomass located near the Taiwan Strait. In general, the starting bloom time was earlier in the south than in the north, and the span time of the former was also longer. During the recent ten years, the phytoplankton biomass around the Yangtze River Estuary decreased obviously. The change of phytoplankton biomass was found to be related with the Nino 3.4 Index. The correlation between the intensity of phytoplankton bloom with the number and square of red tide were 0.63 and 0.74, respectively.
- Published
- 2021
34. MicroRNA-592 Inhibits the Growth of Ovarian Cancer Cells by Targeting ERBB3
- Author
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Qiong Jin, Ning Zhang, Yang Zhan, Xiaohong Xu, Chao Han, Hui Zhao, Xiaodi Hu, Hongbo Tang, and Yumei Wu
- Subjects
Cancer Research ,Oncology - Abstract
Objectives: Ovarian cancer is the most lethal gynecologic malignancy, and targeted therapy for different pathological types and molecular phenotypes is urgent to be studied. Studies have shown that MicroRNA-592 (miR-592) plays an important negative regulatory role in the occurrence of gastrointestinal malignancies, breast cancer, non-small cell lung cancer, and glioma, but the expression of miR-592 in ovarian cancer and the mechanism of action are still unclear. Methods: The expressions of miR-592 were examined by RT-PCR and Western Blot. Cell viability and migratory capacity were detected by CCK-8 and transwell assay. TargetScan ( http://www.targetscan.org ) was analyzed to predict potential targets of miR-592. Then Dual-luciferase reporter gene assay was performed to verify the targeting relationship between miR-592 and ERBB3. A mouse xenograft model was applied to confirm the effect of miR-592. Results: In our study, we found that the expression of miR-592 is reduced in epithelial ovarian cancer tissues. The exogenous expression of miR-592 inhibits the proliferation, migration, and invasion in epithelial ovarian cancer tumor cells. Furthermore, the exogenous expression of miR-592 inhibits tumor growth in the nude mouse xenograft model. Therefore, miR-592 may play a role of tumor suppressor miRNA in the occurrence and development of ovarian cancer. Further experiments demonstrated that tumor-related ERBB3 is a target gene mediated by miRNA-592. The dual-luciferase reporter system was used to identify miRNA-592 target genes; qPCR and Western Blot were used to detect the expression of ERBB3. Mechanical experiments confirmed that miRNA-592 negatively regulated ERBB3.Conclusion: Together, these findings identify a heretofore unrecognized link between miR-592 and ERBB3 and suggest that targeting on miR-592 warrants attention as a novel and potential therapeutic strategy for ovarian cancer.
- Published
- 2023
35. A partnership of the lipid scramblase XK and of the lipid transfer protein VPS13A at the plasma membrane
- Author
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Andrés Guillén Samander, Yumei Wu, S. Sebastian Pineda, Francisco J. García, Julia N. Eisen, Marianna Leonzino, Berrak Uğur, Manolis Kellis, Myriam Heiman, and Pietro De Camilli
- Abstract
Chorea-acanthocytosis and McLeod syndrome are diseases with shared clinical manifestations caused by mutations in VPS13A and XK, respectively. Key features of these conditions are the degeneration of caudate neurons and the presence of abnormally shaped erythrocytes. XK belongs to a family of plasma membrane (PM) lipid scramblases whose action results in exposure of PtdSer at the cell surface. VPS13A is an ER-anchored lipid transfer protein with a putative role in the transport of lipids at contacts of the ER with other membranes. Recently VPS13A and XK were reported to interact by still unknown mechanisms. So far, however, there is no evidence for a colocalization of the two proteins at contacts of the ER with the PM, where XK resides, as VPS13A was shown to be localized at contacts between the ER and either mitochondria or lipid droplets. Here we show that VPS13A can also localize at ER-PM contacts via the binding of its PH domain to a cytosolic loop of XK, that such interaction is regulated by an intramolecular interaction within XK and that both VPS13A and XK are highly expressed in the caudate neurons. Binding of the PH domain of VPS13A to XK is competitive with its binding to intracellular membranes that mediate other tethering functions of VPS13A. Our findings support a model according to which VPS13A-dependent lipid transfer between the ER and the PM is coupled to lipid scrambling within the PM. They raise the possibility that defective cell surface exposure of PtdSer may be responsible for neurodegeneration.
- Published
- 2022
36. Sex-Specific Risk Factors Associated with
- Author
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Yumei, Wu, Hui, Zeng, Meiping, Zhang, Chunyan, Li, Yuanlin, Tang, Xiufen, Li, Shanyou, Yuan, Qifeng, Wei, Jinghua, Wang, Xianjia, Ning, and Xiaoyin, Zhang
- Abstract
This study enrolled consecutive healthy individuals who underwent regular health examinations at a hospital physical examination center between September 2020 and September 2021. Anthropometric characteristics and biochemical profiles were measured. All individuals underwent carbon-13 urea breath tests. Univariate and multivariate analyses were used to evaluate the factors associated withA total of 5035 individuals (men, 59.1%; women, 40.9%) were included in the analyses. The total rate ofThese findings suggest that physicians must be aware of the metabolic factors associated with
- Published
- 2022
37. In situ architecture of the lipid transport protein VPS13C at ER-lysosomes membrane contacts
- Author
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Shujun Cai, Yumei Wu, Andres Guillen-Samander, William Hancock-Cerutti, Jun Liu, and Pietro De Camilli
- Abstract
VPS13 is a eukaryotic lipid transport protein localized at membrane contact sites. Previous studies suggested that it may transfer lipids between adjacent bilayers by a bridge-like mechanism. Direct evidence for this hypothesis from a full-length structure and from EM studies in situ, however, is still missing. Here we have capitalized on AlphaFold predictions to complement the structural information already available about VPS13 and to generate a full-length model of human VPS13C, the Parkinson’s disease-linked VPS13 paralog localized at contacts between the ER and endo/lysosomes. Such model predicts a ~30-nm rod with a hydrophobic groove that extends throughout its length. We further investigated whether such a structure can be observed in situ at ER-endo/lysosome contacts. To this aim, we combined genetic approaches with cryo-focused-ion-beam (cryo-FIB) milling and cryo-electron tomography (cryo-ET) to examine HeLa cells overexpressing this protein (either full length or with an internal truncation) along with VAP, its anchoring binding partner at the ER. Using these methods we identified rod-like densities that span the space separating the two adjacent membranes and that match the predicted structures of either full length VPS13C or its shorter truncated mutant, thus providing the first in-situ evidence for a bridge-model of VPS13 in lipid transport. Intriguingly, the majority of the VPS13C rods were separated from the ER membranes by a narrow gap, suggesting that while VAP anchors the protein to the ER, direct contact of the VPS13C rod with the ER bilayer to allow lipid transport may be independently regulated.
- Published
- 2022
38. 3D FIBSEM CLEM v1
- Author
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Pietro De Camilli and Yumei Wu
- Abstract
This protocol details the procedure of Correlative Light Microscopy and Electron Microscopy (CLEM) with 3D Focus Ion Beam Scanning Electron Microscopy (FIBSEM) technique in Zeiss Crossbeam 550 FIBSEM system.
- Published
- 2022
39. 2D TEM CLEM (Correlative Light Microscopy and Electron Microscopy) v1
- Author
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Pietro De Camilli and Yumei Wu
- Abstract
This protocol details the general procedure of Correlative Light Microscopy and Electron Microscopy (CLEM) with conventional chemical fixation and 2D Transmission Electron Microscopy (TEM) imaging.
- Published
- 2022
40. Mutations in Parkinsonism-linked endocytic proteins synaptojanin1 and auxilin have synergistic effects on dopaminergic axonal pathology
- Author
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Xin Yi Ng, Yumei Wu, Youneng Lin, Sidra Mohamed Yaqoob, Lois E. Greene, Pietro De Camilli, and Mian Cao
- Subjects
Cellular and Molecular Neuroscience ,Neurology ,Neurology (clinical) - Abstract
Parkinson’s disease (PD) is a neurodegenerative disorder characterized by defective dopaminergic (DAergic) input to the striatum. Mutations in two genes encoding synaptically enriched clathrin-uncoating factors, synaptojanin 1 (SJ1) and auxilin, have been implicated in atypical Parkinsonism. SJ1 knock-in (SJ1-KIRQ) mice carrying a disease-linked mutation display neurological manifestations reminiscent of Parkinsonism. Here we report that auxilin knockout (Aux-KO) mice display dystrophic changes of a subset of nigrostriatal DAergic terminals similar to those of SJ1-KIRQ mice. Furthermore, Aux-KO/SJ1-KIRQ double mutant mice have shorter lifespan and more severe synaptic defects than single mutant mice. These include increase in dystrophic striatal nerve terminals positive for DAergic markers and for the PD risk protein SV2C, as well as adaptive changes in striatal interneurons. The synergistic effect of the two mutations demonstrates a special lability of DAergic neurons to defects in clathrin uncoating, with implications for PD pathogenesis in at least some forms of this condition.
- Published
- 2022
41. Pinocembrin suppresses oxidized low-density lipoprotein-triggered NLRP3 inflammasome/GSDMD-mediated endothelial cell pyroptosis through an Nrf2-dependent signaling pathway
- Author
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Tong Wang, Hua Tian, Tianqi Pan, Shutong Yao, Huayun Yu, Yumei Wu, and Shijun Wang
- Subjects
Lipoproteins, LDL ,Mice ,Multidisciplinary ,Inflammasomes ,NF-E2-Related Factor 2 ,Caspase 1 ,Flavanones ,NLR Family, Pyrin Domain-Containing 3 Protein ,Animals ,Endothelial Cells ,Signal Transduction - Abstract
Pinocembrin (Pin) has been confirmed to exert anti-inflammatory and antiatherosclerotic effects. Here we have explored whether and how Pin would protect vascular endothelial cells against pyroptosis elicited by the exposure to oxidized low density lipoprotein (oxLDL). Our results showed that Pin preconditioning dose-dependently suppressed oxLDL-stimulated HUVEC injury and pyroptosis, which were manifested by improved cell viability, lower lactate dehydrogenase (LDH) levels and DNA damage as well as decreased expression of pyroptosis-related markers, such as NOD-like receptor pyrin domain-containing 3 (NLRP3), apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC), pro-Caspase-1, cleaved Caspase-1, N-terminus of Gasdermin D-N (GSDMD-N), pro-interleukins-1β (pro-IL-1β), IL-1β and inflammatory cytokines (IL-18 and IL-1β). All of the effects were similar to those of MCC950 (an NLRP3 inhibitor). As expected, Pin distinctly activated the Nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidative signaling pathway assessed through increased expressions of Nrf2, heme oxygenase-1 (HO-1) and NAD(P)H quinone oxidoreductase 1 (NQO1). Furthermore, after transfection with small interfering RNA of Nrf2, the inhibitory effects of Pin on oxLDL-triggered NLRP3 inflammasome/GSDMD-mediated pyroptosis and oxidative stress in HUVECs were weakened. Additionally, Pin up-regulated Nrf2/HO-1 axis and down-regulated NLRP3 inflammasome/GSDMD-mediated pyroptosis signals in Apoe−/− mice fed with high fat diet. These results contribute to the understanding of the anti-pyroptosis mechanisms of Pin and provide a reference for future research on the anti-atherosclerotic effect of Pin.
- Published
- 2022
42. Heat Stress and SCA48 Mutations Reveal the Metamorphic Structure and Function of the Ubiquitin Ligase CHIP
- Author
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Ran Ming, Jamie B. Scaglione, Adam J. Kanack, Erik Soderblom, Anna Umano, Kanesha L. Travis, Yumei Wu, Oliver J. Newsom, Matthew G. Thompson, and K. Matthew Scaglione
- Subjects
History ,Polymers and Plastics ,Business and International Management ,Industrial and Manufacturing Engineering - Published
- 2022
43. Absence of Sac2/INPP5F enhances the phenotype of a Parkinson’s disease mutation of synaptojanin 1
- Author
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Yumei Wu, Mian Cao, Daehun Park, and Pietro De Camilli
- Subjects
medicine.medical_specialty ,Parkinson's disease ,Dopamine ,INPP5F ,Phosphatase ,Endocytic cycle ,Biology ,Mice ,Internal medicine ,medicine ,endocytosis ,Animals ,Humans ,Synaptic vesicle recycling ,synaptojanin 1 ,Gene ,Sac2 ,Mice, Knockout ,Nerve Endings ,Multidisciplinary ,Inositol Polyphosphate 5-Phosphatases ,Dopaminergic ,PI4P ,Parkinson Disease ,Biological Sciences ,medicine.disease ,Molecular biology ,Phenotype ,Mice, Inbred C57BL ,Endocrinology ,Mutation ,Synapses ,Knockout mouse ,Neuroscience ,Genome-Wide Association Study - Abstract
Significance Extensive genetic studies have identified numerous genes whose mutations results on Parkinson’s disease (PD), including synaptojanin 1 (SJ1/Park20), a nerve terminal enriched protein that includes an inositol 4-phosphatase domain (Sac domain). In addition, many PD candidate genes have been identified by genome-wide association studies, but for most of these genes, the link to PD remains hypothetical. One such gene is Sac2/INPP5F, which, interestingly, also includes an inositol 4-phosphatase domain. While Sac2KO mice do not show obvious defects, we show a striking synthetic effect in mice of the KO of Sac2 and the Sac domain mutation of SJ1 found in PD patients. These findings support a synergistic role of SJ1 and Sac2 on a PI4P pool whose dysfunction results in PD., Numerous genes whose mutations cause, or increase the risk of, Parkinson’s disease (PD) have been identified. An inactivating mutation (R258Q) in the Sac inositol phosphatase domain of synaptojanin 1 (SJ1/PARK20), a phosphoinositide phosphatase implicated in synaptic vesicle recycling, results in PD. The gene encoding Sac2/INPP5F, another Sac domain-containing protein, is located within a PD risk locus identified by genome-wide association studies. Knock-In mice carrying the SJ1 patient mutation (SJ1RQKI) exhibit PD features, while Sac2 knockout mice (Sac2KO) do not have obvious neurologic defects. We report a “synthetic” effect of the SJ1 mutation and the KO of Sac2 in mice. Most mice with both mutations died perinatally. The occasional survivors had stunted growth, died within 3 wk, and showed abnormalities of striatal dopaminergic nerve terminals at an earlier stage than SJ1RQKI mice. The abnormal accumulation of endocytic factors observed at synapses of cultured SJ1RQKI neurons was more severe in double-mutant neurons. Our results suggest that SJ1 and Sac2 have partially overlapping functions and are consistent with a potential role of Sac2 as a PD risk gene.
- Published
- 2020
44. The Potential Vertical Distribution of Bigeye Tuna (Thunnus obesus) and Its Influence on the Spatial Distribution of CPUEs in the Tropical Atlantic Ocean
- Author
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Liming Song, Wei Fan, Zhang Bianbian, Yumei Wu, Yu Zhang, Heng Zhang, Yang Dai, Shengmao Zhang, and Shenglong Yang
- Subjects
Stock assessment ,biology ,Buoy ,Bigeye tuna ,Ocean Engineering ,Pelagic zone ,04 agricultural and veterinary sciences ,Catch per unit effort ,Oceanography ,biology.organism_classification ,040102 fisheries ,0401 agriculture, forestry, and fisheries ,Environmental science ,Thermocline ,Thunnus ,Argo - Abstract
Understanding the potential vertical distribution of bigeye tuna (Thunnus obesus) is necessary to understand the catch rate fluctuations and the stock assessment of bigeye tuna. To characterize the potential vertical distribution of this fish while foraging and determine the influences of the distribution on longline efficiency in the tropical Atlantic Ocean, the catch per unit effort (CPUE) data were compiled from the International Commission for the Conservation of Atlantic Tunas and the Argo buoy data were downloaded from the Argo data center. The raw Argo buoy data were processed by data mining methods. The CPUE was standardized by support vector machine before analysis. We assumed the depths with the upper and lower limits of the optimum water temperatures of 15°C and 9°C as the preferred swimming depth, while the lower limit of the temperature (12°C) associated with the highest hooking rate as the preferred foraging depth (D12) of bigeye tuna during the daytime in the Atlantic Ocean. The preferred swimming depth and foraging depth range in the daytime were assessed by plotting the isobath based on Argo buoy data. The preferred swimming depth and vertical structure of the water column were identified to investigate the spatial effects on the CPUE by using a generalized additive model (GAM). The empirical cumulative distribution function was used to assess the relationship between the spatial distribution of CPUE and the depth of 12°C isolines and thermocline. The results indicate that 1) the preferred swimming depth of bigeye tuna in the tropical Atlantic is from 100 m to 400 m and displays spatial variation; 2) the preferred foraging depth of bigeye tuna is between 190 and 300 m and below the thermocline; 3) the number of CPUEs peaks at a relative depth of 30-50 m (difference between the 12°C isolines and the lower boundary of the thermocline); and 4) most CPUEs are within the lower depth boundary of the thermocline levels (LDBT) which is from 160 m to 230 m. GAM analysis indicates that the general relationship between the nominal CPUE and LDBT is characterized by a dome shape and peaks at approximately 190 m. The oceanographic features influence the habitat of tropical pelagic fish and fisheries. Argo buoy data can be an important tool to describe the habitat of oceanic fish. Our results provide new insights into how oceanographic features influence the habitat of tropical pelagic fish and fisheries and how fisheries exploit these fish using a new tool (Argo profile data).
- Published
- 2020
45. ErCas12a CRISPR-MAD7 for Model Generation in Human Cells, Mice, and Rats
- Author
-
John A. Schiel, Zhenyi Liu, Angela Bartels, Guojun Zhao, Žaklina Strezoska, Elena Maksimova, Anja van Brabant Smith, Emily M. Anderson, Joe Warren, Yumei Wu, Kevin P. Forbes, and Chris E. Lowe
- Subjects
CRISPR-Associated Proteins ,Mice ,Bacterial Proteins ,Dna genetics ,Genome editing ,Genetics ,Animals ,Humans ,CRISPR ,Clustered Regularly Interspaced Short Palindromic Repeats ,Eubacterium rectale ,Research Articles ,Gene Editing ,Nuclease ,Endodeoxyribonucleases ,Genome ,biology ,Eubacterium ,Cas9 ,RNA ,DNA ,Endonucleases ,HCT116 Cells ,Molecular biology ,Rats ,biology.protein ,CRISPR-Cas Systems ,RNA, Guide, Kinetoplastida ,Biotechnology - Abstract
MAD7 is an engineered class 2 type V-A CRISPR-Cas (Cas12a/Cpf1) system isolated from Eubacterium rectale. Analogous to Cas9, it is an RNA-guided nuclease with demonstrated gene editing activity in Escherichia coli and yeast cells. Here, we report that MAD7 is capable of generating indels and fluorescent gene tagging of endogenous genes in human HCT116 and U2OS cancer cell lines, respectively. In addition, MAD7 is highly proficient in generating indels, small DNA insertions (23 bases), and larger integrations ranging from 1 to 14 kb in size in mouse and rat embryos, resulting in live-born transgenic animals. Due to the different protospacer adjacent motif requirement, small-guide RNA, and highly efficient targeted gene disruption and insertions, MAD7 can expand the CRISPR toolbox for genome enginnering across different systems and model organisms.
- Published
- 2020
46. Properties and proximity proteomics of synaptopodin provide insight into the molecular organization of the spine apparatus of dendritic spines
- Author
-
Hanieh Falahati, Yumei Wu, Vanessa Feuerer, and Pietro De Camilli
- Abstract
SUMMARYThe spine apparatus is a specialization of the neuronal ER in dendritic spines consisting of stacks of interconnected cisterns separated by a dense matrix. Synaptopodin, a specific actin binding protein of the spine apparatus, is essential for its formation, but the underlying mechanisms remain unknown. We show that synaptopodin, when expressed in fibroblasts, forms actin-rich structures with connections to the ER, and that an ER-tethered synaptopodin assembles into liquid condensates. We also identified protein neighbors of synaptopodin in spines by in vivo proximity biotinylation. We validated a small subset of such proteins and showed that they co-assemble with synaptopodin in living cells. One of them is Pdlim7, an actin binding protein not previously identified in spines, and we show its precise colocalization with synaptopodin. We suggest that the matrix of the spine apparatus has the property of a liquid protein condensate generated by a multiplicity of low affinity interactions.Graphical abstract
- Published
- 2021
47. SHIP164 is a Chorein Motif Containing Lipid Transport Protein that Controls Membrane Dynamics and Traffic at the Endosome-Golgi Interface
- Author
-
Michael G. Hanna, Patreece Suen, Karin M. Reinisch, Yumei Wu, and Pietro De Camilli
- Subjects
symbols.namesake ,Membrane ,Lipid Chemistry ,Endosome ,Chemistry ,Vesicle ,Endocytic cycle ,Organelle ,symbols ,Biophysics ,Golgi apparatus ,Lipid Transport - Abstract
Cellular membranes differ in protein and lipid composition as well as in the protein-lipid ratio. Thus, progression of membranous organelles along traffic routes requires mechanisms to control bilayer lipid chemistry and their abundance relative to proteins. The recent structural and functional characterization of VPS13-family proteins has suggested a mechanism through which lipids can be transferred in bulk from one membrane to another at membrane contact sites, and thus independently of vesicular traffic. Here we show that SHIP164 (UHRF1BP1L) shares structural and lipid transfer properties with these proteins and is localized on a subpopulation of vesicle clusters in the early endocytic pathway whose membrane cargo includes the cation-independent mannose-6-phosphate receptor (MPR) and ATG9. Loss of SHIP164 disrupts retrograde traffic of these organelles to the Golgi complex. Our findings raise the possibility that bulk transfer of lipids to endocytic membranes may play a role in their traffic.
- Published
- 2021
48. English Classroom Face-to-face and Online Discussion Based on Information Technology
- Author
-
Yumei Wu
- Published
- 2021
49. Inhibition of GPR17 with cangrelor improves cognitive impairment and synaptic deficits induced by Aβ
- Author
-
ShiYu, Jin, Xin, Wang, XiaoTong, Xiang, YuMei, Wu, Jie, Hu, YueYue, Li, Yue, Lin Dong, YueQiang, Tan, and Xian, Wu
- Subjects
Mice, Inbred ICR ,Amyloid beta-Peptides ,NF-E2-Related Factor 2 ,NF-kappa B ,Membrane Proteins ,Nerve Tissue Proteins ,Adenosine Monophosphate ,Peptide Fragments ,Receptors, G-Protein-Coupled ,Mice ,Electrical Synapses ,Alzheimer Disease ,Animals ,Humans ,Cognitive Dysfunction ,Heme Oxygenase-1 ,Platelet Aggregation Inhibitors ,Signal Transduction - Abstract
The accumulation of amyloid beta (Aβ) in the brain is thought to be associated with cognitive deficits in Alzheimer's disease (AD). However, current methods to combat Aβ neurotoxicity are still lacking. G protein-coupled receptor 17 (GPR17) has become a target for treating inflammation in brain diseases, but it is unclear whether it has a role in AD. Here, we investigated the effects of cangrelor, a GPR17 antagonist, on neurotoxicity and memory impairment induced by intracerebroventricular (i.c.v.) injection of Aβ
- Published
- 2021
50. Development of a Positive Selection High Throughput Genetic Screen in Dictyostelium discoideum
- Author
-
Felicia N. Williams, Yumei Wu, and K. Matthew Scaglione
- Subjects
biology ,QH301-705.5 ,ved/biology ,fungi ,ved/biology.organism_classification_rank.species ,food and beverages ,Mutagenesis (molecular biology technique) ,Cell Biology ,Computational biology ,Dictyostelium discoideum ,biology.organism_classification ,Dictyostelium ,Genome ,protein aggregation ,genetic screen ,Slime mold ,5-FOA ,Biology (General) ,Model organism ,polyglutamine ,Gene ,Developmental Biology ,Genetic screen - Abstract
The cellular slime mold Dictyostelium discoideum is a powerful model organism that can be utilized to investigate human health and disease. One particular strength of Dictyostelium is that it can be utilized for high throughput genetic screens. For many phenotypes, one limitation of utilizing Dictyostelium is that screening can be an arduous and time-consuming process, limiting the genomic depth one can cover. Previously, we utilized a restriction enzyme-mediated integration screen to identify suppressors of polyglutamine aggregation in Dictyostelium. However, due to the time required to perform the screen, we only obtained ∼4% genome coverage. Here we have developed an efficient screening pipeline that couples chemical mutagenesis with the 5-fluoroorotic acid counterselection system to enrich for mutations in genes of interest. Here we describe this new screening methodology and highlight how it can be utilized for other biological systems.
- Published
- 2021
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