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1.
ACS Appl Mater Interfaces ; 15(12): 15884-15892, 2023 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-36929869

RESUMO

Flexible positive pressure sensors have been studied extensively and have been used in a lot of scenarios. However, negative pressure detection is also in demand in some scenarios, such as fluid mechanics analysis, air pressure sensing, and so on. Flexible wearable sensors that can detect both positive and negative pressures will greatly broaden the application field. In this paper, we report a flexible highly sensitive ionic gel (IG) pressure sensor, which is simple and of low cost to prepare and can reliably detect a large pressure range from -98 to 100 kPa under an atmospheric pressure of about 982 hPa. The IG dielectric layer is composed of polyvinyl alcohol and phosphoric acid with a random microstructure of sandpaper inversion. The sensor exhibits flexibility, cycling stability, and high sensitivity under both negative and positive pressures (S = 84.45 nF/kPa for the negative pressure section, S = 25.61 nF/kPa for the positive pressure section). These sensors could be worn on the body not only to test breathing and pulse but also to measure air pressure for estimating the altitude, showing that the flexible full-pressure sensors have a wider application range in wearable electronics.

2.
Nature ; 597(7877): 549-554, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34497417

RESUMO

Monoclonal antibody therapies targeting tumour antigens drive cancer cell elimination in large part by triggering macrophage phagocytosis of cancer cells1-7. However, cancer cells evade phagocytosis using mechanisms that are incompletely understood. Here we develop a platform for unbiased identification of factors that impede antibody-dependent cellular phagocytosis (ADCP) using complementary genome-wide CRISPR knockout and overexpression screens in both cancer cells and macrophages. In cancer cells, beyond known factors such as CD47, we identify many regulators of susceptibility to ADCP, including the poorly characterized enzyme adipocyte plasma membrane-associated protein (APMAP). We find that loss of APMAP synergizes with tumour antigen-targeting monoclonal antibodies and/or CD47-blocking monoclonal antibodies to drive markedly increased phagocytosis across a wide range of cancer cell types, including those that are otherwise resistant to ADCP. Additionally, we show that APMAP loss synergizes with several different tumour-targeting monoclonal antibodies to inhibit tumour growth in mice. Using genome-wide counterscreens in macrophages, we find that the G-protein-coupled receptor GPR84 mediates enhanced phagocytosis of APMAP-deficient cancer cells. This work reveals a cancer-intrinsic regulator of susceptibility to antibody-driven phagocytosis and, more broadly, expands our knowledge of the mechanisms governing cancer resistance to macrophage phagocytosis.


Assuntos
Citotoxicidade Celular Dependente de Anticorpos/genética , Sistemas CRISPR-Cas , Citofagocitose/genética , Macrófagos/imunologia , Neoplasias/imunologia , Neoplasias/patologia , Animais , Anticorpos Monoclonais/imunologia , Citotoxicidade Celular Dependente de Anticorpos/imunologia , Antígenos de Neoplasias/imunologia , Antígeno CD47/antagonistas & inibidores , Linhagem Celular Tumoral , Células Cultivadas , Feminino , Edição de Genes , Técnicas de Inativação de Genes , Humanos , Linfoma de Células T/imunologia , Linfoma de Células T/patologia , Macrófagos/citologia , Macrófagos/metabolismo , Masculino , Glicoproteínas de Membrana/deficiência , Glicoproteínas de Membrana/genética , Camundongos , Receptores Acoplados a Proteínas G/metabolismo
3.
Nat Genet ; 53(5): 638-649, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33859415

RESUMO

A central question in the post-genomic era is how genes interact to form biological pathways. Measurements of gene dependency across hundreds of cell lines have been used to cluster genes into 'co-essential' pathways, but this approach has been limited by ubiquitous false positives. In the present study, we develop a statistical method that enables robust identification of gene co-essentiality and yields a genome-wide set of functional modules. This atlas recapitulates diverse pathways and protein complexes, and predicts the functions of 108 uncharacterized genes. Validating top predictions, we show that TMEM189 encodes plasmanylethanolamine desaturase, a key enzyme for plasmalogen synthesis. We also show that C15orf57 encodes a protein that binds the AP2 complex, localizes to clathrin-coated pits and enables efficient transferrin uptake. Finally, we provide an interactive webtool for the community to explore our results, which establish co-essentiality profiling as a powerful resource for biological pathway identification and discovery of new gene functions.


Assuntos
Redes Reguladoras de Genes , Genes , Genoma , Clatrina/metabolismo , Endocitose , Epigênese Genética , Regulação da Expressão Gênica , Células HeLa , Humanos , Anotação de Sequência Molecular , Neoplasias/genética , Plasmalogênios/biossíntese , Transdução de Sinais/genética
4.
Genes (Basel) ; 9(8)2018 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-30103455

RESUMO

Glutamine synthetase (GS) plays a key role in nitrogen metabolism. Here, two types of tobacco transformants, overexpressing Triticum aestivum GS1 (TaGS1) or GS2 (TaGS2), were analysed. Four independent transformed lines, GS1-TR1, GS1-TR2, GS2-TR1 and GS2-TR2, were used for the nitrogen treatment. Under nitrogen-sufficient conditions, the leaves of GS2-TR showed high accumulation of the TaGS2 transcript, while those of GS1-TR showed a low TaGS1 transcript levels. However, compared with nitrogen-sufficient conditions, the TaGS1 transcript level increased in the leaves under nitrogen starvation, but the TaGS2 transcript level decreased. In addition, the TaGS1 and TaGS2 transcript levels were highest in the middle leaves under nitrogen-sufficient and starvation conditions. These results show that nitrogen supply and leaf age regulate TaGS expression, even when they are driven by a super-promoter. Additionally, in regard to nitrogen metabolism level, the lower leaves of the GS1-TR exhibited lower NH4⁺ and higher amino acid contents, while the upper leaves exhibited higher amino acid, soluble protein and chlorophyll contents. The leaves of the GS2-TR exhibited lower NH4⁺ but higher amino acid, soluble protein and chlorophyll contents. Given the role that GS isoforms play in nitrogen metabolism, these data suggest that TaGS1 overexpression may improve nitrogen transport, and that TaGS2 overexpression may improve nitrogen assimilation under nitrogen stress.

5.
Sheng Wu Gong Cheng Xue Bao ; 34(2): 264-274, 2018 Feb 25.
Artigo em Chinês | MEDLINE | ID: mdl-29424140

RESUMO

Glutamine synthetase is a key enzyme in plant nitrogen assimilation. To study the structure of wheat glutamine synthetase isoenzymes, GS1, GSr, GSe, GS2 and GS2p of wheat were cloned into pET-21a, and the expression condition was optimized. Although wheat glutamine synthetase isoenzymes had 70%-80% amino acid sequence homology, the isoforms expressed with different characteristics. Induced at 30 °C, the most expression level of GSr, GSe and GS2 was after 3 h, and of GS1 was at the 7 h whereas no GS2p was expressed, and the GS isoenzymes showed different expression level, with the order of GS1 (22%)>GSr (15%)>GS2 (12%)>GSe (5%). GSe expressed as soluble protein, and GS1 expressed mainly as soluble protein whereas GSr and GS2 expressed as insoluble proteins. Induced at 30 °C for 3 h, mRNA transcript levels of GS isoforms were different, with the order of GSr (7.59)>GS2 (1.84)>GS2p (1.66)>GSe (1.46)>GS1 (1.00). The levels of mRNA transcription were not consistent with the level of the protein translation. The analysis of mRNA secondary structure showed the free energy of translation initiation region of glutamine synthetase isoforms was different, with the order of GS1 (14.4)GSr (13%)>GS2 (10%)>GSe (7%), and different activities with GS1>GSe>GS2, and the activity of GSr was not detected. The gene sequence of glutamine synthetase isoenzymes determines the amount, status and activity of proteins expressed in prokaryotic cells.


Assuntos
Glutamato-Amônia Ligase/biossíntese , Proteínas de Plantas/biossíntese , Triticum/enzimologia , Escherichia coli/metabolismo , Glutamato-Amônia Ligase/genética , Isoenzimas/biossíntese , Conformação de Ácido Nucleico , Proteínas de Plantas/genética , RNA Mensageiro/genética
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