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2021 ◽  
Author(s):  
Zeng Cong ◽  
John P Evans ◽  
Panke Qu ◽  
Julia Faraone ◽  
Yi-Min Zheng ◽  
...  

The SARS-CoV-2 B.1.1.529/Omicron variant was first characterized in South Africa and was swiftly designated a variant of concern. Of great concern is its high number of mutations, including 30-40 mutations in the virus spike (S) protein compared to 7-10 for other variants. Some of these mutations have been shown to enhance escape from vaccine-induced immunity, while others remain uncharacterized. Additionally, reports of increasing frequencies of the Omicron variant may indicate a higher rate of transmission compared to other variants. However, the transmissibility of Omicron and its degree of resistance to vaccine-induced immunity remain unclear. Here we show that Omicron exhibits significant immune evasion compared to other variants, but antibody neutralization is largely restored by mRNA vaccine booster doses. Additionally, the Omicron spike exhibits reduced receptor binding, cell-cell fusion, S1 subunit shedding, but increased cell-to-cell transmission, and homology modeling indicates a more stable closed S structure. These findings suggest dual immune evasion strategies for Omicron, due to altered epitopes and reduced exposure of the S receptor binding domain, coupled with enhanced transmissibility due to enhanced S protein stability. These results highlight the importance of booster vaccine doses for maintaining protection against the Omicron variant, and provide mechanistic insight into the altered functionality of the Omicron spike protein.


2021 ◽  
Author(s):  
Laijian Sui ◽  
Jianyuan Zeng ◽  
Lin Ye ◽  
Andrew J Sanders ◽  
Huishan Zhao ◽  
...  

2021 ◽  
Vol 41 (6) ◽  
pp. 2859-2866
Author(s):  
JAESIK SHIN ◽  
SOON KOO BAIK ◽  
YONGDAE YOON ◽  
SOONJAE HWANG ◽  
JOON HYUNG SOHN ◽  
...  

2020 ◽  
Author(s):  
Xuejiao Zhu ◽  
Baochao Fan ◽  
Junming Zhou ◽  
Dandan Wang ◽  
Huiying Fan ◽  
...  

Abstract Background: African Swine Fever Virus (ASFV) has been identified as the agent of ASF, which has resulting in a mortality rate of nearly 100% in domestic pigs worldwide. Protein p22 encoded by pKP177L was reported to be localized at the inner envelope of the virus, while the function of p22 remains unclear.Methods: Protein p22 interacted proteins of the host were immune-precipitated and identified by Liquid Chromatography Mass Spectrometry, analyzed by Go terms and KEGG pathways. Results: Numerous cellular proteins in 293-T that interacted with p22 protein were identified. These interacted proteins were related to the biological processes of binding, cell structure, signal transduction, cell adhesion, etc., and their interactions. At the same time, the interacted proteins participated in several KEGG pathways like ribosome, splicesome, etc. The key proteins in PPI network were closely related to actin filament organization and movement, resulting in affecting the process of phagocytosis and endocytosis. Conclusions: The identified high number of proteins interacted with p22 and as a large database should be very useful to elucidate the function of p22 in the near future, and lay the foundation for elucidating the mechanism of ASFV.


2020 ◽  
Vol 144 ◽  
pp. 110009 ◽  
Author(s):  
Imran Khan ◽  
Mustafa Aziz Hatiboglu
Keyword(s):  

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2238
Author(s):  
Ayon A. Hassan ◽  
Margarita Artemenko ◽  
Maggie K.S. Tang ◽  
Alice S.T. Wong

Ovarian cancer is the most lethal gynecological malignancy worldwide. Unlike most other tumor types that metastasize via the vasculature, ovarian cancer metastasizes predominantly via the transcoelomic route within the peritoneal cavity. As cancer metastasis accounts for the majority of deaths, there is an urge to better understand its determinants. In the peritoneal cavity, tumor-mesothelial adhesion is an important step for cancer dissemination. Selectins are glycan-binding molecules that facilitate early steps of this adhesion cascade by mediating heterotypic cell-cell interaction under hydrodynamic flow. Here, we review the function and regulation of selectins in peritoneal carcinomatosis of ovarian cancer, and highlight how dysregulation of selectin ligand biogenesis affects disease outcome. Further, we will introduce the latest tools in studying selectin-glycan interaction. Finally, an overview of potential therapeutic intervention points that may lead to the development of efficacious therapies for ovarian cancer is provided.


2020 ◽  
Vol 21 (12) ◽  
pp. 4477 ◽  
Author(s):  
Ya-ru Huang ◽  
Rui-tian Liu

It is widely accepted that β-amyloid oligomers (Aβos) play a key role in the progression of Alzheimer’s disease (AD) by inducing neuron damage and cognitive impairment, but Aβos are highly heterogeneous in their size, structure and cytotoxicity, making the corresponding studies tough to carry out. Nevertheless, a number of studies have recently made remarkable progress in the describing the characteristics and pathogenicity of Aβos. We here review the mechanisms by which Aβos exert their neuropathogenesis for AD progression, including receptor binding, cell membrane destruction, mitochondrial damage, Ca2+ homeostasis dysregulation and tau pathological induction. We also summarize the characteristics and pathogenicity such as the size, morphology and cytotoxicity of dimers, trimers, Aβ*56 and spherical oligomers, and suggest that Aβos may play a different role at different phases of AD pathogenesis, resulting in differential consequences on neuronal synaptotoxicity and survival. It is warranted to investigate the temporal sequence of Aβos in AD human brain and examine the relationship between different Aβos and cognitive impairment.


2020 ◽  
Vol 7 (4) ◽  
pp. e767
Author(s):  
Gauri Saxena ◽  
James M. Moore ◽  
Meleri Jones ◽  
Gareth Pryce ◽  
Liaqat Ali ◽  
...  

ObjectiveTo test the hypothesis that antidrug antibodies (ADAs) against alemtuzumab could become relevant after repeated treatments for some individuals, possibly explaining occasional treatment resistance.MethodsRecombinant alemtuzumab single-chain variable fragment antibody with a dual tandem nanoluciferase reporter linker was made and used to detect binding ADAs. Alemtuzumab immunoglobulin G Alexa Fluor 488 conjugate was used in a competitive binding cell-based assay to detect neutralizing ADAs. The assays were used to retrospectively screen, blinded, banked serum samples from people with MS (n = 32) who had received 3 or more cycles of alemtuzumab. Lymphocyte depletion was measured between baseline and about 1 month postinfusion.ResultsThe number of individuals showing limited depletion of lymphocytes increased with the number of treatment cycles. Lack of depletion was also a poor prognostic feature for future disease activity. ADA responses were detected in 29/32 (90.6%) individuals. Neutralizing antibodies occurred before the development of limited depletion in 6/7 individuals (18.8% of the whole sample). Preinfusion, ADA levels predicted limited, postinfusion lymphocyte depletion.ConclusionsAlthough ADAs to alemtuzumab have been portrayed as being of no clinical significance, alemtuzumab-specific antibodies appear to be clinically relevant for some individuals, although causation remains to be established. Monitoring of lymphocyte depletion and the antidrug response may be of practical value in patients requiring additional cycles of alemtuzumab. ADA detection may help to inform on retreatment or switching to another treatment.


2019 ◽  
Vol 5 ◽  
pp. 100032 ◽  
Author(s):  
Sarah Finke ◽  
Annette Fagerlund ◽  
Veronika Smith ◽  
Veronica Krogstad ◽  
Mimmi Jingxi Zhang ◽  
...  

ACS Omega ◽  
2019 ◽  
Vol 4 (8) ◽  
pp. 13231-13240 ◽  
Author(s):  
Rahul Nag ◽  
Sirilata Polepalli ◽  
Mohammed Althaf Hussain ◽  
Chebrolu Pulla Rao

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