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#34698307   2021/10/18 To Up

Influence of Host-Related Factors and Exposure to Mosquito Bites on the Dynamics of Antibody Response to Antigens.

Humoral immunity to is acquired after repeated infections, and can lead to clinical protection. This study aimed to evaluate how human-, parasite-, and environment-related determinants can modulate the dynamics of IgG responses to after an infection. Individuals ( = 68, average age = 8.2 years) with uncomplicated malaria were treated with ACT and followed up for 42 days. IgG responses to merozoite antigens (MSP1MSP3AMA1GLURP-R0), to whole schizont extract (Schz), and to gSG6-P1 and Nterm-34 kDa salivary peptides were measured. Regression analyses were used to identify factors that influence the dynamics of IgG response to antigen between D0 and D42, including demographic and biological factors and the level of exposure to mosquito bites. The dynamics of IgG response to differed according to the antigen. According to multivariate analysis, IgG responses to Schz and to GLURP-R0 appear to be affected by exposure to saliva and are associated with age, parasite density, and anti- pre-existing immune response at study inclusion. The present work shows that human exposure to saliva may contribute, in addition to other factors, to the regulation of anti- immune responses during a natural infection.
Kakou G Aka, Serge S Yao, Eric A Gbessi, Akré M Adja, Vincent Corbel, Alphonsine A Koffi, Christophe Rogier, Serge B Assi, Offianan A Toure, Franck Remoue, Anne Poinsignon

2352 related Products with: Influence of Host-Related Factors and Exposure to Mosquito Bites on the Dynamics of Antibody Response to Antigens.

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#34689556   2021/10/25 To Up

Delivery of Ultrasmall Nanoparticles to the Cytosolic Compartment of Pyroptotic J774A.1 Macrophages via GSDMD Membrane Pores.

Endosome capture is a major physiological barrier to the successful delivery of nanomedicine. Here, we found a strategy to deliver ultrasmall nanoparticles (<10 nm) to the cytosolic compartment of pyroptotic cells with spontaneous endosomal escape. To mimic pathological pyroptotic cells, J774A.1 macrophages were stimulated with lipopolysaccharide (LPS) plus nigericin (Nig) or adenosine triphosphate (ATP) to form specific gasdermin D protein-driven membrane pores at an N-terminal domain (GSDMD). Through GSDMD membrane pores, both anionic and cationic nanoparticles (NPs) with diameters less than 10 nm were accessed into the cytosolic compartment of pyroptotic cells in an energy- and receptor-independent manner, while NPs larger than the size of GSDMD membrane pores failed to enter pyroptotic cells. NPs pass through GSDMD membrane pores via free diffusion and then access into the cytoplasm of pyroptotic cells in a microtubule-independent manner. Interestingly, we found that LPS-primed NPs may act as Trojan horse, deliver extracellular LPS into normal cells through endocytosis, and in turn induce GSDMD membrane pores, which facilitate further internalization of NPs. This study presented a straightforward method of distinguishing normal and pyroptotic cells through GSDMD membrane pores, implicating their potential application in monitoring the delivery of desired nanomedicines in pyroptosis-related diseases and conditions.
Di Wu, Xiangyu Zhu, Jian Ao, Erqun Song, Yang Song

2055 related Products with: Delivery of Ultrasmall Nanoparticles to the Cytosolic Compartment of Pyroptotic J774A.1 Macrophages via GSDMD Membrane Pores.

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#34043621   2021/05/27 To Up

Serological biomarker for assessing human exposure to Aedes mosquito bites during a randomized vector control intervention trial in northeastern Thailand.

Aedes mosquitoes are vectors for several major arboviruses of public health concern including dengue viruses. The relationships between Aedes infestation and disease transmission are complex wherein the epidemiological dynamics can be difficult to discern because of a lack of robust and sensitive indicators for predicting transmission risk. This study investigates the use of anti-Aedes saliva antibodies as a serological biomarker for Aedes mosquito bites to assess small scale variations in adult Aedes density and dengue virus (DENV) transmission risk in northeastern Thailand. Individual characteristics, behaviors/occupation and socio-demographics, climatic and epidemiological risk factors associated with human-mosquito exposure are also addressed.
Benedicte Fustec, Thipruethai Phanitchat, Sirinart Aromseree, Chamsai Pientong, Kesorn Thaewnongiew, Tipaya Ekalaksananan, Dominique Cerqueira, Anne Poinsignon, Eric Elguero, Michael J Bangs, Neal Alexander, Hans J Overgaard, Vincent Corbel

1797 related Products with: Serological biomarker for assessing human exposure to Aedes mosquito bites during a randomized vector control intervention trial in northeastern Thailand.

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#33904380   // To Up

N-terminal selective conjugation method widens the therapeutic window of antibody-drug conjugates by improving tolerability and stability.

Antibody-drug conjugates (ADCs) are targeted therapeutic agents that treat cancers by selective delivery of highly potent cytotoxic drugs to tumor cells via cancer-specific antibodies. However, their clinical benefit is limited by off-target toxicity and narrow therapeutic windows. To overcome these limitations, we have applied reductive alkylation to develop a new type of ADC that has cytotoxic drugs conjugated to the N-terminal of an antibody through amine bonds introduced via reductive alkylation reactions (NTERM). To test whether the NTERM-conjugated ADCs can widen therapeutic windows, we synthesized three different ADCs by conjugating trastuzumab and monomethyl auristatin-F using three different methods, and compared their stability, efficacy, and toxicity. The NTERM-conjugated ADC was more stable and than the thiol-conjugated and the lysine-conjugated ADCs. The NTERM-conjugated ADC showed lower toxicity compared to other ADCs, whereas its efficacy was comparable to that of the thiol-conjugated ADC and better than that of the lysine-conjugated ADC. These results suggest that the NTERM conjugation method could widen the therapeutic window of ADCs by enhancing its stability and reducing toxicity.
Min Ji Ko, Daehae Song, Juhee Kim, Jae Yong Kim, Jaehyun Eom, Byungje Sung, Yong-Gyu Son, Young Min Kim, Sang Hoon Lee, Weon-Kyoo You, Jinwon Jung

1782 related Products with: N-terminal selective conjugation method widens the therapeutic window of antibody-drug conjugates by improving tolerability and stability.

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#33001972   2020/10/01 To Up

Complex relationships between Aedes vectors, socio-economics and dengue transmission-Lessons learned from a case-control study in northeastern Thailand.

Dengue fever is an important public health concern in most tropical and subtropical countries, and its prevention and control rest on vector surveillance and control. However, many aspects of dengue epidemiology remain unclear; in particular, the relationship between Aedes vector abundance and dengue transmission risk. This study aims to identify entomological and immunological indices capable of discriminating between dengue case and control (non-case) houses, based on the assessment of candidate indices, as well as individual and household characteristics, as potential risk factors for acquiring dengue infection.
Benedicte Fustec, Thipruethai Phanitchat, Mohammad Injamul Hoq, Sirinart Aromseree, Chamsai Pientong, Kesorn Thaewnongiew, Tipaya Ekalaksananan, Michael J Bangs, Vincent Corbel, Neal Alexander, Hans J Overgaard

2891 related Products with: Complex relationships between Aedes vectors, socio-economics and dengue transmission-Lessons learned from a case-control study in northeastern Thailand.



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#32611767   2020/07/01 To Up

Hairpin RNA-induced conformational change of a eukaryotic-specific lysyl-tRNA synthetase extension and role of adjacent anticodon-binding domain.

Human lysyl-tRNA synthetase (hLysRS) is essential for aminoacylation of tRNA Higher eukaryotic LysRSs possess an N-terminal extension (Nterm) previously shown to facilitate high-affinity tRNA binding and aminoacylation. This eukaryote-specific appended domain also plays a critical role in hLysRS nuclear localization, thus facilitating noncanonical functions of hLysRS. The structure is intrinsically disordered and therefore remains poorly characterized. Findings of previous studies are consistent with the Nterm domain undergoing a conformational transition to an ordered structure upon nucleic acid binding. In this study, we used NMR to investigate how the type of RNA, as well as the presence of the adjacent anticodon-binding domain (ACB), influences the Nterm conformation. To explore the latter, we used sortase A ligation to produce a segmentally labeled tandem-domain protein, Nterm-ACB. In the absence of RNA, Nterm remained disordered regardless of ACB attachment. Both alone and when attached to ACB, Nterm structure remained unaffected by titration with single-stranded RNAs. The central region of the Nterm domain adopted α-helical structure upon titration of Nterm and Nterm-ACB with RNA hairpins containing double-stranded regions. Nterm binding to the RNA hairpins resulted in CD spectral shifts consistent with an induced helical structure. NMR and fluorescence anisotropy revealed that Nterm binding to hairpin RNAs is weak but that the binding affinity increases significantly upon covalent attachment to ACB. We conclude that the ACB domain facilitates induced-fit conformational changes and confers high-affinity RNA hairpin binding, which may be advantageous for functional interactions of LysRS with a variety of different binding partners.
Sheng Liu, Maryanne Refaei, Shuohui Liu, Aaron Decker, Jennifer M Hinerman, Andrew B Herr, Mike Howell, Karin Musier-Forsyth, Pearl Tsang

2728 related Products with: Hairpin RNA-induced conformational change of a eukaryotic-specific lysyl-tRNA synthetase extension and role of adjacent anticodon-binding domain.

100ul 100ul100ug100ug1000 TESTS/0.65ml25 Tests4 Membranes/Box100μg250ul4 Arrays/Slide

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#32332915   2020/04/24 To Up

HSPA12A attenuates lipopolysaccharide-induced liver injury through inhibiting caspase-11-mediated hepatocyte pyroptosis via PGC-1α-dependent acyloxyacyl hydrolase expression.

Liver dysfunction is strongly associated with poor survival of sepsis patients. Cytosolic lipopolysaccharide (LPS) sensing by Caspase-4/5/11 for pyroptosis activation is a major driver of the development of sepsis. Studies in macrophages and endothelial cells have demonstrated that LPS is inactivated by acyloxyacyl hydrolase (AOAH) and leading to desensitizing Caspase-4/5/11 to LPS. However, little is known about the cytosolic LPS-induced pyroptosis in hepatocytes during sepsis. Heat shock protein 12A (HSPA12A) is a novel member of the HSP70 family. Here, we report that LPS increased HSPA12A nuclear translocation in hepatocytes, while knockout of HSPA12A (Hspa12a) in mice promoted LPS-induced acute liver injury. We also noticed that the LPS-induced Caspase-11 activation and its cleavage of gasdermin D (GSDMD) to produce the membrane pore-forming GSDMD (markers of pyroptosis) were greater in livers of Hspa12a mice compared with its wild type controls. Loss- and gain-of-function studies showed that HSPA12A deficiency promoted, whereas HSPA12A overexpression inhibited, cytosolic LPS accumulation, Caspase-11 activation and GSDMD generation in primary hepatocytes following LPS incubation. Notably, LPS-induced AOAH expression was suppressed by HSPA12A deficiency, whereas AOAH overexpression reversed the HSPA12A deficiency-induced promotion of LPS-evoked and Caspase-11-mediated pyroptosis of hepatocytes. In-depth molecular analysis showed that HSPA12A interacted directly with peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) and increased its nuclear translocation, thereby inducing AOAH expression for cytosolic LPS inactivation, which ultimately leading to inhibition of the Caspase-11 mediated pyroptosis of hepatocytes. Taken together, these findings revealed HSPA12A as a novel player against LPS-induced liver injury by inhibiting cytosolic LPS-induced hepatocyte pyroptosis via PGC-1α-mediated AOAH expression. Therefore, targeting hepatocyte HSPA12A represents a viable strategy for the management of liver injury in sepsis patients.
Jiali Liu, Shuya Du, Qiuyue Kong, Xiaojin Zhang, Surong Jiang, Xiaofei Cao, Yuehua Li, Chuanfu Li, Huaqun Chen, Zhengnian Ding, Li Liu

2905 related Products with: HSPA12A attenuates lipopolysaccharide-induced liver injury through inhibiting caspase-11-mediated hepatocyte pyroptosis via PGC-1α-dependent acyloxyacyl hydrolase expression.

N/A N/A 1000 assays1000 assays 100ul400 assays100ug/vial1000 assays100 units1 kit100ug Lyophilized

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#31596312   2019/10/07 To Up

A simple, ex vivo phagocytosis assay of Plasmodium vivax merozoites by flow cytometry.

As phagocytosis is the first line of defense against malaria, we developed a phagocytosis assay with Plasmodium vivax (P. vivax) merozoites that can be applied to evaluate vaccine candidates. Briefly, after leukocyte removal with loosely packed cellulose powder in a syringe, P. vivax trophozoites matured to the merozoite-rich schizont stages in the presence of the E64 protease inhibitor. The Percoll gradient-enriched schizonts were chemically disrupted to release merozoites that were submitted to merozoite opsonin-dependent phagocytosis in two phagocytic lines with human and mouse antibodies against the N- and C-terminus of P. vivax Merozoite Surface Protein-1 (Nterm-PvMSP1 and MSP119). The resulting assay is simple and efficient for use as a routine phagocytic assay for the evaluation of merozoite stage vaccine candidates.
Elizangela Farias, Fhabiane Bezerra, Djane Clarys Baia-da-Silva, Yury Oliveira Chaves, Tatiana Bacry Cardoza, Maria Edilene Martins de Almeida, Lucas Barbosa Oliveira, Pritesh Lalwani, Patrícia Puccinelli Orlandi, Marcus Vinicius Guimaraes Lacerda, Stefanie Costa Pinto Lopes, Paulo Afonso Nogueira

1000 related Products with: A simple, ex vivo phagocytosis assay of Plasmodium vivax merozoites by flow cytometry.

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