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21.
Willoughby de Broke Rudyard Kipling Hugh Elliot E. Ray Lankester Leonard Hill Laurence R. Philipps Wm. Arbuthnot Lane James Crichton-Browne H. Bryan Donkin Francis Lloyd R. A. Lyster John MacAlister F. W. Mott William Osler C. W. Saleeby J. H. Sequeira Humphry Rolleston Hugh Wansey Bayly 《BMJ (Clinical research ed.)》1919,2(3074):725
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Meal prepared from unheated rapeseed (Brassica napus cv. Zephyr) showed the presence of t,iocyanate ion, while meal from heated seed of the same cultivar did not show detectable amounts. Unheated seed meal on autolysis, and heated seed meal on incubation with thioglucosidase, yielded increased amounts of thiocyanate ion. Various commercial rapeseed meals showed the presence of t,iocyanate ion only after enzyme incubation. Low glucosinolate, cv. Bronowski, and higher glucosinolate, cv. Zephyr on enzymic incubation yielded comparable amounts of thiocyanate ion, suggesting that the precursor responsible in the two varieties was the same and present in similar quantities. No formation of thiocyanate ion was observed on incubation of sinigrin with thioglucosidase. Rats dosed with heated meal, containing intact glucosinolate, showed a slight increase of thiocyanate ion in the urine as compared with control rats dosed with water, while a relatively large increase followed dosing with sinigrin. Rats dosed with meal containing free thiocyanate ion excreted the ingested thiocyanate ion almost quantitatively. 相似文献
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Marie Armani-Tourret Zhicheng Zhou Romain Gasser Isabelle Staropoli Vincent Cantaloube-Ferrieu Yann Benureau Javier Garcia-Perez Mayte Prez-Olmeda Valrie Lorin Bndicte Puissant-Lubrano Lambert Assoumou Constance Delaugerre Jean-Daniel Lelivre Yves Lvy Hugo Mouquet Guillaume Martin-Blondel Jose Alcami Fernando Arenzana-Seisdedos Jacques Izopet Philippe Colin Bernard Lagane 《PLoS pathogens》2021,17(4)
HIV-1 infects CD4 T lymphocytes (CD4TL) through binding the chemokine receptors CCR5 or CXCR4. CXCR4-using viruses are considered more pathogenic, linked to accelerated depletion of CD4TL and progression to AIDS. However, counterexamples to this paradigm are common, suggesting heterogeneity in the virulence of CXCR4-using viruses. Here, we investigated the role of the CXCR4 chemokine CXCL12 as a driving force behind virus virulence. In vitro, CXCL12 prevents HIV-1 from binding CXCR4 and entering CD4TL, but its role in HIV-1 transmission and propagation remains speculative. Through analysis of thirty envelope glycoproteins (Envs) from patients at different stages of infection, mostly treatment-naïve, we first interrogated whether sensitivity of viruses to inhibition by CXCL12 varies over time in infection. Results show that Envs resistant (RES) to CXCL12 are frequent in patients experiencing low CD4TL levels, most often late in infection, only rarely at the time of primary infection. Sensitivity assays to soluble CD4 or broadly neutralizing antibodies further showed that RES Envs adopt a more closed conformation with distinct antigenicity, compared to CXCL12-sensitive (SENS) Envs. At the level of the host cell, our results suggest that resistance is not due to improved fusion or binding to CD4, but owes to viruses using particular CXCR4 molecules weakly accessible to CXCL12. We finally asked whether the low CD4TL levels in patients are related to increased pathogenicity of RES viruses. Resistance actually provides viruses with an enhanced capacity to enter naive CD4TL when surrounded by CXCL12, which mirrors their situation in lymphoid organs, and to deplete bystander activated effector memory cells. Therefore, RES viruses seem more likely to deregulate CD4TL homeostasis. This work improves our understanding of the pathophysiology and the transmission of HIV-1 and suggests that RES viruses’ receptors could represent new therapeutic targets to help prevent CD4TL depletion in HIV+ patients on cART. 相似文献
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