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Antimicrobial Activity of a Cys-Rich Peptide Derived from a Centrosema virginianum Vicilin

American Journal of Plant Sciences 2016年第1期7卷 92-107页

作者： Zhongyu Xie Nibedita Saha Caryl Chlan Biology Department The University of Louisiana at Lafayette Lafayette LA USA sanofi genzyme Corporation Cambridge MA USA

Many antimicrobial peptides (AMPs) have been identified in plants. These peptides are highly divergent at the primary sequence level and vary in their hierarchical structures. Some common biochemical features include the ability to form disulfide bonds, tandemly repeated amino acid sequences and a net charge at pH 7. Unusual Cysteine containing repeats has been identified in several plant seed storage proteins that may act as AMPs. We identified a Cys repeat within a vicilin (seed storage protein) of a wild legume, Centrosema virginianum. Cleavage of the vicilin protein during germination would generate a vicilin derived Cys peptide (VDCP). We investigated the antimicrobial properties of this VDCP and compared its efficacy as an antimicrobial agent to VDCPs from other species. We developed transgenic tobacco plants that expressed cloned sequences encoding the Cysteine repeat unit from C. virginianum, Theobroma cacao and Gossypium hirsutum. Extracts from fully expanded leaves were tested for antimicrobial activity against a fungal pathogen, Botrytis cinerea. The Cys motif from C. virginianum was also expressed in two E. coli cell lines (reducing or oxidizing cytoplasm) and peptide fusion protein fractions were tested for antimicrobial activity against a battery of fungal strains. The unique Cysteine repeat single unit from C. virginianum exhibited antimicrobial properties greater than or equal to the antimicrobial activity associated with expression of the multiple Cys-repeat VDCPs from G. hirsutum or T. cacao in transgenic tobacco. When expressed in bacteria, a C. virginianum VDCP fusion protein exhibited antifungal activity against 3 of the 4 fungi tested. Although the primary role of seed storage proteins is to provide a pool of amino acids and nitrogen for germinating seeds and developing plantlets, it is likely that seed storage protein proteolytic products also provide beneficial antimicrobial properties during germination and young plantlet development.

关键词： Seed Storage Proteins Vicilins Antimicrobial Peptides C. virginianum

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Dupilumab in Children with Uncontrolled Moderate-to-Severe Asthma

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四川生理科学杂志 2021年第10期43卷 1816-1816页

作者： Leonard B Bacharier From Monroe Carell Jr. Children’s Hospital at Vanderbilt Nashville (L.B.B.) Fundación CIDEA Buenos Aires (J.F.M.) Campbelltown Hospital Campbelltown NSW and Western Sydney University Sydney (C.H.K.) — both in Australia Bambino Gesù Children’s Hospital IRCCS Rome (A.G.F.) Clinique Spécialisée en Allergie de la Capitale Quebec QC Canada (R.G.) Hospital Vall d’Hebron Barcelona (I.M.) Arizona Allergy and Immunology Research Gilbert (N.J.) Peninsula Research Associates Rolling Hills Estates CA (L.D.S.) sanofi Bridgewater NJ (X.M. U.K. P.J.R. E.L.) sanofi Beijing (D.L.) Regeneron Pharmaceuticals Tarrytown NY (Y.Z. F.A.K. Y.D. M.R. D.M.W. G.D.Y. N.A. D.J.L.) sanofi Chilly-Mazarin France (A.H.K. L.P.M.) and sanofi genzyme Cambridge MA (N.P. M.H.).

Background:Children with moderate-to-severe asthma continue to have disease complications despite the receipt of standardof-care *** monoclonal antibody dupilumab has been approved for the treatment of adults and adolescents with asthma as well as with other type 2 inflammatory ***:In this 52-week phase 3,randomized,double-blind,placebo-controlled trial,we assigned 408 children between the ages of 6 and 11 years who had uncontrolled moderate-to-severe asthma to receive a subcutaneous injection of dupilumab(at a dose of 100 mg for those weighing≤30 kg and 200 mg for those weighing>30 kg)or matched placebo every 2 *** the children continued to receive a stable dose of standard background *** primary end point was the annualized rate of severe asthma *** end points included the change from baseline in the percentage of predicted prebronchodilator forced expiratory volume in 1 second(ppFEV1)at week 12 and in the score on the Asthma Control Questionnaire 7 Interviewer-Administered(ACQ-7-IA)at week *** points were evaluated in the two primary efficacy populations who had either a type 2 inflammatory asthma phenotype(≥150 blood eosinophils per cubic millimeter or a fraction of exhaled nitric oxide of≥20 ppb at baseline)or a blood eosinophil count of at least 300 cells per cubic millimeter at baseline.

关键词： millimeter cubic continued

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