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Safety,immunogenicity,and protection provided by unadjuvanted and adjuvanted formulations of a recombinant plant-derived virus-like particle vaccine candidate for COvID-19 in nonhuman primates

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Cellular & Molecular Immunology 2022年第2期19卷 222-233页

作者： Stéphane Pillet Prabhu SArunachalam Guadalupe Andreani Nadia Golden Jane Fontenot Pyone Pyone Aye Katharina Röltgen Gabrielle Lehmicke Philipe Gobeil Charlotte Dubé Sonia Trépanier Nathalie Charland Marc-AndréD’Aoust Kasi Russell-Lodrigue Christopher Monjure Robert v.blair Scott D.Boyd Rudolf P.Bohm Jay Rappaport François villinger Nathalie Landry Bali Pulendran Brian J.Ward Medicago Inc. QuébecQCCanada. Institute for Immunity Transplantation and InfectionStanford University School of MedicineStanford UniversityStanfordCAUSA. Tulane National Primate Research Center CovingtonLAUSA. New Iberia Research Center University of Louisiana at LafayetteNew IberiaLAUSA. Department of Pathology Stanford University School of MedicineStanford UniversityStanfordCAUSA. Department of Microbiology and Immunology Tulane University School of MedicineNew OrleansLAUSA. Department of Microbiology and Immunology Stanford University School of MedicineStanford UniversityStanfordCAUSA. Institute for Immunity Transplantation&InfectionStanford University School of MedicineStanford UniversityStanfordCAUSA Research Institute of the McGill University Health Centre MontrealQCCanada.

Although antivirals are important tools to control severe acute respiratory syndrome coronavirus 2(SARS-Cov-2)infection,effective vaccines are essential to control the current coronavirus disease 2019(COvID-19)***-derived virus-like particle(vLP)vaccine candidates have previously demonstrated immunogenicity and efficacy against ***,we report the immunogenicity and protection induced in rhesus macaques by intramuscular injections of a vLP bearing a SARS-Cov-2 spike protein(CovLP)vaccine candidate formulated with or without Adjuvant System 03(AS03)or cytidine-phospho-guanosine(CpG)*** a single dose of the unadjuvanted CovLP vaccine candidate stimulated humoral and cell-mediated immune responses,booster immunization(at 28 days after priming)and adjuvant administration significantly improved both responses,with higher immunogenicity and protection provided by the AS03-adjuvanted *** micrograms of CovLP adjuvanted with AS03 induced a polyfunctional interleukin-2(IL-2)-driven response and IL-4 expression in CD4 T *** were challenged by multiple routes(i.e.,intratracheal,intranasal,and ocular)with a total viral dose of 106 plaque-forming units of *** viral replication in nasal swabs and bronchoalveolar lavage fluid(BALF)as well as fewer SARS-Cov-2-infected cells and immune cell infiltrates in the lungs concomitant with reduced levels of proinflammatory cytokines and chemotactic factors in the BALF were observed in animals immunized with the CovLP adjuvanted with *** clinical,pathologic,or virologic evidence of vaccineassociated enhanced disease was observed in vaccinated *** CovLP adjuvanted with AS03 was therefore selected for vaccine development and clinical trials.

关键词： SARS-Cov-2 virus-like particles Non-humane primates AS03 CpG1018

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色素内镜监测遗传弥漫性低分化胃癌:预防性胃切除术的另一种替代性选择?

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世界核心医学期刊文摘（胃肠病学分册） 2005年第8期1卷 39-40页

作者： Shaw D blair v Framp A 赵天智 Tauranga Hospital Private Bag 12 024 Tauranga New Zealand.Dr

Background: Hereditary diffuse gastric cancer (HDGC) is defined by germline mu tations in the E-cadherin gene, *** first family in which CDH-1 mutatio ns were identified was a large Maori kindred, where lifetime penetrance is 70%. Prophylactic gastrectomy is an unacceptable option for many mutation carriers. T he results of annual chromoendoscopic surveillance using the methylene blue/cong o red technique in 33 mutation carriers over a five year period are described. P atients and methods: Thirty three confirmed CDH-1 mutation carriers(18 males, 1 5 females), median age 32 years (range 14-69),were enrolled in 1999-2003. Medi cal records, endoscopy, and pathology were reviewed retrospectively. Results: Ov er five years, 99 surveillance endoscopies were performed, of which 93 were chro mo-dye enhanced. Sixty nine chromoendoscopies were normal. In 24 procedures, 1 -6 pale areas/stomach (size 2-10 mm) were detected post chromo-dye applicatio n (totalling 56 pale lesions). One biopsy was taken from each pale lesion: 23 le sions (41%) showed signet ring cell carcinoma (10 patients),10 lesions (18%) g astritis (four patients), and 23 (41%) normal mucosa (10 patients). No chromo- dyes were used in six procedures with macroscopic lesions (two HDGC, four ulcera tion).Total gastrectomies from patients with carcinoma were macroscopically norm al but pathological mapping showed multiple microscopic foci of early signet rin g cell carcinoma. Correlation of chromoendoscopic and gastrectomy findings showe d that congo red/methylene blue detected carcinoma foci 4-10 mm in size but not focivisible with white light gastroscopy. If these findings are validated in other HDGC kind red, chromogastroscopy represents an improved survei- llance technique that can be safely considered alongside prophylactic gastrect omy.

关键词：低分化胃癌色素内镜胃切除术性选择弥漫性亚甲蓝染色钙黏蛋白早期胃癌印戒细胞癌携带者

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Genetic differentiation of grain, fodder and pod vegetable type cowpeas (vigna unguiculata L.) identified through single nucleotide polymorphisms from genotyping-by-sequencing

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Molecular Horticulture 2022年第1期2卷 101-115页

作者： Xingbo Wu Andrés JCortés Matthew W.blair Department of Agricultural and Environmental Sciences Tennessee State UniversityNashvilleTN 37209USA Tropical Research and Education Center Department of Environmental HorticulturalUniversity of Florida18905 SW 280th StHomesteadFL 33031USA Corporación Colombiana de Investigación Agropecuaria AGROSAvIA C.I.La SelvaKm 7 vía Rionegro–Las PalmasRionegroColombia Universidad Nacional de Colombia–Sede Medellín Facultad de Ciencias Agrarias–Departamento de Ciencias ForestalesMedellínColombia

The species vigna unguiculata L.(Walp),commonly known as cowpea,is a multi-purpose legume that has been selected into three subspecies that are divided into grain,fodder and pod(yardlong bean)***,genetic bases for distinctions are not well *** purpose of this study was to apply genotyping-by-sequencing(GBS)and current reference genome for *** to distinguish three subspecies and identify signatures of *** collection of 130 accessions included 128 cultivated from:1)***,fodder type;2)***,pod vegetable type;and 3)***,grain *** wilds genotypes from *** and ***,were used to anchor phylogeny.A total of 11,083 highly informative single nucleotide polymorphisms(SNPs)were *** accessions showed distinct genetic fingerprints and were separated from cultivated *** component analysis showed closer relationship between *** and *** compared to *** differentiation of cultivated subspecies(with Fixation Index,FST)indicated the existence of discrete signatures of *** work clarifies the population structure,phylogeny,and domestication of cultivated ***,significant genetic differences between grain and pod vegetable types can provide valuable information for future breeding in three cowpea groups.

关键词： Genomic landscape of divergence Relative differentiation FST GBS-derived SNP markers

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Influence of harvest date on seed yield and quality in forage kochia

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Frontiers of Agricultural Science and Engineering 2018年第1期5卷 71-79页

作者： Cody F.CREECH blair L.WALDRON Corey v.RANSOM Dale R.ZOBELL Joseph Earl CREECH Department of Plants Soils and Climate Utah State University USDA-ARS Forage and Range Research Laboratory Department of Animal Dairy and Veterinary Sciences Utah State University

Forage kochia(Bassia prostrata) is used for rangeland reclamation and livestock and wildlife forage,but limited research has been conducted on its seed production. Therefore, this research evaluated the effect of harvest date on seed weight, germination, and seed yield of forage kochia subspecies virescens and grisea. Seed was harvested from individual plants for 3 years during October, November, and December. October harvest had the lightest 100-seed weights, with the November harvest slightly heavier than December, for most *** Snowstorm and breeding line Sahsel, both subsp. grisea, had the greatest 100-seed weights in November, 155 and 143 mg, respectively, whereas, ***(subsp. virescens), the standard for forage kochia, ranked among the least for 100-seed weight. For most accessions, germination was lowest from the October harvest(11%–43%), with greater germination with November and December harvested seeds(43%–64%).viable seed yields were greatest in November with the exception of two accessions, which peaked in October,indicating earlier maturity. Results indicate that forage kochia usually reaches optimum seed maturity by early November, after plants are exposed to freezing temperatures; however, earlier maturing accessions exist in both subspecies virescens and grisea.

关键词： forage rangeland seed germination seed quality

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Systemic RNAi in western corn rootworm, Diabrotica virgifera virgifera, does not involve transitive pathways

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Insect Science 2018年第1期25卷 45-56页

作者： Huarong Li Andrew J. Bowling Premchand Gandra Murugesan Rangasamy Heather E. Pence Robert E. McEwan Chitvan Khajuria blair D. Siegfried Kenneth E. Narva Dow AgroSciences LLC 9330 Zionsville Rd. Indianapolis Indiana USA Department of Entomology University of Nebraska Lincoln Nebraska USA Monsanto Company Chesterfield Missouri USA Entomology and Nematology Department University of Florida Gainesville Florida USA

Western corn rootworm （WCR, Diabrotica virgifera virgifera LeConte） is highly sensitive to orally delivered double-stranded RNA （dsRNA）. RNAi in WCR is systemic and spreads throughout the insect body. This raises the question whether transitive RNAi is a mechanism that functions in WCR to amplify the RNAi response via production of secondary siRNA. Secondary siRNA production is achieved through RNA-dependent RNA polymerase （RdRP） activity in other eukaryotic organisms, but RdRP has not been identified in WCR and any other insects. This study visualized the spread of the RNAi- mediated knockdown of Dr v-ATPase C mRNA throughout the WCR gut and other tissues using high-sensitivity branched DNA in situ hybridization. Furthermore, we did not detect either secondary siRNA production or transitive RNAi in WCR through siRNA sequence profile analysis. Nucleotide mismatched sequences introduced into either the sense or antisense strand of v-ATPase C dsRNAs were maintained in siRNAs derived from WCR fed with the mismatched dsRNAs in a strand specific manner. The distribution of all siRNAs was restricted to within the original target sequence regions, which may indicate the lack of new dsRNA synthesis leading to production of secondary siRNA. Thus, the systemic spread of RNAi in WCR may be derived from the original dsRNA molecules taken up from the gut lumen. These results indicate that the initial dsRNA dose is important for a lethal systemic RNAi response in WCR and have implications in developing effective dsRNA traits to control WCR and in resistance management to prolong the durability of RNAi trait technology.

关键词： corn rootworm Diabrotica secondary siRNA production systemic RNAi transitive RNAi

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骨保护素抑制肿瘤坏死因子诱导的成骨细胞凋亡(英文)

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中国临床康复 2005年第19期9卷 243-245页

作者：步荣发李亚男 Jennifer I Oakley Harry C blair 解放军总医院全军口腔医学研究所口腔颌面外科 Department of Pathology and Cell Biology & Physiology University of Pittsburgh School of Medicineand Veteran's Affairs MedicalCenterPittsburghPA15243

背景:骨质疏松涉及破骨细胞分化成熟和成骨类细胞凋亡两方面,肿瘤坏死因子α能诱导多种细胞凋亡且效率差异很大,骨保护素能抑制破骨细胞成熟,但对成骨类细胞凋亡的作用未见报道。目的:探讨肿瘤坏死因子α能否诱导成骨类细胞凋亡及骨保... 详细信息

背景:骨质疏松涉及破骨细胞分化成熟和成骨类细胞凋亡两方面,肿瘤坏死因子α能诱导多种细胞凋亡且效率差异很大,骨保护素能抑制破骨细胞成熟,但对成骨类细胞凋亡的作用未见报道。目的:探讨肿瘤坏死因子α能否诱导成骨类细胞凋亡及骨保护素能否抑制其凋亡。设计:以成骨细胞和MG63细胞作为实验对象、以鼠WEHI164细胞系用于阳性对照的观察对比分析。单位:解放军总医院全军口腔医学研究所、美国匹茨堡医学院退伍军人医疗中心。材料:本实验于2001-01/2003-12在***实验室和口腔研究所实验室完成。选择商品化细胞系,RPMI1640培养液和各种相关蛋白用于实验。方法:用人间充质干细胞在分化培养液中培养21d使之成为成骨细胞,与MG63一起用于凋亡实验。Annexinv和原位末端标记法检测肿瘤坏死因子α诱导成骨类细胞凋亡。主要观察指标:全部细胞数及凋亡细胞数。结果:和FasL诱导细胞凋亡一样,肿瘤坏死因子α能引起MG63骨肉瘤细胞,间充质干细胞和成骨细胞的凋亡,并表现为明显的浓度依赖和时间依赖。低浓度肿瘤坏死因子α(170～500pmol/L)作用于细胞2～4h就显示了较明显的凋亡,而骨保护素在0.45～1.5nmol/L浓度时,几乎完全抑制了500pmol/L肿瘤坏死因子α诱导的凋亡。成骨细胞分泌骨保护素,而破骨细胞及破骨前体细胞产生肿瘤坏死因子α,它们相互作用降低成骨细胞的凋亡。结论:肿瘤坏死因子α能诱导成骨类细胞凋亡,骨保护素能够抑制肿瘤坏死因子α的凋亡诱导作用,从抑制破骨细胞成熟和成骨细胞凋亡两方面表现骨保护素防治骨质疏松的作用机制。

关键词：骨质疏松肿瘤坏死因子脱噬作用

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OPG对TNF诱导的成骨细胞凋亡的抑制作用

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解放军医学杂志 2004年第4期29卷 338-341页

作者：步荣发李亚男 Jennifer I Oakley Harry C blair 解放军总医院 Departments of Pathology and Cell Biology&Physiology University of Pittsburgh School of Medicineand Veteran’s Affairs Medical CenterPittsburghPA15243

目的　探讨TNF α能否诱导成骨类细胞凋亡及OPG能否抑制其凋亡 ,开辟一条防治骨质疏松的新路。方法　将人间充质干细胞在分化培养液中培养 2 1天使之成为成骨细胞 ,与MG6 3一起用于凋亡实验。鼠WEHI 16 4细胞系用于阳性对照。Annexinv和... 详细信息

目的　探讨TNF α能否诱导成骨类细胞凋亡及OPG能否抑制其凋亡 ,开辟一条防治骨质疏松的新路。方法　将人间充质干细胞在分化培养液中培养 2 1天使之成为成骨细胞 ,与MG6 3一起用于凋亡实验。鼠WEHI 16 4细胞系用于阳性对照。Annexinv和TUNEL分析方法检测成骨类细胞凋亡。结果　和FasL诱导细胞凋亡一样 ,TNF α能引起MG6 3骨肉瘤细胞、间充质干细胞和成骨细胞的凋亡 ,并表现为明显的浓度依赖和时间依赖。低浓度TNF α(170～ 5 0 0 pmol/L)作用于细胞 2～ 4h就显示了较明显的凋亡 ,而 0 4 5～1 5nmol/LOPG几乎完全抑制了 5 0 0 pmol/LTNF α诱导的凋亡。结论　OPG能够抑制TNF α诱导的成骨类细胞凋亡。

关键词：肿瘤坏死因子骨质疏松凋亡

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Permanent transvenous pacemaker implantation in a patient with Cor triatriatum dextrum

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World Journal of Cardiology 2015年第1期7卷 43-46页

作者： Kun Xiang George v Moukarbel blair Grubb Division of Cardiovascular Medicine University of Toledo Medical Center Toledo OH 43614 United States

Cor triatriatum dextrum is an extremely rare congenital heart abnormality in which the right atrium is separatedinto two chambers by a persistent fibrous membrane. A transvenous approach to place a dual-chamber pacemaker in such patients is technically challenging. We report the first case of a transvenous permanent pacemaker placement in a patient with cor triatriatum dextrum. An 87-year-old woman was diagnosed with paroxysmal atrial fibrillation. She was accidentally found to have cor triatriatum dextrum during the transesophageal echocardiography(TEE) prior to cardioversion. Later during her hospital stay, it was indicated to place a permanant pacemaker due to high grade atrioventricular block. After thorough reviewing TEE imagings, a transvenous catheter-based approach was decided feasible. Patient successfully received a dual chamber pacemaker through left subclavian venous approach. Furthermore in our case, using specially designed pacemaker leads and cautious intra-procedural maneuvering under fluoroscopic guidance ensured procedural success. In summary, a thorough pre-operative evaluation with transesophageal echocardiography is critical for the planning and eventual success of the transvenous placement of rightsided leads.

关键词： Congenital heart defect Complete heart block Inter-atrial membrane Dual-chamber pacemaker

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v-ras基因点突变与转化细胞恶性表型的研究

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中国科学（B辑） 1992年第11期B卷 1182-1188页

作者：吕有勇 D.G.blair T.Y.Shih D.J.Clanton S.Segal 北京市肿瘤防治研究所北京100034 Molecalar oncology Nautional Cancer Institule (NCI) U. S. A. Department Of Microbilogy Ben-Gurion University Iseral

为进一步确定ras基因突变与肿瘤恶性表型的关系,我们构建了一系列的v-ras突变体并将其导入NIH 3T3细胞,观察这些细胞的恶性表型,如致瘤性,转移能力及细胞膜组织相容性抗原(MHC-I)的表达水平。实验证明不是全部具有形态转化的细胞都能在... 详细信息

为进一步确定ras基因突变与肿瘤恶性表型的关系,我们构建了一系列的v-ras突变体并将其导入NIH 3T3细胞,观察这些细胞的恶性表型,如致瘤性,转移能力及细胞膜组织相容性抗原(MHC-I)的表达水平。实验证明不是全部具有形态转化的细胞都能在正常的Balb/c小鼠致瘤和形成远端转移。ras基因不仅能影响细胞的形态、致瘤性、转移能力,而且还通过调节MHC-I的表达水平来影响ras转化细胞的恶性表型。

关键词： v-ras基因点突变转化细胞肿瘤

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牛裂体吸虫线粒体DNA序列和基因排序分析

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中国寄生虫学与寄生虫病杂志 2010年第4期28卷 252-256页

作者：肖景莹蔡连顺長瀧充德弘慎治 Jarilla Blanca R. 嶋田雅暁 David blair 吾妻健日本高知大学医学部高知783-8505 佳木斯大学基础医学院佳木斯154007 日本长崎大学热带医学研究所长崎852-8523 澳大利亚詹姆斯库克大学热带生物学院汤斯维尔QLD 4811

目的为探讨牛裂体吸虫(Schistosoma bovis)在裂体属内的系统发生位置,测定牛裂体吸虫线粒体基因部分序列,并分析该编码区域的基因序列和基因排序。方法以GNT-K法抽提牛裂体吸虫成虫基因组DNA,用兼并和特异引物扩增目的基因。扩增产物经... 详细信息

目的为探讨牛裂体吸虫(Schistosoma bovis)在裂体属内的系统发生位置,测定牛裂体吸虫线粒体基因部分序列,并分析该编码区域的基因序列和基因排序。方法以GNT-K法抽提牛裂体吸虫成虫基因组DNA,用兼并和特异引物扩增目的基因。扩增产物经纯化后克隆于pGEM1T质粒载体,并转化大肠埃希菌。抽提和纯化阳性质粒DNA,并测序。以纯化后的阳性质粒DNA为模板,根据已获得的序列设计内部特异引物,采用引物步移法获得全长目的片段。在GenBank中查找曼氏血吸虫等相关血吸虫线粒体基因序列,作基因排序及比较分析后,以邻接法绘制系统发生树。结果测定了牛裂体吸虫线粒体烟酰胺腺嘌呤二核苷酸脱氢酶亚基Ⅳ～Ⅰ基因序列(nicotinamide adeninedinucleotide dehydrogenase subunit4-1gene,nad4-nad1),其长度为2214bp。分析该编码区基因排序为nad4-trnQ(Gln)-trnK(Lys)-nad3-trnD(Asp)-nad1。牛裂体吸虫在该区域的线粒体基因排序与非洲支系血吸虫相似,与亚洲支系血吸虫有很大的不同;根据牛裂体吸虫与其他8种吸虫部分nad4,nad3,部分nad1和部分nad4+nad3+nad1基因序列比对结果,分别构建系统发生树。结果表明,牛裂体吸虫与埃及血吸虫位于同一簇,归属于非洲血吸虫支系,这与由基因排序推测的牛裂体吸虫的系统发生位置结果相一致。结论牛裂体吸虫属于非洲支系而非亚洲支系血吸虫。

关键词：牛裂体吸虫 nad4 nad3 nad1 基因排序系统发生关系

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