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Ankara : İhsan Doğramacı Bilkent Üniversitesi İktisadi, İdari ve Sosyal Bilimler Fakültesi, Tarih Bölümü, 2012.This work is a student project of the The Department of History, Faculty of Economics, Administrative and Social Sciences, İhsan Doğramacı Bilkent University.by Nahide Işık Demirakın.Demirakın, Nahide Işık. HIST 200-08DEMİRAKIN HIST 200-08/2 2011-1

Production and Characterization of Nucleocapsid and RBD Cocktail Antigens of SARS-CoV-2 in Nicotiana benthamiana Plant as a Vaccine Candidate against COVID-19

The COVID-19 pandemic has put global public health at high risk, rapidly spreading around the world. Although several COVID-19 vaccines are available for mass immunization, the world still urgently needs highly effective, reliable, cost-effective, and safe SARS-CoV-2 coronavirus vaccines, as well as antiviral and therapeutic drugs, to control the COVID-19 pandemic given the emerging variant strains of the virus. Recently, we successfully produced receptor-binding domain (RBD) variants in the Nicotiana benthamiana plant as promising vaccine candidates against COVID-19 and demonstrated that mice immunized with these antigens elicited a high titer of RBD-specific antibodies with potent neutralizing activity against SARS-CoV-2. In this study, we engineered the nucleocapsid (N) protein and co-expressed it with RBD of SARS-CoV-2 in Nicotiana benthamiana plant to produce an antigen cocktail. The purification yields were about 22 or 24 mg of pure protein/kg of plant biomass for N or N+RBD antigens, respectively. The purified plant produced N protein was recognized by N protein-specific monoclonal and polyclonal antibodies demonstrating specific reactivity of mAb to plant-produced N protein. In this study, for the first time, we report the co-expression of RBD with N protein to produce a cocktail antigen of SARS-CoV-2, which elicited high-titer antibodies with potent neutralizing activity against SARS-CoV-2. Thus, obtained data support that a plant-produced antigen cocktail, developed in this study, is a promising vaccine candidate against COVID-19

Plant-Produced Glycosylated and In Vivo Deglycosylated Receptor Binding Domain Proteins of SARS-CoV-2 Induce Potent Neutralizing Responses in Mice

The COVID-19 pandemic, caused by SARS-CoV-2, has rapidly spread to more than 222 countries and has put global public health at high risk. The world urgently needs cost-effective and safe SARS-CoV-2 vaccines, antiviral, and therapeutic drugs to control it. In this study, we engineered the receptor binding domain (RBD) of the SARS-CoV-2 spike (S) protein and produced it in the plant Nicotiana benthamiana in a glycosylated and deglycosylated form. Expression levels of both glycosylated (gRBD) and deglycosylated (dRBD) RBD were greater than 45 mg/kg fresh weight. The purification yields were 22 mg of pure protein/kg of plant biomass for gRBD and 20 mg for dRBD, which would be sufficient for commercialization of these vaccine candidates. The purified plant-produced RBD protein was recognized by an S protein-specific monoclonal antibody, demonstrating specific reactivity of the antibody to the plant-produced RBD proteins. The SARS-CoV-2 RBD showed specific binding to angiotensin converting enzyme 2 (ACE2), the SARS-CoV-2 receptor. In mice, the plant-produced RBD antigens elicited high titers of antibodies with a potent virus-neutralizing activity. To our knowledge, this is the first report demonstrating that mice immunized with plant-produced deglycosylated RBD form elicited high titer of RBD-specific antibodies with potent neutralizing activity against SARS-CoV-2 infection. Thus, obtained data support that plant-produced glycosylated and in vivo deglycosylated RBD antigens, developed in this study, are promising vaccine candidates for the prevention of COVID-19

Deciphering the Clinical Presentations in LMNA-related Lipodystrophy: Report of 115 Cases and a Systematic Review

Context: Lipodystrophy syndromes are a heterogeneous group of rare genetic or acquired disorders characterized by generalized or partial loss of adipose tissue. LMNA-related lipodystrophy syndromes are classified based on the severity and distribution of adipose tissue loss. Objective: We aimed to annotate all clinical and metabolic features of patients with lipodystrophy syndromes carrying pathogenic LMNA variants and assess potential genotype-phenotype relationships. Methods: We retrospectively reviewed and analyzed all our cases (n = 115) and all published cases (n = 379) curated from 94 studies in the literature. Results: The study included 494 patients. The most common variants in our study, R482Q and R482W, were associated with similar metabolic characteristics and complications though those with the R482W variant were younger (aged 33 [24] years vs 44 [25] years; P < .001), had an earlier diabetes diagnosis (aged 27 [18] vs 40 [17] years; P < .001) and had lower body mass index levels (24 [5] vs 25 [4]; P = .037). Dyslipidemia was the earliest biochemical evidence described in 83% of all patients at a median age of 26 (10) years, while diabetes was reported in 61% of cases. Among 39 patients with an episode of acute pancreatitis, the median age at acute pancreatitis diagnosis was 20 (17) years. Patients who were reported to have diabetes had 3.2 times, while those with hypertriglyceridemia had 12.0 times, the odds of having pancreatitis compared to those who did not. Conclusion: This study reports the largest number of patients with LMNA-related lipodystrophy syndromes to date. Our report helps to quantify the prevalence of the known and rare complications associated with different phenotypes and serves as a comprehensive catalog of all known cases