The Experts below are selected from a list of 327 Experts worldwide ranked by ideXlab platform
Adolfo Garciasastre - One of the best experts on this subject based on the ideXlab platform.
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newcastle disease virus ndv expressing the spike protein of sars cov 2 as a live virus vaccine candidate
EBioMedicine, 2020Co-Authors: Weina Sun, Sarah R Leist, Stephen Mccroskery, Yonghong Liu, Stefan Slamanig, Justine Oliva, Fatima Amanat, Alexandra Schafer, Kenneth H Dinnon, Adolfo GarciasastreAbstract:Abstract Background Due to the lack of protective immunity of humans towards the newly emerged SARS-CoV-2, this virus has caused a massive pandemic across the world resulting in hundreds of thousands of deaths. Thus, a vaccine is urgently needed to contain the spread of the virus. Methods Here, we describe Newcastle disease virus (NDV) vector vaccines expressing the spike protein of SARS-CoV-2 in its wild type format or a membrane-anchored format lacking the polybasic cleavage site. All described NDV vector vaccines grow to high titers in embryonated chicken eggs. In a proof of principle Mouse Study, the immunogenicity and protective efficacy of these NDV-based vaccines were investigated. Findings We report that the NDV vector vaccines elicit high levels of antibodies that are neutralizing when the vaccine is given intramuscularly in mice. Importantly, these COVID-19 vaccine candidates protect mice from a Mouse-adapted SARS-CoV-2 challenge with no detectable viral titer and viral antigen in the lungs. Interpretation The results suggested that the NDV vector expressing either the wild type S or membrane-anchored S without the polybasic cleavage site could be used as live vector vaccine against SARS-CoV-2. Funding This work is supported by an NIAID funded Center of Excellence for Influenza Research and Surveillance (CEIRS) contract, the Collaborative Influenza Vaccine Innovation Centers (CIVIC) contract, philanthropic donations and NIH grants.
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newcastle disease virus ndv expressing the spike protein of sars cov 2 as vaccine candidate
bioRxiv, 2020Co-Authors: Weina Sun, Sarah R Leist, Stephen Mccroskery, Yonghong Liu, Stefan Slamanig, Justine Oliva, Fatima Amanat, Alexandra Schafer, Kenneth H Dinnon, Adolfo GarciasastreAbstract:Due to the lack of protective immunity of humans towards the newly emerged SARS-CoV-2, this virus has caused a massive pandemic across the world resulting in hundreds of thousands of deaths. Thus, a vaccine is urgently needed to contain the spread of the virus. Here, we describe Newcastle disease virus (NDV) vector vaccines expressing the spike protein of SARS-CoV-2 in its wild type or a pre-fusion membrane anchored format. All described NDV vector vaccines grow to high titers in embryonated chicken eggs. In a proof of principle Mouse Study, we report that the NDV vector vaccines elicit high levels of antibodies that are neutralizing when the vaccine is given intramuscularly. Importantly, these COVID-19 vaccine candidates protect mice from a Mouse-adapted SARS-CoV-2 challenge with no detectable viral titer and viral antigen in the lungs.
Gérard Mage - One of the best experts on this subject based on the ideXlab platform.
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impact of intraperitoneal pressure and duration of surgery on levels of tissue plasminogen activator and plasminogen activator inhibitor 1 mrna in peritoneal tissues during laparoscopic surgery
Human Reproduction, 2011Co-Authors: Sachiko Matsuzaki, Kris Jardon, Elodie Maleysson, Michel Canis, Revaz Botchorishvili, Gérard MageAbstract:results: Human Study: The tPA/PAI-1 mRNA ratio was significantly decreased in the 12 mmHg group at 1 h [P , 0.0001 versus matched initial peritoneal biopsies (MI)]. The tPA/PAI-1 mRNA ratio decreased in both groups at 2 h (P , .0.01 versus MI). Mouse Study: The tPA/ PAI-1 ratio was decreased at 0 h, and the difference was significant at 4 h in both the laparotomy (P , 0.001 versus controls, 0 h, 5 and 7 days) and high-IPP (P , 0.0001 versus 0, 48 and 72 h, 5 and 7 days) groups. No changes in tPA/PAI-1 ratio were observed in the low-IPP group. conclusions: A low IPP and shorter duration of surgery appear to minimally impact the fibrinolytic system during a CO2
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Carbon dioxide pneumoperitoneum, intraperitoneal pressure, and peritoneal tissue hypoxia: a Mouse Study with controlled respiratory support
Surgical endoscopy, 2010Co-Authors: Sachiko Matsuzaki, Kris Jardon, Elodie Maleysson, Francis D’arpiany, Michel Canis, Jean-etienne Bazin, Gérard MageAbstract:Background Animal experiments have suggested that the laparoscopic peritoneal environment is hypoxic. This Study aimed to investigate whether peritoneal tissue is hypoxic on a cellular level during a carbon dioxide (CO2) pneumoperitoneum at different intraperitoneal pressures (IPPs) and to determine the short-term effects of surgical injury on the hypoxia status of peritoneal tissue in the injured peritoneum and the distant noninjured peritoneum at cellular and molecular levels.
Yair Anikster - One of the best experts on this subject based on the ideXlab platform.
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Man made disease: clinical manifestations of low phenylalanine levels in an inadequately treated phenylketonuria patient and Mouse Study.
Molecular genetics and metabolism, 2013Co-Authors: Ben Pode-shakked, Lilach Shemer-meiri, Alon Harmelin, Noa Stettner, Ori Brenner, Smadar Abraham, Gerard Schwartz, Yair AniksterAbstract:Phenylalanine (Phe) deficiency and its clinical manifestations have been previously described mostly as sporadic case reports dating back to the 1960's and 1970's. In these reports, low plasma Phe levels were associated with listlessness, eczematous eruptions and failure to gain weight, most often in infants in their first year of life. Herein we describe a 9 month old female patient with known phenylketonuria, who presented with an unusual constellation of symptoms, including severe erythema and desquamation, alopecia, keratomalacia, corneal perforation, failure to thrive and prolonged diarrhea. The diagnostic possibilities of acrodermatitis enteropathica and vitamin deficiencies were ruled out, and further investigation into her medical history led to the conclusion that during the weeks preceding the hospitalization, the patient's diet consisted of the phenylalanine-free medical formula alone, without the addition of a standard infant formula or food as recommended. Subsequently, dietary control of the blood phenylalanine levels brought swift and marked resolution of the dermatological lesions, with renewal of hair growth. Following this experience, and due to the relative paucity of data regarding the clinical manifestations of low serum phenylalanine levels in humans and their putative pathogenetic mechanisms, we sought to further investigate the effects of a phenylalanine-free diet in a Mouse Study. For this purpose, twenty mice were randomly allocated to receive either a phenylalanine-deficient diet (n=10) or a normal diet (n=10). Weight was measured weekly, and laboratory tests were obtained including complete blood count, electrolyte studies, and phenylalanine and tyrosine levels. Finally, necropsies and histopathological examinations of different tissues were performed in selected mice, either early after diet initiation, late after diet initiation or following re-introduction of normal diets. The Study was then repeated in additional two groups of mice, for a period of up to thirteen weeks, with a total of 63 mice. Gross lesions noted on necropsy in the Phe-deficient mice included scruffy coat, tendency toward weight loss, a reduction in thymic mass, and most notably severe gastric dilation, all of which were not seen in the controls. Histologic findings included thymic depletion, hepatocellular vacuolation, and exocrine pancreatic atrophy. No histopathological lesions were evident in the brain, nor were significant lesions in the eyes. Diagnosis of the iatrogenic condition of phenylalanine deficiency, which manifests in gastrointestinal, dermatological and ocular findings, requires a high index of suspicion. Mice fed a phenylalanine-deficient diet display to some extent similar organ involvement, although no eye abnormalities were evident. © 2013.
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Man made disease: Clinical manifestations of low phenylalanine levels in an inadequately treated phenylketonuria patient and Mouse Study
Molecular Genetics and Metabolism, 2013Co-Authors: Ben Pode-shakked, Lilach Shemer-meiri, Alon Harmelin, Noa Stettner, Ori Brenner, Smadar Abraham, Gerard Schwartz, Yair AniksterAbstract:Abstract Introduction Phenylalanine (Phe) deficiency and its clinical manifestations have been previously described mostly as sporadic case reports dating back to the 1960's and 1970's. In these reports, low plasma Phe levels were associated with listlessness, eczematous eruptions and failure to gain weight, most often in infants in their first year of life. Case report Herein we describe a 9 month old female patient with known phenylketonuria, who presented with an unusual constellation of symptoms, including severe erythema and desquamation, alopecia, keratomalacia, corneal perforation, failure to thrive and prolonged diarrhea. The diagnostic possibilities of acrodermatitis enteropathica and vitamin deficiencies were ruled out, and further investigation into her medical history led to the conclusion that during the weeks preceding the hospitalization, the patient's diet consisted of the phenylalanine-free medical formula alone, without the addition of a standard infant formula or food as recommended. Subsequently, dietary control of the blood phenylalanine levels brought swift and marked resolution of the dermatological lesions, with renewal of hair growth. Objective Following this experience, and due to the relative paucity of data regarding the clinical manifestations of low serum phenylalanine levels in humans and their putative pathogenetic mechanisms, we sought to further investigate the effects of a phenylalanine-free diet in a Mouse Study. Materials and methods For this purpose, twenty mice were randomly allocated to receive either a phenylalanine-deficient diet (n = 10) or a normal diet (n = 10). Weight was measured weekly, and laboratory tests were obtained including complete blood count, electrolyte studies, and phenylalanine and tyrosine levels. Finally, necropsies and histopathological examinations of different tissues were performed in selected mice, either early after diet initiation, late after diet initiation or following re-introduction of normal diets. The Study was then repeated in additional two groups of mice, for a period of up to thirteen weeks, with a total of 63 mice. Results Gross lesions noted on necropsy in the Phe-deficient mice included scruffy coat, tendency toward weight loss, a reduction in thymic mass, and most notably severe gastric dilation, all of which were not seen in the controls. Histologic findings included thymic depletion, hepatocellular vacuolation, and exocrine pancreatic atrophy. No histopathological lesions were evident in the brain, nor were significant lesions in the eyes. Conclusions Diagnosis of the iatrogenic condition of phenylalanine deficiency, which manifests in gastrointestinal, dermatological and ocular findings, requires a high index of suspicion. Mice fed a phenylalanine-deficient diet display to some extent similar organ involvement, although no eye abnormalities were evident.
Stacey D Finley - One of the best experts on this subject based on the ideXlab platform.
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in silico Mouse Study identifies tumour growth kinetics as biomarkers for the outcome of anti angiogenic treatment
Journal of the Royal Society Interface, 2018Co-Authors: Alyssa D Arnheim, Stacey D FinleyAbstract:Angiogenesis is a crucial step in tumour progression, as this process allows tumours to recruit new blood vessels and obtain oxygen and nutrients to sustain growth. Therefore, inhibiting angiogenes...
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in silico Mouse Study identifies tumor growth kinetics as biomarkers for the outcome of anti angiogenic treatment
bioRxiv, 2018Co-Authors: Alyssa D Arnheim, Stacey D FinleyAbstract:Angiogenesis is a crucial step in tumor progression, as this process allows tumors to recruit new blood vessels and obtain oxygen and nutrients to sustain growth. Therefore, inhibiting angiogenesis remains a viable strategy for cancer therapy. However, anti-angiogenic therapy has not proved to be effective in reducing tumor growth across a wide range of tumors, and no reliable predictive biomarkers have been found to determine the efficacy of anti-angiogenic treatment. Using our previously established computational model of tumor-bearing mice, we sought to determine whether tumor growth kinetic parameters could be used to predict the outcome of anti-angiogenic treatment. A model trained with datasets from six in vivo mice studies was used to generate a randomized in silico tumor-bearing Mouse population. We analyzed tumor growth in untreated mice (control) and mice treated with an anti-angiogenic agent and determined the Kaplan-Meier survival estimates based on simulated tumor volume data. We found that the ratio between two kinetic parameters, k0 and k1, which characterize the tumor's exponential and linear growth rates, as well as k1 alone, can be used as prognostic biomarkers of population survival outcome. Our work demonstrates a robust, quantitative approach for identifying tumor growth kinetic parameters as prognostic biomarkers and serves as a template that can be used to identify other biomarkers for anti-angiogenic treatment.
Weina Sun - One of the best experts on this subject based on the ideXlab platform.
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newcastle disease virus ndv expressing the spike protein of sars cov 2 as a live virus vaccine candidate
EBioMedicine, 2020Co-Authors: Weina Sun, Sarah R Leist, Stephen Mccroskery, Yonghong Liu, Stefan Slamanig, Justine Oliva, Fatima Amanat, Alexandra Schafer, Kenneth H Dinnon, Adolfo GarciasastreAbstract:Abstract Background Due to the lack of protective immunity of humans towards the newly emerged SARS-CoV-2, this virus has caused a massive pandemic across the world resulting in hundreds of thousands of deaths. Thus, a vaccine is urgently needed to contain the spread of the virus. Methods Here, we describe Newcastle disease virus (NDV) vector vaccines expressing the spike protein of SARS-CoV-2 in its wild type format or a membrane-anchored format lacking the polybasic cleavage site. All described NDV vector vaccines grow to high titers in embryonated chicken eggs. In a proof of principle Mouse Study, the immunogenicity and protective efficacy of these NDV-based vaccines were investigated. Findings We report that the NDV vector vaccines elicit high levels of antibodies that are neutralizing when the vaccine is given intramuscularly in mice. Importantly, these COVID-19 vaccine candidates protect mice from a Mouse-adapted SARS-CoV-2 challenge with no detectable viral titer and viral antigen in the lungs. Interpretation The results suggested that the NDV vector expressing either the wild type S or membrane-anchored S without the polybasic cleavage site could be used as live vector vaccine against SARS-CoV-2. Funding This work is supported by an NIAID funded Center of Excellence for Influenza Research and Surveillance (CEIRS) contract, the Collaborative Influenza Vaccine Innovation Centers (CIVIC) contract, philanthropic donations and NIH grants.
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newcastle disease virus ndv expressing the spike protein of sars cov 2 as vaccine candidate
bioRxiv, 2020Co-Authors: Weina Sun, Sarah R Leist, Stephen Mccroskery, Yonghong Liu, Stefan Slamanig, Justine Oliva, Fatima Amanat, Alexandra Schafer, Kenneth H Dinnon, Adolfo GarciasastreAbstract:Due to the lack of protective immunity of humans towards the newly emerged SARS-CoV-2, this virus has caused a massive pandemic across the world resulting in hundreds of thousands of deaths. Thus, a vaccine is urgently needed to contain the spread of the virus. Here, we describe Newcastle disease virus (NDV) vector vaccines expressing the spike protein of SARS-CoV-2 in its wild type or a pre-fusion membrane anchored format. All described NDV vector vaccines grow to high titers in embryonated chicken eggs. In a proof of principle Mouse Study, we report that the NDV vector vaccines elicit high levels of antibodies that are neutralizing when the vaccine is given intramuscularly. Importantly, these COVID-19 vaccine candidates protect mice from a Mouse-adapted SARS-CoV-2 challenge with no detectable viral titer and viral antigen in the lungs.
