scholarly journals A Lethal Murine Infection Model for Dengue Virus 3 in AG129 Mice Deficient in Type I and II Interferon Receptors Leads to Systemic Disease

2014 ◽  
Vol 89 (2) ◽  
pp. 1254-1266 ◽  
Author(s):  
Vanessa V. Sarathy ◽  
Mellodee White ◽  
Li Li ◽  
Summer R. Gorder ◽  
Richard B. Pyles ◽  
...  
Keyword(s):  
Animal Model ◽  
Systemic Disease ◽  
Acute Illness ◽  
Human Isolate ◽  
The Other ◽  
Infection Model ◽  
Type I ◽  
Denv Serotypes ◽  
Lethal Infection ◽  
Immunocompromised Mice

ABSTRACTThe mosquito-borne disease dengue (DEN) is caused by four serologically and genetically related viruses, termed DENV-1 to DENV-4. Infection with one DENV usually leads to acute illness and results in lifelong homotypic immunity, but individuals remain susceptible to infection by the other three DENVs. The lack of a small-animal model that mimics systemic DEN disease without neurovirulence has been an obstacle, but DENV-2 models that resemble human disease have been recently developed in AG129 mice (deficient in interferon alpha/beta and interferon gamma receptor signaling). However, comparable DENV-1, -3, and -4 models have not been developed. We utilized a non-mouse-adapted DENV-3 Thai human isolate to develop a lethal infection model in AG129 mice. Intraperitoneal inoculation of six to eight-week-old animals with strain C0360/94 led to rapid, fatal disease. Lethal C0360/94 infection resulted in physical signs of illness, high viral loads in the spleen, liver, and large intestine, histological changes in the liver and spleen tissues, and increased serum cytokine levels. Importantly, the animals developed vascular leakage, thrombocytopenia, and leukopenia. Overall, we have developed a lethal DENV-3 murine infection model, with no evidence of neurotropic disease based on a non-mouse-adapted human isolate, which can be used to investigate DEN pathogenesis and to evaluate candidate vaccines and antivirals. This suggests that murine models utilizing non-mouse-adapted isolates can be obtained for all four DENVs.IMPORTANCEDengue (DEN) is a mosquito-borne disease caused by four DENV serotypes (DENV-1, -2, -3, and -4) that have no treatments or vaccines. Primary infection with one DENV usually leads to acute illness followed by lifelong homotypic immunity, but susceptibility to infection by the other three DENVs remains. Therefore, a vaccine needs to protect from all four DENVs simultaneously. To date a suitable animal model to mimic systemic human illness exists only for DENV-2 in immunocompromised mice using passaged viruses; however, models are still needed for the remaining serotypes. This study describes establishment of a lethal systemic DENV-3 infection model with a human isolate in immunocompromised mice and is the first report of lethal infection by a nonadapted clinical DENV isolate without evidence of neurological disease. Our DENV-3 model provides a relevant platform to test DEN vaccines and antivirals.

scholarly journals Charged Residues Flanking the Transmembrane Domain of Two Related Toxin–Antitoxin System Toxins Affect Host Response

Toxins ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 329
Author(s):  
Andrew Holmes ◽  
Jessie Sadlon ◽  
Keith Weaver
Keyword(s):  
Amino Acid ◽  
Enterococcus Faecalis ◽  
Host Response ◽  
Cytoplasmic Membrane ◽  
Transmembrane Domain ◽  
The Other ◽  
Type I ◽  
Transcriptomic Response ◽  
Specific Amino Acid ◽  
Transporter Protein

A majority of toxins produced by type I toxin–antitoxin (TA-1) systems are small membrane-localized proteins that were initially proposed to kill cells by forming non-specific pores in the cytoplasmic membrane. The examination of the effects of numerous TA-1 systems indicates that this is not the mechanism of action of many of these proteins. Enterococcus faecalis produces two toxins of the Fst/Ldr family, one encoded on pheromone-responsive conjugative plasmids (FstpAD1) and the other on the chromosome, FstEF0409. Previous results demonstrated that overexpression of the toxins produced a differential transcriptomic response in E. faecalis cells. In this report, we identify the specific amino acid differences between the two toxins responsible for the differential response of a gene highly induced by FstpAD1 but not FstEF0409. In addition, we demonstrate that a transporter protein that is genetically linked to the chromosomal version of the TA-1 system functions to limit the toxicity of the protein.

scholarly journals Ferret animal model of severe fever with thrombocytopenia syndrome phlebovirus for human lethal infection and pathogenesis

2018 ◽  
Vol 4 (3) ◽  
pp. 438-446 ◽  
Author(s):  
Su-Jin Park ◽  
Young-Il Kim ◽  
Angela Park ◽  
Hyeok-Il Kwon ◽  
Eun-Ha Kim ◽  
...  
Keyword(s):  
Animal Model ◽  
Lethal Infection ◽  
Severe Fever

scholarly journals A Cronobacter turicensis O1 Antigen-Specific Monoclonal Antibody Inhibits Bacterial Motility and Entry into Epithelial Cells

2014 ◽  
Vol 83 (3) ◽  
pp. 876-887 ◽  
Author(s):  
Kristina Schauer ◽  
Angelika Lehner ◽  
Richard Dietrich ◽  
Ina Kleinsteuber ◽  
Rocío Canals ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Epithelial Cells ◽  
Foodborne Pathogen ◽  
Antimicrobial Effect ◽  
Infection Model ◽  
Cell Agglutination ◽  
Content Type ◽  
O Antigen ◽  
Lethal Infection ◽  
Insight Into

Cronobacter turicensisis an opportunistic foodborne pathogen that can cause a rare but sometimes lethal infection in neonates. Little is known about the virulence mechanisms and intracellular lifestyle of this pathogen. In this study, we developed an IgG monoclonal antibody (MAb; MAb 2G4) that specifically recognizes the O1 antigen ofC. turicensiscells. The antilipopolysaccharide antibody bound predominantly monovalently to the O antigen and reduced bacterial growth without causing cell agglutination. Furthermore, binding of the antibody to the O1 antigen ofC. turicensiscells caused a significant reduction of the membrane potential which is required to energize flagellar rotation, accompanied by a decreased flagellum-based motility. These results indicate that binding of IgG to the O antigen ofC. turicensiscauses a direct antimicrobial effect. In addition, this feature of the antibody enabled new insight into the pathogenicity ofC. turicensis. In a tissue culture infection model, pretreatment ofC. turicensiswith MAb 2G4 showed no difference in adhesion to human epithelial cells, whereas invasion of bacteria into Caco-2 cells was significantly inhibited.

Burn-in procedures for a generalized model

2001 ◽  
Vol 38 (02) ◽  
pp. 542-553 ◽  
Author(s):  
Ji Hwan Cha
Keyword(s):  
The Other ◽  
Replacement Policy ◽  
Type I ◽  
Type Ii ◽  
Failure Model ◽  
Minimal Repair ◽  
Optimal Replacement ◽  
Complete Repair ◽  
Optimal Replacement Policy ◽  
Type Of Failure

In this paper two burn-in procedures for a general failure model are considered. There are two types of failure in the general failure model. One is Type I failure (minor failure) which can be removed by a minimal repair or a complete repair and the other is Type II failure (catastrophic failure) which can be removed only by a complete repair. During a burn-in process, with burn-in Procedure I, the failed component is repaired completely regardless of the type of failure, whereas, with burn-in Procedure II, only minimal repair is done for the Type I failure and a complete repair is performed for the Type II failure. In field use, the component is replaced by a new burned-in component at the ‘field use age’ T or at the time of the first Type II failure, whichever occurs first. Under the model, the problems of determining optimal burn-in time and optimal replacement policy are considered. The two burn-in procedures are compared in cases when both the procedures are applicable.

Comparison of Means: An F Test Followed by a Modified Multiple Range Procedure

1979 ◽  
Vol 4 (1) ◽  
pp. 14-23 ◽  
Author(s):  
Juliet Popper Shaffer
Keyword(s):  
Error Control ◽  
Type I Error ◽  
Critical Value ◽  
The Other ◽  
Type I ◽  
F Test ◽  
Range Test

If used only when a preliminary F test yields significance, the usual multiple range procedures can be modified to increase the probability of detecting differences without changing the control of Type I error. The modification consists of a reduction in the critical value when comparing the largest and smallest means. Equivalence of modified and unmodified procedures in error control is demonstrated. The modified procedure is also compared with the alternative of using the unmodified range test without a preliminary F test, and it is shown that each has advantages over the other under some circumstances.

Type I Collagen Biosynthesis by Skin Fibroblasts from Patients with Idiopathic Juvenile Osteoporosis

1995 ◽  
Vol 89 (1) ◽  
pp. 69-73 ◽  
Author(s):  
Andrew E. Pocock ◽  
Martin J. O. Francis ◽  
Roger Smith
Keyword(s):  
Osteogenesis Imperfecta ◽  
Type I Collagen ◽  
The Other ◽  
Type I ◽  
Osteogenesis Imperfecta Type ◽  
Unrelated Control ◽  
Type Iii ◽  
Collagen Peptides ◽  
Idiopathic Juvenile Osteoporosis ◽  
Osteogenesis Imperfecta Type I

1. Skin fibroblast lines were cultured from nine patients who had the features of idiopathic juvenile osteoporosis, six relatives, five unrelated control subjects and three unrelated patients with osteogenesis imperfecta type I. Some patients with idiopathic juvenile osteoporosis were adults whose previous osteoporosis was in remission. Two patients with idiopathic juvenile osteoporosis were siblings and one patient with idiopathic juvenile osteoporosis had a daughter with severe osteogenesis imperfecta (type III). 2. The ratio of type III to type I collagen, synthesized by fibroblasts, was increased in two of the patients with osteogenesis imperfecta type I and in the daughter with osteogenesis imperfecta type III, but was normal in all the other patients with idiopathic juvenile osteoporosis and the other relatives. 3. Radiolabelled collagen was digested by cyanogen bromide and separated on SDS-PAGE. Unreduced collagen peptides migrated normally, except those from both the two siblings with idiopathic juvenile osteoporosis. In these two lines, abnormal migration suggested the presence of collagen I mutations. 4. The secretion of synthesized collagen by these two idiopathic juvenile osteoporosis lines and two others was reduced to only 43–45% as compared with a line from a 13-year-old control subject, which was defined as 100%. The three osteogenesis imperfecta type I lines secreted 18–37%, the other five idiopathic juvenile osteoporosis lines secreted 57–75%, the relatives (including the daughter with severe osteogenesis imperfecta) secreted 49–115% and the controls secreted 69–102%. 5. We conclude that qualitative abnormalities of type I collagen associated with a reduction in total secreted collagen synthesis may occur in a minority of patients with idiopathic juvenile osteoporosis; these patients could represent a subset of patients with this disorder.

scholarly journals sigE facilitates the adaptation of Bordetella bronchiseptica to stress conditions and lethal infection in immunocompromised mice

2012 ◽  
Vol 12 (1) ◽  
pp. 179 ◽  
Author(s):  
Sarah E Barchinger ◽  
Xuqing Zhang ◽  
Sara E Hester ◽  
Maria E Rodriguez ◽  
Eric T Harvill ◽  
...  
Keyword(s):  
Stress Conditions ◽  
Bordetella Bronchiseptica ◽  
Lethal Infection ◽  
Immunocompromised Mice

Psychophysical interactions with a double-slit interference pattern: Exploratory evidence of a causal influence

2021 ◽  
Vol 34 (1) ◽  
pp. 79-88
Author(s):  
Dean Radin ◽  
Helané Wahbeh ◽  
Leena Michel ◽  
Arnaud Delorme
Keyword(s):  
Experimental Data ◽  
Interference Pattern ◽  
Type I Error ◽  
Human Mind ◽  
The Other ◽  
Type I ◽  
Fringe Visibility ◽  
Future Studies ◽  
Before And After ◽  
Double Slit

An experiment we conducted from 2012 to 2013, which had not been previously reported, was designed to explore possible psychophysical effects resulting from the interaction of a human mind with a quantum system. Participants focused their attention toward or away from the slits in a double-slit optical system to see if the interference pattern would be affected. Data were collected from 25 people in individual half-hour sessions; each person repeated the test ten times for a total of 250 planned sessions. “Sham” sessions designed to mimic the experimental sessions without observers present were run immediately before and after as controls. Based on the planned analysis, no evidence for a psychophysical effect was found. Because this experiment differed in two essential ways from similar, previously reported double-slit experiments, two exploratory analyses were developed, one based on a simple spectral analysis of the interference pattern and the other based on fringe visibility. For the experimental data, the outcome supported a pattern of results predicted by a causal psychophysical effect, with the spectral metric resulting in a 3.4 sigma effect (p = 0.0003), and the fringe visibility metric resulting in 7 of 22 fringes tested above 2.3 sigma after adjustment for type I error inflation, with one of those fringes at 4.3 sigma above chance (p = 0.00001). The same analyses applied to the sham data showed uniformly null outcomes. Other analyses exploring the potential that these results were due to mundane artifacts, such as fluctuations in temperature or vibration, showed no evidence of such influences. Future studies using the same protocols and analytical methods will be required to determine if these exploratory results are idiosyncratic or reflect a genuine psychophysical influence.

Candy-Plug Generation II for False Lumen Occlusion in Chronic Aortic Dissection: Feasibility and Early Results

2019 ◽  
Vol 26 (6) ◽  
pp. 782-786 ◽  
Author(s):  
Ahmed Eleshra ◽  
Tilo Kölbel ◽  
Nikolaos Tsilimparis ◽  
Giuseppe Panuccio ◽  
Martin Scheerbaum ◽  
...  
Keyword(s):  
Aortic Dissection ◽  
Clinical Success ◽  
False Lumen ◽  
The Other ◽  
Type I ◽  
Technical Success ◽  
Chronic Aortic Dissection ◽  
Early Results ◽  
Aortic Remodeling

Purpose: To present the early results of false lumen (FL) occlusion in chronic aortic dissection using the Candy-Plug generation II (CP II), which has a self-closing fabric channel that obviates the need for separate occlusion of its center. Materials and Methods: Fourteen consecutive patients (mean age 60±11 years; 10 men) with persistent FL backflow and aneurysm formation at the thoracic segment in chronic aortic dissection underwent thoracic endovascular aortic repair (TEVAR) with FL occlusion using the refined CP II. Primary endpoints were technical success (successful deployment) and clinical success (no FL backflow at the CP II level). Secondary endpoints included 30-day mortality and morbidity and aortic remodeling during follow-up. Results: Technical success was 100%. One patient required additional intraprocedural FL embolization at the CP II level due to persistent FL backflow on final angiography (clinical success 93%), though there was no flow through the CP II center. There were no intraprocedural complications. Immediate complete FL occlusion was achieved in 12 patients; the other 2 required reintervention. One had contrast enhancement in the distal FL proximal to the CP II and was treated with coil embolization. The other patient had persistent type I endoleak at the level of the left subclavian artery (LSA) and underwent left carotid–LSA bypass and proximal stent-graft extension. One patient died due to retrograde type A aortic dissection that was not related to CP II placement. Over a mean 8-month follow-up (range 3–12), 9 patients had computed tomography angiography; 8 patients had evidence of aortic remodeling, while 1 aneurysm sac was stable. Conclusion: The CP II reduces the number of procedural steps and offers good seal, with minimal morbidity and mortality and a high rate of aortic remodeling.

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