scholarly journals Assessing the functional impact of PfRh5 genetic diversity on ex vivo erythrocyte invasion inhibition

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Adam J. Moore ◽  
Khadidiatou Mangou ◽  
Fatoumata Diallo ◽  
Seynabou D. Sene ◽  
Mariama N. Pouye ◽  
...  

AbstractThe PfRh5-Basigin ligand–receptor interaction is an essential step in the merozoite invasion process and represents an attractive vaccine target. To reveal genotype–phenotype associations between naturally occurring allelic variants of PfRh5 and invasion inhibition, we performed ex vivo invasion inhibition assays with monoclonal antibodies targeting basigin coupled with PfRh5 next-generation amplicon sequencing. We found dose-dependent inhibition of invasion across all isolates tested, and no statistically significant difference in invasion inhibition for any single nucleotide polymorphisms. This study demonstrates that PfRh5 remains highly conserved and functionally essential, even in a highly endemic setting, supporting continued development as a strain-transcendent malaria vaccine target.

2020 ◽  
Author(s):  
Adam J. Moore ◽  
Khadidiatou Mangou ◽  
Fatoumata Diallo ◽  
Seynabou D. Sene ◽  
Mariama N. Pouye ◽  
...  

The PfRh5-Basigin ligand-receptor interaction is an essential step in the merozoite invasion process and represents an attractive vaccine target. To reveal genotype-phenotype associations between naturally occurring allelic variants of PfRh5 and invasion inhibition, we performed ex vivo invasion inhibition assays with monoclonal antibodies targeting basigin coupled with PfRh5 next-generation amplicon sequencing. We found dose-dependent inhibition of invasion across all isolates tested, and no statistically significant difference in invasion inhibition for any single nucleotide polymorphisms. This study demonstrates that PfRh5 remains highly conserved and functionally essential, even in a highly endemic setting, supporting continued development as a strain-transcendent malaria vaccine target.


Reproduction ◽  
2000 ◽  
pp. 15-23 ◽  
Author(s):  
K Jewgenow ◽  
M Rohleder ◽  
I Wegner

Despite many efforts, the control of reproduction in feral cat populations is still a problem in urban regions around the world. Immunocontraception is a promising approach; thus the present study examined the suitability of the widely used pig zona pellucida proteins (pZP) for contraception in feral domestic cats. Purified zona pellucida proteins obtained from pig and cat ovaries were used to produce highly specific antisera in rabbits. Antibodies against pZP raised in rabbits or lions were not effective inhibitors of either in vitro sperm binding (cat spermatozoa to cat oocytes) or in vitro fertilization in cats, whereas antibodies against feline zona pellucida proteins (fZP) raised in rabbits showed a dose-dependent inhibition of in vitro fertilization. Immunoelectrophoresis, ELISA and immunohistology of ovaries confirmed these results, showing crossreactivity of anti-fZP sera to fZP and to a lesser extent to pZP, but no interaction of anti-pZP sera with fZP. It is concluded that cat and pig zonae pellucidae express a very small number of shared antigenic determinants, making the use of pZP vaccine in cats questionable. A contraceptive vaccine based on feline zona pellucida determinants will be a better choice for the control of reproduction in feral cats if immunogenity can be achieved.


Author(s):  
Putthiporn Khongkaew ◽  
Phanphen Wattanaarsakit ◽  
Konstantinos I. Papadopoulos ◽  
Watcharaphong Chaemsawang

Background: Cancer is a noncommunicable disease with increasing incidence and mortality rates both worldwide and in Thailand. Its apparent lack of effective treatments is posing challenging public health issues. Introduction: Encouraging research results indicating probable anti-cancer properties of the Delonix regia flower extract (DRE) have prompted us to evaluate the feasibility of developing a type of product for future cancer prevention or treatment. Methods and Results: In the present report, using High Performance Liquid Chromatography (HPLC), we demonstrate in the DRE, the presence of high concentrations of three identifiable flavonoids, namely rutin 4.15±0.30 % w/w, isoquercitrin 3.04±0.02 %w/w, and myricetin 2.61±0.01 % w/w respectively while the IC50 of DPPH and ABTS assay antioxidation activity was 66.88±6.30 µg/ml and 53.65±7.24 µg/ml respectively. Discussion: Our cancer cell line studies using the MTT assay demonstrated DREs potent and dose dependent inhibition of murine leukemia cell line (P-388: 35.28±4.07% of cell viability remaining), as well as of human breast adenocarcinoma (MCF-7), human cervical carcinoma (HeLa), human oral cavity carcinoma (KB), and human colon carcinoma (HT-29) cell lines in that order of magnitude. Conclusion: Three identifiable flavonoids (rutin, isoquercitrin and myricetin) with high antioxidation activity and potent and dose dependent inhibition of murine leukemia cell line and five other cancer cell lines were documented in the DRE. The extract’s lack of cytotoxicity in 3 normal cell lines is a rare advantage not usually seen in current antineoplastic agents. Yet another challenge of the DRE was its low dissolution rate and long-term storage stability, issues to be resolved before a future product can be formulated.


Author(s):  
Virginia Fuochi ◽  
Massimo Caruso ◽  
Rosalia Emma ◽  
Aldo Stivala ◽  
Riccardo Polosa ◽  
...  

Background: The key ingredients of e-cigarettes liquid are commonly propane-1,2-diol (also called propylene glycol) and propane-1,2,3-triol (vegetal glycerol) and their antimicrobial effects are already established. The nicotine and flavors which are often present in e-liquids can interfere with the growth of some microorganisms. Objective: The effect of the combining these elements in e-liquids is unknown. The aim of the study was to investigate the possible effects of these liquids on bacterial growth in the presence or absence of nicotine and flavors. Methods: Susceptibilities of pathogenic strains (Klebsiella pneumoniae, Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter baumannii, Escherichia coli, Enterococcus faecalis and Sarcina lutea) were studied by means of a multidisciplinary approach. Cell viability and antioxidant assays were also evaluated. Results: All e-liquids investigated showed antibacterial activity against at least one pathogenic strain. A higher activity was correlated to the presence of flavors and nicotine. Discussion: In most cases the value of minimal bactericidal concentration is equal to the value of minimal inhibitory concentration showing that these substances have a bactericidal effect. This effect was observed in concentrations up to 6.25% v/v. Antioxidant activity was also correlated to presence of flavors. Over time, the viability assay in human epithelial lung A549 cells showed a dose-dependent inhibition of cell growth. Conclusion: Our results have shown that flavors considerably enhance the antibacterial activity of propane-1,2-diol and propane-1,2,3-triol. This study provides important evidence that should be taken into consideration in further investigative approaches, to clarify the different sensitivity of the various bacterial species to e-liquids, including the respiratory microbiota, to highlight the possible role of flavors and nicotine.


2020 ◽  
pp. bjophthalmol-2020-317214
Author(s):  
Hasan Naveed ◽  
Fong May Chew ◽  
Hanbin Lee ◽  
Edward Hughes ◽  
Mayank A Nanavaty

PurposeTo assess whether pars plana vitrectomy (PPV) is an aerosol-generating procedure (AGP) in an ex vivo experimental model.MethodsIn this ex vivo study on 10 porcine eyes, optical particle counter was used to measure particles ≤10 μm using cumulative mode in the six in-built channels: 0.3 μm, 0.5 μm, 1 μm, 2.5 μm, 5 μm and 10 μm aerosols during PPV. Two parts of the study were as follows: (1) to assess the pre-experimental baseline aerosol count in the theatre environment where there are dynamic changes in temperature and humidity and (2) to measure aerosol generation with 23-gauge and 25-gauge set-up. For each porcine eye, five measurements were taken for each consecutive step in the experiment including pre-PPV, during PPV, fluid–air exchange (FAX) and venting using a flute with 23-gauge set-up and a chimney with 25-gauge set-up. Therefore, a total of 200 measurements were recorded.ResultsWith 23-gauge and 25-gauge PPV, there was no significant difference in aerosol generation in all six channels comparing pre-PPV versus PPV or pre-PPV versus FAX. Venting using flute with 23-gauge PPV showed significant reduction of aerosol ≤1 μm. Air venting using chimney with 25-gauge set-up showed no significant difference in aerosol of ≤1 μm. For cumulative aerosol counts of all particles measuring ≤5 μm, compared with pre-PPV, PPV or FAX, flute venting in 23-gauge set-up showed significant reduction unlike the same comparison for chimney venting in 25-gauge set-up.ConclusionPPV and its associate steps do not generate aerosols ≤10 μm with 23-gauge and 25-gauge set-ups.


2017 ◽  
Vol 34 (1) ◽  
pp. 8-17 ◽  
Author(s):  
Stephanie Goldschmidt ◽  
Catherine Zimmerman ◽  
Caitlyn Collins ◽  
Scott Hetzel ◽  
Heidi-Lynn Ploeg ◽  
...  

Biomechanical studies of the elongated canine tooth of animals are few, and thus our understanding of mechanical and physical properties of animal teeth is limited. The objective of the present study was to evaluate the influence of force direction on fracture resistance and fracture pattern of canine teeth in an ex vivo dog cadaver model. Forty-five extracted canine teeth from laboratory beagle dogs were standardized by hard tissue volume and randomly distributed among 3 force direction groups. The teeth were secured within a universal testing machine and a load was applied at different directions based on testing group. The maximum force to fracture and the fracture pattern classification were recorded for each tooth. After correcting for hard tissue cross-sectional area in a multivariate analysis, no significant difference in the amount of force required for fracture was apparent between the different force direction groups. However, the influence of force direction on fracture pattern was significant. The results of this study may allow the clinician to educate clients on possible causal force directions in clinically fractured teeth and, thus, help prevent any contributing behavior in the future.


2015 ◽  
Vol 59 (5) ◽  
pp. 2867-2874 ◽  
Author(s):  
Atteneri López-Arencibia ◽  
Daniel García-Velázquez ◽  
Carmen M. Martín-Navarro ◽  
Ines Sifaoui ◽  
María Reyes-Batlle ◽  
...  

ABSTRACTThein vitroactivity of a novel group of compounds, hexaazatrinaphthylene derivatives, against two species ofLeishmaniais described in this study. These compounds showed a significant dose-dependent inhibition effect on the proliferation of the parasites, with 50% inhibitory concentrations (IC50s) ranging from 1.23 to 25.05 μM against the promastigote stage and 0.5 to 0.7 μM against intracellular amastigotes. Also, a cytotoxicity assay was carried out to in order to evaluate the possible toxic effects of these compounds. Moreover, different assays were performed to determine the type of cell death induced after incubation with these compounds. The obtained results highlight the potential use of hexaazatrinaphthylene derivatives againstLeishmaniaspecies, and further studies should be undertaken to establish them as novel leishmanicidal therapeutic agents.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Alan Feiveson ◽  
Kerry George ◽  
Mark Shavers ◽  
Maria Moreno-Villanueva ◽  
Ye Zhang ◽  
...  

AbstractSpace radiation consists of energetic protons and other heavier ions. During the International Space Station program, chromosome aberrations in lymphocytes of astronauts have been analyzed to estimate received biological doses of space radiation. More specifically, pre-flight blood samples were exposed ex vivo to varying doses of gamma rays, while post-flight blood samples were collected shortly and several months after landing. Here, in a study of 43 crew-missions, we investigated whether individual radiosensitivity, as determined by the ex vivo dose–response of the pre-flight chromosome aberration rate (CAR), contributes to the prediction of the post-flight CAR incurred from the radiation exposure during missions. Random-effects Poisson regression was used to estimate subject-specific radiosensitivities from the preflight dose–response data, which were in turn used to predict post-flight CAR and subject-specific relative biological effectiveness (RBEs) between space radiation and gamma radiation. Covariates age, gender were also considered. Results indicate that there is predictive value in background CAR as well as radiosensitivity determined preflight for explaining individual differences in post-flight CAR over and above that which could be explained by BFO dose alone. The in vivo RBE for space radiation was estimated to be approximately 3 relative to the ex vivo dose response to gamma irradiation. In addition, pre-flight radiosensitivity tended to be higher for individuals having a higher background CAR, suggesting that individuals with greater radiosensitivity can be more sensitive to other environmental stressors encountered in daily life. We also noted that both background CAR and radiosensitivity tend to increase with age, although both are highly variable. Finally, we observed no significant difference between the observed CAR shortly after mission and at > 6 months post-mission.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kyung Seok Kim ◽  
Kevin J. Roe

AbstractDetailed information on species delineation and population genetic structure is a prerequisite for designing effective restoration and conservation strategies for imperiled organisms. Phylogenomic and population genomic analyses based on genome-wide double digest restriction-site associated DNA sequencing (ddRAD-Seq) data has identified three allopatric lineages in the North American freshwater mussel genus Cyprogenia. Cyprogenia stegaria is restricted to the Eastern Highlands and displays little genetic structuring within this region. However, two allopatric lineages of C. aberti in the Ozark and Ouachita highlands exhibit substantial levels (mean uncorrected FST = 0.368) of genetic differentiation and each warrants recognition as a distinct evolutionary lineage. Lineages of Cyprogenia in the Ouachita and Ozark highlands are further subdivided reflecting structuring at the level of river systems. Species tree inference and species delimitation in a Bayesian framework using single nucleotide polymorphisms (SNP) data supported results from phylogenetic analyses, and supports three species of Cyprogenia over the currently recognized two species. A comparison of SNPs generated from both destructively and non-destructively collected samples revealed no significant difference in the SNP error rate, quality and amount of ddRAD sequence reads, indicating that nondestructive or trace samples can be effectively utilized to generate SNP data for organisms for which destructive sampling is not permitted.


Author(s):  
W. Leontiev ◽  
E. Magni ◽  
C. Dettwiler ◽  
C. Meller ◽  
R. Weiger ◽  
...  

Abstract Objectives The aim of the present study was to compare the accuracy of the conventional illumination method (CONV) and the fluorescence-aided identification technique (FIT) for distinguishing between composite restorations and intact teeth using different fluorescence-inducing devices commonly used for FIT. Materials and methods Six groups of six dentists equipped with one of six different FIT systems each independently attempted to identify composite restorations and intact teeth on a full-mouth model with 22 composite restorations using CONV and, 1 h later, FIT. The entire procedure was repeated 1 week later. Sensitivity, specificity, and positive (PPV) and negative (NPV) predictive values, including 95% confidence intervals (CI), were calculated for CONV and FIT overall and for each device. The influence of examiner age, method, and device on each parameter was assessed by multivariate analysis of variance. Results The sensitivity (84%, CI 81–86%), specificity (94%, CI 93–96%), PPV (92%, CI 90–94%), and NPV (90%, CI 88–91%) of FIT was significantly higher than that of CONV (47%, CI 44–50%; 82%, CI 79–84%; 66%, CI 62–69%, and 69%, CI 68–71%, respectively; p<0.001). The differences between CONV and FIT were significant for all parameters and FIT systems except VistaCam, which achieved no significant difference in specificity. Examiners younger than 40 years attained significantly higher sensitivity and negative predictive values than older examiners. Conclusions FIT is more reliable for detecting composite restorations than the conventional illumination method. Clinical relevance FIT can be considered an additional or alternative tool for improving the detection of composite restorations.


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