scholarly journals In Vitro Activities of MMV Malaria Box Compounds against the Apicomplexan Parasite Neospora caninum, the Causative Agent of Neosporosis in Animals

Molecules ◽  
2020 ◽  
Vol 25 (6) ◽  
pp. 1460
Author(s):  
Joachim Müller ◽  
Pablo A. Winzer ◽  
Kirandeep Samby ◽  
Andrew Hemphill

(1) Background: Neospora caninum is a major cause of abortion in cattle and represents a veterinary health problem of great economic significance. In order to identify novel chemotherapeutic agents for the treatment of neosporosis, the Medicines for Malaria Venture (MMV) Malaria Box, a unique collection of anti-malarial compounds, were screened against N. caninum tachyzoites, and the most efficient compounds were characterized in more detail. (2) Methods: A N. caninum beta-galactosidase reporter strain grown in human foreskin fibroblasts was treated with 390 compounds from the MMV Malaria Box. The IC50s of nine compounds were determined, all of which had been previously been shown to be active against another apicomplexan parasite, Theileria annulata. The effects of three of these compounds on the ultrastructure of N. caninum tachyzoites were further investigated by transmission electron microscopy at different timepoints after initiation of drug treatment. (3) Results: Five MMV Malaria Box compounds exhibited promising IC50s below 0.2 µM. The compound with the lowest IC50, namely 25 nM, was MMV665941. This compound and two others, MMV665807 and MMV009085, specifically induced distinct alterations in the tachyzoites. More specifically, aberrant structural changes were first observed in the parasite mitochondrion, and subsequently progressed to other cytoplasmic compartments of the tachyzoites. The pharmacokinetic (PK) data obtained in mice suggest that treatment with MMV665941 could be potentially useful for further in vivo studies. (4) Conclusions: We have identified five novel compounds with promising activities against N. caninum, the effects of three of these compounds were studies by transmission electron microscopy (TEM). Their modes of action are unknown and require further investigation.

Author(s):  
Ann M. Thomas ◽  
Virginia Shemeley

Those samples which swell rapidly when exposed to water are, at best, difficult to section for transmission electron microscopy. Some materials literally burst out of the embedding block with the first pass by the knife, and even the most rapid cutting cycle produces sections of limited value. Many ion exchange resins swell in water; some undergo irreversible structural changes when dried. We developed our embedding procedure to handle this type of sample, but it should be applicable to many materials that present similar sectioning difficulties.The purpose of our embedding procedure is to build up a cross-linking network throughout the sample, while it is in a water swollen state. Our procedure was suggested to us by the work of Rosenberg, where he mentioned the formation of a tridimensional structure by the polymerization of the GMA biproduct, triglycol dimethacrylate.


Zootaxa ◽  
2018 ◽  
Vol 4521 (1) ◽  
pp. 145
Author(s):  
URFA BIN TAHIR ◽  
DENG QIONG ◽  
WANG ZHE ◽  
LI SEN ◽  
LIU YANG ◽  
...  

Tokophrya species are either free-living or facultative ectosymbiotic suctorians associated with copepods, isopods, mysids, decapods and amphipods. Tokophrya huangmeiensis in particular is found to be epizoic with the redclaw crayfish Cherax quadricarinatus Von Martens, 1868, which has been observed as part of an ongoing investigation of freshwater ciliates biodiversity in Huanggang, Hubei, China (Tahir et al. 2017). This first study on T. huangmeiensis based on morphological features using light microscopy and small subunit ribosomal DNA sequence (Tahir et al. 2017), suggested that more detailed descriptions on the physiological and structural changes of this species should be done. Thus, in this study, we looked at the ultrastructures of T. huangmeiensis using electron microscopy, including both scanning (SEM) and transmission electron microscopy (TEM). 


2013 ◽  
Vol 57 (11) ◽  
pp. 5747-5754 ◽  
Author(s):  
Fabienne Barna ◽  
Karim Debache ◽  
Carsten A. Vock ◽  
Tatiana Küster ◽  
Andrew Hemphill

ABSTRACTUpon the screening of 16 antiproliferative compounds againstToxoplasma gondiiandNeospora caninum, two hydrolytically stable ruthenium complexes (compounds 16 and 18) exhibited 50% inhibitory concentrations of 18.7 and 41.1 nM (T. gondii) and 6.7 and 11.3 nM (N. caninum). To achieve parasiticidal activity with compound 16, long-term treatment (22 to 27 days at 80 to 160 nM) was required. Transmission electron microscopy demonstrated the rapid impact on and ultrastructural alterations in both parasites. These preliminary findings suggest that the potential of ruthenium-based compounds should thus be further exploited.


1996 ◽  
Vol 11 (12) ◽  
pp. 3146-3151 ◽  
Author(s):  
E. Czerwosz ◽  
P. Byszewski ◽  
R. Diduszko ◽  
H. Wronka ◽  
P. Dluźewski ◽  
...  

C60/C70: Ni films with 1.5 wt. % Ni concentration obtained by vacuum deposition under different thermal conditions have been investigated. The structural changes of the layers were investigated by transmission electron microscopy, electron and x-ray diffraction, and Raman spectroscopy. The polycrystalline structure was detected for the layers grown at approximately 450 K on the substrate. At elevated temperature and maintained temperature gradient on the substrate during the process, the changes of the layer's structure and the formation of Ni microcrystals were observed. The Ni microcrystals (5–10 nm in the diameter) and the elongated shapes dimensioned 10 × 150 nm were perceived.


1987 ◽  
Vol 103 ◽  
Author(s):  
W. M. Stobbs

ABSTRACTT.E.M. methods are described for the quantitative characterisation of the compositional and structural changes at interfaces and in homo- and hetero-phase multilayer structures. Many of the newer approaches described including the Fresnel and Centre Stop Dark Field Imaging Methods were developed specifically for such characterisations. The range of applications of each of the techniques is assessed as is the importance of delineating the limiting effects of inelastic and inelastic/elastic multiple scattering.


Blood ◽  
2004 ◽  
Vol 104 (13) ◽  
pp. 3979-3985 ◽  
Author(s):  
Rustem I. Litvinov ◽  
Chandrasekaran Nagaswami ◽  
Gaston Vilaire ◽  
Henry Shuman ◽  
Joel S. Bennett ◽  
...  

Abstract The divalent cation Mn2+ and the reducing agent dithiothreitol directly shift integrins from their inactive to their active states. We used transmission electron microscopy and laser tweezers-based force spectroscopy to determine whether structural rearrangements induced by these agents in the integrin αIIbβ3 correlate with its ability to bind fibrinogen. Mn2+ increased the probability of specific fibrinogen-αIIbβ3 interactions nearly 20-fold in platelets, and both Mn2+ and dithiothreitol increased the probability more than 2-fold using purified proteins. Of 3 αIIbβ3 conformations, closed with stalks touching, open with stalks separated, and globular without visible stalks, Mn2+ and dithiothreitol induced a significant increase in the proportion of open structures, as well as structural changes in the αIIbβ3 headpiece. Mn2+ also increased the number of complexes between fibrinogen and purified αIIbβ3 molecules, all of which were in the open conformation. Finally, Mn2+ induced the formation of αIIbβ3 clusters that resulted from interactions exclusively involving the distal ends of the stalks. These results indicate that there is a direct correlation between αIIbβ3 activation and the overall conformation of the molecule. Further, they are consistent with the presence of a linked equilibrium between single inactive and single active αIIbβ3 molecules and active αIIbβ3 clusters. (Blood. 2004;104:3979-3985)


2016 ◽  
Vol 24 (1) ◽  
pp. 24-29 ◽  
Author(s):  
Xiao Feng Zhang

Abstract: Hitachi Lab-in-Gap transmission electron microscopy (TEM) technologies are introduced. The term Lab-in-Gap refers to a special function that allows in situ and in operando TEM studies of materials in gas or liquid environments while stimulations, such as thermal or electrical fields, are applied to the specimen sitting in the pole piece gap in a TEM system. Physical or chemical process can be activated and imaged in real time using TEM or other imaging modes. The new generation environmental TEM platform with large pole piece gap and advanced aberration correctors opens wide possibilities for integrating multiple stimuli sources as well as large-area, sub-Å resolution live imaging for dynamic structural changes.


2002 ◽  
Vol 17 (2) ◽  
pp. 479-486 ◽  
Author(s):  
T. Gorelik ◽  
U. Kaiser ◽  
Ch. Schubert ◽  
W. Wesch ◽  
U. Glatzel

Hexagonal 6H– and 4H–SiC wafers were implanted with (1−1.5) × 1016 cm−2 germanium ions at room temperature and at 700 °C with subsequent annealing between 1000 and 1600 °C. Structural changes in the SiC matrix were studied in detail by means of transmission electron microscopy (TEM). After implantation at room temperature the hexagonal SiC matrix becomes amorphous and, after annealing, recrystallizes into cubic SiC. The latter process was accompanied by the creation of voids and cracks. In case of high-temperature (700 °C) implantation, where amorphization was avoided, no polytype change in as-implanted and annealed SiC wafers was observed. In annealed samples nanocrystalline precipitates with high Ge content were observed in high-resolution TEM images.


Sign in / Sign up

Export Citation Format

Share Document