scholarly journals Functional analysis of Toxoplasma lactate dehydrogenases suggests critical roles of lactate fermentation for parasite growth in vivo

2017 ◽  
Vol 20 (1) ◽  
pp. e12794 ◽  
Author(s):  
Ningbo Xia ◽  
Jichao Yang ◽  
Shu Ye ◽  
Lihong Zhang ◽  
Yanqin Zhou ◽  
...  
2011 ◽  
Vol 82 (3) ◽  
pp. 591-601 ◽  
Author(s):  
Marc Valls ◽  
Rafael Silva-Rocha ◽  
Ildefonso Cases ◽  
Amalia Muñoz ◽  
Víctor de Lorenzo

2008 ◽  
Vol 36 (5) ◽  
pp. 868-873 ◽  
Author(s):  
Ana Talamillo ◽  
Jonatan Sánchez ◽  
Rosa Barrio

SUMOylation, a reversible process used as a ‘fine-tuning’ mechanism to regulate the role of multiple proteins, is conserved throughout evolution. This post-translational modification affects several cellular processes by the modulation of subcellular localization, activity or stability of a variety of substrates. A growing number of proteins have been identified as targets for SUMOylation, although, for many of them, the role of SUMO conjugation on their function is unknown. The use of model systems might facilitate the study of SUMOylation implications in vivo. In the present paper, we have compiled what is known about SUMOylation in Drosophila melanogaster, where the use of genetics provides new insights on SUMOylation's biological roles.


2019 ◽  
Author(s):  
Francisco Cai ◽  
Tiffany M. DeSimone ◽  
Elsa Hansen ◽  
Cameron V. Jennings ◽  
Amy K. Bei ◽  
...  

AbstractThe growth of the malaria parasitePlasmodium falciparumin human blood causes all clinical manifestations of malaria, a process that begins with the invasion of red blood cells. Parasites enter red blood cells using distinct pairs of parasite ligands and host receptors that define particular invasion pathways. Parasite strains have the capacity to switch between invasion pathways. This flexibility is thought to facilitate immune evasion against particular parasite ligands, but may also reflect the fact that red blood cell surfaces are dynamic and composed of heterogeneous invasion targets. Different host genetic backgrounds affecting red blood cell structure have long been recognized to impact parasite growthin vivo, but even within a host, red blood cells undergo dramatic changes in morphology and receptor density as they age. The consequences of these heterogeneities for parasite growthin vivoremain unclear. Here, we measured the ability of laboratory strains ofP. falciparumrelying on distinct invasion pathways to enter red blood cells of different ages. We estimated invasion efficiency while accounting for the fact that even if the red blood cells display the appropriate receptors, not all are physically accessible to invading parasites. This approach revealed a tradeoff made by parasites between the fraction of susceptible cells and their invasion rate into them. We were able to distinguish between “specialist” strains exhibiting high invasion rate in fewer cells versus “generalist” strains invading less efficiently into a larger fraction of cells. We developed a mathematical model to predict that infection with a generalist strain would lead to higher peak parasitemiasin vivowhen compared with a specialist strain with similar overall proliferation rate. Thus, the heterogeneous ecology of red blood cells may play a key role in determining the rate of parasite proliferation between different strains ofP. falciparum.


2011 ◽  
Vol 124 (11) ◽  
pp. 1844-1856 ◽  
Author(s):  
S. J. Ellis ◽  
M. Pines ◽  
M. J. Fairchild ◽  
G. Tanentzapf

1998 ◽  
Vol 18 (8) ◽  
pp. 4679-4688 ◽  
Author(s):  
Deok Ryong Kim ◽  
Marjorie A. Oettinger

ABSTRACT V(D)J recombination in vivo requires a pair of signals with distinct spacer elements of 12 and 23 bp that separate conserved heptamer and nonamer motifs. Cleavage in vitro by the RAG1 and RAG2 proteins can occur at individual signals when the reaction buffer contains Mn2+, but cleavage is restricted to substrates containing two signals when Mg2+ is the divalent cation. By using a novel V(D)J cleavage substrate, we show that while the RAG proteins alone establish a moderate preference for a 12/23 pair versus a 12/12 pair, a much stricter dependence of cleavage on the 12/23 signal pair is produced by the inclusion of HMG1 and competitor double-stranded DNA. The competitor DNA serves to inhibit the cleavage of substrates carrying a 12/12 or 23/23 pair, as well as the cutting at individual signals in 12/23 substrates. We show that a 23/33 pair is more efficiently recombined than a 12/33 pair, suggesting that the 12/23 rule can be generalized to a requirement for spacers that differ from each other by a single helical turn. Furthermore, we suggest that a fixed spatial orientation of signals is required for cleavage. In general, the same signal variants that can be cleaved singly can function under conditions in which a signal pair is required. However, a chemically modified substrate with one noncleavable signal enables us to show that formation of a functional cleavage complex is mechanistically separable from the cleavage reaction itself and that although cleavage requires a pair of signals, cutting does not have to occur simultaneously at both. The implications of these results are discussed with respect to the mechanism of V(D)J recombination and the generation of chromosomal translocations.


PLoS ONE ◽  
2019 ◽  
Vol 14 (4) ◽  
pp. e0215960 ◽  
Author(s):  
Santosh K. Srivastava ◽  
Kelcey S. King ◽  
Nader F. AbuSara ◽  
Chelsea J. Malayny ◽  
Brandon M. Piercey ◽  
...  

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