scholarly journals Metabolic selection of a homologous recombination mediated loss of glycosomal fumarate reductase in Trypanosoma brucei

2020 ◽  
Author(s):  
Marion Wargnies ◽  
Nicolas Plazolles ◽  
Robin Schenk ◽  
Oriana Villafraz ◽  
Jean-William Dupuy ◽  
...  

AbstractThe genome of trypanosomatids is rearranged at the level of repeated sequences, where serve as platforms for amplification or deletion of genomic segments. We report here that the PEPCK gene knockout (Δpepck) leads to the selection of such a deletion event between the FRDg and FRDm2 genes to produce a chimeric FRDg-m2 gene in the Δpepck* cell line. FRDg is expressed in peroxisome-like organelles, named glycosomes, expression of FRDm2 has not been detected to date, and FRDg-m2 is a non-functional cytosolic FRD. Re-expression of FRDg significantly impaired growth of the Δpepck* cells, while inhibition of FRDg-m2 expression had no effect, which indicated that this recombination event has been selected in the Δpepck* cells to eliminate FRDg. FRD activity was not involved in the FRDg-mediated negative effect, while its auto-flavinylation motif is required to impair growth. Considering that (i) FRDs are known to generate reactive oxygen species (ROS) by transferring electrons from their flavin moiety(ies) to oxygen, (ii) intracellular ROS production is essential for the differentiation of procyclic to epimastigote forms of the parasite and (iii) the fumarate reductase activity is not essential for the parasite, we propose that the main role of FRD is to produce part of the ROS necessary to complete the parasitic cycle in the tsetse fly. In this context, the negative effect of FRDg expression in the PEPCK null background is interpreted as an increased production of ROS from oxygen since fumarate, the natural electron acceptor of FRDg, is no longer produced in glycosomes.

Hematology ◽  
2019 ◽  
Vol 2019 (1) ◽  
pp. 532-538 ◽  
Author(s):  
Katharina Fleischhauer

Abstract Matched unrelated donors (URD) are the most frequent source of stem cells for allogeneic hematopoietic cell transplantation (HCT) to date, with HCT performed mainly under conventional immunosuppression by methotrexate and cyclosporine. In this setting, every single allelic donor–recipient mismatch for HLA-A, -B, -C, -DRB1 (8/8), but not for HLA-DQB1, -DPB1, has a significant negative effect on overall survival (OS). When several 8/8 HLA-matched URD are available, donor age is the most important factor impacting OS. Moving forward from the traditional way of counting the number of donor–recipient HLA allele mismatches to biology-driven algorithms for functional matching has led to the unraveling of an association between permissive, low-risk HLA-DPB1 mismatches and improved outcome after URD HCT for malignant disease but not for nonmalignant disease. Functional HLA matching might prove to have increasing importance for URD selection in the era of new immunosuppressive regimens that have the potential to substantially reshuffle the role of HLA mismatches in URD HCT.


2007 ◽  
Vol 85 (4) ◽  
pp. 463-476 ◽  
Author(s):  
J. Adam Hall ◽  
Philippe T. Georgel

Chromodomain/helicase/DNA-binding domain (CHD) proteins have been identified in a variety of organisms. Despite common features, such as their chromodomain and helicase domain, they have been described as having multiple roles and interacting partners. However, a common theme for the main role of CHD proteins appears to be linked to their ATP-dependent chromatin-remodeling activity. Their actual activity as either repressor or activator, and their cell or gene specificity, is connected to their interacting partner(s). In this minireview, we attempt to match the members of the CHD family with the presence of structural domains, cofactors, and cellular roles in the regulation of gene expression, recombination, genome organization, and chromatin structure, as well as their potential activity in RNA processing.


2012 ◽  
Vol 57 (1) ◽  
pp. 45-52 ◽  
Author(s):  
T. Węgrzyn ◽  
R. Wieszała

Significant Alloy Elements in Welded Steel Structures of Car Body Structure, safety and exploitation conditions of welding steel in car body depend on many factors. The main role of that conditions is connected with car body material, welding technology, state of stress and temperature. Because of that, a good selection of steel and welding method is very important for proper steel structure. Low alloy steel is used for car body structure, very often with small amount of carbon and the amount of alloy elements such as Ni, Mn, Mo, Cr and V in car body and welded joints. Depending on the kind of steel which is used, a proper welding method and adequate filler materials should be applied. The present paper describes the influence of Mn, Ni, Mo, Cr, V in WMD (Weld Metal Deposit) on the behaviour of steel structure especially for low temperature service.


Author(s):  
Ayşe Gürsoy ◽  
Nazlı Türkmen

Cheese ripening involves highly complex biochemical events. Coagulant enzymes as well as the utilized starters play an important role in these events. Two types of starters are used: primary and secondary. The main role of the primary culture, which consists of lactic acid bacteria, is to carry out lactic production during fermentation. They contribute to proteolysis and limited flavor formation with the enzymes they possess. Secondary or adjunct cultures are used to develop the texture and to accelerate the ripening. During the selection of this type of culture, enzyme profiles (i.e., proteolytic and lipolytic activities and their autolyse levels) in cheese are the primary factors to be taken into consideration. Apart from these, the other factors are their positive effects on health, availability, and economy. Adjunct cultures include yeast, molds, and bacteria. Some of the heterofermentative lactobacilli species, in particular weakened strains, are used as adjunct cultures in order to accelerate the ripening and shorten the ripening time in fat-reduced and low-fat cheeses. This chapter explores adjunct cultures in cheese technology.


2003 ◽  
Vol 10 (1-2) ◽  
pp. 107-120 ◽  
Author(s):  
Henk J. Groenewegen

This paper briefly reviews the functional anatomy of the basal ganglia and their relationships with the thalamocortical system. The basal ganglia, including the striatum, pallidum, subthalamic nucleus, and substantia nigra, are involved in a number of parallel, functionally segregated cortical-subcortical circuits. These circuits support a wide range of sensorimotor, cognitive and emotional-motivational brain functions. A main role of the basal ganglia is the learning and selection of the most appropriate motor or behavioral programs. The internal functional organization of the basal ganglia is very well suited for such selection mechanisms, both in development and in adulthood. The question of whether clumsiness may be, at least in part, attributed to dysfunction of the basal ganglia is discussed in the context of the differential, complementary, or interactive roles of the basal ganglia and the cerebellum in the development of motor control.


Author(s):  
Hideo Hayashi ◽  
Yoshikazu Hirai ◽  
John T. Penniston

Spectrin is a membrane associated protein most of which properties have been tentatively elucidated. A main role of the protein has been assumed to give a supporting structure to inside of the membrane. As reported previously, however, the isolated spectrin molecule underwent self assemble to form such as fibrous, meshwork, dispersed or aggregated arrangements depending upon the buffer suspended and was suggested to play an active role in the membrane conformational changes. In this study, the role of spectrin and actin was examined in terms of the molecular arrangements on the erythrocyte membrane surface with correlation to the functional states of the ghosts.Human erythrocyte ghosts were prepared from either freshly drawn or stocked bank blood by the method of Dodge et al with a slight modification as described before. Anti-spectrin antibody was raised against rabbit by injection of purified spectrin and partially purified.


2020 ◽  
Vol 48 (2) ◽  
pp. 429-439 ◽  
Author(s):  
Jorge Gago ◽  
Danilo M. Daloso ◽  
Marc Carriquí ◽  
Miquel Nadal ◽  
Melanie Morales ◽  
...  

Besides stomata, the photosynthetic CO2 pathway also involves the transport of CO2 from the sub-stomatal air spaces inside to the carboxylation sites in the chloroplast stroma, where Rubisco is located. This pathway is far to be a simple and direct way, formed by series of consecutive barriers that the CO2 should cross to be finally assimilated in photosynthesis, known as the mesophyll conductance (gm). Therefore, the gm reflects the pathway through different air, water and biophysical barriers within the leaf tissues and cell structures. Currently, it is known that gm can impose the same level of limitation (or even higher depending of the conditions) to photosynthesis than the wider known stomata or biochemistry. In this mini-review, we are focused on each of the gm determinants to summarize the current knowledge on the mechanisms driving gm from anatomical to metabolic and biochemical perspectives. Special attention deserve the latest studies demonstrating the importance of the molecular mechanisms driving anatomical traits as cell wall and the chloroplast surface exposed to the mesophyll airspaces (Sc/S) that significantly constrain gm. However, even considering these recent discoveries, still is poorly understood the mechanisms about signaling pathways linking the environment a/biotic stressors with gm responses. Thus, considering the main role of gm as a major driver of the CO2 availability at the carboxylation sites, future studies into these aspects will help us to understand photosynthesis responses in a global change framework.


2017 ◽  
Vol 76 (4) ◽  
pp. 145-153 ◽  
Author(s):  
Jana Nikitin ◽  
Alexandra M. Freund

Abstract. Establishing new social relationships is important for mastering developmental transitions in young adulthood. In a 2-year longitudinal study with four measurement occasions (T1: n = 245, T2: n = 96, T3: n = 103, T4: n = 85), we investigated the role of social motives in college students’ mastery of the transition of moving out of the parental home, using loneliness as an indicator of poor adjustment to the transition. Students with strong social approach motivation reported stable and low levels of loneliness. In contrast, students with strong social avoidance motivation reported high levels of loneliness. However, this effect dissipated relatively quickly as most of the young adults adapted to the transition over a period of several weeks. The present study also provides evidence for an interaction between social approach and social avoidance motives: Social approach motives buffered the negative effect on social well-being of social avoidance motives. These results illustrate the importance of social approach and social avoidance motives and their interplay during developmental transitions.


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