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Clinical Applications of Gene Therapy for Immuno-Deficiencies
Published in Yashwant Pathak, Gene Delivery, 2022
Khushboo Faldu, Sakshi Gurbani, Jigna Shah
WAS, X-linked inheritable PID presents itself as autoimmunity, recurrent infections, tendency to develop lymphoid cancer, macrothrombocytopenia, and severe eczema. WAS gene mutation hinders WAS protein (WASp) which is essential for actin polymerization. Actin is crucial for entire hematopoietic lineages, as it plays an important role in formation of immunological synapse, cell migration, and cytotoxicity [46]. AlloHSCT has provided conservative benefits in WAS, with benefits deteriorating for patients aged more than five years [27]. γRV vectors led to the development of leukemogenesis [47]. A SIN-LV vector utilizing a fragment of endogenous WAS gene promoter, together with fludarabine and busulfan conditioning, is showing promise in clinical trials with patients not requiring Ig-replacement therapy [48]. Yet the platelet counts were below normal, maybe attributed to WASp expression in platelet precursors [49, 50].
Molecular Organization of Entamoeba Histolytica
Published in Roberto R. Kretschmer, Amebiasis: Infection and Disease by Entamoeba histolytica, 2020
Isaura Meza, Haydee K. Torres-Guerrero, Marco A. Meraz
Apparently only one isoform of actin is expressed in trophozoites58 although at least 4 actin genes have been found in the genome.7,8 If the same actin gene is expressed during the cell cycle of E. histolytica is still an unresolved question. The lack of binding to DNAse I is also unexplained as the 5′ end amino acids, described in other actins as involved in the binding, are present in the E. histolytica actin. The regulation of actin polymerization or actin binding proteins is likewise unexplored. In free living amebas such as Acanthamoeba and Dictyostelium, actin binding proteins that nucleate or sever actin filaments have been found.62,63 Meza et al.58 observed that Entamoeba actin polymerization is inhibited at 4°C. This property may explain the rounding and detachment of amebas produced by cooling, but as so far, only actin has been clearly identified in Entamoeba, we need more information about actin-regulating proteins to understand its functioning. In Dictyostelium and other eukaryotic cells, there are besides actin-binding proteins, plasma membrane proteins that bind to actin filaments.64 A coordinated interaction of all these proteins would provide the bases for ameboid movement and plasticity.
Inter- and Intracellular Signaling in Plant Cells with Participation of Neurotransmitters (Biomediators)
Published in Akula Ramakrishna, Victoria V. Roshchina, Neurotransmitters in Plants, 2018
Involvement of contractile components in chemical signal transduction from the cell surface to the organelles was studied using anticontractile agents (Figure 9.5) such as (1) binding with actin of microfilaments—cytochalasin В (an inhibitor of actin polymerization in microfilaments) and phalloidin (binds with actin of microfilaments and hinders its depolymerization) and (2) binding with tubulin-containing microtubules—alkaloids colchicine and vinblastine (inhibitors of tubulin polymerization in microtubules) or taxol (stabilizer of microtubules depolymerization by suppressing that disrupts the normal process of dynamic reorganization of the network of microtubules, which is important for cellular functions at the stage of mitosis and cell cycle interphases). Besides above-mentioned reagents, latrunculins A and B are used as inhibitors of G-actin-polymerization, toxins from marine sponges (for example from genus Latrunculia) or phalloidin, bicyclic heptapeptide from fungi Amanita phalloides, that binds with F-actin and stops is depolymerization (Figure 9.5).
Modelling the role of membrane mechanics in cell adhesion on titanium oxide nanotubes
Published in Computer Methods in Biomechanics and Biomedical Engineering, 2023
Matej Daniel, Kristina Eleršič Filipič, Eva Filová, Tobias Judl, Jaroslav Fojt
It is shown that the bending energy is greater that the adhesion energy for short protrusion (Figure 4C) and during formation of protrusion an energy barrier needs to be overcome to bend and protrude the plasma membrane into TiNTs. Therefore, active cytoskeletal forces driven by actin polymerization are required. High curvature at the protrusion tip induced by TiNT can mediate activation of actin bundles that generate the pushing force. The forces exerted by filopodia have been reported in the range from pN to nN (Leijnse et al. 2015). The magnitude of the force could be estimated from the free energy and the protrusion length in Figure 4C to be around 100 pN for TiNT of diameter 30 nm and length 100 nm. If the protrusion is long, the adhesion force prevalence the bending force and the stable anchoring of cell to the nanostructured surface is formed without active cytoskeletal force.
The molecular basis of platelet biogenesis, activation, aggregation and implications in neurological disorders
Published in International Journal of Neuroscience, 2020
Abhilash Ludhiadch, Abhishek Muralidharan, Renuka Balyan, Anjana Munshi
These interactions of receptor and ligands on platelet surface recruit a signaling cascade that leads to the activation of platelets. For the sake of recognition of receptors by their ligands, change of shape occurs from usual discoidal to spike like filopodia along with the change from non-adhesive to sticky form. Resting platelets have inactive and bent 2+ and a signal which promotes binding of talin to 38]. In resting platelet the microtubules are aligned to the peripheral area (responsible for the discoidal shape) whereas upon activation the microtubules are constricted and changes to a coiled form, giving it a saddle like structure [39]. The actin polymerization leads to the formation of filopodia [38]. Platelet activation affects cytoskeleton system, which adds on to the changed shape. The increased calcium content on activation changes the dynein and kinesin which leads to the sliding of microtubules from marginal area thus aiding the shape change. In contrast to nonactivated platelets, activated platelets changes thier shape in a sequential order upon activation. The cellular shape and filopodia of platelets change in the following order; first filopodia extrusion, blebbing, second filopodia extrusion, shrinkage of cell and detachment [40].
Deletion of the lon gene augments expression of Salmonella Pathogenicity Island (SPI)-1 and metal ion uptake genes leading to the accumulation of bactericidal hydroxyl radicals and host pro-inflammatory cytokine-mediated rapid intracellular clearance
Published in Gut Microbes, 2020
Perumalraja Kirthika, Amal Senevirathne, Vijayakumar Jawalagatti, SungWoo Park, John Hwa Lee
HeLa, HepG2 and Caco-2 cells growing on a coverslip were infected with stress exposed JOL 401, JOL 909, or JOL 909::lon cells at 20 MOI. Uninfected cells at t = 0 were considered as the control. Cells were incubated for 20 min and washed three times with PBS. Slides containing infected cells were fixed with 4% paraformaldehyde for 30 min at room temperature and washed three times with 1X PBS. Cells were permeabilized with 0.01% Triton X-100 in PBS for 10 min at room temperature. After washing, cells were blocked with 5% bovine serum albumin. To stain actin filaments, 100 μL of 1X phalloidin (Abnova, Taiwan) was prepared in 1% BSA and incubated with cells for 1 h in the dark. Nuclear staining was carried out using DAPI (Sigma, CA, USA) and observed under fluorescence microscopy (Leica). The extent of actin polymerization by each ST strain was compared in three independent experiments.