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[en] Molecular motors convert chemical energy into mechanical motion and power the transport of material within living cells; the motion of a motor is thought to be influenced by stochastic chemical state transitions of the molecule as well as intramolecular diffusion of one motor head seeking the next binding site. Existing models for the motility of single-headed monomeric motors that map the system to a simplified two-state Brownian ratchet have some predictive power, but in general are unable to elucidate the contributions of different molecular level processes to the overall effective parameters. In this work, we build a detailed molecular level model of monomeric kinesin motility that naturally incorporates conformational changes (power strokes) and biased diffusion. Our results predict that mean velocity is most sensitive to the power stroke size, while run length distribution is sensitive primarily to the strength of the microtubule bias potential with a weak dependence on power stroke that can be tuned by the strength of an applied load. In addition, we demonstrate that motor pairs attached to the same cargo can cooperatively function to increase motility in both the plus- and minus-end directions. These findings illustrate the importance of a detailed mechanochemical model for dissecting the contributions of microscopic parameters to monomeric kinesin dynamics. (paper)
[en] The mechanisms by which cytoskeletal flows and cell-substrate interactions interact to generate cell motion are explored by using a simplified model of the cytoskeleton as a viscous gel containing active stresses. This model yields explicit general results relating cell speed and traction forces to the distributions of active stress and cell-substrate friction. It is found that (i) the cell velocity is given by a function that quantifies the asymmetry of the active-stress distribution, (ii) gradients in cell-substrate friction can induce motion even when the active stresses are symmetrically distributed, (iii) the traction-force dipole is enhanced by protrusive stresses near the cell edges or contractile stresses near the center of the cell and (iv) the cell velocity depends biphasically on the cell-substrate adhesion strength if active stress is enhanced by adhesion. Specific experimental tests of the calculated dependences are proposed.
[en] The Glucocorticoïd-induced leucine zipper (GILZ) protein has profound anti-inflammatory activities in haematopoietic cells. GILZ regulates numerous signal transduction pathways involved in proliferation and survival of normal and neoplastic cells. Here, we have demonstrated the potential of GILZ in alleviating apoptosis induced by ER stress inducers. Whereas the glucocorticoid, dexamethasone, protects from tunicamycin-induced cell death, silencing endogeneous GILZ in dexamethasone-treated cancer cells alter the capacity of glucocorticoids to protect from tunicamycin-mediated apoptosis. Under ER stress conditions, overexpression of GILZ significantly reduced activation of mitochondrial pathway of apoptosis by maintaining Bcl-xl level. GILZ protein affects the UPR signaling shifting the balance towards pro-survival signals as judged by down-regulation of CHOP, ATF4, XBP1s mRNA and increase in GRP78 protein level. Interestingly, GILZ sustains high mitochondrial OXPHOS during ER stress and cytoprotection mediated by GILZ is abolished in cells depleted of mitochondrial DNA, which are OXPHOS-deficient. These findings reveal a new role of GILZ, which acts as a cytoprotector against ER stress through a pathway involving mitochondrial OXPHOS. - Highlights: • GILZ attenuates apoptotic cell death induced by ER stress conditions. • GILZ promotes pro-survival signaling of the UPR. • GILZ overexpression sustains high mitochondrial activity under ER stress. • Mitochondrial OXPHOX is required for GILZ protective effects against ER stress-mediated apoptosis.
[en] Highlights: ► This is the first functional characterization of UQCRB in vivo model. ► Angiogenesis is inhibited with UQCRB loss of function in zebrafish. ► UQCRB is introduced as a prognostic marker for mitochondria- and angiogenesis-related diseases. -- Abstract: As a subunit of mitochondrial complex III, UQCRB plays an important role in complex III stability, electron transport, and cellular oxygen sensing. Herein, we report UQCRB function regarding angiogenesis in vivo with the zebrafish (Danio rerio). UQCRB knockdown inhibited angiogenesis in zebrafish leading to the suppression of VEGF expression. Moreover, the UQCRB-targeting small molecule terpestacin also inhibited angiogenesis and VEGF levels in zebrafish, supporting the role of UQCRB in angiogenesis. Collectively, UQCRB loss of function by either genetic and pharmacological means inhibited angiogenesis, indicating that UQCRB plays a key role in this process and can be a prognostic marker of angiogenesis- and mitochondria-related diseases
[en] Cell migration is important for the function of many eukaryotic cells. Recently the nucleus has been shown to play an important role in cell motility. After giving an overview of cell motility mechanisms we review what is currently known about the mechanical properties of the nucleus and the connections between it and the cytoskeleton. We also discuss connections to the extracellular matrix and mechanotransduction. We identify key physical roles of the nucleus in cell migration. (topical review)
[en] The radiosensitive cell populations, such as resting lymphocytes from thymus, spleen, lymph node and blood, have much smaller nuclei (Vsub(n) (nuclear volume) approx. 20 to 70 μm3) compared to radioresistant G0 cells from non-lymphoid tissues (liver, kidney, brain, heart; Vsub(n) approx. 75 to 2700 μm3). It is suggested that radiation-induced disorganization of nuclear structures and cell pycnosis (interphase death) are promoted in G0 lymphocytes because in normal physiological conditions their nuclei assume a higher degree of chromatin condensation. In contrast, dispersion of chromatin into larger nuclear volumes, such as those of most non-lymphoid G0 cells, may hinder or delay radiation-induced cell death. (author)
[en] Hybridization has been observed in several multi-species genera of mangroves; however, there has been no report on hybridization in Avicennia in the Indo-West Pacific region. In this study, we sequenced 5 low-copy nuclear genes of Avicennia marina, A. rumphiana and 2 individuals of their putative hybrid in the Southeast Asia region to test the hypothesis of natural hybridization between these 2 species. We demonstrated that both putative hybrid individuals possessed two types of sequences at each of the 5 genes, perfectly corresponding to those of A. marina and A. rumphiana, confirming the hybridization between these 2 Avicennia species, and the 2 hybrid individuals are most likely F1 hybrids. Sequencing of the chloroplast trnH-psbA regions indicated that A. marina was the maternal parent of the two hybrid individuals. (author)
[en] This study was conducted to optimize Agrobacterium tumefaciens mediated transformation for Eucalyptus camaldulensis. Transformation was done by using LBA4404 containing binary plasmid pGA482 with uidA (Gus) gene under CamV35S promoter and nptII gene under nos promoter. For optimization, different explants (Cotyledonary leaves, plantlet leaves and hypocotyls of young In vitro plants and calli) with and without preculture were infected with a range of optical densities (O.D.600nm=0.3-0.6). Effect of different concentrations of Acetosyringone, infection time and co-cultivation time on transformation efficiency was evaluated. Confirmation of transformation was done through GUS histochemical staining and through PCR. Callogenesis and regeneration was found fast on MS medium containing 0.5 mg/L NAA and 1.5 mg/L BAP. Highest transformation efficiency was obtained with bacterial suspension of O.D.600nm = 0.5 for non-precultured explants and O.D.600nm=0.3 for precultured explants. (author)
[en] In the most varied areas of human medicine, there is a demand for cryopreserved biological cells. Through the cooling down of cells to temperatures in the range of -80 C down to -196 C, the metabolic processes come to a standstill, so that the cells can be stored for a long time with the maintenance of their vitality. Only through the addition of cryoprotectives, cryoconservation of numerous cells succeeds at technically realizable cooling rates. For the process optimization, the exact accomodation of influencing parameters such as cell type and concentration, protection additive type and composition as well as cooling and heating rate are stringent. (orig.)
[de]In den verschiedensten Bereichen der Humanmedizin besteht Bedarf fuer kryokonservierte biologische Zellen. Durch die Abkuehlung der Zellen auf Temperaturen im Bereich von -80 C bis -196 C kommen die Stoffwechselvorgaenge praktisch zum Stillstand, so dass die Zellen bei Erhalt ihrer Vitalitaet langzeitgelagert werden koennen. Erst durch den Zusatz von Kryoprotektiven gelingt die Kryokonservierung der Zellen in ausreichender Anzahl bei technisch realisierbaren Kuehlraten. Bei der Verfahrensoptimierung ist die genaue Abstimmung der Einflussparameter Zellart und -konzentration, Schutzadditivart und -zusammensetzung sowie Kuehl- und Erwaermungsrate zwingend. (orig.)
[en] Both RhoA/ROCK and Raf-1/CK2 pathway play essential roles in cell proliferation, apoptosis, differentiation, and multiple other common cellular functions. We previously reported that vimentin is responsible for TNF-α-induced cell apoptosis. Herein, we investigated the regulation of RhoA/ROCK and Raf-1/CK2 signaling on vimentin filaments and endothelial apoptosis mediated by TNF-α. Treatment with TNF-α significantly induced the activation of RhoA and ROCK, and the expression of ROCK1. RhoA deficiency could obviously inhibit ROCK activation and ROCK1 expression induced by TNF-α. Both RhoA deficiency and ROCK activity inhibition (Y-27632) greatly inhibited endothelial apoptosis and preserved cell viability in TNF-α-induced human umbilical vein endothelial cells (HUVECs). Also vimentin phosphorylation and the remodeling of vimentin or phospho-vimentin induced by TNF-α were obviously attenuated by RhoA suppression and ROCK inhibition. TNF-α-mediated vimentin cleavage was significantly inhibited by RhoA suppression and ROCK inhibition through decreasing the activation of caspase3 and 8. Furthermore, TNF-α treatment greatly enhanced the activation of Raf-1. Suppression of Raf-1 or CK2 by its inhibitor (GW5074 or TBB) blocked vimentin phosphorylation, remodeling and endothelial apoptosis, and preserved cell viability in TNF-α-induced HUVECs. However, Raf-1 inhibition showed no significant effect on TNF-α-induced ROCK expression and activation, suggesting that the regulation of Raf-1/CK2 signaling on vimentin was independent of ROCK. Taken together, these results indicate that both RhoA/ROCK and Raf-1/CK2 pathway are responsible for TNF-α-mediated endothelial cytotoxicity via regulating vimentin cytoskeleton.