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https://www.readbyqxmd.com/read/28719882/antileishmanial-activity-and-tubulin-polymerization-inhibition-of-podophyllotoxin-derivatives-on-leishmania-infantum
#1
José Miguel Escudero-Martínez, Yolanda Pérez-Pertejo, Rosa M Reguera, María Ángeles Castro, María Victoria Rojo, Carolina Santiago, Andrés Abad, Pablo Anselmo García, José Luis López-Pérez, Arturo San Feliciano, Rafael Balaña-Fouce
Leishmania microtubules play an important role not only in cell division, but also in keeping the shape of the parasite and motility of its free-living stages. Microtubules result from the self-assembly of alpha and beta tubulins, two phylogenetically conserved and very abundant eukaryotic proteins in kinetoplastids. The colchicine binding domain has inspired the discovery and development of several drugs currently in clinical use against parasites. However, this domain is less conserved in kinetoplastids and may be selectively targeted by new compounds...
June 28, 2017: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/28719204/norditerpenoids-and-dinorditerpenoids-from-the-seeds-of-podocarpus-nagi-as-cytotoxic-agents-and-autophagy-inducers
#2
Zhe-Ling Feng, Le-Le Zhang, Yuan-Dong Zheng, Qian-Yu Liu, Jing-Xin Liu, Lu Feng, Li Huang, Qing-Wen Zhang, Jin-Jian Lu, Li-Gen Lin
Nine new norditerpenoids and dinorditerpenoids, 2-oxonagilactone A (1), 7β-hydroxynagilactone D (2), nagilactones K and L (3 and 4), 3β-hydroxynagilactone L (5), 2β-hydroxynagilactone L (6), 3-epi-15-hydroxynagilactone D (7), 1α-chloro-2β,3β,15-trihydroxynagilactone L (8), and 15-hydroxynagilactone L (9), were isolated from the seeds of Podocarpus nagi, along with eight known analogues. The structures of the new compounds were established based on detailed NMR and HRESIMS analysis, as well as from their ECD spectra...
July 18, 2017: Journal of Natural Products
https://www.readbyqxmd.com/read/28718761/the-human-cytoplasmic-dynein-interactome-reveals-novel-activators-of-motility
#3
Willam B Redwine, Morgan E DeSantis, Ian Hollyer, Zaw Min Htet, Phuoc Tien Tran, Selene K Swanson, Laurence Florens, Michael P Washburn, Samara L Reck-Peterson
In human cells, cytoplasmic dynein-1 is essential for long-distance transport of many cargos, including organelles, RNAs, proteins, and viruses, towards microtubule minus ends. To understand how a single motor achieves cargo specificity, we identified the human dynein interactome by attaching a promiscuous biotin ligase ("BioID") to seven components of the dynein machinery, including a subunit of the essential cofactor dynactin. This method reported spatial information about the large cytosolic dynein/dynactin complex in living cells...
July 18, 2017: ELife
https://www.readbyqxmd.com/read/28717875/mast-like-protein-kinase-ireh1-from-arabidopsis-thaliana-co-localizes-with-the-centrosome-when-expressed-in-animal-cells
#4
Elena M Chudinova, Pavel A Karpov, Artem I Fokin, Alla I Yemets, Dmytro I Lytvyn, Elena S Nadezhdina, Yaroslav B Blume
The similarity of IREH1 (Incomplete Root Hair Elongation 1) and animal MAST kinases was confirmed; IREH1cDNA was cloned while expressing in cultured animal cells co-localized with the centrosome. In mammals and fruit flies, microtubule-associated serine/threonine-protein kinases (MAST) are strongly involved in the regulation of the microtubule system. Higher plants also possess protein kinases homologous to MASTs, but their function and interaction with the cytoskeleton remain unclear. Here, we confirmed the sequence and structural similarity of MAST-related putative protein kinase IREH1 (At3g17850) and known animal MAST kinases...
July 17, 2017: Planta
https://www.readbyqxmd.com/read/28716960/bacterial-tubulin-a-b-exhibit-polarized-growth-mixed-polarity-bundling-and-destabilization-by-gtp-hydrolysis
#5
César Díaz-Celis, Viviana I Risca, Felipe Hurtado, Jessica K Polka, Scott D Hansen, Daniel Maturana, Rosalba Lagos, R Dyche Mullins, Octavio Monasterio
Bacteria of the genus Prosthecobacter express homologs of eukaryotic α- and β-tubulin, called BtubA and BtubB, that have been observed to assemble into filaments in presence of GTP. BtubA/B polymers are proposed to be composed in vitro by two to six protofilaments, in contrast to in vivo where they have been reported to form 5-protofilaments tubes named bacterial microtubules (bMTs). The btubAB genes likely entered the Prosthecobacter lineage via horizontal gene transfer and may derive from an early ancestor of the modern eukaryotic microtubule (MT)...
July 17, 2017: Journal of Bacteriology
https://www.readbyqxmd.com/read/28716728/cytochrome-p450-3a-selectively-affects-the-pharmacokinetic-interaction-between-erlotinib-and-docetaxel-in-rats
#6
Xuan Qin, Jian Lu, Peili Wang, Peipei Xu, Mingyao Liu, Xin Wang
Erlotinib as a first-line drug is used in non-small cell lung cancer (NSCLC) patients with sensitive EGFR mutations, while resistance to this drug will occur after several years of treatment. Therefore, the microtubule disturber docetaxel is introduced as combined regimen in clinical trials. This report investigated the potentials and mechanisms of drug-drug interaction (DDI) between erlotinib and docetaxel using wild type (WT) and Cyp3a1/2 knockout (KO) rats. The erlotinib O-demethylation and docetaxel hydroxylation reactions in the absence or the presence of another drug were analyzed in vitro via the assay of rat liver microsomes...
July 14, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28714031/effects-of-neuritin-on-the-differentiation-of-bone-marrow%C3%A2-derived-mesenchymal-stem-cells-into-neuron%C3%A2-like-cells
#7
Jingling Zhu, Pingping Meng, Qian Wang, Haiyan Wang, Jinli Zhang, Yuanyuan Li, Dongzheng Li, Xiaohua Tan, Lei Yang, Jin Huang
While the neurotrophic factor neuritin is known to be involved in neurodevelopment, the effects of this compound on cell differentiation remain unclear. The present study demonstrated that neuritin treatment induced the differentiation of rat bone marrow‑derived mesenchymal stem cells (rBM‑MSCs) into neuron‑like (NL) cells. For these analyses, rBM‑MSCs were incubated with 0.5 µg/ml neuritin for 24 h. Following induction, 27% of the rBM‑MSCs exhibited typical NL cell morphologies. Subsequently, NL cells were characterized by examining the expression of neuronal markers and by analysis of cell functions...
July 14, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28713934/upregulation-of-connexin-43-and-apoptosis%C3%A2-associated-protein-expression-by-high-glucose-in-h9c2-cells-was-improved-by-resveratrol-via-the-autophagy-signaling-pathway
#8
Guang-Yu Wang, Ya-Guang Bi, Xiang-Dong Liu, Jun-Feng Han, Meng Wei, Qing-Yong Zhang
The expression of connexin43 (Cx43) protein and the apoptotic rate of cardiomyocytes may be regulated by autophagy and associated with diabetic cardiomyopathy. It is possible that the beneficial effect of resveratrol on diabetic cardiomyocytes occurs via the autophagy pathway. However, it remains to be elucidated whether resveratrol treatment may attenuate the hyperglycemia‑induced remodeling of Cx43 and apoptosis through the regulation of autophagy. H9c2 cardiac cells were incubated with 5.5 and 25 mM glucose, 25 mM glucose with chloroquine (50 µM), and 25 mM glucose with or without resveratrol (10, 25 µM) for 24 h...
July 12, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28713614/condition-medium-of-cerebrospinal-fluid-and-retinoic-acid-induces-the-transdifferentiation-of-human-dental-pulp-stem-cells-into-neuroglia-and-neural-like-cells
#9
Sara Haratizadeh, Maryam Nazm Bojnordi, Shahram Darabi, Narges Karimi, Mehrdad Naghikhani, Hatef Ghasemi Hamidabadi, Morteza Seifi
Cerebrospinal fluid (CSF) contains several molecules which are essential for neurogenesis. Human dental pulp stem cells (hDPSCs) are putatively neural crest cell-derived that can differentiate into neurons and glial cells under appropriate neurotrophic factors. The aim of this study was to induce differentiation of hDPSCs into neuroglial phenotypes using retinoic acid (RA) and CSF. The hDPSCs from an impacted third molar were isolated by mechanical and digestion and cultured. The cells have treated by 10(-7) µM RA (RA group) for 8 days, 10% CSF (CSF group) for 8 days and RA with CSF for 8 days (RA/CSF group)...
June 2017: Anatomy & Cell Biology
https://www.readbyqxmd.com/read/28713242/the-distance-between-n-and-c-termini-of-tau-and-of-ftdp-17-mutants-is-modulated-by-microtubule-interactions-in-living-cells
#10
Cristina Di Primio, Valentina Quercioli, Giacomo Siano, Matteo Rovere, Branislav Kovacech, Michal Novak, Antonino Cattaneo
The microtubule (MT)-associated protein Tau is a natively unfolded protein, involved in a number of neurodegenerative disorders, collectively called tauopathies, aggregating in neurofibrillary tangles (NFT). It is an open question how the conversion from a MT bound molecule to an aggregation-prone Tau species occurs and, also, if and how tauopathy-related mutations affect its behavior in the cell. To address these points, we exploited a genetically encoded FRET sensor based on the full length Tau protein, to monitor in real time Tau conformational changes in different conditions in live cells...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28711300/raft-dependent-endocytic-movement-and-intracellular-cluster-formation-during-t%C3%A2-cell-activation-triggered-by-concanavalin-a
#11
Satomi Yabuuchi, Satoshi Endo, KeangOk Baek, Kunihide Hoshino, Yoshio Tsujino, Mun'delanji C Vestergaard, Masahiro Takagi
Certain food ingredients can stimulate the human immune system. A lectin, concanavalin A (ConA), from Canavalia ensiformis (jack bean) is one of the most well-known food-derived immunostimulants and mediates activation of cell-mediated immunity through T cell proliferation. Generally, T cell activation is known to be triggered by the interaction between T cells and antigen-presenting cells (APCs) via a juxtacrine (contact-dependent) signaling pathway. The mechanism has been well characterized and is referred to as formation of the immunological synapse (IS)...
July 12, 2017: Journal of Bioscience and Bioengineering
https://www.readbyqxmd.com/read/28710795/phospholipase-d-%C3%AE-negatively-regulates-plant-thermotolerance-by-destabilizing-cortical-microtubules-in-arabidopsis
#12
Qun Zhang, Ping Song, Yana Qu, Peipei Wang, Qianru Jia, Liang Guo, Chuanpeng Zhang, Tonglin Mao, Ming Yuan, Xuemin Wang, Wenhua Zhang
The pattern of cortical microtubule arrays plays an important role in plant growth and adaptation in response to hormonal and environmental changes. Cortical microtubules are connected with the plasma membrane (PM); however, how the membrane affects cortical microtubule organization is not well understood. Here, we showed that phospholipase Dδ (PLDδ) was associated with the PM and co-localized with microtubules in cells. In vitro analysis revealed that PLDδ bound to microtubules, resulting in microtubule disorganization...
July 14, 2017: Plant, Cell & Environment
https://www.readbyqxmd.com/read/28710464/analysis-of-mitochondrial-organization-and-function-in-the-drosophila-blastoderm-embryo
#13
Sayali Chowdhary, Darshika Tomer, Dnyanesh Dubal, Devashree Sambre, Richa Rikhy
Mitochondria are inherited maternally as globular and immature organelles in metazoan embryos. We have used the Drosophila blastoderm embryo to characterize their morphology, distribution and functions in embryogenesis. We find that mitochondria are relatively small, dispersed and distinctly distributed along the apico-basal axis in proximity to microtubules by motor protein transport. Live imaging, photobleaching and photoactivation analyses of mitochondrially targeted GFP show that they are mobile in the apico-basal axis along microtubules and are immobile in the lateral plane thereby associating with one syncytial cell...
July 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28709975/buckling-analysis-of-orthotropic-protein-microtubules-under-axial-and-radial-compression-based-on-couple-stress-theory
#14
Yaghoub Tadi Beni, M Karimi Zeverdejani, F Mehralian
Protein microtubules (MTs) are one of the important intercellular components and have a vital role in the stability and strength of the cells. Due to applied external loads, protein microtubules may be involved buckling phenomenon. Due to impact of protein microtubules in cell reactions, it is important to determine their critical buckling load. Considering nature of protein microtubules, various parameters are effective on microtubules buckling. The small size of microtubules and also lack of uniformity of MTs properties in different directions caused the necessity of accuracy in the analysis of these bio-structure...
July 11, 2017: Mathematical Biosciences
https://www.readbyqxmd.com/read/28709747/interaction-of-the-innate-immune-system-with-positive-strand-rna-virus-replication-organelles
#15
Enzo Maxim Scutigliani, Marjolein Kikkert
The potential health risks associated with (re-)emerging positive-strand RNA (+RNA) viruses emphasizes the need for understanding host-pathogen interactions for these viruses. The innate immune system forms the first line of defense against pathogenic organisms like these and is responsible for detecting pathogen-associated molecular patterns (PAMPs). Viral RNA is a potent inducer of antiviral innate immune signaling, provoking an antiviral state by directing expression of interferons (IFNs) and pro-inflammatory cytokines...
June 27, 2017: Cytokine & Growth Factor Reviews
https://www.readbyqxmd.com/read/28707901/toward-chemically-resolved-computer-simulations-of-dynamics-and-remodeling-of-biological-membranes
#16
Thereza A Soares, Stefano Vanni, Giuseppe Milano, Michele Cascella
Cellular membranes are fundamental constituents of living organisms. Apart from defining the boundaries of the cells, they are involved in a wide range of biological functions, associated to both their structural and the dynamical properties. Bio-membranes can undergo large-scale transformations when subject to specific environmental changes, including gel-liquid phase transitions, change of aggregation structure, formation of microtubules, or rupture into vesicles. All these processes are dependent on a delicate interplay between intermolecular forces, molecular crowding, and entropy, and their understanding requires approaches that are able to capture and rationalize the details of all the involved interactions...
July 14, 2017: Journal of Physical Chemistry Letters
https://www.readbyqxmd.com/read/28707220/application-of-quasi-steady-state-methods-to-nonlinear-models-of-intracellular-transport-by-molecular-motors
#17
Cole Zmurchok, Tim Small, Michael J Ward, Leah Edelstein-Keshet
Molecular motors such as kinesin and dynein are responsible for transporting material along microtubule networks in cells. In many contexts, motor dynamics can be modelled by a system of reaction-advection-diffusion partial differential equations (PDEs). Recently, quasi-steady-state (QSS) methods have been applied to models with linear reactions to approximate the behaviour of the full PDE system. Here, we extend this QSS reduction methodology to certain nonlinear reaction models. The QSS method relies on the assumption that the nonlinear binding and unbinding interactions of the cellular motors occur on a faster timescale than the spatial diffusion and advection processes...
July 13, 2017: Bulletin of Mathematical Biology
https://www.readbyqxmd.com/read/28706219/high-temperature-induced-production-of-unreduced-pollen-and-its-cytological-effects-in-populus
#18
Jun Wang, Daili Li, Fengnan Shang, Xiangyang Kang
Temperature change is of potential to trigger the formation of unreduced gametes. In this study, we showed that short periods of high temperature treatment can induce the production of 2n pollen in Populus pseudo-simonii Kitag. The meiotic stage, duration of treatment, and temperature have significant effects on the induction of 2n pollen. Heat stress resulted in meiotic abnormalities, including failure of chromosome separation, chromosome stickiness, laggards and micronuclei. Spindle disorientations in the second meiotic division, such as parallel, fused, and tripolar spindles, either increased in frequency or were induced de novo by high temperature treatment...
July 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28706153/inhibitor-of-growth-protein-4-interacts-with-beclin-1-and-represses-autophagy
#19
Valentina Sica, José Manuel Bravo-San Pedro, Guo Chen, Guillermo Mariño, Sylvie Lachkar, Valentina Izzo, Maria Chiara Maiuri, Mireia Niso-Santano, Guido Kroemer
Beclin 1 (BECN1) is a multifunctional protein that activates the pro-autophagic class III phosphatidylinositol 3-kinase (PIK3C3, best known as VPS34), yet also interacts with multiple negative regulators. Here we report that BECN1 interacts with inhibitor of growth family member 4 (ING4), a tumor suppressor protein that is best known for its capacity to interact with the tumor suppressor protein p53 (TP53) and the acetyltransferase E1A binding protein p300 (EP300). Removal of TP53 or EP300 did not affect the BECN1/ING4 interaction, which however was lost upon culture of cells in autophagy-inducing, nutrient free conditions...
July 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28706108/novel-function-of-a-dynein-light-chain-in-actin-assembly-during-clathrin-mediated-endocytosis
#20
Kristen B Farrell, Seth McDonald, Andrew K Lamb, Colette Worcester, Olve B Peersen, Santiago M Di Pietro
Clathrin- and actin-mediated endocytosis is essential in eukaryotic cells. In this study, we demonstrate that Tda2 is a novel protein of the endocytic machinery necessary for normal internalization of native cargo in yeast. Tda2 has not been classified in any protein family. Unexpectedly, solving the crystal structure of Tda2 revealed it belongs to the dynein light chain family. However, Tda2 works independently of the dynein motor complex and microtubules. Tda2 forms a tight complex with the polyproline motif-rich protein Aim21, which interacts physically with the SH3 domain of the Arp2/3 complex regulator Bbc1...
July 13, 2017: Journal of Cell Biology
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