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https://www.readbyqxmd.com/read/29458174/networks-that-link-cytoskeletal-regulators-and-diaphragm-proteins-underpin-filtration-function-in-drosophila-nephrocytes
#1
Simi Muraleedharan, Aksah Sam, Helen Skaer, Maneesha S Inamdar
Insect nephrocytes provide a valuable model for kidney disease, as they are structurally and functionally homologous to mammalian kidney podocytes. They possess an exceptional macromolecular assembly, the nephrocyte diaphragm (ND), which serves as a filtration barrier and helps maintain tissue homeostasis by filtering out wastes and toxic products. However, the elements that maintain nephrocyte architecture and the ND are not understood. We show that Drosophila nephrocytes have a unique cytoplasmic cluster of F-actin, which is maintained by the microtubule cytoskeleton and Rho-GTPases...
February 16, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29458018/5-chloro-n4-2-isopropylsulfonyl-phenyl-n2-2-methoxy-4-4-4-methylpiperazin-1-yl-methyl-1h-1-2-3-triazol-1-yl-phenyl-pyrimidine-2-4-diamine-wy-135-a-novel-alk-inhibitor-induces-cell-cycle-arrest-and-apoptosis-through-inhibiting-alk-and-its-downstream-pathways
#2
Mengting Han, Jiwei Shen, Lijing Wang, Yu Wang, Xin Zhai, Yao Li, Meiqiao Liu, Zengqiang Li, Daiying Zuo, Yingliang Wu
Anaplastic lymphoma kinase (ALK)-positive cancers have rising morbidity and mortality in recent years, and novel chemotherapeutic drugs with no drug resistance and high activity for treating ALK-positive cancers are needed urgently. In this study, we investigated the anti-cancer effect of 5-chloro-N4-(2-(isopropylsulfonyl)phenyl)-N2-(2-methoxy-4-(4-((4-methylpiperazin-1-yl)methyl)-1H-1,2,3-triazol-1-yl)phenyl)pyrimidine-2,4-diamine (WY-135), a novel ALK inhibitor, on nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) positive cancer cell line Karpas299 and echinoderm microtubule associated protein like 4-anaplastic lymphoma kinase (EML4-ALK) positive cancer cell line H2228...
February 16, 2018: Chemico-biological Interactions
https://www.readbyqxmd.com/read/29457987/the-rap2c-gtpase-facilitates-b-cell-receptor-induced-reorientation-of-the-microtubule-organizing-center
#3
Jia C Wang, Jeff Y-J Lee, May Dang-Lawson, Caitlin Pritchard, Michael R Gold
When B lymphocytes encounter antigen-bearing surfaces, B-cell receptor (BCR) signaling initiates remodeling of the F-actin network and reorientation of the microtubule-organizing center (MTOC) towards the antigen contact site. We have previously shown that the Rap1 GTPase, an evolutionarily conserved regulator of cell polarity, is essential for these processes and that Rap1-regulated actin remodeling is required for MTOC polarization. The role of Rap2 proteins in establishing cell polarity is not well understood...
February 19, 2018: Small GTPases
https://www.readbyqxmd.com/read/29457976/radiosynthesis-and-in-vivo-evaluation-of-11c-mpc-6827-the-first-brain-penetrant-microtubule-pet-ligand
#4
J S Dileep Kumar, Kiran Kumar Solingapuram Sai, Jaya Prabhakaran, Hakeem R Oufkir, Gayathri Ramanathan, Christopher T Whitlow, Hima Dileep, Akiva Mintz, J John Mann
Abnormalities of microtubules (MTs) are implicated in the pathogenesis of many CNS diseases. Despite the potential of an MT imaging agents, no PET ligand is currently available for in vivo imaging of MTs in the brain. We radiolabeled [11C]MPC-6827, a high affinity MTA, demonstrated its specific binding in rat and mice brain using PET imaging. Our experiments show that [11C]MPC-6827 has specific binding to MT in brain, and it is the first MT-binding PET ligand.
February 19, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29457125/enhanced-differentiation-of-dental-pulp-cells-cultured-on-microtubular-polymer-scaffolds-in-vitro
#5
Morteza Haeri, Karen Sagomonyants, Mina Mina, Liisa T Kuhn, A Jon Goldberg
Dental caries (tooth decay) is the most common chronic disease. Dental tissue engineering is a promising alternative approach to alleviate the shortcomings of the currently available restorative materials. Mimicking the natural extracellular matrix (ECM) could enhance the performance of tissue engineering scaffolds. In this study, we developed microtubular (~20 μm diameter) polymethyl methacrylate (PMMA) scaffolds resembling the tubular (~2.5 μm diameter) structure of dentin, the collagen-based mineralized tissue that forms the major portion of teeth, to study the effect of scaffold architecture on differentiation of mouse dental pulp cells in vitro ...
June 2017: Regenerative Engineering and Translational Medicine
https://www.readbyqxmd.com/read/29456853/crizotinib-associated-toxic-epidermal-necrolysis-in-an-alk-positive-advanced-nsclc-patient
#6
Shaoyu Yang, Liming Wu, Xin Li, Jie Huang, Jianbo Zhong, Xueqin Chen
Crizotinib is an oral small-molecule inhibitor of anaplastic lymphoma kinase (ALK) tyrosine-kinase that has been approved for treating patients with advanced echinoderm microtubule associated protein like 4-ALK rearranged non-small-cell lung cancer (NSCLC). Toxic epidermal necrolysis (TEN) is a rare adverse event associated with crizotinib. The present study reported a case of a 75-year-old Chinese male patient with advanced NSCLC with ALK fusion, who developed TEN after 56 days of crizotinib treatment and demised due to this dermatological adverse event...
March 2018: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/29456707/resveratrol-induces-autophagic-apoptosis-via-the-lysosomal-cathepsin-d-pathway-in-human-drug-resistant-k562-adm-leukemia-cells
#7
Zhewen Zhang, Zhuan Liu, Jing Chen, Juan Yi, Juan Cheng, Wangqing Dun, Hulai Wei
The aim of the present study was to investigate the crosstalk between resveratrol (Res)-induced autophagy and apoptosis, and the molecular pathway by which autophagy leads to apoptotic death in drug-resistant K562/ADM leukemia cells. The viability of K562/ADM cells was determined using the MTT assay. The formation of autophagic vacuoles was detected using transmission electron microscopy and monodansylcadaverine (MDC) staining. Cell apoptosis was evaluated using flow cytometry. The expression of apoptosis- or autophagy-associated proteins was measured using western blotting...
March 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29456644/eudesmin-attenuates-helicobacter-pylori-induced-epithelial-autophagy-and-apoptosis-and-leads-to-eradication-of-h-pylori-infection
#8
Jai-Sing Yang, Chao-Min Wang, Chiu-Hsian Su, Han-Chen Ho, Chiung-Hung Chang, Chang-Hung Chou, Yuan-Man Hsu
Eudesmin has been proven to possess anti-inflammatory effects. In the present study, the effects of eudesmin on Helicobacter pylori (H. pylori) -mediated autophagy, apoptosis, immune response and inflammation were determined in human gastric adenocarcinoma (AGS) cells in vitro and in C57BL/6 mice in vivo . Detection of the production of interleukin (IL)-8, IL-1β and immunoglobulin M (IgM) was performed using ELISA. Identification of the activation of apoptosis-associated caspase-3, -8 and -9 proteins, Bcl-2-associated X protein (Bax) and BH3 interacting domain death agonist (Bid) protein, was determined through western blot analysis...
March 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29456633/crosstalk-between-apoptosis-and-autophagy-in-prostate-epithelial-cells-under-androgen-deprivation
#9
Rong-Fu Liu, Jian Li, Jie Zhang, Pei-De Bai, Yu-Feng Yang, Wei Li, Zhun Wu, Jia-Xin Zheng
The present study investigated the molecular mechanism of apoptosis and autophagy in prostate epithelial cells under androgen deprivation (AD). BPH-1 cells were divided into four groups as follows: Control (Cont), AD, autophagy inhibition (AI) and AD + AI groups. Cells in the four groups were treated accordingly, and the level of apoptosis was subsequently measured via flow cytometry. The expression of the microtubule-associated proteins 1A/1B light chain 3 (LC3), caspase-3, poly (ADP-ribose) polymerase 1 (PARP-1) and Beclin-1 proteins of BPH-1 cells was detected at different time points following culture in androgen-deprived medium...
March 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29456473/adverse-events-of-trastuzumab-emtansine-t-dm1-in-the-treatment-of-her2-positive-breast-cancer-patients
#10
REVIEW
Lidia Kowalczyk, Rupert Bartsch, Christian F Singer, Alex Farr
The human epidermal growth factor receptor 2 (HER2) is commonly associated with poor prognosis and is overexpressed in approximately 15-20% of all breast cancers. The introduction of HER2-targeted therapies led to significant improvement in the prognosis of patients with HER2-positive breast cancer, for both early and advanced disease. These targeted therapies include the antibodies trastzumab and pertuzumab, the tyrosine kinase inhibitor lapatinib, and the antibody-drug conjugate trastuzumab emtansine (T-DM1)...
December 2017: Breast Care
https://www.readbyqxmd.com/read/29456109/synthetic-strigolactone-analogues-reveal-anti-cancer-activities-on-hepatocellular-carcinoma-cells
#11
Mohammed Nihal Hasan, Hani Choudhry, Syed Shoeb Razvi, Said Salama Moselhy, Taha Abduallah Kumosani, Mazin A Zamzami, Ziad Omran, Majed A Halwani, Salim Al-Babili, Khalid Omer Abualnaja, Abdulrahman Labeed Al-Malki, Mahmoud Alhosin, Tadao Asami
Hepatocellular carcinoma (HCC) remains one of the leading causes of death worldwide. The complex etiology is attributed to many factors like heredity, cirrhosis, hepatitis infections or the dysregulation of the different molecular pathways. Nevertheless, the current treatment regimens have either severe side effects or tumors gradually acquire resistance upon prolonged use. Thus, developing a new selective treatment for HCC is the need of the hour. Many anticancer agents derived from plants have been evaluated for their cytotoxicity towards many human cancer cell lines...
February 9, 2018: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29455366/phospholipase-d%C3%AE-assists-to-cortical-microtubule-recovery-after-salt-stress
#12
Jindřiška Angelini, Stanislav Vosolsobě, Petr Skůpa, Angela Yeuan Yen Ho, Erica Bellinvia, Olga Valentová, Jan Marc
The dynamic microtubule cytoskeleton plays fundamental roles in the growth and development of plants including regulation of their responses to environmental stress. Plants exposed to hyper-osmotic stress commonly acclimate, acquiring tolerance to variable stress levels. The underlying cellular mechanisms are largely unknown. Here, we show, for the first time, by in vivo imaging approach that linear patterns of phospholipase Dδ match the localization of microtubules in various biological systems, validating previously predicted connection between phospholipase Dδ and microtubules...
January 24, 2018: Protoplasma
https://www.readbyqxmd.com/read/29455064/the-dynamics-of-both-filamentous-and-globular-mammalian-reovirus-viral-factories-rely-on-the-microtubule-network
#13
Catherine Eichwald, Mathias Ackermann, Max L Nibert
Mammalian reovirus viral factories (VFs) form filamentous or globular structures depending on the viral strain. In this study, we attempt to characterize the dynamics of both filamentous and globular VFs. Here, we present evidence demonstrating that globular VFs are dynamic entities coalescing between them, thereby gaining in size and concomitantly decreasing in numbers during the course of the infection. Additionally, both kinds of VFs condense into a perinuclear position. Our results show that globular VFs rely on an intact MT-network for dynamic motion, structural assembly, and maintenance and for perinuclear condensation...
February 15, 2018: Virology
https://www.readbyqxmd.com/read/29454860/velocity-landscape-correlation-resolves-multiple-flowing-protein-populations-from-fluorescence-image-time-series
#14
Elvis Pandžić, Asmahan Abu-Arish, Renee W Whan, John W Hanrahan, Paul W Wiseman
Molecular, vesicular and organellar flows are of fundamental importance for the delivery of nutrients and essential components used in cellular functions such as motility and division. With recent advances in fluorescence/super-resolution microscopy modalities we can resolve the movements of these objects at higher spatio-temporal resolutions and with better sensitivity. Previously, spatio-temporal image correlation spectroscopy has been applied to map molecular flows by correlation analysis of fluorescence fluctuations in image series...
February 15, 2018: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/29454703/synthesis-and-evaluation-of-novel-dolastatin-10-derivatives-for-versatile-conjugations
#15
Shinya Yokosaka, Akiko Izawa, Chizuka Sakai, Eri Sakurada, Yasuhiro Morita, Yukihiro Nishio
Dolastatin 10 (1) is a highly potent cytotoxic microtubule inhibitor (cytotoxicity IC50 < 5.0 nM) and several of its analogs have recently been used as payloads in antibody drug conjugates. Herein, we describe the design and synthesis of a series of novel dolastatin 10 analogs useful as payloads for conjugated drugs. We explored analogs containing functional groups at the thiazole moiety at the C-terminal of dolastatin 10. The functional groups included amines, alcohols, and thiols, which are representative structures used in known conjugated drugs...
February 11, 2018: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/29454259/the-cellular-mechanisms-and-consequences-of-centromere-drive
#16
REVIEW
Lisa E Kursel, Harmit S Malik
During female meiosis, only one of four meiotic products is retained in the egg. It was previously proposed that chromosomes might compete for inclusion in the egg via their centromere 'strength'. Recent findings have revealed the primary requirements for such 'centromere drive'. First, CDC42 signaling from the oocyte cortex renders the meiotic I spindle asymmetric. Second, 'stronger' centromeres preferentially detach from microtubules in cortical proximity, making them more likely to orient away from the cortex, and be included in the egg...
February 14, 2018: Current Opinion in Cell Biology
https://www.readbyqxmd.com/read/29453798/melatonin-protects-against-defects-induced-by-deoxynivalenol-during-mouse-oocyte-maturation
#17
Mei Lan, Jun Han, Meng-Hao Pan, Xiang Wan, Zhen-Nan Pan, Shao-Chen Sun
Deoxynivalenol (DON) is one of the most prevalent Fusarium mycotoxins in feedstuff and food. DON causes detrimental effects on human and animal reproductive systems by inducing oxidative stress and apoptosis. While melatonin is a multifunctional endogenous hormone which plays crucial roles in the development of animal germ cells and embryos as a robust deoxidizer. In present study, we explored the effects of melatonin on the DON-exposure mouse oocytes. Our in vitro and in vivo results showed that DON adversely affected mouse oocyte maturation and early embryo cleavage, while melatonin administration ameliorated the toxic effects of DON...
February 17, 2018: Journal of Pineal Research
https://www.readbyqxmd.com/read/29453740/arrestins-structural-disorder-creates-rich-functionality
#18
REVIEW
Vsevolod V Gurevich, Eugenia V Gurevich, Vladimir N Uversky
Arrestins are soluble relatively small 44-46 kDa proteins that specifically bind hundreds of active phosphorylated GPCRs and dozens of non-receptor partners. There are binding partners that demonstrate preference for each of the known arrestin conformations: free, receptor-bound, and microtubule-bound. Recent evidence suggests that conformational flexibility in every functional state is the defining characteristic of arrestins. Flexibility, or plasticity, of proteins is often described as structural disorder, in contrast to the fixed conformational order observed in high-resolution crystal structures...
February 16, 2018: Protein & Cell
https://www.readbyqxmd.com/read/29453575/regulation-of-blood-testis-barrier-btb-dynamics-role-of-actin-and-microtubule-based-cytoskeletons
#19
Qing Wen, Elizabeth I Tang, Nan Li, Dolores D Mruk, Will M Lee, Bruno Silvestrini, C Yan Cheng
The blood-testis barrier (BTB) is an important ultrastructure in the testis that supports meiosis and postmeiotic spermatid development since a delay in the establishment of a functional Sertoli cell barrier during postnatal development in rats or mice by 17-20 day postpartum (dpp) would lead to a delay of the first wave of meiosis. Furthermore, irreversible disruption of the BTB by toxicants also induces infertility in rodents. Herein, we summarize recent findings that BTB dynamics (i.e., disassembly, reassembly, and stabilization) are supported by the concerted efforts of the actin- and microtubule (MT)-based cytoskeletons...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29450503/the-mechanical-contribution-of-vimentin-to-cellular-stress-generation
#20
Inge A E W van Loosdregt, Giulia Weissenberger, Marc P F H L van Maris, Cees W J Oomens, Sandra Loerakker, Oscar Stassen, Carlijn V C Bouten
Contractile stress generation by adherent cells is largely determined by the interplay of forces within their cytoskeleton. It is known that actin stress fibers, connected to focal adhesions, provide contractile stress generation, while microtubules and intermediate filaments provide cells compressive stiffness. Recent studies have shown the importance of the interplay between stress fibers and the intermediate filament vimentin. Therefore, the effect of the interplay between the stress fibers and vimentin on stress generation was quantified in this study...
February 14, 2018: Journal of Biomechanical Engineering
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