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Johanna Block, Hannes Witt, Andrea Candelli, Jordi Cabanas Danes, Erwin J G Peterman, Gijs J L Wuite, Andreas Janshoff, Sarah Köster
Structure and dynamics of living matter rely on design principles fundamentally different from concepts of traditional material science. Specialized intracellular filaments in the cytoskeleton permit living systems to divide, migrate, and grow with a high degree of variability and durability. Among the three filament systems, microfilaments, microtubules, and intermediate filaments (IFs), the physical properties of IFs and their role in cellular mechanics are the least well understood. We use optical trapping of individual vimentin filaments to investigate energy dissipation, strain history dependence, and creep behavior of stretched filaments...
June 2018: Science Advances
Jian Qin, Qingyun Li, Zhi Zeng, Ping Wu, Yanping Jiang, Tao Luo, Xiang Ji, Qiuping Zhang, Yarong Hao, Lang Chen
Euchromatic histone-lysine N-methyltransferase (G9A), the primary histone methyltransferase for histone H3 Lys9 , has been identified to be upregulated in numerous types of cancer. The aim of the present study was to analyze the clinical significance of G9A, and preliminarily explore its function in hepatocellular carcinoma (HCC). An increased expression level of G9A was demonstrated in the HCC samples and also in 5 publically available datasets. By analyzing GSE14520, it was revealed that its expression level was significantly associated with serum α-fetoprotein level of patients with HCC, and may serve as a potential prognostic indicator for patients with multinodular HCC...
June 2018: Oncology Letters
Rijk de Rooij, Ellen Kuhl
Excessive physical impacts to the head have direct implications on the structural integrity at the axonal level. Increasing evidence suggests that tau, an intrinsically disordered protein that stabilizes axonal microtubules, plays a critical role in the physical biology of axonal injury. However, the precise mechanisms of axonal damage remain incompletely understood. Here we propose a biophysical model of the axon to correlate the dynamic behavior of individual tau proteins under external physical forces to the evolution of axonal damage...
2018: Frontiers in Cellular Neuroscience
Min Liu, Jie Ran, Jun Zhou
Kinesins are widely expressed, microtubule-dependent motors that play vital roles in microtubule-associated cellular activities, such as cell division and intracellular transport. Eg5, also known as kinesin-5 or kinesin spindle protein, is a member of the kinesin family that contributes to the formation and maintenance of the bipolar mitotic spindle during cell division. Small-molecule compounds that inhibit Eg5 activity have been shown to impair spindle assembly, block mitotic progression, and possess anti-cancer activity...
June 21, 2018: Thoracic Cancer
Wen-Hua Sang, Mei-Chun Zeng, Sha Chen, Ran Chen, Xiao-Fang Fan, Yong-Sheng Gong, Hai-Lin Zhang, Hong-Yu Zhang, Xiao-Xia Kong
OBJECTIVES: To investigate the role of autophagy inhibitor chloroquine (CQ) in acute ethanol-induced liver injury and its mechenism. METHODS: Twenty-one C57BL/6 male mice were randomly divided into three groups:control group, ethanol group, CQ + ethanol group ( n =7). Mice in ethanol group were administered 33% (v/v) ethanol at a dose of 4.5 g/kg body weight. Ethanol-induced liver steatosis in each group was detected by hematoxylin and eosin staining. Hepatic lipid accumulation was detected by staining with Oil red O...
February 8, 2018: Chinese Journal of Applied Physiology
Chikako Ikeda, Osamu Yokota, Tomoko Miki, Shintaro Takenoshita, Hideki Ishizu, Seishi Terada, Norihito Yamada
Neurodegenerative diseases in which tau accumulation plays a cardinal role in the pathogenic process are called tauopathies, and when tau isoforms having four repeats of the microtubule binding sites, four-repeat tau, are selectively accumulated as pathological hallmarks, the term four-repeat tauopathy is used. The major four-repeat tauopathies are progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and argyrophilic grain disease (AGD). Historically, neuronal cytopathologies, e.g., neurofibrillary tangles and ballooned neurons, were emphasized as characteristic lesions in PSP and CBD...
June 2018: Acta Medica Okayama
Li-Fu Li, Yung-Yang Liu, Ning-Hung Chen, Yen-Huey Chen, Chung-Chi Huang, Kuo-Chin Kao, Chih-Hao Chang, Li-Pang Chuang, Li-Chung Chiu
Mechanical ventilation (MV) is often used to maintain life in patients with sepsis and sepsis-related acute lung injury. However, controlled MV may cause diaphragm weakness due to muscle injury and atrophy, an effect termed ventilator-induced diaphragm dysfunction (VIDD). Toll-like receptor 4 (TLR4) and nuclear factor-κB (NF-κB) signaling pathways may elicit sepsis-related acute inflammatory responses and muscle protein degradation and mediate the pathogenic mechanisms of VIDD. However, the mechanisms regulating the interactions between VIDD and endotoxemia are unclear...
June 20, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
Kateřina Melková, Vojtěch Zapletal, Séverine Jansen, Erik Nomilner, Milan Zachrdla, Jozef Hritz, Jiří Nováček, Markus Zweckstetter, Malene R Jensen, Martin Blackledge, Lukas Zidek
Microtubule-associated protein 2c (MAP2c)1 is a 49-kDa intrinsically disordered protein regulating the dynamics of microtubules in developing neurons. MAP2c differs from its sequence homologue Tau in the pattern and kinetics of phosphorylation by cAMP-dependent protein kinase (PKA). Moreover, the mechanisms through which MAP2c interacts with its binding partners and the conformational changes and dynamics associated with these interactions remain unclear. Here, we used NMR relaxation and paramagnetic relaxation enhancement techniques to determine the dynamics and long-range interactions within MAP2c...
June 20, 2018: Journal of Biological Chemistry
Olga Martzoukou, George Diallinas, Sotiris Amillis
The AP-1 complex is essential for membrane protein traffic via its role in the pinching-off and sorting of secretory vesicles from the trans-Golgi and/or endosomes. While its essentiality is undisputed in metazoa, its role in simpler eukaryotes seems less clear. Here we dissect the role of AP-1 in the filamentous fungus Aspergillus nidulans and show that it is absolutely essential for growth due to its role in clathrin-dependent maintenance of polar traffic of specific membrane cargoes towards the apex of growing hyphae...
June 20, 2018: Genetics
Michiko Suma, Teppei Kitagawa, Yukiko Nakase, Norihiko Nakazawa, Mitsuhiro Yanagida, Tomohiro Matsumoto
The centromere is a chromosomal locus where a microtubule attachment site, termed kinetochore, is assembled in mitosis. In most eukaryotes, with the exception of holocentric species, each chromosome contains a single distinct centromere. A chromosome with an additional centromere undergoes successive rounds of anaphase bridge formation and breakage, or triggers a cell cycle arrest imposed by DNA damage and replication checkpoints. We report here a study in Schizosaccharomyces pombe to characterize a mutant ( cnp3-1 ) in a gene encoding a homolog of mammalian centromere-specific protein, CENP-C...
June 20, 2018: G3: Genes—Genomes—Genetics
Kohei Arasaki, Haruki Nagashima, Yuri Kurosawa, Hana Kimura, Naoki Nishida, Naoshi Dohmae, Akitsugu Yamamoto, Shigeru Yanagi, Yuichi Wakana, Hiroki Inoue, Mitsuo Tagaya
In fed cells, syntaxin 17 (Stx17) is associated with microtubules at the endoplasmic reticulum-mitochondria interface and promotes mitochondrial fission by determining the localization and function of the mitochondrial fission factor Drp1. Upon starvation, Stx17 dissociates from microtubules and Drp1, and binds to Atg14L, a subunit of the phosphatidylinositol 3-kinase complex, to facilitate phosphatidylinositol 3-phosphate production and thereby autophagosome formation, but the mechanism underlying this phenomenon remains unknown...
June 19, 2018: EMBO Reports
Jeong Hwan Park, Cheol Lee, Mee Soo Chang, Kwangsoo Kim, Seongmin Choi, Hyunjung Lee, Hyun-Seob Lee, Kyung Chul Moon
Tuberous sclerosis complex-associated renal cell carcinoma (TSC-RCC) has distinct clinical and histopathologic features and is considered a specific subtype of RCC. The genetic alterations of TSC1 or TSC2 are responsible for the development of TSC. In this study, we assessed the mTOR pathway activation and aimed to evaluate molecular characteristics and pathogenic pathways of TSC-RCC. Two cases of TSC-RCC, one from a 31-year-old female and the other from an 8-year-old male, were assessed. The mTOR pathway activation was determined by immunohistochemistry...
June 17, 2018: Translational Oncology
Wenlong Xu, Elaheh Alizadeh, Ashok Prasad
A single-cell assay of active and passive intracellular mechanical properties of mammalian cells could give significant insight into cellular processes. Force spectrum microscopy (FSM) is one such technique, which combines the spontaneous motion of probe particles and the mechanical properties of the cytoskeleton measured by active microrheology using optical tweezers to determine the force spectrum of the cytoskeleton. A simpler and noninvasive method to perform FSM would be very useful, enabling its widespread adoption...
June 19, 2018: Biophysical Journal
Yuan Gao, Stephen M Anthony, Yanqi Yu, Yi Yi, Yan Yu
Intracellular cargos are transported by molecular motors along actin and microtubules, but how their dynamics depends on the complex structure of the cytoskeletal network remains unclear. In this study, we investigated this longstanding question by measuring simultaneously the rotational and translational dynamics of cargos at microtubule intersections in living cells. We engineered two-faced particles that are fluorescent on one hemisphere and opaque on the other and used their optical anisotropy to report the rotation of cargos...
June 19, 2018: Biophysical Journal
Chie Araki, Nobuyuki Okahashi, Kousuke Maeda, Hiroshi Shimizu, Fumio Matsuda
Cancer cells often respond to chemotherapeutic inhibitors by redirecting carbon flow in the central metabolism. To understand the metabolic redirections of inhibitor treatment on cancer cells, this study established a 13 C-metabolic flux analysis (13 C-MFA)-based method to evaluate metabolic redirection in MCF-7 breast cancer cells using mass spectrometry. A metabolic stationary state necessary for accurate 13 C-MFA was confirmed during an 8-24 h window using low-dose treatments of various metabolic inhibitors...
2018: Mass Spectrometry
Andrey Aristov, Benoit Lelandais, Elena Rensen, Christophe Zimmer
Single molecule localization microscopy can generate 3D super-resolution images without scanning by leveraging the axial variations of normal or engineered point spread functions (PSF). Successful implementation of these approaches for extended axial ranges remains, however, challenging. We present Zernike Optimized Localization Approach in 3D (ZOLA-3D), an easy-to-use computational and optical solution that achieves optimal resolution over a tunable axial range. We use ZOLA-3D to demonstrate 3D super-resolution imaging of mitochondria, nuclear pores and microtubules in entire nuclei or cells up to ~5 μm deep...
June 19, 2018: Nature Communications
Sabine Grønborg, Lotte Risom, Jakob Ek, Karen Bonde Larsen, David Scheie, Yanko Petkov, Vibeke André Larsen, Morten Dunø, Fróði Joensen, Elsebet Østergaard
An intact and dynamic microtubule cytoskeleton is crucial for the development, differentiation, and maintenance of the mammalian cortex. Variants in a host of structural microtubulin-associated proteins have been identified to cause a wide spectrum of malformations of cortical development and alterations of microtubule dynamics have been recognized to cause or contribute to progressive neurodegenerative disorders. TBCD is one of the five tubulin-specific chaperones and is required for reversible assembly of the α-/β-tubulin heterodimer...
June 19, 2018: European Journal of Human Genetics: EJHG
Yunfeng Gao, Christoph Spahn, Mike Heilemann, Linda J Kenney
Bacterial pathogens exploit eukaryotic pathways for their own end. Upon ingestion, Salmonella enterica serovar Typhimurium passes through the stomach and then catalyzes its uptake across the intestinal epithelium. It survives and replicates in an acidic vacuole through the action of virulence factors secreted by a type three secretion system located on Salmonella pathogenicity island 2 (SPI-2). Two secreted effectors, SifA and SseJ, are sufficient for endosomal tubule formation, which modifies the vacuole and enables Salmonella to replicate within it...
June 19, 2018: MBio
Vasso Makrantoni, Adele L Marston
Cohesin is a ring-shaped protein complex that organises the genome, enabling its condensation, expression, repair and transmission. Cohesin is best known for its role in chromosome segregation, where it provides the cohesion that is established between the two newly duplicated sister chromatids during S phase. This cohesion enables the proper attachment of sister chromatids to microtubules of the spindle by resisting their opposing pulling forces. Once all chromosomes are correctly attached, cohesin is abruptly destroyed, triggering the equal segregation of sister chromatids to opposite poles in anaphase...
June 18, 2018: Current Biology: CB
Ying Yang, Hui Fang, Gang Xu, Yanfeng Zhen, Yazhong Zhang, Jinli Tian, Dandan Zhang, Guyue Zhang, Jing Xu
Liraglutide is a type of glucagon‑like‑peptide 1 receptor agonist, which has been reported as a novel type of antidiabetic agent with numerous benefits, including cardiovascular and neuroprotective effects. To the best of our knowledge, few studies to date have reported the potential mechanism underlying the neuroprotective effects of liraglutide on rats with type 2 diabetes mellitus (T2DM). The present study aimed to investigate the neuroprotective actions of liraglutide in diabetic rats and to determine the mechanisms underlying these effects...
June 18, 2018: Molecular Medicine Reports
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