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https://www.readbyqxmd.com/read/29925043/molecular-characterization-and-putative-pathogenic-pathways-of-tuberous-sclerosis-complex-associated-renal-cell-carcinoma
#1
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
https://www.readbyqxmd.com/read/29925029/force-spectrum-microscopy-using-mitochondrial-fluctuations-of-control-and-atp-depleted-cells
#2
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
https://www.readbyqxmd.com/read/29925026/cargos-rotate-at-microtubule-intersections-during-intracellular-trafficking
#3
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
https://www.readbyqxmd.com/read/29922569/mass-spectrometry-based-method-to-study-inhibitor-induced-metabolic-redirection-in-the-central-metabolism-of-cancer-cells
#4
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
https://www.readbyqxmd.com/read/29921892/zola-3d-allows-flexible-3d-localization-microscopy-over-an-adjustable-axial-range
#5
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
https://www.readbyqxmd.com/read/29921875/a-faroese-founder-variant-in-tbcd-causes-early-onset-progressive-encephalopathy-with-a-homogenous-clinical-course
#6
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
https://www.readbyqxmd.com/read/29921673/the-pearling-transition-provides-evidence-of-force-driven-endosomal-tubulation-during-salmonella-infection
#7
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
https://www.readbyqxmd.com/read/29920258/cohesin-and-chromosome-segregation
#8
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
https://www.readbyqxmd.com/read/29916537/liraglutide-improves-cognitive-impairment-via-the-ampk-and-pi3k-akt-signaling-pathways-in-type-2-diabetic-rats
#9
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
https://www.readbyqxmd.com/read/29916143/mast-cell-proteases-activate-astrocytes-and-glia-neurons-and-release-interleukin-33-by-activating-p38-and-erk1-2-mapks-and-nf-%C3%AE%C2%BAb
#10
Duraisamy Kempuraj, Ramasamy Thangavel, Gvindhasamy Pushpavathi Selvakumar, Mohammad Ejaz Ahmed, Smita Zaheer, Sudhanshu P Raikwar, Haris Zahoor, Daniyal Saeed, Iuliia Dubova, Gema Giler, Shelby Herr, Shankar S Iyer, Asgar Zaheer
Inflammatory mediators released from activated microglia, astrocytes, neurons, and mast cells mediate neuroinflammation. Parkinson's disease (PD) is characterized by inflammation-dependent dopaminergic neurodegeneration in substantia nigra. 1-Methyl-4-phenylpyridinium (MPP+ ), a metabolite of parkinsonian neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), induces inflammatory mediators' release from brain cells and mast cells. Brain cells' interaction with mast cells is implicated in neuroinflammation...
June 18, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29915359/dynamic-kinetochore-size-regulation-promotes-microtubule-capture-and-chromosome-biorientation-in-mitosis
#11
Carlos Sacristan, Misbha Ud Din Ahmad, Jenny Keller, Job Fermie, Vincent Groenewold, Eelco Tromer, Alexander Fish, Roberto Melero, José María Carazo, Judith Klumperman, Andrea Musacchio, Anastassis Perrakis, Geert Jpl Kops
Faithful chromosome segregation depends on the ability of sister kinetochores to attach to spindle microtubules. The outer layer of kinetochores transiently expands in early mitosis to form a fibrous corona, and compacts following microtubule capture. Here we show that the dynein adaptor Spindly and the RZZ (ROD-Zwilch-ZW10) complex drive kinetochore expansion in a dynein-independent manner. C-terminal farnesylation and MPS1 kinase activity cause conformational changes of Spindly that promote oligomerization of RZZ-Spindly complexes into a filamentous meshwork in cells and in vitro...
June 18, 2018: Nature Cell Biology
https://www.readbyqxmd.com/read/29915050/separating-the-effects-of-nucleotide-and-eb-binding-on-microtubule-structure
#12
Rui Zhang, Benjamin LaFrance, Eva Nogales
Microtubules (MTs) are polymers assembled from αβ-tubulin heterodimers that display the hallmark behavior of dynamic instability. MT dynamics are driven by GTP hydrolysis within the MT lattice, and are highly regulated by a number of MT-associated proteins (MAPs). How MAPs affect MTs is still not fully understood, partly due to a lack of high-resolution structural data on undecorated MTs, which need to serve as a baseline for further comparisons. Here we report three structures of MTs in different nucleotide states (GMPCPP, GDP, and GTPγS) at near-atomic resolution and in the absence of any binding proteins...
June 18, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29914543/hepatitis-b-core-vlp-based-mis-disordered-tau-vaccine-elicits-strong-immune-response-and-alleviates-cognitive-deficits-and-neuropathology-progression-in-tau-p301s-mouse-model-of-alzheimer-s-disease-and-frontotemporal-dementia
#13
Mei Ji, Xi-Xiu Xie, Dong-Qun Liu, Xiao-Lin Yu, Yue Zhang, Ling-Xiao Zhang, Shao-Wei Wang, Ya-Ru Huang, Rui-Tian Liu
BACKGROUND: Truncated mis-disordered tau protein plays an important role in the pathogenesis of Alzheimer's disease (AD) and frontotemporal dementia (FTD). Tau294-305 , an epitope in the truncated tau, is essential for pathological tau-tau interaction and aggregation. A tau294-305 -targeted approach may have beneficial effects in the treatment of AD and FTD. METHODS: In this study, we genetically fused tau294-305 epitope to the hepatitis B virus core protein (HBc) major immunodominant region (MIR) (with the resultant protein termed T294-HBc), and we subcutaneously immunized a Tau...
June 19, 2018: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/29913432/transcriptome-analysis-reveals-novel-insights-into-the-response-of-low-dose-benzo-a-pyrene-exposure-in-male-tilapia
#14
Reyna Cristina Colli-Dula, Xiefan Fang, David Moraga-Amador, Nacira Albornoz-Abud, Roberto Zamora-Bustillos, Ana Conesa, Omar Zapata-Perez, Diego Moreno, Emanuel Hernandez-Nuñez
Despite a wide number of toxicological studies that describe benzo[a]pyrene (BaP) effects, the metabolic mechanisms that underlie these effects in fish are largely unknown. Of great concern is the presence of BaP in aquatic systems, especially those in close proximity to human activity leading to consumption of potentially contaminated foods. BaP is a known carcinogen and it has been reported to have adverse effects on the survival, development and reproduction of fish. The purpose of this study was to investigate if a low dose of BaP can alter genes and key metabolic pathways in the liver and testis in male adult tilapia, and whether these could be associated with biological endpoints disruption...
June 8, 2018: Aquatic Toxicology
https://www.readbyqxmd.com/read/29913154/interactions-between-monomeric-cct%C3%AE-and-p150-glued-a-novel-function-for-cct%C3%AE-at-the-cell-periphery-distinct-from-the-protein-folding-activity-of-the-molecular-chaperone-cct
#15
Meriem Echbarthi, Josefine Vallin, Julie Grantham
Chaperonin containing tailless complex polypeptide 1 (CCT) is a molecular chaperone consisting of eight distinct protein subunits, that when oligomeric is essential for the folding of newly synthesized tubulin and actin. In addition to folding, CCT activity includes functions of individual subunits in their monomeric form. For example, when CCTδ monomer levels are increased in cultured mammalian cells, numerous cell surface protrusions are formed from retraction fibres, indicating that an underlying function for the CCTδ monomer exists...
June 15, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29913076/formin-proteins-in-megakaryocytes-and-platelets-regulation-of-actin-and-microtubule-dynamics
#16
Malou Zuidscherwoude, Hannah L H Green, Steven G Thomas
The platelet and megakaryocyte cytoskeletons are essential for formation and function of these cells. A dynamic, properly organised tubulin and actin cytoskeleton is critical for the development of the megakaryocyte and the extension of proplatelets. Tubulin in particular plays a pivotal role in the extension of these proplatelets and the release of platelets from them. Tubulin is further required for the maintenance of platelet size, and actin is the driving force for shape change, spreading and platelet contraction during platelet activation...
June 18, 2018: Platelets
https://www.readbyqxmd.com/read/29912852/emodin-attenuates-autophagy-response-to-protect-the-pancreas-from-acute-pancreatitis-failure
#17
Xiaozheng Yu, Chunyun Li, Hechao Song, Xueyan Wang, Yinan Guo, Lijian Cui, Xiaoya Liu, Cheng Chi, Ruixia Liu, Chenghong Yin
OBJECTIVES: The aim of this study was to investigate the effects of emodin on attenuating autophagy response in acute pancreatitis (AP) models. METHODS: Acute pancreatitis was induced in Wistar rats by injecting 3% sodium taurocholate into the biliopancreatic duct. Emodin (40 mg/kg per day) was then given intragastrically, administrated 2 hours after AP induction. Rats were killed 24 hours after AP induction. The pancreatic injury was assessed using biochemical and histological approaches...
June 16, 2018: Pancreas
https://www.readbyqxmd.com/read/29910809/sailing-to-and-docking-at-the-immune-synapse-role-of-tubulin-dynamics-and-molecular-motors
#18
REVIEW
Noa Beatriz Martín-Cófreces, Francisco Sánchez-Madrid
The different cytoskeleton systems and their connecting molecular motors move vesicles and intracellular organelles to shape cells. Polarized cells with specialized functions display an exquisite spatio-temporal regulation of both cytoskeletal and organelle arrangements that support their specific tasks. In particular, T cells rapidly change their shape and cellular function through the establishment of cell surface and intracellular polarity in response to a variety of cues. This review focuses on the contribution of the microtubule-based dynein/dynactin motor complex, the tubulin and actin cytoskeletons, and different organelles to the formation of the antigen-driven immune synapse...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29910073/activity-dependent-actin-remodeling-at-the-base-of-dendritic-spines-promotes-microtubule-entry
#19
Philipp Schätzle, Marta Esteves da Silva, Roderick P Tas, Eugene A Katrukha, Hai Yin Hu, Corette J Wierenga, Lukas C Kapitein, Casper C Hoogenraad
In neurons, microtubules form dense bundles and run along the length of axons and dendrites. Occasionally, dendritic microtubules can grow from the shaft directly into dendritic spines. Microtubules target dendritic spines that are undergoing activity-dependent changes, but the mechanism by which microtubules enter spines has remained poorly understood. Using live-cell imaging, high-resolution microscopy, and local glutamate uncaging, we show that local actin remodeling at the base of a spine promotes microtubule spine targeting...
June 5, 2018: Current Biology: CB
https://www.readbyqxmd.com/read/29909279/the-kank-family-proteins-in-adhesion-dynamics
#20
REVIEW
Nan-Peng Chen, Zhiqi Sun, Reinhard Fässler
Integrin-mediated cell adhesion plays key roles for cell movement during development and tissue homeostasis. The dynamic life cycle of various integrin adhesions structures is required for the cell movements and regulated by the coordinated actions of both actomyosin and the microtubule (MT) cytoskeleton. The evolutionarily conserved Kank family proteins have emerged as regulators of adhesion dynamics by coordinating integrin-mediated force transmission with the recruitment of microtubules to integrins. These novel functions may play important roles in vivo and in human diseases...
June 14, 2018: Current Opinion in Cell Biology
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