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https://www.readbyqxmd.com/read/28345763/the-role-of-runx2-in-facilitating-autophagy-in-metastatic-breast-cancer-cells
#1
Manish Tandon, Ahmad H Othman, Vivek Ashok, Gary S Stein, Jitesh Pratap
Breast cancer metastases cause significant patient mortality. During metastases, cancer cells use autophagy, a catabolic process to recycle nutrients via lysosomal degradation, to overcome nutritional stress for their survival. The Runt-related transcription factor, Runx2, promotes cell survival under metabolic stress and regulates breast cancer progression and bone metastases. Here, we identify that Runx2 enhances autophagy in metastatic breast cancer cells. We defined Runx2 function in cellular autophagy by monitoring microtubule-associated protein light chain (LC3B-II) levels, an autophagy-specific marker...
March 27, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28342295/intraflagellar-transport-mechanisms-of-motor-action-cooperation-and-cargo-delivery
#2
REVIEW
Bram Prevo, Jonathan M Scholey, Erwin J G Peterman
Intraflagellar transport (IFT) is a form of motor-dependent cargo transport that is essential for the assembly, maintenance and length-control of cilia, which play critical roles in motility, sensory reception and signal transduction in virtually all eukaryotic cells. During IFT, anterograde kinesin-2 and retrograde IFT-dynein motors drive the bidirectional transport of IFT trains that deliver cargo, for example axoneme precursors such as tubulins as well as molecules of the signal transduction machinery, to their site of assembly within the cilium...
March 25, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28340411/synthesis-and-biological-evaluation-of-novel-chalcone-derivatives-as-a-new-class-of-microtubule-destabilizing-agents
#3
Xiaochao Huang, Rizhen Huang, Lingxue Li, Shaohua Gou, Hengshan Wang
A series of novel chalcone derivatives were designed and synthesized as potential antitumor agents. Structures of target molecules were confirmed by (1)H NMR, (13)C NMR and HR-MS, and evaluated for their in vitro anti-proliferative activities using MTT assay. Among them, compound 12k displayed potent activity against the test tumor cell lines including multidrug resistant human cancer lines, with the IC50 values ranged from 3.75 to 8.42 μM. In addition, compound 12k was found to induce apoptosis in NCI-H460 cells via the mitochondrial pathway, including an increase of the ROS level, loss of mitochondrial membrane potential, release of cytochrome c, down-regulation of Bcl-2, up-regulation of Bax, activation of caspase-9 and caspase-3, respectively...
March 18, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28340181/different-expression-patterns-of-sperm-motility-related-genes-in-testis-of-diploid-and-tetraploid-cyprinid-fish1
#4
Fangzhou Hu, Kang Xu, Yunfan Zhou, Chang Wu, Shi Wang, Jun Xiao, Min Wen, Rurong Zhao, Kaikun Luo, Min Tao, Wei Duan, Shaojun Liu
Sperm motility is an important standard to measure the fertility of male. In our previous study, we found that the diploid spermatozoa from allotetraploid hybrid (4nAT) had longer durations of rapid and slow progressive motility than haploid spermatozoa from common carp (COC). In this study, to explore sperm motility-related molecular mechanisms, we compared the testis tissues transcriptomes from two years old male COC and 4nAT. The RNA-seq data revealed that 2985 genes were differentially expressed between COC and 4nAT, including 2216 up-regulated and 769 down-regulated genes in 4nAT...
March 7, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/28338387/comparison-of-the-effects-of-curcumin-and-rg108-on-ngf-induced-pc-12%C3%A2-adh-cell-differentiation-and-neurite-outgrowth
#5
Miriş Dikmen
DNA methyltransferases (DNMTs) are promising epigenetic targets for the development of novel drugs, especially for neurodegenerative disorders. In recent years, there has been increased interest in small molecules that can cross the blood-brain barrier for the treatment of neurodegenerative diseases. Therefore, comparing the neuronal differentiative effects of a natural compound curcumin and a synthetic small molecule RG108 was the aim of this study. The effects of curcumin and RG108 on neuronal differentiation and neurite outgrowth were investigated in the PC-12 Adh cell line...
March 24, 2017: Journal of Medicinal Food
https://www.readbyqxmd.com/read/28337976/antiproliferative-activity-of-crocin-involves-targeting-of-microtubules-in-breast-cancer-cells
#6
Rupali R Hire, Shalini Srivastava, Melissa B Davis, Ananda Kumar Konreddy, Dulal Panda
Crocin, a component of saffron spice, is known to have an anticancer activity. However, the targets of crocin are not known. In this study, crocin was found to inhibit the proliferation of HCC70, HCC1806, HeLa and CCD1059sk cells by targeting microtubules. Crocin depolymerized both the interphase and mitotic microtubules of different cancer cells, inhibited mitosis and induced multipolar spindle formation in these cells. In vitro, crocin inhibited the assembly of pure tubulin as well as the assembly of microtubule-associated protein rich tubulin...
March 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28337381/hla-e-inhibitor-enhances-the-killing-of-neuroblastoma-stem-cells-by-co-cultured-dendritic-cells-and-cytokine-induced-killer-cells-loaded-with-membrane-based-microparticles
#7
Zijun Zhen, Kaibin Yang, Litong Ye, Zhiyao You, Rirong Chen, Ying Liu, Youjian He
Neuroblastoma stem cells (NSCs) can cause drug resistance and tumor recurrence. This study aimed to enhance the lytic effect of dendritic cells (DCs) co-cultured with cytokine-induced killer (CIK) cells. NSCs were obtained by suspension culture, and DC-CIK cells were loaded with extracted NSC membrane-based microparticles (MMPs) before evaluating the lytic effect of DC-CIK cells on NSCs. After inhibiting the function or expression of human leukocyte antigen-E (HLA-E) in NSCs by anti-HLA-E monoclonal antibody or siRNA, the DC-CIK cell lytic effect on NSCs was re-assessed...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/28336393/contributions-of-%C3%AE-tubulin-to-cellular-morphology-sporulation-and-virulence-in-the-insect-fungal-pathogen-metarhizium-acridum
#8
Jie Zhang, Kai Jin, Yuxian Xia
β-tubulin is an elementary subunit of microtubules that form the cytoskeleton, participating in a wide range of cellular processes. The contributions of the single β-tubulin gene in affecting cell morphology, sporulation and virulence were examined in the entomopathogenic fungus Metarhizium acridum. Targeted gene knockout of β-tubulin resulted in resistance to benomyl but impaired proper nuclear segregation, lipid droplet transport, and deposition of chitin to the cell wall. M. acridum β-tubulin mutants displayed wavy hyphal growth and densely packed, wrinkled colonies...
March 20, 2017: Fungal Genetics and Biology: FG & B
https://www.readbyqxmd.com/read/28336134/evaluation-of-matrix-assisted-laser-desorption-ionization-time-of-fight-mass-spectrometry-for-identification-of-345-clinical-isolates-of-aspergillus-species-from-11-korean-hospitals-comparison-with-molecular-identification
#9
Ju Heon Park, Jong Hee Shin, Min Ji Choi, Jin Un Choi, Yeon-Joon Park, Sook Jin Jang, Eun Jeong Won, Soo Hyun Kim, Seung Jung Kee, Myung Geun Shin, Soon Pal Suh
We evaluated the ability of the Filamentous Fungi Library 1.0 of the MALDI-TOF MS Biotyper system to identify 345 clinical Aspergillus isolates from 11 Korean hospitals. Compared with results of the internal transcribed spacer region sequencing, the frequencies of correct identification at the species-complex level were 94.5% and 98.8% with cutoff values of 2.0 and 1.7, respectively. Compared with results of β-tubulin gene sequencing, the frequencies of correct identification at the species level were 96.0% (cutoff 2...
January 2017: Diagnostic Microbiology and Infectious Disease
https://www.readbyqxmd.com/read/28335606/isolation-and-identification-of-the-novel-tubulin-polymerization-inhibitor-bifidenone
#10
Russell B Williams, Steven M Martin, Julie A Lawrence, Vanessa L Norman, Mark O'Neil-Johnson, Gary R Eldridge, Courtney M Starks
The pursuit of structurally novel compounds has led to the isolation of a series of neolignans (2-6), for which the structures have been determined from microgram quantities using microcryoprobe NMR technology. Compounds 2-6 provided some unexpectedly clear structure-activity relationship data, with compound 2 demonstrating significantly more potency in the in vitro cytotoxicity assay than the other analogues. Further screening found that compound 2 induces apoptosis with activation of caspase 3/7. The NCI Compare algorithm suggested that compound 2 acts through the inhibition of tubulin/microtubule dynamics...
March 24, 2017: Journal of Natural Products
https://www.readbyqxmd.com/read/28335076/fine-mapping-of-chromosome-5p15-33-identifies-novel-lung-cancer-susceptibility-loci-in-han-chinese
#11
Jing Dong, Yang Cheng, Meng Zhu, Yang Wen, Cheng Wang, Yuzhuo Wang, Liguo Geng, Wei Shen, Jia Liu, Zhihua Li, Jiahui Zhang, Hongxia Ma, Juncheng Dai, Guangfu Jin, Zhibin Hu, Hongbing Shen
Genome-wide association studies in European and Asian populations have consistently identified chromosome 5p15.33 as a lung cancer susceptibility region. To investigate further the genetic architecture of common variants in this region, we conducted a two-stage fine-mapping analysis discovered by targeted resequencing of 200 cases and 300 controls individually, and validated in multiethnic lung cancer GWASs with 12,843 cases and 12,639 controls. Two independent variants were identified in approximate conditional analysis with GCTA and consistently validated in lung cancer GWASs in both Asian and European populations...
March 23, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28334871/proteomics-insights-into-infantile-neuronal-ceroid-lipofuscinosis-cln1-point-to-the-involvement-of-cilia-pathology-in-the-disease
#12
Michal Segal-Salto, Karin Hansson, Tamar Sapir, Anna Kaplan, Talia Levy, Michaela Schwizer, Michael Frotscher, Peter James, Orly Reiner
Mutations in the depalmitoylation enzyme, palmitoyl protein thioesterase (PPT1), result in the early onset neurodegenerative disease known as Infantile Neuronal Ceroid Lipofuscinosis. Here, we provide proteomic evidence suggesting that PPT1 deficiency could be considered as a ciliopathy. Analysis of membrane proteins from brain enriched for acylated proteins from neonate Ppt1 knock out and control mice revealed a list of 88 proteins with differential expression levels. Amongst them, we identified Rab3IP, which regulates ciliogenesis in concert with Rab8 and Rab11...
March 6, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28334696/effects-of-hypergravity-on-the-angiogenic-potential-of-endothelial-cells
#13
Raquel Costa-Almeida, Daniel T O Carvalho, Miguel J S Ferreira, Guilherme Aresta, Manuela E Gomes, Jack J W A van Loon, Kim Van der Heiden, Pedro L Granja
Angiogenesis, the formation of blood vessels from pre-existing ones, is a key event in pathology, including cancer progression, but also in homeostasis and regeneration. As the phenotype of endothelial cells (ECs) is continuously regulated by local biomechanical forces, studying endothelial behaviour in altered gravity might contribute to new insights towards angiogenesis modulation. This study aimed at characterizing EC behaviour after hypergravity exposure (more than 1g), with special focus on cytoskeleton architecture and capillary-like structure formation...
November 2016: Journal of the Royal Society, Interface
https://www.readbyqxmd.com/read/28333984/synthesis-and-bioevaluation-of-n-4-diaryl-1-3-thiazole-2-amines-as-tubulin-inhibitors-with-potent-antiproliferative-activity
#14
Maolin Sun, Qile Xu, Jingwen Xu, Yue Wu, Yueting Wang, Daiying Zuo, Qi Guan, Kai Bao, Jian Wang, Yingliang Wu, Weige Zhang
A series of N,4-diaryl-1,3-thiazole-2-amines containing three aromatic rings with an amino linker were designed and synthesized as tubulin inhibitors and evaluated for their antiproliferative activity in three human cancer cell lines. Most of the target compounds displayed moderate antiproliferative activity, and N-(2,4-dimethoxyphenyl)-4-(4-methoxyphenyl)-1,3-thiazol-2-amine (10s) was determined to be the most potent compound. Tubulin polymerization and immunostaining experiments revealed that 10s potently inhibited tubulin polymerization and disrupted tubulin microtubule dynamics in a manner similar to CA-4...
2017: PloS One
https://www.readbyqxmd.com/read/28333264/single-cell-transcriptomics-mega-phylogeny-and-the-genetic-basis-of-morphological-innovations-in-rhizaria
#15
Anders K Krabberød, Russell J S Orr, Jon Bråte, Tom Kristensen, Kjell R Bjørklund, Kamran Shalchian-Tabrizi
The innovation of the eukaryote cytoskeleton enabled phagocytosis, intracellular transport and cytokinesis, and is responsible for the diversity of eukaryotic morphologies. Still, the relationship between phenotypic innovations in the cytoskeleton and their underlying genotype is poorly understood. To explore the genetic mechanism of morphological evolution of the eukaryotic cytoskeleton we provide the first single cell transcriptomes from uncultured, free-living unicellular eukaryotes: the polycystine radiolarian Lithomelissa setosa (Nassellaria) and Sticholonche zanclea (Taxopodida)...
March 1, 2017: Molecular Biology and Evolution
https://www.readbyqxmd.com/read/28333241/dysmorphic-patterns-are-associated-with-cytoskeletal-alterations-in-human-oocytes
#16
Mariabeatrice Dal Canto, Maria Cristina Guglielmo, Mario Mignini Renzini, Rubens Fadini, Clarissa Moutier, Maria Merola, Elena De Ponti, Giovanni Coticchio
Study Question: Are specific morphological anomalies in human mature oocytes, as revealed by transmitted light microscopy, associated with intrinsic damage to the meiotic spindle and actin cytoskeleton? SUMMARY ANSWER: Aggregates of smooth endoplasmic reticulum (SER) and domains of centrally localized granular cytoplasm (GC) reflect intrinsic damage to the oocyte cytoskeleton, namely alterations in spindle size, chromosome misalignment and cortical actin disorganization...
March 1, 2017: Human Reproduction
https://www.readbyqxmd.com/read/28328318/toward-discovery-of-novel-microtubule-targeting-agents-a-snap-tag-based-high-content-screening-assay-for-the-analysis-of-microtubule-dynamics-and-cell-cycle-progression
#17
Nina Berges, Katharina Arens, Verena Kreusch, Rainer Fischer, Stefano Di Fiore
Microtubule targeting agents (MTAs) are used for the treatment of cancer. Novel MTAs could provide additional and beneficial therapeutic options. To improve the sensitivity and throughput of standard immunofluorescence assays for the characterization of MTAs, we used SNAP-tag technology to produce recombinant tubulin monomers. To visualize microtubule filaments, A549 cells transfected with SNAP-tubulin were stained with a membrane-permeable, SNAP-reactive dye. The treatment of SNAP-tubulin cells with stabilizing MTAs such as paclitaxel resulted in the formation of coarsely structured microtubule filaments, whereas depolymerizing MTAs such as nocodazole resulted in diffuse staining patterns in which the tubulin filaments were no longer distinguishable...
April 2017: SLAS Discov
https://www.readbyqxmd.com/read/28328017/dental-pulp-stem-cells-promote-regeneration-of-damaged-neuron-cells-on-the-cellular-model-of-alzheimer-s-disease
#18
Feixiang Wang, Yali Jia, Jiajing Liu, Jinglei Zhai, Ning Cao, Wen Yue, Huixia He, Xuetao Pei
Alzheimer's disease (AD) is an incurable neurodegenerative disease and many types of stem cells have been used in AD therapy with some favorable effects. In this study, we investigated the potential therapeutical effects of human dental pulp stem cells (hDPSCs) on AD cellular model which established by okadaic acid (OA)-induced damage to human neuroblastoma cell line, SH-SY5Y, in vitro for 24h. After confirmed the AD cellular model, the cells were co-culture with hDPSCs by transwell co-culture system till 24 h for treatment...
March 22, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28325758/the-tubulin-code-at-a-glance
#19
REVIEW
Sudarshan Gadadhar, Satish Bodakuntla, Kathiresan Natarajan, Carsten Janke
Microtubules are key cytoskeletal elements of all eukaryotic cells and are assembled of evolutionarily conserved α-tubulin-β-tubulin heterodimers. Despite their uniform structure, microtubules fulfill a large diversity of functions. A regulatory mechanism to control the specialization of the microtubule cytoskeleton is the 'tubulin code', which is generated by (i) expression of different α- and β-tubulin isotypes, and by (ii) post-translational modifications of tubulin. In this Cell Science at a Glance article and the accompanying poster, we provide a comprehensive overview of the molecular components of the tubulin code, and discuss the mechanisms by which these components contribute to the generation of functionally specialized microtubules...
March 21, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28323401/zinc-and-copper-effects-on-stability-of-tubulin-and-actin-networks-in-dendrites-and-spines-of-hippocampal-neurons
#20
Laura Perrin, Stephane Roudeau, Asuncion Carmona, Florelle Domart, Jennifer D Petersen, Sylvain Bohic, Yang Yang, Peter Cloetens, Richard Ortega
Zinc and copper ions can modulate the activity of glutamate-receptors. However, labile zinc and copper ions likely represent only the tip of the iceberg and other neuronal functions are suspected for these metals in their bound state. We performed synchrotron X-ray fluorescence imaging with 30 nm resolution to image total biometals in dendrites and spines from hippocampal neurons. We found that zinc is distributed all along the dendrites while copper is mainly pinpointed within the spines. In spines, zinc content is higher within the spine head while copper is higher within the spine neck...
March 21, 2017: ACS Chemical Neuroscience
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