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https://www.readbyqxmd.com/read/28342760/correction-of-hirschsprung-associated-mutations-in-human-induced-pluripotent-stem-cells-via-crispr-cas9-restores-neural-crest-cell-function
#1
Frank Pui-Ling Lai, Sin-Ting Lau, John Kwong-Leong Wong, Hongsheng Gui, Reeson Xu Wang, Tingwen Zhou, Wing Hon Lai, Hung-Fat Tse, Paul Kwong-Hang Tam, Maria-Mercedes Garcia-Barcelo, Elly Sau-Wai Ngan
BACKGROUND & AIM: Hirschsprung disease is caused by failure of enteric neural crest cells (ENCCs) to fully colonize the bowel, leading to bowel obstruction and megacolon. Heterozygous mutations in the coding region of the RET gene cause a severe form of Hirschsprung disease (total colonic aganglionosis). However, 80% of HSCR patients have short-segment Hirschsprung disease (S-HSCR), which has not been associated with genetic factors. We sought to identify mutations associated S-HSCR, and used the CRISPR/Cas9 gene editing system to determine how mutations affect ENCC function...
March 22, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28316141/dasatinib-inhibits-actin-fiber-reorganization-and-promotes-endothelial-cell-permeability-through-rhoa-rock-pathway
#2
Swapan K Dasgupta, Anhquyen Le, K Vinod Vijayan, Perumal Thiagarajan
Treatment with dasatinib, a tyrosine kinase inhibitor, is associated with edema, pleural effusion, and pulmonary edema. We investigated the effect of dasatinib on the barrier function of human microvascular endothelial cells-1 (HMEC-1) in vitro and in vivo. The permeability of HMEC-1 to fluorescein isothiocyante (FITC)-dextran increased in Transwell chambers within 5 min following the addition of therapeutic concentrations of dasatinib. The change in permeability was associated with increased activation of RhoA GTPase and its effector Rho-associated coiled-coil kinase 1(ROCK1)...
March 18, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28302906/distinct-focal-adhesion-protein-modules-control-different-aspects-of-mechanotransduction
#3
Ben Stutchbury, Paul Atherton, Ricky Tsang, De-Yao Wang, Christoph Ballestrem
Focal adhesions (FAs) are macromolecular complexes that regulate cell adhesion and mechanotransduction. Using fluorescence recovery after photobleaching (FRAP) and fluorescence loss after photoactivation (FLAP), we found that the mobility of core FA proteins correlates with protein function. Structural proteins such as tensin, talin and vinculin are significantly less mobile in FAs than signaling proteins such as FAK and paxillin. The mobilities of the structural proteins are directly influenced by substrate stiffness, suggesting they are involved in sensing the rigidity of the extracellular environment...
March 16, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28299994/the-changes-of-cytoskeletal-proteins-induced-by-the-fast-effect-of-estrogen-in-mouse-blastocysts-and-its-roles-in-implantation
#4
Shi-Mao Zhang, Lin-Lin Yu, Ting Qu, Ying Hu, Dong-Zhi Yuan, Sheng Zhang, Qian Xu, You-Bo Zhao, Jin-Hu Zhang, Li-Min Yue
It is necessary for estrogen to activate mouse blastocysts, so that they can attach to endometrial epithelium in implantation and in our previous research, we have proved estrogen can induce a fast increase in intracellular calcium of mouse blastocysts through acting on G protein-coupled receptor 30 (GPR30), which further promotes their implantation. Moreover, there has been evidence that cytoskeletal proteins are involved in integrin-mediated adhesion of many kinds of cells, which also plays an important role in implantation...
January 1, 2017: Reproductive Sciences
https://www.readbyqxmd.com/read/28292367/myofibroblast-mediated-contraction
#5
Wae M Al Kattan, Seham F Alarfaj, Bayan M Alnooh, Hadeel F Alsaif, Hayfa S Alabdul Karim, Noha M Al-Qattan, Mohammad M Al-Qattan, Amel A F El-Sayed
Myofibroblast-mediated contraction is viewed as a cycle of four steps. The first step is stimulation of myofibroblasts by lysophospholipids leading to the activation of G proteins and ending with contraction of the actin-myosin complex. The next step is the transmission of the intracellular contractile force at the focal adhesions of myofibroblasts; a step that involves talin, vinculin, paxillin, Hic-5, and the integrin receptors. In the third step, fibronectin will act as the extracellular link between the integrin receptors and the extracellular collagen...
January 2017: Journal of the College of Physicians and Surgeons—Pakistan: JCPSP
https://www.readbyqxmd.com/read/28286026/clonorchis-sinensis-excretory-secretory-products-promote-the-migration-and-invasion-of-cholangiocarcinoma-cells-by-activating-the-integrin-%C3%AE-4-fak-src-signaling-pathway
#6
Jhang Ho Pak, Qudsia Bashir, In Ki Kim, Sung-Jong Hong, Sejung Maeng, Young Yil Bahk, Tong-Soo Kim
Cholangiocarcinoma (CCA) is a slow-growing but highly metastatic cancer. Its metastatic potential largely explains its high mortality rate. A recognized risk factor for CCA development is infection with the liver flukes Opisthorchis viverrini and Clonorchis sinensis. We previously reported that the excretory-secretory products (ESPs) of C. sinensis promoted the three-dimensional aggregation and invasion of CCA cells. In the present study, a quantitative real-time PCR array of extracellular matrix (ECM) and adhesion molecules was used to examine the regulatory mechanism of ESP-mediated CCA cell migration and invasion...
March 8, 2017: Molecular and Biochemical Parasitology
https://www.readbyqxmd.com/read/28273809/proteome-analysis-of-human-follicular-thyroid-cancer-cells-exposed-to-the-random-positioning-machine
#7
Johann Bauer, Sascha Kopp, Elisabeth Maria Schlagberger, Jirka Grosse, Jayashree Sahana, Stefan Riwaldt, Markus Wehland, Ronald Luetzenberg, Manfred Infanger, Daniela Grimm
Several years ago, we detected the formation of multicellular spheroids in experiments with human thyroid cancer cells cultured on the Random Positioning Machine (RPM), a ground-based model to simulate microgravity by continuously changing the orientation of samples. Since then, we have studied cellular mechanisms triggering the cells to leave a monolayer and aggregate to spheroids. Our work focused on spheroid-related changes in gene expression patterns, in protein concentrations, and in factors secreted to the culture supernatant during the period when growth is altered...
March 3, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28266545/loss-of-er%C3%AE-induces-amoeboid-like-migration-of-breast-cancer-cells-by-downregulating-vinculin
#8
Yuan Gao, Zhaowei Wang, Qiang Hao, Weina Li, Yujin Xu, Juliang Zhang, Wangqian Zhang, Shuning Wang, Shuo Liu, Meng Li, Xiaochang Xue, Wei Zhang, Cun Zhang, Yingqi Zhang
Oestrogen receptor alpha (ERα) is a well-known target of endocrine therapy for ERα-positive breast cancer. ERα-negative cells, which are enriched during endocrine therapy, are associated with metastatic relapse. Here we determine that loss of ERα in the invasive front and in lymph node metastasis in human breast cancer is significantly correlated with lymphatic metastasis. Using in vivo and in vitro experiments, we demonstrate that ERα inhibits breast cancer metastasis. Furthermore, we find that ERα is a novel regulator of vinculin expression in breast cancer...
March 7, 2017: Nature Communications
https://www.readbyqxmd.com/read/28262301/effects-of-alcohol-on-postoperative-adhesion-formation-in-ischemic-myocardium-and-pericardium
#9
Nassrene Y Elmadhun, Ashraf A Sabe, Antonio D Lassaletta, Rahul S Dalal, Frank W Sellke
BACKGROUND: Postoperative formation of adhesions increases risk of complications during cardiac reoperations. We previously demonstrated that swine supplemented with vodka had a significant reduction in adhesions at sternotomy after previous thoracotomy. This follow-up study was conducted to determine reproducibility and the mechanism for adhesion reduction in swine supplemented with ethanol. METHODS: An ameroid constrictor was placed in the left circumflex in 14 male Yorkshire swine to induce chronic myocardial ischemia through left minithoracotomy...
March 2, 2017: Annals of Thoracic Surgery
https://www.readbyqxmd.com/read/28251141/vinculin-at-the-heart-of-aging
#10
COMMENT
William H Bradford, Jeffrey H Omens, Farah Sheikh
No abstract text is available yet for this article.
February 2017: Annals of Translational Medicine
https://www.readbyqxmd.com/read/28230777/cryptomphalus-aspersa-mollusc-egg-extract-promotes-regenerative-effects-in-human-dermal-papilla-stem-cells
#11
María Teresa Alameda, Esther Morel, Concepción Parrado, Salvador González, Ángeles Juarranz
The aim of this study was to test, by an in vitro approach, whether a natural extract derived from eggs of the mollusc Cryptomphalus aspersa (e-CAF) that seems to present regenerative properties, can enhance the mobilization of human hair dermal papilla cells (HHDPCs) and play a role on tissue repair and regeneration. We have tested HHDPCs proliferation by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium-bromide (MTT) assay; cell migration by using a wound healing assay, as well as the modulation of the expression of cytoskeletal (F-actin and vimentin) and cell adhesion to the extracellular matrix (ECM) (vinculin and P-FAK) proteins...
February 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28223221/the-atheroma-plaque-secretome-stimulates-the-mobilization-of-endothelial-progenitor-cells-ex-vivo
#12
Francisco M Vega, Violette Gautier, Cecilia M Fernandez-Ponce, M J Extremera, A F M Altelaar, Jaime Millan, Juan C Tellez, Jose A Hernandez-Campos, Rosario Conejero, Jorge Bolivar, Ricardo Pardal, Francisco J Garcia-Cózar, Enrique Aguado, Albert J R Heck, Mª Carmen Duran-Ruiz
Endothelial progenitor cells (EPCs) constitute a promising alternative in cardiovascular regenerative medicine due to their assigned role in angiogenesis and vascular repair. In response to injury, EPCs promote vascular remodeling by replacement of damaged endothelial cells and/or by secreting angiogenic factors over the damaged tissue. Nevertheless, such mechanisms need to be further characterized. In the current approach we have evaluated the initial response of early EPCs (eEPCs) from healthy individuals after direct contact with the factors released by carotid arteries complicated with atherosclerotic plaques (AP), in order to understand the mechanisms underlying the neovascularization and remodeling properties assigned to these cells...
February 20, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28218910/a-mechanically-active-heterotypic-e-cadherin-n-cadherin-adhesion-enables-fibroblasts-to%C3%A2-drive-cancer-cell-invasion
#13
Anna Labernadie, Takuya Kato, Agustí Brugués, Xavier Serra-Picamal, Stefanie Derzsi, Esther Arwert, Anne Weston, Victor González-Tarragó, Alberto Elosegui-Artola, Lorenzo Albertazzi, Jordi Alcaraz, Pere Roca-Cusachs, Erik Sahai, Xavier Trepat
Cancer-associated fibroblasts (CAFs) promote tumour invasion and metastasis. We show that CAFs exert a physical force on cancer cells that enables their collective invasion. Force transmission is mediated by a heterophilic adhesion involving N-cadherin at the CAF membrane and E-cadherin at the cancer cell membrane. This adhesion is mechanically active; when subjected to force it triggers β-catenin recruitment and adhesion reinforcement dependent on α-catenin/vinculin interaction. Impairment of E-cadherin/N-cadherin adhesion abrogates the ability of CAFs to guide collective cell migration and blocks cancer cell invasion...
February 20, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28218286/vinculin-variant-m94i-identified-in-sudden-unexplained-nocturnal-death-syndrome-decreases-cardiac-sodium-current
#14
Jianding Cheng, John W Kyle, Brandi Wiedmeyer, Di Lang, Ravi Vaidyanathan, Jonathan C Makielski
Sudden unexplained nocturnal death syndrome (SUNDS) remains an autopsy negative disorder with unclear etiology. Vinculin (VCL) was linked to sudden arrhythmia death in VCL knockout mice prior to the appearance of cardiomyopathy. We hypothesized VCL mutations underlie risk for SUNDS. A rare heterozygous variant VCL-M94I was found in a SUNDS victim who suffered sudden nocturnal tachypnea and lacked pathogenic variants in known arrhythmia-causing genes. VCL was identified to interact with SCN5A in vitro/vivo. The VCL-M94I was co-expressed with the cardiac sodium channel in HEK293 cells and also overexpressed in induced pluripotent stem cells derived cardiomyocytes (iPSCs-CM)...
February 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28205330/effect-of-matrix-stiffness-on-osteoblast-functionalization
#15
Tao Zhang, Shiyu Lin, Xiaoru Shao, Qi Zhang, Changyue Xue, Shu Zhang, Yunfeng Lin, Bofeng Zhu, Xiaoxiao Cai
OBJECTIVES: Stiffness of bone tissue differs response to its physiological or pathological status, such as osteoporosis or osteosclerosis. Consequently, the function of cells residing in bone tissue including osteoblasts (OBs), osteoclasts and osteocytes will be affected. However, to the best of our knowledge, the detailed mechanism of how extracellular matrix stiffness affects OB function remains unclear. MATERIALS AND METHODS: We conducted a study that exposed rat primary OBs to polydimethylsiloxane substrates with varied stiffness to investigate the alterations of cell morphology, osteoblastic differentiation and its potential mechanism in mechanotransduction...
February 15, 2017: Cell Proliferation
https://www.readbyqxmd.com/read/28185193/activation-and-differentiation-of-mesenchymal-stem-cells
#16
Pravin J Mishra, Debabrata Banerjee
Mesenchymal stem cells (MSCs) are multipotent cells and exhibit two main characteristics that define stem cells: self-renewal and differentiation. MSCs can migrate to sites of injury, inflammation, and tumor. Moreover, MSCs undergo myofibroblast like differentiation, including increased production of α-SMA in response to transforming growth factor-β (TGF-β), a growth factor commonly secreted by tumor cells to evade immune surveillance. Based on our previous finding hMSCs become activated and resemble carcinoma-associated myofibroblasts upon prolonged exposure to conditioned medium from MDAMB231 human breast cancer cells...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28174098/effects-of-organophosphates-on-the-regulation-of-mesenchymal-stem-cell-proliferation-and-differentiation
#17
Amber M Prugh, Stephanie D Cole, Trevor Glaros, Daniel J Angelini
Mesenchymal stem cells (MSCs) are multipotent cells located within various adult tissues. Recent literature has reported that human bone marrow-derived MSCs express active acetylcholinesterase (AChE) and that disruption of AChE activity by organophosphate (OP) chemicals decreases the ability of MSCs to differentiate into osteoblasts. The potential role of AChE in regulating MSC proliferation and differentiation is currently unknown. In the present study, we demonstrate that MSCs exposed to OPs have both decreased AChE activity and abundance...
March 25, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28168610/the-spatiotemporal-control-of-osteoblast-cell-growth-behavior-and-function-dictated-by-nanostructured-stainless-steel-artificial-microenvironments
#18
Udesh Dhawan, Hsu-An Pan, Meng-Je Shie, Ying Hao Chu, Guewha S Huang, Po-Chun Chen, Wen Liang Chen
The successful application of a nanostructured biomaterial as an implant is strongly determined by the nanotopography size triggering the ideal cell response. Here, nanoporous topography on 304L stainless steel substrates was engineered to identify the nanotopography size causing a transition in the cellular characteristics, and accordingly, the design of nanostructured stainless steel surface as orthopedic implants is proposed. A variety of nanopore diameters ranging from 100 to 220 nm were fabricated by one-step electrolysis process and collectively referred to as artificial microenvironments...
December 2017: Nanoscale Research Letters
https://www.readbyqxmd.com/read/28155694/%C3%AE-1-integrin-signaling-in-asymmetric-migration-of-keratinocytes-under-mechanical-stretch-in-a-co-cultured-wound-repair-model
#19
Dongyuan Lü, Zhan Li, Yuxin Gao, Chunhua Luo, Fan Zhang, Lu Zheng, Jiawen Wang, Shujin Sun, Mian Long
BACKGROUND: Keratinocyte (KC) migration in re-epithelization is crucial in repairing injured skin. But the mechanisms of how mechanical stimuli regulate the migration of keratinocytes have been poorly understood. METHODS: Human immortalized keratinocyte HaCaT cells were co-cultured with skin fibroblasts on PDMS membranes and transferred to the static stretch device developed in-house for additional 6 day culture under mechanical stretch to mimic surface tension in skin...
December 28, 2016: Biomedical Engineering Online
https://www.readbyqxmd.com/read/28147641/monitoring-in-real-time-focal-adhesion-protein-dynamics-in-response-to-a-discrete-mechanical-stimulus
#20
Catalina von Bilderling, Martín Caldarola, Martín E Masip, Andrea V Bragas, Lía I Pietrasanta
The adhesion of cells to the extracellular matrix is a hierarchical, force-dependent, multistage process that evolves at several temporal scales. An understanding of this complex process requires a precise measurement of forces and its correlation with protein responses in living cells. We present a method to quantitatively assess live cell responses to a local and specific mechanical stimulus. Our approach combines atomic force microscopy with fluorescence imaging. Using this approach, we evaluated the recruitment of adhesion proteins such as vinculin, focal adhesion kinase, paxillin, and zyxin triggered by applying forces in the nN regime to live cells...
January 2017: Review of Scientific Instruments
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