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221.
Anchorage-independent growth is a characteristic feature of cancer cells. However, it is unclear whether it represents a cause or a consequence of tumorigenesis. For normal cells, integrin-mediated adhesion is required for completion of the G1 and cytokinesis stages of the cell cycle. This study identified a mechanism that can drive anchorage-independent growth if the G1 checkpoint is suppressed. Cells with defective G1 checkpoint progressed through several rounds of the cell cycle in suspension in spite of uncompleted cytokinesis, thereby forming bi- and multilobular cells. Aurora B and CEP55 were localized to midbodies between the lobes, suggesting that the cytokinesis process reached close to abscission. Integrin-mediated re-attachment of such cells induced cytokinesis completion uncoupled from karyokinesis in most cells. However, a portion of the cells instead lost the constriction and became binucleated. Also, long-term suspension culture in soft agar produced colonies where the cytokinesis block was overcome. This process was fibronectin-dependent since fibronectin-deficient cells did not form colonies unless fibronectin was expressed or exogenously added. While fibronectin normally is not deposited on non-adherent single cells, bi/multilobular cells accumulated fibronectin in the intussusceptions. Based on our data we conclude: 1) Suppression of the G1 checkpoint allows multiple rounds of the cell cycle in detached cells and thereby enables matrix formation on their surface. 2) Uncompleted cytokinesis due to cell detachment resumes if integrin interactions are re-formed, allowing colony formation in soft agar 3) Such delayed cell division can generate binucleated cells, a feature known to cause chromosomal instability. 相似文献
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Guixin Shi Wenjin Cui Michael Benchimol Yu-Tsueng Liu Robert F. Mattrey Rajesh Mukthavaram Santosh Kesari Sadik C. Esener Dmitri Simberg 《PloS one》2013,8(3)
Circulating tumor cells (CTCs) are exfoliated at various stages of cancer, and could provide invaluable information for the diagnosis and prognosis of cancers. There is an urgent need for the development of cost-efficient and scalable technologies for rare CTC enrichment from blood. Here we report a novel method for isolation of rare tumor cells from excess of blood cells using gas-filled buoyant immuno-microbubbles (MBs). MBs were prepared by emulsification of perfluorocarbon gas in phospholipids and decorated with anti-epithelial cell adhesion molecule (EpCAM) antibody. EpCAM-targeted MBs efficiently (85%) and rapidly (within 15 minutes) bound to various epithelial tumor cells suspended in cell medium. EpCAM-targeted MBs efficiently (88%) isolated frequent tumor cells that were spiked at 100,000 cells/ml into plasma-depleted blood. Anti-EpCAM MBs efficiently (>77%) isolated rare mouse breast 4T1, human prostate PC-3 and pancreatic cancer BxPC-3 cells spiked into 1, 3 and 7 ml (respectively) of plasma-depleted blood. Using EpCAM targeted MBs CTCs from metastatic cancer patients were isolated, suggesting that this technique could be developed into a valuable clinical tool for isolation, enumeration and analysis of rare cells. 相似文献
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Addressing the neural mechanisms underlying complex learned behaviors requires training animals in well-controlled tasks, an often time-consuming and labor-intensive process that can severely limit the feasibility of such studies. To overcome this constraint, we developed a fully computer-controlled general purpose system for high-throughput training of rodents. By standardizing and automating the implementation of predefined training protocols within the animal’s home-cage our system dramatically reduces the efforts involved in animal training while also removing human errors and biases from the process. We deployed this system to train rats in a variety of sensorimotor tasks, achieving learning rates comparable to existing, but more laborious, methods. By incrementally and systematically increasing the difficulty of the task over weeks of training, rats were able to master motor tasks that, in complexity and structure, resemble ones used in primate studies of motor sequence learning. By enabling fully automated training of rodents in a home-cage setting this low-cost and modular system increases the utility of rodents for studying the neural underpinnings of a variety of complex behaviors. 相似文献
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Meena Rajesh Kumar Reddy Kanubothula Sitarami Gautam Ranjana Maddela Surender Reddy Attipalli Ramachandra Gudipalli Padmaja 《Photosynthesis research》2021,147(3):253-267
Photosynthesis Research - Heterosis is a phenomenon wherein F1 hybrid often displays phenotypic superiority and surpasses its parents in terms of growth and agronomic traits. Investigations on the... 相似文献
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Preliminary results on the photoluminescence and optically stimulated luminescence in Cu‐doped and Ag‐doped ZnB2X4 (B = Li,Na, K: X = Cl,Br) compounds
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Photoluminescence, and optically stimulated luminescence in ZnB2X4 (B; Li,Na,K: X; Cl,Br) compounds doped with Cu+ or Ag+ were studied. Double humped emission bands attributable to the activators were observed in all the samples. The observed photoluminescence of Cu+ and Ag+ could be identified with 3d94s1?3d10 and 4d95s1?5d10 transitions respectively. The longer wavelength band (400–500 nm range) could be attributed to the Cu+ or Ag+ ion replacing alkali ion at the octahedral alkali site whereas short wavelength band (340–400 nm range) is attributed to a Cu or Ag ion at tetrahedral zinc site. The short wavelength band was found to be intense compared with long wavelength and gave an indication that most of the Cu or Ag ions prefered a tetrahedral Zn site compared with the octahedral alkali site. All the samples exhibit optically stimulated luminescence (OSL). The sensitivity was found to be lattice dependent. The lowest sensitivity of about 1% compared with Al2O3:C was observed in lithium lattices whereas highest the sensitivity of about 290% was observed in the case of Cu‐doped ZnNa2Br4. 相似文献
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Daniel K. Afosah Stephen Verespy Rami A. Al-Horani Rio S. Boothello Rajesh Karuturi Umesh R. Desai 《Bioorganic & medicinal chemistry letters》2018,28(6):1101-1105
Despite the development of promising direct oral anticoagulants, which are all orthosteric inhibitors, a sizable number of patients suffer from bleeding complications. We have hypothesized that allosterism based on the heparin-binding exosites presents a major opportunity to induce sub-maximal inhibition of coagulation proteases, thereby avoiding/reducing bleeding risk. We present the design of a group of sulfated benzofuran dimers that display heparin-binding site-dependent partial allosteric inhibition of thrombin against fibrinogen (ΔY?=?55–75%), the first time that a small molecule (MW??<?800) has been found to thwart macromolecular cleavage by a monomeric protease in a controlled manner. The work leads to the promising concept that it should be possible to develop allosteric inhibitors that reduce clotting, but do not completely eliminate it, thereby avoiding major bleeding complications that beset anticoagulants today. 相似文献
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Carlson Courtney Singh Nitin K. Bibra Mohit Sani Rajesh K. Venkateswaran Kasthuri 《Applied microbiology and biotechnology》2018,102(4):1869-1887
Applied Microbiology and Biotechnology - We have characterized a broad collection of extremophilic bacterial isolates from a deep subsurface mine, compost dumping sites, and several hot spring... 相似文献