Structural, biochemical, cellular, and functional changes in skeletal muscle extracellular matrix with aging

DEFF Research Database (Denmark)

Kragstrup, Tue Wenzel; Kjaer, M; Mackey, A L

2011-01-01

The extracellular matrix (ECM) of skeletal muscle is critical for force transmission and for the passive elastic response of skeletal muscle. Structural, biochemical, cellular, and functional changes in skeletal muscle ECM contribute to the deterioration in muscle mechanical properties with aging......-links and a buildup of advanced glycation end-product cross-links. Altered mechanotransduction, poorer activation of satellite cells, poorer chemotactic and delayed inflammatory responses, and a change in modulators of the ECM are important cellular changes. It is possible that the structural and biochemical changes...... in skeletal muscle ECM contribute to the increased stiffness and impairment in force generated by the contracting muscle fibers seen with aging. The cellular interactions provide and potentially coordinate an adaptation to mechanical loading and ensure successful regeneration after muscle injury. Some...

A global interaction network maps a wiring diagram of cellular function

Science.gov (United States)

Costanzo, Michael; VanderSluis, Benjamin; Koch, Elizabeth N.; Baryshnikova, Anastasia; Pons, Carles; Tan, Guihong; Wang, Wen; Usaj, Matej; Hanchard, Julia; Lee, Susan D.; Pelechano, Vicent; Styles, Erin B.; Billmann, Maximilian; van Leeuwen, Jolanda; van Dyk, Nydia; Lin, Zhen-Yuan; Kuzmin, Elena; Nelson, Justin; Piotrowski, Jeff S.; Srikumar, Tharan; Bahr, Sondra; Chen, Yiqun; Deshpande, Raamesh; Kurat, Christoph F.; Li, Sheena C.; Li, Zhijian; Usaj, Mojca Mattiazzi; Okada, Hiroki; Pascoe, Natasha; Luis, Bryan-Joseph San; Sharifpoor, Sara; Shuteriqi, Emira; Simpkins, Scott W.; Snider, Jamie; Suresh, Harsha Garadi; Tan, Yizhao; Zhu, Hongwei; Malod-Dognin, Noel; Janjic, Vuk; Przulj, Natasa; Troyanskaya, Olga G.; Stagljar, Igor; Xia, Tian; Ohya, Yoshikazu; Gingras, Anne-Claude; Raught, Brian; Boutros, Michael; Steinmetz, Lars M.; Moore, Claire L.; Rosebrock, Adam P.; Caudy, Amy A.; Myers, Chad L.; Andrews, Brenda; Boone, Charles

2017-01-01

We generated a global genetic interaction network for Saccharomyces cerevisiae, constructing over 23 million double mutants, identifying ~550,000 negative and ~350,000 positive genetic interactions. This comprehensive network maps genetic interactions for essential gene pairs, highlighting essential genes as densely connected hubs. Genetic interaction profiles enabled assembly of a hierarchical model of cell function, including modules corresponding to protein complexes and pathways, biological processes, and cellular compartments. Negative interactions connected functionally related genes, mapped core bioprocesses, and identified pleiotropic genes, whereas positive interactions often mapped general regulatory connections among gene pairs, rather than shared functionality. The global network illustrates how coherent sets of genetic interactions connect protein complex and pathway modules to map a functional wiring diagram of the cell. PMID:27708008

Effect of liniment levamisole on cellular immune functions of patients with chronic hepatitis B.

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Wang, Ke-Xia; Zhang, Li-Hua; Peng, Jiang-Long; Liang, Yong; Wang, Xue-Feng; Zhi, Hui; Wang, Xiang-Xia; Geng, Huan-Xiong

2005-12-07

To explore the effects of liniment levamisole on cellular immune functions of patients with chronic hepatitis B. The levels of T lymphocyte subsets and mIL-2R in peripheral blood mononuclear cells (PBMCs) were measured by biotin-streptavidin (BSA) technique in patients with chronic hepatitis B before and after the treatment with liniment levamisole. After one course of treatment with liniment levamisole, the levels of CD3(+), CD4(+), and the ratio of CD4(+)/CD8(+) increased as compared to those before the treatment but the level of CD8(+) decreased. The total expression level of mIL-2R in PBMCs increased before and after the treatment with liniment levamisole. Liniment levamisole may reinforce cellular immune functions of patients with chronic hepatitis B.

Functionalized graphene oxide/Fe3O4 hybrids for cellular magnetic resonance imaging and fluorescence labeling.

Science.gov (United States)

Zhou, Chaohui; Wu, Hui; Wang, Mingliang; Huang, Chusen; Yang, Dapeng; Jia, Nengqin

2017-09-01

In this work, we developed a T 2 -weighted contrast agent based on graphene oxide (GO)/Fe 3 O 4 hybrids for efficient cellular magnetic resonance imaging (MRI). The GO/Fe 3 O 4 hybrids were obtained by combining with co-precipitation method and pyrolysis method. The structural, surface and magnetic characteristics of the hybrids were systematically characterized by transmission electron microscopy (TEM), vibrating sample magnetometer (VSM), AFM, Raman, FT-IR and XRD. The GO/Fe 3 O 4 hybrids were functionalized by modifying with anionic and cationic polyelectrolyte through layer-by-layer assembling. The fluorescence probe fluorescein isothiocyanate (FITC) was further loaded on the surface of functionalized GO/Fe 3 O 4 hybrids to trace the location of GO/Fe 3 O 4 hybrids in cells. Functionalized GO/Fe 3 O 4 hybrids possess good hydrophilicity, less cytotoxicity, high MRI enhancement with the relaxivity (r 2 ) of 493mM -1 s -1 as well as cellular MRI contrast effect. These obtained results indicated that the functionalized GO/Fe 3 O 4 hybrids could have great potential to be utilized as cellular MRI contrast agents for tumor early diagnosis and monitoring. Copyright © 2017 Elsevier B.V. All rights reserved.

One-way hash function based on hyper-chaotic cellular neural network

International Nuclear Information System (INIS)

Yang Qunting; Gao Tiegang

2008-01-01

The design of an efficient one-way hash function with good performance is a hot spot in modern cryptography researches. In this paper, a hash function construction method based on cell neural network with hyper-chaos characteristics is proposed. First, the chaos sequence is gotten by iterating cellular neural network with Runge–Kutta algorithm, and then the chaos sequence is iterated with the message. The hash code is obtained through the corresponding transform of the latter chaos sequence. Simulation and analysis demonstrate that the new method has the merit of convenience, high sensitivity to initial values, good hash performance, especially the strong stability. (general)

Toxicity of cadmium in Japanese quail: Evaluation of body weight, hepatic and renal function, and cellular immune response

International Nuclear Information System (INIS)

Sant'Ana, M.G.; Moraes, R.; Bernardi, M.M.

2005-01-01

Cadmium (Cd) is an environmental pollutant that is able to alter the immune function. Previous studies have shown that, in mammals, chronic exposure to Cd decreases the release of macrophagic cytokines such as IL1 and TNα and decreases phagocytosis activity. On the other hand contradictory results showed an increase in the humoral response. The cellular response could be decreased by exposure to Cd. These alterations were observed in mammals. The present study aimed to investigate some of the toxic effects of Cd exposure in birds. In particular, the main objective of this work was to elucidate the effects of exposure to this pollutant on the cellular immune function of the Japanese quail as a model for the study of toxicity in animals exposed in nature. The animals were exposed to the metal (100 ppm, per os) during development, i.e., from 1 to 28 days old. Body weight, biochemical parameters, and cellular immune response were measured during and at the end of treatment. The results showed that the exposure to Cd for 28 days significantly reduced the body weight and induced hepatic toxicity. The kidney function and cellular immune response were not affected by the Cd exposure

Hijacking of host cellular functions by an intracellular parasite, the microsporidian Anncaliia algerae.

Directory of Open Access Journals (Sweden)

Johan Panek

Full Text Available Intracellular pathogens including bacteria, viruses and protozoa hijack host cell functions to access nutrients and to bypass cellular defenses and immune responses. These strategies have been acquired through selective pressure and allowed pathogens to reach an appropriate cellular niche for their survival and growth. To get new insights on how parasites hijack host cellular functions, we developed a SILAC (Stable Isotope Labeling by Amino Acids in Cell culture quantitative proteomics workflow. Our study focused on deciphering the cross-talk in a host-parasite association, involving human foreskin fibroblasts (HFF and the microsporidia Anncaliia algerae, a fungus related parasite with an obligate intracellular lifestyle and a strong host dependency. The host-parasite cross-talk was analyzed at five post-infection times 1, 6, 12 and 24 hours post-infection (hpi and 8 days post-infection (dpi. A significant up-regulation of four interferon-induced proteins with tetratricopeptide repeats IFIT1, IFIT2, IFIT3 and MX1 was observed at 8 dpi suggesting a type 1 interferon (IFN host response. Quantitative alteration of host proteins involved in biological functions such as signaling (STAT1, Ras and reduction of the translation activity (EIF3 confirmed a host type 1 IFN response. Interestingly, the SILAC approach also allowed the detection of 148 A. algerae proteins during the kinetics of infection. Among these proteins many are involved in parasite proliferation, and an over-representation of putative secreted effectors proteins was observed. Finally our survey also suggests that A. algerae could use a transposable element as a lure strategy to escape the host innate immune system.

New structural and functional defects in polyphosphate deficient bacteria: A cellular and proteomic study

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Chávez Francisco P

2010-01-01

Full Text Available Abstract Background Inorganic polyphosphate (polyP, a polymer of tens or hundreds of phosphate residues linked by ATP-like bonds, is found in all organisms and performs a wide variety of functions. PolyP is synthesized in bacterial cells by the actions of polyphosphate kinases (PPK1 and PPK2 and degraded by exopolyphosphatase (PPX. Bacterial cells with polyP deficiencies due to knocking out the ppk1 gene are affected in many structural and important cellular functions such as motility, quorum sensing, biofilm formation and virulence among others. The cause of this pleiotropy is not entirely understood. Results The overexpression of exopolyphosphatase in bacteria mimicked some pleitropic defects found in ppk1 mutants. By using this approach we found new structural and functional defects in the polyP-accumulating bacteria Pseudomonas sp. B4, which are most likely due to differences in the polyP-removal strategy. Colony morphology phenotype, lipopolysaccharide (LPS structure changes and cellular division malfunction were observed. Finally, we used comparative proteomics in order to elucidate the cellular adjustments that occurred during polyP deficiency in this bacterium and found some clues that helped to understand the structural and functional defects observed. Conclusions The results obtained suggest that during polyP deficiency energy metabolism and particularly nucleoside triphosphate (NTP formation were affected and that bacterial cells overcame this problem by increasing the flux of energy-generating metabolic pathways such as tricarboxilic acid (TCA cycle, β-oxidation and oxidative phosphorylation and by reducing energy-consuming ones such as active transporters and amino acid biosynthesis. Furthermore, our results suggest that a general stress response also took place in the cell during polyP deficiency.

Rejuvenating cellular respiration for optimizing respiratory function: targeting mitochondria.

Science.gov (United States)

Agrawal, Anurag; Mabalirajan, Ulaganathan

2016-01-15

Altered bioenergetics with increased mitochondrial reactive oxygen species production and degradation of epithelial function are key aspects of pathogenesis in asthma and chronic obstructive pulmonary disease (COPD). This motif is not unique to obstructive airway disease, reported in related airway diseases such as bronchopulmonary dysplasia and parenchymal diseases such as pulmonary fibrosis. Similarly, mitochondrial dysfunction in vascular endothelium or skeletal muscles contributes to the development of pulmonary hypertension and systemic manifestations of lung disease. In experimental models of COPD or asthma, the use of mitochondria-targeted antioxidants, such as MitoQ, has substantially improved mitochondrial health and restored respiratory function. Modulation of noncoding RNA or protein regulators of mitochondrial biogenesis, dynamics, or degradation has been found to be effective in models of fibrosis, emphysema, asthma, and pulmonary hypertension. Transfer of healthy mitochondria to epithelial cells has been associated with remarkable therapeutic efficacy in models of acute lung injury and asthma. Together, these form a 3R model--repair, reprogramming, and replacement--for mitochondria-targeted therapies in lung disease. This review highlights the key role of mitochondrial function in lung health and disease, with a focus on asthma and COPD, and provides an overview of mitochondria-targeted strategies for rejuvenating cellular respiration and optimizing respiratory function in lung diseases. Copyright © 2016 the American Physiological Society.

A global genetic interaction network maps a wiring diagram of cellular function.

Science.gov (United States)

Costanzo, Michael; VanderSluis, Benjamin; Koch, Elizabeth N; Baryshnikova, Anastasia; Pons, Carles; Tan, Guihong; Wang, Wen; Usaj, Matej; Hanchard, Julia; Lee, Susan D; Pelechano, Vicent; Styles, Erin B; Billmann, Maximilian; van Leeuwen, Jolanda; van Dyk, Nydia; Lin, Zhen-Yuan; Kuzmin, Elena; Nelson, Justin; Piotrowski, Jeff S; Srikumar, Tharan; Bahr, Sondra; Chen, Yiqun; Deshpande, Raamesh; Kurat, Christoph F; Li, Sheena C; Li, Zhijian; Usaj, Mojca Mattiazzi; Okada, Hiroki; Pascoe, Natasha; San Luis, Bryan-Joseph; Sharifpoor, Sara; Shuteriqi, Emira; Simpkins, Scott W; Snider, Jamie; Suresh, Harsha Garadi; Tan, Yizhao; Zhu, Hongwei; Malod-Dognin, Noel; Janjic, Vuk; Przulj, Natasa; Troyanskaya, Olga G; Stagljar, Igor; Xia, Tian; Ohya, Yoshikazu; Gingras, Anne-Claude; Raught, Brian; Boutros, Michael; Steinmetz, Lars M; Moore, Claire L; Rosebrock, Adam P; Caudy, Amy A; Myers, Chad L; Andrews, Brenda; Boone, Charles

2016-09-23

We generated a global genetic interaction network for Saccharomyces cerevisiae, constructing more than 23 million double mutants, identifying about 550,000 negative and about 350,000 positive genetic interactions. This comprehensive network maps genetic interactions for essential gene pairs, highlighting essential genes as densely connected hubs. Genetic interaction profiles enabled assembly of a hierarchical model of cell function, including modules corresponding to protein complexes and pathways, biological processes, and cellular compartments. Negative interactions connected functionally related genes, mapped core bioprocesses, and identified pleiotropic genes, whereas positive interactions often mapped general regulatory connections among gene pairs, rather than shared functionality. The global network illustrates how coherent sets of genetic interactions connect protein complex and pathway modules to map a functional wiring diagram of the cell. Copyright © 2016, American Association for the Advancement of Science.

A viral microRNA functions as an ortholog of cellular miR-155

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Gottwein, Eva; Mukherjee, Neelanjan; Sachse, Christoph; Frenzel, Corina; Majoros, William H.; Chi, Jen-Tsan A.; Braich, Ravi; Manoharan, Muthiah; Soutschek, Jürgen; Ohler, Uwe; Cullen, Bryan R.

2008-01-01

All metazoan eukaryotes express microRNAs (miRNAs), ∼22 nt regulatory RNAs that can repress the expression of mRNAs bearing complementary sequences1. Several DNA viruses also express miRNAs in infected cells, suggesting a role in viral replication and pathogenesis2. While specific viral miRNAs have been shown to autoregulate viral mRNAs3,4 or downregulate cellular mRNAs5,6, the function of the majority of viral miRNAs remains unknown. Here, we report that the miR-K12−11 miRNA encoded by Kaposi's Sarcoma Associated Herpesvirus (KSHV) shows significant homology to cellular miR-155, including the entire miRNA “seed” region7. Using a range of assays, we demonstrate that expression of physiological levels of miR-K12−11 or miR-155 results in the downregulation of an extensive set of common mRNA targets, including genes with known roles in cell growth regulation. Our findings indicate that viral miR-K12−11 functions as an ortholog of cellular miR-155 and has likely evolved to exploit a pre-existing gene regulatory pathway in B-cells. Moreover, the known etiological role of miR-155 in B-cell transformation8-10 suggests that miR-K12−11 may contribute to the induction of KSHV-positive B-cell tumors in infected patients. PMID:18075594

Contribution of cellular autolysis to tissular functions during plant development.

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Escamez, Sacha; Tuominen, Hannele

2017-02-01

Plant development requires specific cells to be eliminated in a predictable and genetically regulated manner referred to as programmed cell death (PCD). However, the target cells do not merely die but they also undergo autolysis to degrade their cellular corpses. Recent progress in understanding developmental cell elimination suggests that distinct proteins execute PCD sensu stricto and autolysis. In addition, cell death alone and cell dismantlement can fulfill different functions. Hence, it appears biologically meaningful to distinguish between the modules of PCD and autolysis during plant development. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Molecular design and nanoparticle-mediated intracellular delivery of functional proteins to target cellular pathways

Science.gov (United States)

Shah, Dhiral Ashwin

Intracellular delivery of specific proteins and peptides represents a novel method to influence stem cells for gain-of-function and loss-of-function. Signaling control is vital in stem cells, wherein intricate control of and interplay among critical pathways directs the fate of these cells into either self-renewal or differentiation. The most common route to manipulate cellular function involves the introduction of genetic material such as full-length genes and shRNA into the cell to generate (or prevent formation of) the target protein, and thereby ultimately alter cell function. However, viral-mediated gene delivery may result in relatively slow expression of proteins and prevalence of oncogene insertion into the cell, which can alter cell function in an unpredictable fashion, and non-viral delivery may lead to low efficiency of genetic delivery. For example, the latter case plagues the generation of induced pluripotent stem cells (iPSCs) and hinders their use for in vivo applications. Alternatively, introducing proteins into cells that specifically recognize and influence target proteins, can result in immediate deactivation or activation of key signaling pathways within the cell. In this work, we demonstrate the cellular delivery of functional proteins attached to hydrophobically modified silica (SiNP) nanoparticles to manipulate specifically targeted cell signaling proteins. In the Wnt signaling pathway, we have targeted the phosphorylation activity of glycogen synthase kinase-3beta (GSK-3beta) by designing a chimeric protein and delivering it in neural stem cells. Confocal imaging indicates that the SiNP-chimeric protein conjugates were efficiently delivered to the cytosol of human embryonic kidney cells and rat neural stem cells, presumably via endocytosis. This uptake impacted the Wnt signaling cascade, indicated by the elevation of beta-catenin levels, and increased transcription of Wnt target genes, such as c-MYC. The results presented here suggest that

Telmisartan enhances mitochondrial activity and alters cellular functions in human coronary artery endothelial cells via AMP-activated protein kinase pathway.

Science.gov (United States)

Kurokawa, Hirofumi; Sugiyama, Seigo; Nozaki, Toshimitsu; Sugamura, Koichi; Toyama, Kensuke; Matsubara, Junichi; Fujisue, Koichiro; Ohba, Keisuke; Maeda, Hirofumi; Konishi, Masaaki; Akiyama, Eiichi; Sumida, Hitoshi; Izumiya, Yasuhiro; Yasuda, Osamu; Kim-Mitsuyama, Shokei; Ogawa, Hisao

2015-04-01

Mitochondrial dysfunction plays an important role in cellular senescence and impaired function of vascular endothelium, resulted in cardiovascular diseases. Telmisartan is a unique angiotensin II type I receptor blocker that has been shown to prevent cardiovascular events in high risk patients. AMP-activated protein kinase (AMPK) plays a critical role in mitochondrial biogenesis and endothelial function. This study assessed whether telmisartan enhances mitochondrial function and alters cellular functions via AMPK in human coronary artery endothelial cells (HCAECs). In cultured HCAECs, telmisartan significantly enhanced mitochondrial activity assessed by mitochondrial reductase activity and intracellular ATP production and increased the expression of mitochondria related genes. Telmisartan prevented cellular senescence and exhibited the anti-apoptotic and pro-angiogenic properties. The expression of genes related anti-oxidant and pro-angiogenic properties were increased by telmisartan. Telmisartan increased endothelial NO synthase and AMPK phosphorylation. Peroxisome proliferator-activated receptor gamma signaling was not involved in telmisartan-induced improvement of mitochondrial function. All of these effects were abolished by inhibition of AMPK. Telmisartan enhanced mitochondrial activity and exhibited anti-senescence effects and improving endothelial function through AMPK in HCAECs. Telmisartan could provide beneficial effects on vascular diseases via enhancement of mitochondrial activity and modulating endothelial function through AMPK activation. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Comprehensive interrogation of the cellular response to fluorescent, detonation and functionalized nanodiamonds.

Science.gov (United States)

Moore, Laura; Grobárová, Valéria; Shen, Helen; Man, Han Bin; Míčová, Júlia; Ledvina, Miroslav; Štursa, Jan; Nesladek, Milos; Fišerová, Anna; Ho, Dean

2014-10-21

Nanodiamonds (NDs) are versatile nanoparticles that are currently being investigated for a variety of applications in drug delivery, biomedical imaging and nanoscale sensing. Although initial studies indicate that these small gems are biocompatible, there is a great deal of variability in synthesis methods and surface functionalization that has yet to be evaluated. Here we present a comprehensive analysis of the cellular compatibility of an array of nanodiamond subtypes and surface functionalization strategies. These results demonstrate that NDs are well tolerated by multiple cell types at both functional and gene expression levels. In addition, ND-mediated delivery of daunorubicin is less toxic to multiple cell types than treatment with daunorubicin alone, thus demonstrating the ability of the ND agent to improve drug tolerance and decrease therapeutic toxicity. Overall, the results here indicate that ND biocompatibility serves as a promising foundation for continued preclinical investigation.

Comprehensive interrogation of the cellular response to fluorescent, detonation and functionalized nanodiamonds

Science.gov (United States)

Moore, Laura; Grobárová, Valéria; Shen, Helen; Man, Han Bin; Míčová, Júlia; Ledvina, Miroslav; Štursa, Jan; Nesladek, Milos; Fišerová, Anna; Ho, Dean

2014-09-01

Nanodiamonds (NDs) are versatile nanoparticles that are currently being investigated for a variety of applications in drug delivery, biomedical imaging and nanoscale sensing. Although initial studies indicate that these small gems are biocompatible, there is a great deal of variability in synthesis methods and surface functionalization that has yet to be evaluated. Here we present a comprehensive analysis of the cellular compatibility of an array of nanodiamond subtypes and surface functionalization strategies. These results demonstrate that NDs are well tolerated by multiple cell types at both functional and gene expression levels. In addition, ND-mediated delivery of daunorubicin is less toxic to multiple cell types than treatment with daunorubicin alone, thus demonstrating the ability of the ND agent to improve drug tolerance and decrease therapeutic toxicity. Overall, the results here indicate that ND biocompatibility serves as a promising foundation for continued preclinical investigation.

The FPGA realization of the general cellular automata based cryptographic hash functions: Performance and effectiveness

Directory of Open Access Journals (Sweden)

P. G. Klyucharev

2014-01-01

Full Text Available In the paper the author considers hardware implementation of the GRACE-H family general cellular automata based cryptographic hash functions. VHDL is used as a language and Altera FPGA as a platform for hardware implementation. Performance and effectiveness of the FPGA implementations of GRACE-H hash functions were compared with Keccak (SHA-3, SHA-256, BLAKE, Groestl, JH, Skein hash functions. According to the performed tests, performance of the hardware implementation of GRACE-H family hash functions significantly (up to 12 times exceeded performance of the hardware implementation of previously known hash functions, and effectiveness of that hardware implementation was also better (up to 4 times.

THE MITOCHONDRIAL PARADIGM FOR CARDIOVASCULAR DISEASE SUSCEPTIBILITY AND CELLULAR FUNCTION: A COMPLEMENTARY CONCEPT TO MENDELIAN GENETICS

Science.gov (United States)

Kryzwanski, David M.; Moellering, Douglas; Fetterman, Jessica L.; Dunham-Snary, Kimberly J.; Sammy, Melissa J.; Ballinger, Scott W.

2013-01-01

While there is general agreement that cardiovascular disease (CVD) development is influenced by a combination of genetic, environmental, and behavioral contributors, the actual mechanistic basis of how these factors initiate or promote CVD development in some individuals while others with identical risk profiles do not, is not clearly understood. This review considers the potential role for mitochondrial genetics and function in determining CVD susceptibility from the standpoint that the original features that molded cellular function were based upon mitochondrial-nuclear relationships established millions of years ago and were likely refined during prehistoric environmental selection events that today, are largely absent. Consequently, contemporary risk factors that influence our susceptibility to a variety of age-related diseases, including CVD were probably not part of the dynamics that defined the processes of mitochondrial – nuclear interaction, and thus, cell function. In this regard, the selective conditions that contributed to cellular functionality and evolution should be given more consideration when interpreting and designing experimental data and strategies. Finally, future studies that probe beyond epidemiologic associations are required. These studies will serve as the initial steps for addressing the provocative concept that contemporary human disease susceptibility is the result of selection events for mitochondrial function that increased chances for prehistoric human survival and reproductive success. PMID:21647091

Multi-functionality Redefined with Colloidal Carotene Carbon Nanoparticles for Synchronized Chemical Imaging, Enriched Cellular Uptake and Therapy

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Misra, Santosh K.; Mukherjee, Prabuddha; Chang, Huei-Huei; Tiwari, Saumya; Gryka, Mark; Bhargava, Rohit; Pan, Dipanjan

2016-07-01

Typically, multiplexing high nanoparticle uptake, imaging, and therapy requires careful integration of three different functions of a multiscale molecular-particle assembly. Here, we present a simpler approach to multiplexing by utilizing one component of the system for multiple functions. Specifically, we successfully synthesized and characterized colloidal carotene carbon nanoparticle (C3-NP), in which a single functional molecule served a threefold purpose. First, the presence of carotene moieties promoted the passage of the particle through the cell membrane and into the cells. Second, the ligand acted as a potent detrimental moiety for cancer cells and, finally, the ligands produced optical contrast for robust microscopic detection in complex cellular environments. In comparative tests, C3-NP were found to provide effective intracellular delivery that enables both robust detection at cellular and tissue level and presents significant therapeutic potential without altering the mechanism of intracellular action of β-carotene. Surface coating of C3 with phospholipid was used to generate C3-Lipocoat nanoparticles with further improved function and biocompatibility, paving the path to eventual in vivo studies.

Covalent immobilization of penicillin G acylase on aminopropyl-functionalized mesostructured cellular foams.

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Zhao, Junqi; Wang, Yujun; Luo, Guangsheng; Zhu, Shenlin

2010-10-01

Mesostructured cellular foams (MCFs) are suitable for biomolecular immobilization because of their relatively large-pore diameter and pore volume. Penicillin G acylase (PGA) was immobilized on aminopropyl-functionalized MCFs through Schiff base reaction. It is shown that PGA could be fixed more firmly through the covalent immobilization on aminopropyl-functionalized MCFs support than through the adsorption immobilization on blank MCFs. The PGA loading amount on the aminopropyl-functionalized MCFs could reach 443 mg/g (dry support), and the apparent activity could achieve up to 4138 U/g (dry support). The influence of the amount of grafted aminopropyl group was studied, and it is found that the optimal molar ratio of MCFs to APTS was 15/1; in addition, the suitable enzyme distribution density for the specific activity of the immobilized PGA was 0.7 mg enzyme per m(2) of specific area of MCFs. Copyright 2010 Elsevier Ltd. All rights reserved.

Nested cellular automata

International Nuclear Information System (INIS)

Quasthoff, U.

1985-07-01

Cellular automata by definition consist of a finite or infinite number of cells, say of unit length, with each cell having the same transition function. These cells are usually considered as the smallest elements and so the space filled with these cells becomes discrete. Nevertheless, large pictures created by such cellular automata look very fractal. So we try to replace each cell by a couple of smaller cells, which have the same transition functions as the large ones. There are automata where this replacement does not destroy the macroscopic structure. In these cases this nesting process can be iterated. The paper contains large classes of automata with the above properties. In the case of one dimensional automata with two states and next neighbour interaction and a nesting function of the same type a complete classification is given. (author)

The functional micro-organization of grid cells revealed by cellular-resolution imaging.

Science.gov (United States)

Heys, James G; Rangarajan, Krsna V; Dombeck, Daniel A

2014-12-03

Establishing how grid cells are anatomically arranged, on a microscopic scale, in relation to their firing patterns in the environment would facilitate a greater microcircuit-level understanding of the brain's representation of space. However, all previous grid cell recordings used electrode techniques that provide limited descriptions of fine-scale organization. We therefore developed a technique for cellular-resolution functional imaging of medial entorhinal cortex (MEC) neurons in mice navigating a virtual linear track, enabling a new experimental approach to study MEC. Using these methods, we show that grid cells are physically clustered in MEC compared to nongrid cells. Additionally, we demonstrate that grid cells are functionally micro-organized: the similarity between the environment firing locations of grid cell pairs varies as a function of the distance between them according to a "Mexican hat"-shaped profile. This suggests that, on average, nearby grid cells have more similar spatial firing phases than those further apart. Copyright © 2014 Elsevier Inc. All rights reserved.

Experimental approaches to identify cellular G-quadruplex structures and functions.

Science.gov (United States)

Di Antonio, Marco; Rodriguez, Raphaël; Balasubramanian, Shankar

2012-05-01

Guanine-rich nucleic acids can fold into non-canonical DNA secondary structures called G-quadruplexes. The formation of these structures can interfere with the biology that is crucial to sustain cellular homeostases and metabolism via mechanisms that include transcription, translation, splicing, telomere maintenance and DNA recombination. Thus, due to their implication in several biological processes and possible role promoting genomic instability, G-quadruplex forming sequences have emerged as potential therapeutic targets. There has been a growing interest in the development of synthetic molecules and biomolecules for sensing G-quadruplex structures in cellular DNA. In this review, we summarise and discuss recent methods developed for cellular imaging of G-quadruplexes, and the application of experimental genomic approaches to detect G-quadruplexes throughout genomic DNA. In particular, we will discuss the use of engineered small molecules and natural proteins to enable pull-down, ChIP-Seq, ChIP-chip and fluorescence imaging of G-quadruplex structures in cellular DNA. Copyright © 2012 Elsevier Inc. All rights reserved.

Cellular MR Imaging

Directory of Open Access Journals (Sweden)

Michel Modo

2005-07-01

Full Text Available Cellular MR imaging is a young field that aims to visualize targeted cells in living organisms. In order to provide a different signal intensity of the targeted cell, they are either labeled with MR contrast agents in vivo or prelabeled in vitro. Either (ultrasmall superparamagnetic iron oxide [(USPIO] particles or (polymeric paramagnetic chelates can be used for this purpose. For in vivo cellular labeling, Gd3+- and Mn2+- chelates have mainly been used for targeted hepatobiliary imaging, and (USPIO-based cellular imaging has been focused on imaging of macrophage activity. Several of these magneto-pharmaceuticals have been FDA-approved or are in late-phase clinical trials. As for prelabeling of cells in vitro, a challenge has been to induce a sufficient uptake of contrast agents into nonphagocytic cells, without affecting normal cellular function. It appears that this issue has now largely been resolved, leading to an active research on monitoring the cellular biodistribution in vivo following transplantation or transfusion of these cells, including cell migration and trafficking. New applications of cellular MR imaging will be directed, for instance, towards our understanding of hematopoietic (immune cell trafficking and of novel guided (stem cell-based therapies aimed to be translated to the clinic in the future.

Structural, biochemical, cellular, and functional changes in skeletal muscle extracellular matrix with aging

DEFF Research Database (Denmark)

Kragstrup, T W; Kjaer, M; Mackey, A L

2011-01-01

The extracellular matrix (ECM) of skeletal muscle is critical for force transmission and for the passive elastic response of skeletal muscle. Structural, biochemical, cellular, and functional changes in skeletal muscle ECM contribute to the deterioration in muscle mechanical properties with aging....... Structural changes include an increase in the collagen concentration, a change in the elastic fiber system, and an increase in fat infiltration of skeletal muscle. Biochemical changes include a decreased turnover of collagen with potential accumulation of enzymatically mediated collagen cross...

Robust Template Decomposition without Weight Restriction for Cellular Neural Networks Implementing Arbitrary Boolean Functions Using Support Vector Classifiers

Directory of Open Access Journals (Sweden)

Yih-Lon Lin

2013-01-01

Full Text Available If the given Boolean function is linearly separable, a robust uncoupled cellular neural network can be designed as a maximal margin classifier. On the other hand, if the given Boolean function is linearly separable but has a small geometric margin or it is not linearly separable, a popular approach is to find a sequence of robust uncoupled cellular neural networks implementing the given Boolean function. In the past research works using this approach, the control template parameters and thresholds are restricted to assume only a given finite set of integers, and this is certainly unnecessary for the template design. In this study, we try to remove this restriction. Minterm- and maxterm-based decomposition algorithms utilizing the soft margin and maximal margin support vector classifiers are proposed to design a sequence of robust templates implementing an arbitrary Boolean function. Several illustrative examples are simulated to demonstrate the efficiency of the proposed method by comparing our results with those produced by other decomposition methods with restricted weights.

Novel Materials for Cellular Nanosensors

DEFF Research Database (Denmark)

Sasso, Luigi

The monitoring of cellular behavior is useful for the advancement of biomedical diagnostics, drug development and the understanding of a cell as the main unit of the human body. Micro- and nanotechnology allow for the creation of functional devices that enhance the study of cellular dynamics...... modifications for electrochemical nanosensors for the detection of analytes released from cells. Two type of materials were investigated, each pertaining to the two different aspects of such devices: peptide nanostructures were studied for the creation of cellular sensing substrates that mimic in vivo surfaces...... and that offer advantages of functionalization, and conducting polymers were used as electrochemical sensor surface modifications for increasing the sensitivity towards relevant analytes, with focus on the detection of dopamine released from cells via exocytosis. Vertical peptide nanowires were synthesized from...

Functional characterization of novel genotypes and cellular oxidative stress studies in propionic acidemia.

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Gallego-Villar, Lorena; Pérez-Cerdá, Celia; Pérez, Belén; Abia, David; Ugarte, Magdalena; Richard, Eva; Desviat, Lourdes R

2013-09-01

Propionic acidemia (PA), caused by a deficiency of the mitochondrial biotin dependent enzyme propionyl-CoA carboxylase (PCC) is one of the most frequent organic acidurias in humans. PA is caused by mutations in either the PCCA or PCCB genes encoding the α- and β-subunits of the PCC enzyme which are assembled as an α6β6 dodecamer. In this study we have investigated the molecular basis of the defect in ten fibroblast samples from PA patients. Using homology modeling with the recently solved crystal structure of the PCC holoenzyme and a eukaryotic expression system we have analyzed the structural and functional effect of novel point mutations, also revealing a novel splice defect by minigene analysis. In addition, we have investigated the contribution of oxidative stress to cellular damage measuring reactive oxygen species (ROS) levels and apoptosis parameters in patient fibroblasts, as recent studies point to a secondary mitochondrial dysfunction as pathophysiological mechanism in this disorder. The results show an increase in intracellular ROS content compared to controls, correlating with the activation of the JNK and p38 signaling pathways. Highest ROS levels were present in cells harboring functionally null mutations, including one severe missense mutation. This work provides molecular insight into the pathogenicity of PA variants and indicates that oxidative stress may be a major contributing factor to the cellular damage, supporting the proposal of antioxidant strategies as novel supplementary therapy in this rare disease.

Additive Cellular Automata and Volume Growth

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Thomas B. Ward

2000-08-01

Full Text Available Abstract: A class of dynamical systems associated to rings of S-integers in rational function fields is described. General results about these systems give a rather complete description of the well-known dynamics in one-dimensional additive cellular automata with prime alphabet, including simple formulæ for the topological entropy and the number of periodic configurations. For these systems the periodic points are uniformly distributed along some subsequence with respect to the maximal measure, and in particular are dense. Periodic points may be constructed arbitrarily close to a given configuration, and rationality of the dynamical zeta function is characterized. Throughout the emphasis is to place this particular family of cellular automata into the wider context of S-integer dynamical systems, and to show how the arithmetic of rational function fields determines their behaviour. Using a covering space the dynamics of additive cellular automata are related to a form of hyperbolicity in completions of rational function fields. This expresses the topological entropy of the automata directly in terms of volume growth in the covering space.

Lysophosphatidic acid signaling via LPA_1 and LPA_3 regulates cellular functions during tumor progression in pancreatic cancer cells

International Nuclear Information System (INIS)

Fukushima, Kaori; Takahashi, Kaede; Yamasaki, Eri; Onishi, Yuka; Fukushima, Nobuyuki; Honoki, Kanya; Tsujiuchi, Toshifumi

2017-01-01

Lysophosphatidic acid (LPA) signaling via G protein-coupled LPA receptors exhibits a variety of biological effects, such as cell proliferation, motility and differentiation. The aim of this study was to evaluate the roles of LPA_1 and LPA_3 in cellular functions during tumor progression in pancreatic cancer cells. LPA_1 and LPA_3 knockdown cells were generated from PANC-1 cells. The cell motile and invasive activities of PANC-1 cells were inhibited by LPA_1 and LPA_3 knockdown. In gelatin zymography, LPA_1 and LPA_3 knockdown cells indicated the low activation of matrix metalloproteinase-2 (MMP-2) in the presence of LPA. Next, to assess whether LPA_1 and LPA_3 regulate cellular functions induced by anticancer drug, PANC-1 cells were treated with cisplatin (CDDP) for approximately 6 months. The cell motile and invasive activities of long-term CDDP treated cells were markedly higher than those of PANC-1 cells, correlating with the expression levels of LPAR1 and LPAR3 genes. In soft agar assay, the long-term CDDP treated cells formed markedly large sized colonies. In addition, the cell motile and invasive activities enhanced by CDDP were significantly suppressed by LPA_1 and LPA_3 knockdown as well as colony formation. These results suggest that LPA signaling via LPA_1 and LPA_3 play an important role in the regulation of cellular functions during tumor progression in PANC-1 cells. - Highlights: • The cell motile and invasive activities of PANC-1 cells were stimulated by LPA_1 and LPA_3. • LPA_1 and LPA_3 enhanced MMP-2 activation in PANC-1 cells. • The expressions of LPAR1 and LPAR3 genes were elevated in PANC-1 cells treated with cisplatin. • The cell motile and invasive activities of PANC-1 cells treated with cisplatin were suppressed by LPA_1 and LPA_3 knockdown. • LPA_1 and LPA_3 are involved in the regulation of cellular functions during tumor progression in PANC-1 cells.

Agent-Based Modeling of Mitochondria Links Sub-Cellular Dynamics to Cellular Homeostasis and Heterogeneity.

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Giovanni Dalmasso

Full Text Available Mitochondria are semi-autonomous organelles that supply energy for cellular biochemistry through oxidative phosphorylation. Within a cell, hundreds of mobile mitochondria undergo fusion and fission events to form a dynamic network. These morphological and mobility dynamics are essential for maintaining mitochondrial functional homeostasis, and alterations both impact and reflect cellular stress states. Mitochondrial homeostasis is further dependent on production (biogenesis and the removal of damaged mitochondria by selective autophagy (mitophagy. While mitochondrial function, dynamics, biogenesis and mitophagy are highly-integrated processes, it is not fully understood how systemic control in the cell is established to maintain homeostasis, or respond to bioenergetic demands. Here we used agent-based modeling (ABM to integrate molecular and imaging knowledge sets, and simulate population dynamics of mitochondria and their response to environmental energy demand. Using high-dimensional parameter searches we integrated experimentally-measured rates of mitochondrial biogenesis and mitophagy, and using sensitivity analysis we identified parameter influences on population homeostasis. By studying the dynamics of cellular subpopulations with distinct mitochondrial masses, our approach uncovered system properties of mitochondrial populations: (1 mitochondrial fusion and fission activities rapidly establish mitochondrial sub-population homeostasis, and total cellular levels of mitochondria alter fusion and fission activities and subpopulation distributions; (2 restricting the directionality of mitochondrial mobility does not alter morphology subpopulation distributions, but increases network transmission dynamics; and (3 maintaining mitochondrial mass homeostasis and responding to bioenergetic stress requires the integration of mitochondrial dynamics with the cellular bioenergetic state. Finally, (4 our model suggests sources of, and stress conditions

Analyses of Dynein Heavy Chain Mutations Reveal Complex Interactions Between Dynein Motor Domains and Cellular Dynein Functions

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Sivagurunathan, Senthilkumar; Schnittker, Robert R.; Razafsky, David S.; Nandini, Swaran; Plamann, Michael D.; King, Stephen J.

2012-01-01

Cytoplasmic dynein transports cargoes for a variety of crucial cellular functions. However, since dynein is essential in most eukaryotic organisms, the in-depth study of the cellular function of dynein via genetic analysis of dynein mutations has not been practical. Here, we identify and characterize 34 different dynein heavy chain mutations using a genetic screen of the ascomycete fungus Neurospora crassa, in which dynein is nonessential. Interestingly, our studies show that these mutations segregate into five different classes based on the in vivo localization of the mutated dynein motors. Furthermore, we have determined that the different classes of dynein mutations alter vesicle trafficking, microtubule organization, and nuclear distribution in distinct ways and require dynactin to different extents. In addition, biochemical analyses of dynein from one mutant strain show a strong correlation between its in vitro biochemical properties and the aberrant intracellular function of that altered dynein. When the mutations were mapped to the published dynein crystal structure, we found that the three-dimensional structural locations of the heavy chain mutations were linked to particular classes of altered dynein functions observed in cells. Together, our data indicate that the five classes of dynein mutations represent the entrapment of dynein at five separate points in the dynein mechanochemical and transport cycles. We have developed N. crassa as a model system where we can dissect the complexities of dynein structure, function, and interaction with other proteins with genetic, biochemical, and cell biological studies. PMID:22649085

Dimer monomer transition and dimer re-formation play important role for ATM cellular function during DNA repair

International Nuclear Information System (INIS)

Du, Fengxia; Zhang, Minjie; Li, Xiaohua; Yang, Caiyun; Meng, Hao; Wang, Dong; Chang, Shuang; Xu, Ye; Price, Brendan; Sun, Yingli

2014-01-01

Highlights: • ATM phosphorylates the opposite strand of the dimer in response to DNA damage. • The PETPVFRLT box of ATM plays a key role in its dimer dissociation in DNA repair. • The dephosphorylation of ATM is critical for dimer re-formation after DNA repair. - Abstract: The ATM protein kinase, is a serine/threonine protein kinase that is recruited and activated by DNA double-strand breaks, mediates responses to ionizing radiation in mammalian cells. Here we show that ATM is held inactive in unirradiated cells as a dimer and phosphorylates the opposite strand of the dimer in response to DNA damage. Cellular irradiation induces rapid intermolecular autophosphorylation of serine 1981 that causes dimer dissociation and initiates cellular ATM kinase activity. ATM cannot phosphorylate the substrates when it could not undergo dimer monomer transition. After DNA repair, the active monomer will undergo dephosphorylation to form dimer again and dephosphorylation is critical for dimer re-formation. Our work reveals novel function of ATM dimer monomer transition and explains why ATM dimer monomer transition plays such important role for ATM cellular activity during DNA repair

Cellular function of neuropathy target esterase in lysophosphatidylcholine action

International Nuclear Information System (INIS)

Vose, Sarah C.; Fujioka, Kazutoshi; Gulevich, Alex G.; Lin, Amy Y.; Holland, Nina T.; Casida, John E.

2008-01-01

Neuropathy target esterase (NTE) plays critical roles in embryonic development and maintenance of peripheral axons. It is a secondary target of some organophosphorus toxicants including analogs of insecticides and chemical warfare agents. Although the mechanistic role of NTE in vivo is poorly defined, it is known to hydrolyze lysophosphatidylcholine (LPC) in vitro and may protect cell membranes from cytotoxic accumulation of LPC. To determine the cellular function of NTE, Neuro-2a and COS-7 cells were transfected with a full-length human NTE-containing plasmid yielding recombinant NTE (rNTE). We find the same inhibitor sensitivity and specificity profiles for rNTE assayed with LPC or phenyl valerate (a standard NTE substrate) and that this correlation extends to the LPC hydrolases of human brain, lymphocytes and erythrocytes. All of these LPC hydrolases are therefore very similar to each other in respect to a conserved inhibitor binding site conformation. NTE is expressed in brain and lymphocytes and contributes to LPC hydrolase activities in these tissues. The enzyme or enzymes responsible for erythrocyte LPC hydrolase activity remain to be identified. We also show that rNTE protects Neuro-2a and COS-7 cells from exogenous LPC cytotoxicity. Expression of rNTE in Neuro-2a cells alters their phospholipid balance (analyzed by liquid chromatography-mass spectrometry with single ion monitoring) by lowering LPC-16:0 and LPC-18:0 and elevating glycerophosphocholine without a change in phosphatidylcholine-16:0/18:1 or 16:0/18:2. NTE therefore serves an important function in LPC homeostasis and action

Using discrete event simulation to change from a functional layout to a cellular layout in an auto parts industry

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Thiago Buselato Maurício

2015-07-01

Full Text Available This paper presents a discrete event simulation employed in a Brazilian automotive company. There was a huge waste caused by one family scrap. It was believed one reason was the company functional layout. In this case, changing from current to cellular layout, employee synergy and knowledge about this family would increase. Due to the complexity for dimensioning a new cellular layout, mainly because of batch size and client’s demand variation. In this case, discrete event simulation was used, which made possible to introduce those effects improving accuracy in final results. This accuracy will be shown by comparing results obtained with simulation and without it (as company used to do. To conclude, cellular layout was responsible for increasing 15% of productivity, reducing lead-time in 7 days and scrap in 15% for this family.

Targeting Mitochondria to Counteract Age-Related Cellular Dysfunction

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Corina T. Madreiter-Sokolowski

2018-03-01

Full Text Available Senescence is related to the loss of cellular homeostasis and functions, which leads to a progressive decline in physiological ability and to aging-associated diseases. Since mitochondria are essential to energy supply, cell differentiation, cell cycle control, intracellular signaling and Ca2+ sequestration, fine-tuning mitochondrial activity appropriately, is a tightrope walk during aging. For instance, the mitochondrial oxidative phosphorylation (OXPHOS ensures a supply of adenosine triphosphate (ATP, but is also the main source of potentially harmful levels of reactive oxygen species (ROS. Moreover, mitochondrial function is strongly linked to mitochondrial Ca2+ homeostasis and mitochondrial shape, which undergo various alterations during aging. Since mitochondria play such a critical role in an organism’s process of aging, they also offer promising targets for manipulation of senescent cellular functions. Accordingly, interventions delaying the onset of age-associated disorders involve the manipulation of mitochondrial function, including caloric restriction (CR or exercise, as well as drugs, such as metformin, aspirin, and polyphenols. In this review, we discuss mitochondria’s role in and impact on cellular aging and their potential to serve as a target for therapeutic interventions against age-related cellular dysfunction.

Mapping brain structure and function: cellular resolution, global perspective.

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Zupanc, Günther K H

2017-04-01

A comprehensive understanding of the brain requires analysis, although from a global perspective, with cellular, and even subcellular, resolution. An important step towards this goal involves the establishment of three-dimensional high-resolution brain maps, incorporating brain-wide information about the cells and their connections, as well as the chemical architecture. The progress made in such anatomical brain mapping in recent years has been paralleled by the development of physiological techniques that enable investigators to generate global neural activity maps, also with cellular resolution, while simultaneously recording the organism's behavioral activity. Combination of the high-resolution anatomical and physiological maps, followed by theoretical systems analysis of the deduced network, will offer unprecedented opportunities for a better understanding of how the brain, as a whole, processes sensory information and generates behavior.

Novel aspects of cellular action of dipeptidyl peptidase IV/CD26.

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Ansorge, Siegfried; Nordhoff, Karsten; Bank, Ute; Heimburg, Anke; Julius, Heiko; Breyer, Doreen; Thielitz, Anja; Reinhold, Dirk; Täger, Michael

2011-03-01

The cellular dipeptidyl peptidase IV (DPIV, E.C.3.4.14.5, CD26) is a type II membrane peptidase with various physio-logical functions. Our main knowledge on DPIV comes from studies of soluble DPIV which plays a role in regulation of glucose homeostasis by inactivation of the incretins glucagon-like peptide-1 and glucose-dependent insulinotropic poly-peptide. It has been reported that membrane-bound DPIV plays a crucial role in the immune system and in other tissues and cells, but the knowledge on the action of cellular DPIV and its regulation is limited. In this study, we show particularly for immune cells that DPIV and not DP8 or DP9 is the most potent member of the DPIV family in regulating cellular immune functions. Moreover, we provide evidence that soluble and cellular DPIV differ in functions and hand-ling of substrates and inhibitors owing to the different accessibility of peptide substrates to the two access paths of DPIV. The different functions are based on the favored access path of the central pore of cellular DPIV and a special central pore binding site which assists substrate access to the active site of the enzyme. The newly discovered central pore binding site mediates an autosterical regulation of cellular DPIV and is its most crucial target site to regulate cellular functions such as growth and cytokine production. Neuropeptide Y (NPY) processing by cellular DPIV was found to be inhibited by ligands which interact with the central pore binding site. This finding suggests a crucial role of the immunosuppressive cytokine NPY in the function of DPIV in growth regulation.

Effects of electromagnetic interference on the functional usage of medical equipment by 2G/3G/4G cellular phones: A revie

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Periyasamy M. Mariappan

2016-09-01

Full Text Available There has been an increase in the potential use of wireless devices in healthcare domain for a variety of reasons. The most commonly used device is the cellular phone, which emits strong electromagnetic energy affecting thereby the functionality of the vital medical equipment such as ventilators, ECG monitors, cardiac monitors, and defibrillators. This prompted the healthcare concerns to restrict the use of these phones in the proximity of critical and non-critical care medical equipment. Due to the developments made in the design of medical equipment to comply with the EMC standards, the restriction had been slowly laid off. Still, the researchers are concerned about the electromagnetic interference with medical devices by cellular phones in the healthcare domain and recommend for conducting continuous research to study their interaction with medical equipment. This paper overviews the certain investigations carried out in the recent years to study the electromagnetic interference between medical devices and 2G/3G/4G LTE cellular phones. During the initial development of cellular phones, the 2G cellular phones had caused more interference that affects the function and operation of some medical devices. The possibility of interference from 3G cellular phones with medical devices was considerably lower than the 2G phones, but still exists. Furthermore, almost all of the 4G phones have little to no interference with the medical devices. Currently, with the development of the medical devices industry, the current medical devices are designed to operate safely under any conditions of usage. Finally, a careful analysis would require statistics on the frequency of adverse events across the healthcare system, which apparently do not exist.

Picornaviruses and nuclear functions: targeting a cellular compartment distinct from the replication site of a positive-strand RNA virus

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Dylan eFlather

2015-06-01

Full Text Available The compartmentalization of DNA replication and gene transcription in the nucleus and protein production in the cytoplasm is a defining feature of eukaryotic cells. The nucleus functions to maintain the integrity of the nuclear genome of the cell and to control gene expression based on intracellular and environmental signals received through the cytoplasm. The spatial separation of the major processes that lead to the expression of protein-coding genes establishes the necessity of a transport network to allow biomolecules to translocate between these two regions of the cell. The nucleocytoplasmic transport network is therefore essential for regulating normal cellular functioning. The Picornaviridae virus family is one of many viral families that disrupt the nucleocytoplasmic trafficking of cells to promote viral replication. Picornaviruses contain positive-sense, single-stranded RNA genomes and replicate in the cytoplasm of infected cells. As a result of the limited coding capacity of these viruses, cellular proteins are required by these intracellular parasites for both translation and genomic RNA replication. Being of messenger RNA polarity, a picornavirus genome can immediately be translated upon entering the cell cytoplasm. However, the replication of viral RNA requires the activity of RNA-binding proteins, many of which function in host gene expression, and are consequently localized to the nucleus. As a result, picornaviruses disrupt nucleocytoplasmic trafficking to exploit protein functions normally localized to a different cellular compartment from which they translate their genome to facilitate efficient replication. Furthermore, picornavirus proteins are also known to enter the nucleus of infected cells to limit host-cell transcription and down-regulate innate antiviral responses. The interactions of picornavirus proteins and host-cell nuclei are extensive, required for a productive infection, and are the focus of this review.

Nuclear import and export signals are essential for proper cellular trafficking and function of ZIC3.

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Bedard, James E J; Purnell, Jennifer D; Ware, Stephanie M

2007-01-15

Missense, frameshift and nonsense mutations in the zinc finger transcription factor ZIC3 cause heterotaxy as well as isolated congenital heart disease. Previously, we developed transactivation and subcellular localization assays to test the function of ZIC3 point mutations. Aberrant cytoplasmic localization suggested that the pathogenesis of ZIC3 mutations results, at least in part, from failure of appropriate cellular trafficking. To further investigate this hypothesis, the nucleocytoplasmic shuttling properties of ZIC3 have been examined. Subcellular localization assays designed to span the entire open-reading frame of wild-type and mutant ZIC3 proteins identified the presence of nucleocytoplasmic transport signals. ZIC3 domain mapping indicates that a relatively large region containing the zinc finger binding sites and a known GLI interacting domain is required for transport to the nucleus. Site-directed mutagenesis of critical residues within two putative nuclear localization signals (NLSs) leads to loss of nuclear localization. No further decrease was observed when both NLS sites were mutated, suggesting that mutation of either NLS site is sufficient for loss of importin-mediated nuclear localization. Additionally, we identify a cryptic CRM-1-dependent nuclear export signal (NES) within ZIC3, and identify a mutation within this region in a patient with heterotaxy. These results provide the first evidence that control of cellular trafficking of ZIC3 is critical for function and suggest a possible mechanism for transcriptional control during left-right patterning. Identification of mutations in mapped NLS or NES domains in heterotaxy patients demonstrates the functional importance of these domains in cardiac morphogenesis and allows for integration of structural analysis with developmental function.

Taming the sphinx: Mechanisms of cellular sphingolipid homeostasis.

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Olson, D K; Fröhlich, F; Farese, R V; Walther, T C

2016-08-01

Sphingolipids are important structural membrane components of eukaryotic cells, and potent signaling molecules. As such, their levels must be maintained to optimize cellular functions in different cellular membranes. Here, we review the current knowledge of homeostatic sphingolipid regulation. We describe recent studies in Saccharomyces cerevisiae that have provided insights into how cells sense changes in sphingolipid levels in the plasma membrane and acutely regulate sphingolipid biosynthesis by altering signaling pathways. We also discuss how cellular trafficking has emerged as an important determinant of sphingolipid homeostasis. Finally, we highlight areas where work is still needed to elucidate the mechanisms of sphingolipid regulation and the physiological functions of such regulatory networks, especially in mammalian cells. This article is part of a Special Issue entitled: The cellular lipid landscape edited by Tim P. Levine and Anant K. Menon. Copyright © 2015. Published by Elsevier B.V.

The Algorithm of Continuous Optimization Based on the Modified Cellular Automaton

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Oleg Evsutin

2016-08-01

Full Text Available This article is devoted to the application of the cellular automata mathematical apparatus to the problem of continuous optimization. The cellular automaton with an objective function is introduced as a new modification of the classic cellular automaton. The algorithm of continuous optimization, which is based on dynamics of the cellular automaton having the property of geometric symmetry, is obtained. The results of the simulation experiments with the obtained algorithm on standard test functions are provided, and a comparison between the analogs is shown.

Insights into the physiological function of cellular prion protein

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Martins V.R.

2001-01-01

Full Text Available Prions have been extensively studied since they represent a new class of infectious agents in which a protein, PrPsc (prion scrapie, appears to be the sole component of the infectious particle. They are responsible for transmissible spongiform encephalopathies, which affect both humans and animals. The mechanism of disease propagation is well understood and involves the interaction of PrPsc with its cellular isoform (PrPc and subsequently abnormal structural conversion of the latter. PrPc is a glycoprotein anchored on the cell surface by a glycosylphosphatidylinositol moiety and expressed in most cell types but mainly in neurons. Prion diseases have been associated with the accumulation of the abnormally folded protein and its neurotoxic effects; however, it is not known if PrPc loss of function is an important component. New efforts are addressing this question and trying to characterize the physiological function of PrPc. At least four different mouse strains in which the PrP gene was ablated were generated and the results regarding their phenotype are controversial. Localization of PrPc on the cell membrane makes it a potential candidate for a ligand uptake, cell adhesion and recognition molecule or a membrane signaling molecule. Recent data have shown a potential role for PrPc in the metabolism of copper and moreover that this metal stimulates PrPc endocytosis. Our group has recently demonstrated that PrPc is a high affinity laminin ligand and that this interaction mediates neuronal cell adhesion and neurite extension and maintenance. Moreover, PrPc-caveolin-1 dependent coupling seems to trigger the tyrosine kinase Fyn activation. These data provide the first evidence for PrPc involvement in signal transduction.

Epigenetics and Cellular Metabolism

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Wenyi Xu

2016-01-01

Full Text Available Living eukaryotic systems evolve delicate cellular mechanisms for responding to various environmental signals. Among them, epigenetic machinery (DNA methylation, histone modifications, microRNAs, etc. is the hub in transducing external stimuli into transcriptional response. Emerging evidence reveals the concept that epigenetic signatures are essential for the proper maintenance of cellular metabolism. On the other hand, the metabolite, a main environmental input, can also influence the processing of epigenetic memory. Here, we summarize the recent research progress in the epigenetic regulation of cellular metabolism and discuss how the dysfunction of epigenetic machineries influences the development of metabolic disorders such as diabetes and obesity; then, we focus on discussing the notion that manipulating metabolites, the fuel of cell metabolism, can function as a strategy for interfering epigenetic machinery and its related disease progression as well.

Application of TALE-Based Approach for Dissecting Functional MicroRNA-302/367 in Cellular Reprogramming.

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Zhang, Zhonghui; Wu, Wen-Shu

2018-01-01

MicroRNAs are small 18-24 nt single-stranded noncoding RNA molecules involved in many biological processes, including stemness maintenance and cellular reprogramming. Current methods used in loss-of-function studies of microRNAs have several limitations. Here, we describe a new approach for dissecting miR-302/367 functions by transcription activator-like effectors (TALEs), which are natural effector proteins secreted by Xanthomonas and Ralstonia bacteria. Knockdown of the miR-302/367 cluster uses the Kruppel-associated box repressor domain fused with specific TALEs designed to bind the miR-302/367 cluster promoter. Knockout of the miR-302/367 cluster uses two pairs of TALE nucleases (TALENs) to delete the miR-302/367 cluster in human primary cells. Together, both TALE-based transcriptional repressor and TALENs are two promising approaches for loss-of-function studies of microRNA cluster in human primary cells.

The Green Function cellular method and its relation to multiple scattering theory

International Nuclear Information System (INIS)

Butler, W.H.; Zhang, X.G.; Gonis, A.

1992-01-01

This paper investigates techniques for solving the wave equation which are based on the idea of obtaining exact local solutions within each potential cell, which are then joined to form a global solution. The authors derive full potential multiple scattering theory (MST) from the Lippmann-Schwinger equation and show that it as well as a closely related cellular method are techniques of this type. This cellular method appears to have all of the advantages of MST and the added advantage of having a secular matrix with only nearest neighbor interactions. Since this cellular method is easily linearized one can rigorously reduce electronic structure calculation to the problem of solving a nearest neighbor tight-binding problem

Time scale of diffusion in molecular and cellular biology

International Nuclear Information System (INIS)

Holcman, D; Schuss, Z

2014-01-01

Diffusion is the driver of critical biological processes in cellular and molecular biology. The diverse temporal scales of cellular function are determined by vastly diverse spatial scales in most biophysical processes. The latter are due, among others, to small binding sites inside or on the cell membrane or to narrow passages between large cellular compartments. The great disparity in scales is at the root of the difficulty in quantifying cell function from molecular dynamics and from simulations. The coarse-grained time scale of cellular function is determined from molecular diffusion by the mean first passage time of molecular Brownian motion to a small targets or through narrow passages. The narrow escape theory (NET) concerns this issue. The NET is ubiquitous in molecular and cellular biology and is manifested, among others, in chemical reactions, in the calculation of the effective diffusion coefficient of receptors diffusing on a neuronal cell membrane strewn with obstacles, in the quantification of the early steps of viral trafficking, in the regulation of diffusion between the mother and daughter cells during cell division, and many other cases. Brownian trajectories can represent the motion of a molecule, a protein, an ion in solution, a receptor in a cell or on its membrane, and many other biochemical processes. The small target can represent a binding site or an ionic channel, a hidden active site embedded in a complex protein structure, a receptor for a neurotransmitter on the membrane of a neuron, and so on. The mean time to attach to a receptor or activator determines diffusion fluxes that are key regulators of cell function. This review describes physical models of various subcellular microdomains, in which the NET coarse-grains the molecular scale to a higher cellular-level, thus clarifying the role of cell geometry in determining subcellular function. (topical review)

Time scale of diffusion in molecular and cellular biology

Science.gov (United States)

Holcman, D.; Schuss, Z.

2014-05-01

Diffusion is the driver of critical biological processes in cellular and molecular biology. The diverse temporal scales of cellular function are determined by vastly diverse spatial scales in most biophysical processes. The latter are due, among others, to small binding sites inside or on the cell membrane or to narrow passages between large cellular compartments. The great disparity in scales is at the root of the difficulty in quantifying cell function from molecular dynamics and from simulations. The coarse-grained time scale of cellular function is determined from molecular diffusion by the mean first passage time of molecular Brownian motion to a small targets or through narrow passages. The narrow escape theory (NET) concerns this issue. The NET is ubiquitous in molecular and cellular biology and is manifested, among others, in chemical reactions, in the calculation of the effective diffusion coefficient of receptors diffusing on a neuronal cell membrane strewn with obstacles, in the quantification of the early steps of viral trafficking, in the regulation of diffusion between the mother and daughter cells during cell division, and many other cases. Brownian trajectories can represent the motion of a molecule, a protein, an ion in solution, a receptor in a cell or on its membrane, and many other biochemical processes. The small target can represent a binding site or an ionic channel, a hidden active site embedded in a complex protein structure, a receptor for a neurotransmitter on the membrane of a neuron, and so on. The mean time to attach to a receptor or activator determines diffusion fluxes that are key regulators of cell function. This review describes physical models of various subcellular microdomains, in which the NET coarse-grains the molecular scale to a higher cellular-level, thus clarifying the role of cell geometry in determining subcellular function.

Cellular Chaperones As Therapeutic Targets in ALS to Restore Protein Homeostasis and Improve Cellular Function

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Bernadett Kalmar

2017-09-01

Full Text Available Heat shock proteins (Hsps are ubiquitously expressed chaperone proteins that enable cells to cope with environmental stresses that cause misfolding and denaturation of proteins. With aging this protein quality control machinery becomes less effective, reducing the ability of cells to cope with damaging environmental stresses and disease-causing mutations. In neurodegenerative disorders such as Amyotrophic Lateral Sclerosis (ALS, such mutations are known to result in protein misfolding, which in turn results in the formation of intracellular aggregates cellular dysfunction and eventual neuronal death. The exact cellular pathology of ALS and other neurodegenerative diseases has been elusive and thus, hindering the development of effective therapies. However, a common scheme has emerged across these “protein misfolding” disorders, in that the mechanism of disease involves one or more aspects of proteostasis; from DNA transcription, RNA translation, to protein folding, transport and degradation via proteosomal and autophagic pathways. Interestingly, members of the Hsp family are involved in each of these steps facilitating normal protein folding, regulating the rate of protein synthesis and degradation. In this short review we summarize the evidence that suggests that ALS is a disease of protein dyshomeostasis in which Hsps may play a key role. Overwhelming evidence now indicates that enabling protein homeostasis to cope with disease-causing mutations might be a successful therapeutic strategy in ALS, as well as other neurodegenerative diseases. Novel small molecule co-inducers of Hsps appear to be able to achieve this aim. Arimoclomol, a hydroxylamine derivative, has shown promising results in cellular and animal models of ALS, as well as other protein misfolding diseases such as Inclusion Body Myositis (IBM. Initial clinical investigations of Arimoclomol have shown promising results. Therefore, it is possible that the long series of

Disruption of Hox9,10,11 function results in cellular level lineage infidelity in the kidney.

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Drake, Keri A; Adam, Mike; Mahoney, Robert; Potter, S Steven

2018-04-20

Hox genes are important regulators of development. The 39 mammalian Hox genes have considerable functional overlap, greatly confounding their study. In this report, we generated mice with multiple combinations of paralogous and flanking Abd-B Hox gene mutations to investigate functional redundancies in kidney development. The resulting mice developed a number of kidney abnormalities, including hypoplasia, agenesis, and severe cysts, with distinct Hox functions observed in early metanephric kidney formation and nephron progenitor maintenance. Most surprising, however, was that extensive removal of Hox shared function in these kidneys resulted in cellular level lineage infidelity. Strikingly, mutant nephron tubules consisted of intermixed cells with proximal tubule, loop of Henle, and collecting duct identities, with some single cells expressing markers associated with more than one nephron segment. These results indicate that Hox genes are required for proper lineage selection/maintenance and full repression of genes involved in cell fate restriction in the developing kidney.

Cellular metabolism

International Nuclear Information System (INIS)

Hildebrand, C.E.; Walters, R.A.

1977-01-01

Progress is reported on the following research projects: chromatin structure; the use of circular synthetic polydeoxynucleotides as substrates for the study of DNA repair enzymes; human cellular kinetic response following exposure to DNA-interactive compounds; histone phosphorylation and chromatin structure in cell proliferation; photoaddition products induced in chromatin by uv light; pollutants and genetic information transfer; altered RNA metabolism as a function of cadmium accumulation and intracellular distribution in cultured cells; and thymidylate chromophore destruction by water free radicals

Insights into the cellular function of YhdE, a nucleotide pyrophosphatase from Escherichia coli.

Directory of Open Access Journals (Sweden)

Jin Jin

Full Text Available YhdE, a Maf-like protein in Escherichia coli, exhibits nucleotide pyrophosphatase (PPase activity, yet its cellular function remains unknown. Here, we characterized the PPase activity of YhdE on dTTP, UTP and TTP and determined two crystal structures of YhdE, revealing 'closed' and 'open' conformations of an adaptive active site. Our functional studies demonstrated that YhdE retards cell growth by prolonging the lag and log phases, particularly under stress conditions. Morphology studies showed that yhdE-knockout cells transformed the normal rod shape of wild-type cells to a more spherical form, and the cell wall appeared to become more flexible. In contrast, YhdE overexpression resulted in filamentous cells. This study reveals the previously unknown involvement of YhdE in cell growth inhibition under stress conditions, cell-division arrest and cell-shape maintenance, highlighting YhdE's important role in E. coli cell-cycle checkpoints.

Epoxy-functionalized mesostructured cellular foams as effective support for covalent immobilization of penicillin G acylase

Science.gov (United States)

Xue, Ping; Xu, Fang; Xu, Lidong

2008-12-01

The epoxy-functionalized mesoporous cellular foams (G-MCFs) with high specific surface area (˜400 m 2/g) and large-size mesopores (˜17 nm) were obtained by condensation of 3-glycidoxypropyltriethoxysilane (GPTS) and the surface silanol groups of mesoporous cellular foams (MCFs) and used as the support for immobilization of penicillin G acylase (PGA). The structural properties of G-MCF were characterized by FT-IR, N 2 adsorption, TG-DTA and 29Si MAS NMR. The studies indicated that the glycidoxypropyl groups were chemically bonded to the silicon atoms on the surface of MCF. The epoxy-functionalized mesoporous cellular foams can provide the microenvironments suitable for the immobilization of PGA, and the enzyme molecules could be immobilized covalently onto the G-MCF under mild conditions by reaction between the amino groups of the enzyme molecules and the epoxy groups on the surface of G-MCF. The PGA immobilized on G-MCF (PGA/G-MCF) exhibited the apparent activity of 1782 IU/g and 46.6% of activity recovery for hydrolyzing penicillin G potassium to produce 6-aminopenicillanic acid at 37 °C which were higher than that of PGA on pure silica MCF (1521 IU/g and 39.8%, respectively). The kinetic study also indicated that PGA immobilized on G-MCF has a Km of 2.1 × 10 -2 mol/L lower than that of PGA immobilized on the pure silica MCF (5.0 × 10 -2 mol/L). These may be attributed to the enhanced surface affinity between G-MCF support and the substrate molecules. Due to the covalent immobilization of PGA molecules on the surface of G-MCF, the immobilized PGA with considerable operational stability was achieved. The activity of PGA/G-MCF is still about 91.4% of its initial activity at the 10th cycle reuse while that of PGA/MCF only remains 41.5% of its initial activity at the same reuse numbers. In addition, the investigation results show the thermal stability and durability on acid or basic medium of PGA immobilized on G-MCF were improved remarkably.

Epoxy-functionalized mesostructured cellular foams as effective support for covalent immobilization of penicillin G acylase

International Nuclear Information System (INIS)

Xue Ping; Xu Fang; Xu Lidong

2008-01-01

The epoxy-functionalized mesoporous cellular foams (G-MCFs) with high specific surface area (∼400 m 2 /g) and large-size mesopores (∼17 nm) were obtained by condensation of 3-glycidoxypropyltriethoxysilane (GPTS) and the surface silanol groups of mesoporous cellular foams (MCFs) and used as the support for immobilization of penicillin G acylase (PGA). The structural properties of G-MCF were characterized by FT-IR, N 2 adsorption, TG-DTA and 29 Si MAS NMR. The studies indicated that the glycidoxypropyl groups were chemically bonded to the silicon atoms on the surface of MCF. The epoxy-functionalized mesoporous cellular foams can provide the microenvironments suitable for the immobilization of PGA, and the enzyme molecules could be immobilized covalently onto the G-MCF under mild conditions by reaction between the amino groups of the enzyme molecules and the epoxy groups on the surface of G-MCF. The PGA immobilized on G-MCF (PGA/G-MCF) exhibited the apparent activity of 1782 IU/g and 46.6% of activity recovery for hydrolyzing penicillin G potassium to produce 6-aminopenicillanic acid at 37 o C which were higher than that of PGA on pure silica MCF (1521 IU/g and 39.8%, respectively). The kinetic study also indicated that PGA immobilized on G-MCF has a K m of 2.1 x 10 -2 mol/L lower than that of PGA immobilized on the pure silica MCF (5.0 x 10 -2 mol/L). These may be attributed to the enhanced surface affinity between G-MCF support and the substrate molecules. Due to the covalent immobilization of PGA molecules on the surface of G-MCF, the immobilized PGA with considerable operational stability was achieved. The activity of PGA/G-MCF is still about 91.4% of its initial activity at the 10th cycle reuse while that of PGA/MCF only remains 41.5% of its initial activity at the same reuse numbers. In addition, the investigation results show the thermal stability and durability on acid or basic medium of PGA immobilized on G-MCF were improved remarkably.

Epoxy-functionalized mesostructured cellular foams as effective support for covalent immobilization of penicillin G acylase

Energy Technology Data Exchange (ETDEWEB)

Xue Ping [Key Laboratory of Energy Resources and Chemical Engineering, Ningxia University, Yinchuan 750021 (China)], E-mail: Ping@nxu.edu.cn; Xu Fang [Department of Molecule Biology, Ningxia Medical College, Yinchuan 750021 (China); Xu Lidong [Key Laboratory of Energy Resources and Chemical Engineering, Ningxia University, Yinchuan 750021 (China)

2008-12-30

The epoxy-functionalized mesoporous cellular foams (G-MCFs) with high specific surface area ({approx}400 m{sup 2}/g) and large-size mesopores ({approx}17 nm) were obtained by condensation of 3-glycidoxypropyltriethoxysilane (GPTS) and the surface silanol groups of mesoporous cellular foams (MCFs) and used as the support for immobilization of penicillin G acylase (PGA). The structural properties of G-MCF were characterized by FT-IR, N{sub 2} adsorption, TG-DTA and {sup 29}Si MAS NMR. The studies indicated that the glycidoxypropyl groups were chemically bonded to the silicon atoms on the surface of MCF. The epoxy-functionalized mesoporous cellular foams can provide the microenvironments suitable for the immobilization of PGA, and the enzyme molecules could be immobilized covalently onto the G-MCF under mild conditions by reaction between the amino groups of the enzyme molecules and the epoxy groups on the surface of G-MCF. The PGA immobilized on G-MCF (PGA/G-MCF) exhibited the apparent activity of 1782 IU/g and 46.6% of activity recovery for hydrolyzing penicillin G potassium to produce 6-aminopenicillanic acid at 37 {sup o}C which were higher than that of PGA on pure silica MCF (1521 IU/g and 39.8%, respectively). The kinetic study also indicated that PGA immobilized on G-MCF has a K{sub m} of 2.1 x 10{sup -2} mol/L lower than that of PGA immobilized on the pure silica MCF (5.0 x 10{sup -2} mol/L). These may be attributed to the enhanced surface affinity between G-MCF support and the substrate molecules. Due to the covalent immobilization of PGA molecules on the surface of G-MCF, the immobilized PGA with considerable operational stability was achieved. The activity of PGA/G-MCF is still about 91.4% of its initial activity at the 10th cycle reuse while that of PGA/MCF only remains 41.5% of its initial activity at the same reuse numbers. In addition, the investigation results show the thermal stability and durability on acid or basic medium of PGA immobilized on G

The AAA+ ATPase p97, a cellular multitool.

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Stach, Lasse; Freemont, Paul S

2017-08-17

The AAA+ (ATPases associated with diverse cellular activities) ATPase p97 is essential to a wide range of cellular functions, including endoplasmic reticulum-associated degradation, membrane fusion, NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) activation and chromatin-associated processes, which are regulated by ubiquitination. p97 acts downstream from ubiquitin signaling events and utilizes the energy from ATP hydrolysis to extract its substrate proteins from cellular structures or multiprotein complexes. A multitude of p97 cofactors have evolved which are essential to p97 function. Ubiquitin-interacting domains and p97-binding domains combine to form bi-functional cofactors, whose complexes with p97 enable the enzyme to interact with a wide range of ubiquitinated substrates. A set of mutations in p97 have been shown to cause the multisystem proteinopathy inclusion body myopathy associated with Paget's disease of bone and frontotemporal dementia. In addition, p97 inhibition has been identified as a promising approach to provoke proteotoxic stress in tumors. In this review, we will describe the cellular processes governed by p97, how the cofactors interact with both p97 and its ubiquitinated substrates, p97 enzymology and the current status in developing p97 inhibitors for cancer therapy. © 2017 The Author(s).

Neurotransmitter Specific, Cellular-Resolution Functional Brain Mapping Using Receptor Coated Nanoparticles: Assessment of the Possibility

Science.gov (United States)

Forati, Ebrahim; Sabouni, Abas; Ray, Supriyo; Head, Brian; Schoen, Christian; Sievenpiper, Dan

2015-01-01

Receptor coated resonant nanoparticles and quantum dots are proposed to provide a cellular-level resolution image of neural activities inside the brain. The functionalized nanoparticles and quantum dots in this approach will selectively bind to different neurotransmitters in the extra-synaptic regions of neurons. This allows us to detect neural activities in real time by monitoring the nanoparticles and quantum dots optically. Gold nanoparticles (GNPs) with two different geometries (sphere and rod) and quantum dots (QDs) with different sizes were studied along with three different neurotransmitters: dopamine, gamma-Aminobutyric acid (GABA), and glycine. The absorption/emission spectra of GNPs and QDs before and after binding of neurotransmitters and their corresponding receptors are reported. The results using QDs and nanorods with diameter 25nm and aspect rations larger than three were promising for the development of the proposed functional brain mapping approach. PMID:26717196

Functions of NQO1 in Cellular Protection and CoQ10 Metabolism and its Potential Role as a Redox Sensitive Molecular Switch

Directory of Open Access Journals (Sweden)

David Ross

2017-08-01

Full Text Available NQO1 is one of the two major quinone reductases in mammalian systems. It is highly inducible and plays multiple roles in cellular adaptation to stress. A prevalent polymorphic form of NQO1 results in an absence of NQO1 protein and activity so it is important to elucidate the specific cellular functions of NQO1. Established roles of NQO1 include its ability to prevent certain quinones from one electron redox cycling but its role in quinone detoxification is dependent on the redox stability of the hydroquinone generated by two-electron reduction. Other documented roles of NQO1 include its ability to function as a component of the plasma membrane redox system generating antioxidant forms of ubiquinone and vitamin E and at high levels, as a direct superoxide reductase. Emerging roles of NQO1 include its function as an efficient intracellular generator of NAD+ for enzymes including PARP and sirtuins which has gained particular attention with respect to metabolic syndrome. NQO1 interacts with a growing list of proteins, including intrinsically disordered proteins, protecting them from 20S proteasomal degradation. The interactions of NQO1 also extend to mRNA. Recent identification of NQO1 as a mRNA binding protein have been investigated in more detail using SERPIN1A1 (which encodes the serine protease inhibitor α-1-antitrypsin as a target mRNA and indicate a role of NQO1 in control of translation of α-1-antitrypsin, an important modulator of COPD and obesity related metabolic syndrome. NQO1 undergoes structural changes and alterations in its ability to bind other proteins as a result of the cellular reduced/oxidized pyridine nucleotide ratio. This suggests NQO1 may act as a cellular redox switch potentially altering its interactions with other proteins and mRNA as a result of the prevailing redox environment.

Lysophosphatidic acid signaling via LPA{sub 1} and LPA{sub 3} regulates cellular functions during tumor progression in pancreatic cancer cells

Energy Technology Data Exchange (ETDEWEB)

Fukushima, Kaori; Takahashi, Kaede; Yamasaki, Eri; Onishi, Yuka [Division of Molecular Oncology, Department of Life Science, Faculty of Science and Engineering, Kindai University, 3-4-1, Kowakae, Higashiosaka, Osaka 577-8502 (Japan); Fukushima, Nobuyuki [Division of Molecular Neurobiology, Department of Life Science, Faculty of Science and Engineering, Kindai University, 3-4-1, Kowakae, Higashiosaka, Osaka 577-8502 (Japan); Honoki, Kanya [Department of Orthopedic Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521 (Japan); Tsujiuchi, Toshifumi, E-mail: ttujiuch@life.kindai.ac.jp [Division of Molecular Oncology, Department of Life Science, Faculty of Science and Engineering, Kindai University, 3-4-1, Kowakae, Higashiosaka, Osaka 577-8502 (Japan)

2017-03-01

Lysophosphatidic acid (LPA) signaling via G protein-coupled LPA receptors exhibits a variety of biological effects, such as cell proliferation, motility and differentiation. The aim of this study was to evaluate the roles of LPA{sub 1} and LPA{sub 3} in cellular functions during tumor progression in pancreatic cancer cells. LPA{sub 1} and LPA{sub 3} knockdown cells were generated from PANC-1 cells. The cell motile and invasive activities of PANC-1 cells were inhibited by LPA{sub 1} and LPA{sub 3} knockdown. In gelatin zymography, LPA{sub 1} and LPA{sub 3} knockdown cells indicated the low activation of matrix metalloproteinase-2 (MMP-2) in the presence of LPA. Next, to assess whether LPA{sub 1} and LPA{sub 3} regulate cellular functions induced by anticancer drug, PANC-1 cells were treated with cisplatin (CDDP) for approximately 6 months. The cell motile and invasive activities of long-term CDDP treated cells were markedly higher than those of PANC-1 cells, correlating with the expression levels of LPAR1 and LPAR3 genes. In soft agar assay, the long-term CDDP treated cells formed markedly large sized colonies. In addition, the cell motile and invasive activities enhanced by CDDP were significantly suppressed by LPA{sub 1} and LPA{sub 3} knockdown as well as colony formation. These results suggest that LPA signaling via LPA{sub 1} and LPA{sub 3} play an important role in the regulation of cellular functions during tumor progression in PANC-1 cells. - Highlights: • The cell motile and invasive activities of PANC-1 cells were stimulated by LPA{sub 1} and LPA{sub 3}. • LPA{sub 1} and LPA{sub 3} enhanced MMP-2 activation in PANC-1 cells. • The expressions of LPAR1 and LPAR3 genes were elevated in PANC-1 cells treated with cisplatin. • The cell motile and invasive activities of PANC-1 cells treated with cisplatin were suppressed by LPA{sub 1} and LPA{sub 3} knockdown. • LPA{sub 1} and LPA{sub 3} are involved in the regulation of cellular functions during tumor

Poly(methyl vinyl ether-alt-maleic acid)-functionalized porous silicon nanoparticles for enhanced stability and cellular internalization.

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Shahbazi, Mohammad-Ali; Almeida, Patrick V; Mäkilä, Ermei; Correia, Alexandra; Ferreira, Mónica P A; Kaasalainen, Martti; Salonen, Jarno; Hirvonen, Jouni; Santos, Hélder A

2014-03-01

Currently, developing a stable nanocarrier with high cellular internalization and low toxicity is a key bottleneck in nanomedicine. Here, we have developed a successful method to covalently conjugate poly(methyl vinyl ether-co-maleic acid) (PMVE-MA) copolymer on the surface of (3-aminopropyl)triethoxysilane-functionalized thermally carbonized porous silicon nanoparticles (APSTCPSi NPs), forming a surface negatively charged nanovehicle with unique properties. This polymer conjugated NPs could modify surface smoothness, charge, and hydrophilicity of the developed NPs, leading to considerable improvement in the colloidal and plasma stabilities via enhanced suspensibility and charge repulsion. Furthermore, despite the surface negative charge of the polymer-conjugated NPs, the cellular internalization was increased in both MDA-MB-231 and MCF-7 breast cancer cells. These results provide a proof-of-concept evidence that such polymer-based PSi nanocomposite can be extensively used as a promising candidate for intracellular drug delivery. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Selfish cellular networks and the evolution of complex organisms.

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Kourilsky, Philippe

2012-03-01

Human gametogenesis takes years and involves many cellular divisions, particularly in males. Consequently, gametogenesis provides the opportunity to acquire multiple de novo mutations. A significant portion of these is likely to impact the cellular networks linking genes, proteins, RNA and metabolites, which constitute the functional units of cells. A wealth of literature shows that these individual cellular networks are complex, robust and evolvable. To some extent, they are able to monitor their own performance, and display sufficient autonomy to be termed "selfish". Their robustness is linked to quality control mechanisms which are embedded in and act upon the individual networks, thereby providing a basis for selection during gametogenesis. These selective processes are equally likely to affect cellular functions that are not gamete-specific, and the evolution of the most complex organisms, including man, is therefore likely to occur via two pathways: essential housekeeping functions would be regulated and evolve during gametogenesis within the parents before being transmitted to their progeny, while classical selection would operate on other traits of the organisms that shape their fitness with respect to the environment. Copyright © 2012 Académie des sciences. Published by Elsevier SAS. All rights reserved.

Characteristics of Middle School Students Learning Actions in Outdoor Mathematical Activities with the Cellular Phone

Science.gov (United States)

Daher, Wajeeh; Baya'a, Nimer

2012-01-01

Learning in the cellular phone environment enables utilizing the multiple functions of the cellular phone, such as mobility, availability, interactivity, verbal and voice communication, taking pictures or recording audio and video, measuring time and transferring information. These functions together with mathematics-designated cellular phone…

Lipids, lipid droplets and lipoproteins in their cellular context; an ultrastructural approach

NARCIS (Netherlands)

Mesman, R.J.

2013-01-01

Lipids are essential for cellular life, functioning either organized as bilayer membranes to compartmentalize cellular processes, as signaling molecules or as metabolic energy storage. Our current knowledge on lipid organization and cellular lipid homeostasis is mainly based on biochemical data.

Molecular and cellular neurocardiology: development, and cellular and molecular adaptations to heart disease

Science.gov (United States)

Anderson, Mark E.; Birren, Susan J.; Fukuda, Keiichi; Herring, Neil; Hoover, Donald B.; Kanazawa, Hideaki; Paterson, David J.; Ripplinger, Crystal M.

2016-01-01

Abstract The nervous system and cardiovascular system develop in concert and are functionally interconnected in both health and disease. This white paper focuses on the cellular and molecular mechanisms that underlie neural–cardiac interactions during development, during normal physiological function in the mature system, and during pathological remodelling in cardiovascular disease. The content on each subject was contributed by experts, and we hope that this will provide a useful resource for newcomers to neurocardiology as well as aficionados. PMID:27060296

Elastomeric Cellular Structure Enhanced by Compressible Liquid Filler

Science.gov (United States)

Sun, Yueting; Xu, Xiaoqing; Xu, Chengliang; Qiao, Yu; Li, Yibing

2016-05-01

Elastomeric cellular structures provide a promising solution for energy absorption. Their flexible and resilient nature is particularly relevant to protection of human bodies. Herein we develop an elastomeric cellular structure filled with nanoporous material functionalized (NMF) liquid. Due to the nanoscale infiltration in NMF liquid and its interaction with cell walls, the cellular structure has a much enhanced mechanical performance, in terms of loading capacity and energy absorption density. Moreover, it is validated that the structure is highly compressible and self-restoring. Its hyper-viscoelastic characteristics are elucidated.

Viral and cellular SOS-regulated motor proteins: dsDNA translocation mechanisms with divergent functions.

Science.gov (United States)

Wolfe, Annie; Phipps, Kara; Weitao, Tao

2014-01-01

DNA damage attacks on bacterial cells have been known to activate the SOS response, a transcriptional response affecting chromosome replication, DNA recombination and repair, cell division and prophage induction. All these functions require double-stranded (ds) DNA translocation by ASCE hexameric motors. This review seeks to delineate the structural and functional characteristics of the SOS response and the SOS-regulated DNA translocases FtsK and RuvB with the phi29 bacteriophage packaging motor gp16 ATPase as a prototype to study bacterial motors. While gp16 ATPase, cellular FtsK and RuvB are similarly comprised of hexameric rings encircling dsDNA and functioning as ATP-driven DNA translocases, they utilize different mechanisms to accomplish separate functions, suggesting a convergent evolution of these motors. The gp16 ATPase and FtsK use a novel revolution mechanism, generating a power stroke between subunits through an entropy-DNA affinity switch and pushing dsDNA inward without rotation of DNA and the motor, whereas RuvB seems to employ a rotation mechanism that remains to be further characterized. While FtsK and RuvB perform essential tasks during the SOS response, their roles may be far more significant as SOS response is involved in antibiotic-inducible bacterial vesiculation and biofilm formation as well as the perspective of the bacteria-cancer evolutionary interaction.

Characterizing heterogeneous cellular responses to perturbations.

Science.gov (United States)

Slack, Michael D; Martinez, Elisabeth D; Wu, Lani F; Altschuler, Steven J

2008-12-09

Cellular populations have been widely observed to respond heterogeneously to perturbation. However, interpreting the observed heterogeneity is an extremely challenging problem because of the complexity of possible cellular phenotypes, the large dimension of potential perturbations, and the lack of methods for separating meaningful biological information from noise. Here, we develop an image-based approach to characterize cellular phenotypes based on patterns of signaling marker colocalization. Heterogeneous cellular populations are characterized as mixtures of phenotypically distinct subpopulations, and responses to perturbations are summarized succinctly as probabilistic redistributions of these mixtures. We apply our method to characterize the heterogeneous responses of cancer cells to a panel of drugs. We find that cells treated with drugs of (dis-)similar mechanism exhibit (dis-)similar patterns of heterogeneity. Despite the observed phenotypic diversity of cells observed within our data, low-complexity models of heterogeneity were sufficient to distinguish most classes of drug mechanism. Our approach offers a computational framework for assessing the complexity of cellular heterogeneity, investigating the degree to which perturbations induce redistributions of a limited, but nontrivial, repertoire of underlying states and revealing functional significance contained within distinct patterns of heterogeneous responses.

Innovative cellular distance structures from polymeric and metallic threads

Science.gov (United States)

Wieczorek, F.; Trümper, W.; Cherif, C.

2017-10-01

Knitting allows a high individual adaptability of the geometry and properties of flat-knitted spacer fabrics. This offers advantages for the specific adjustment of the mechanical properties of innovative composites based on highly viscous matrix systems such as bone cement, elastomer or foam and cellular reinforcing structures made from e. g. polymeric monofilaments or metallic wires. The prerequisite is the availability of binding solutions for highly productive production of functional, cellular, self-stabilized spacer flat knitted fabrics as supporting and functionalized structures.

Cellular Mechanisms of Somatic Stem Cell Aging

Science.gov (United States)

Jung, Yunjoon

2014-01-01

Tissue homeostasis and regenerative capacity rely on rare populations of somatic stem cells endowed with the potential to self-renew and differentiate. During aging, many tissues show a decline in regenerative potential coupled with a loss of stem cell function. Cells including somatic stem cells have evolved a series of checks and balances to sense and repair cellular damage to maximize tissue function. However, during aging the mechanisms that protect normal cell function begin to fail. In this review, we will discuss how common cellular mechanisms that maintain tissue fidelity and organismal lifespan impact somatic stem cell function. We will highlight context-dependent changes and commonalities that define aging, by focusing on three age-sensitive stem cell compartments: blood, neural, and muscle. Understanding the interaction between extrinsic regulators and intrinsic effectors that operate within different stem cell compartments is likely to have important implications for identifying strategies to improve health span and treat age-related degenerative diseases. PMID:24439814

Neutrophil degranulation and immunosuppression in patients with GBM: restoration of cellular immune function by targeting arginase I.

Science.gov (United States)

Sippel, Trisha R; White, Jason; Nag, Kamalika; Tsvankin, Vadim; Klaassen, Marci; Kleinschmidt-DeMasters, B K; Waziri, Allen

2011-11-15

The source of glioblastoma (GBM)-associated immunosuppression remains multifactorial. We sought to clarify and therapeutically target myeloid cell-derived peripheral immunosuppression in patients with GBM. Direct ex vivo T-cell function, serum Arginase I (ArgI) levels, and circulating myeloid lineage populations were compared between patients with GBM and normal donors or patients with other intracranial tumors. Immunofunctional assays were conducted using bulk and sorted cell populations to explore the potential transfer of myeloid cell-mediated immunosuppression and to identify a potential mechanism for these effects. ArgI-mediated immunosuppression was therapeutically targeted in vitro through pharmacologic inhibition or arginine supplementation. We identified a significantly expanded population of circulating, degranulated neutrophils associated with elevated levels of serum ArgI and decreased T-cell CD3ζ expression within peripheral blood from patients with GBM. Sorted CD11b(+) cells from patients with GBM were found to markedly suppress normal donor T-cell function in coculture, and media harvested from mitogen-stimulated GBM peripheral blood mononuclear cell (PBMC) or GBM-associated mixed lymphoid reactions showed ArgI levels that were significantly higher than controls. Critically, T-cell suppression in both settings could be completely reversed through pharmacologic ArgI inhibition or with arginine supplementation. These data indicate that peripheral cellular immunosuppression in patients with GBM is associated with neutrophil degranulation and elevated levels of circulating ArgI, and that T-cell function can be restored in these individuals by targeting ArgI. These data identify a novel pathway of GBM-mediated suppression of cellular immunity and offer a potential therapeutic window for improving antitumor immunity in affected patients.

High-Concentrate Diet-Induced Change of Cellular Metabolism Leads to Decreases of Immunity and Imbalance of Cellular Activities in Rumen Epithelium.

Science.gov (United States)

Lu, Zhongyan; Shen, Hong; Shen, Zanming

2018-01-01

In animals, the immune and cellular processes of tissue largely depend on the status of local metabolism. However, in the rumen epithelium, how the cellular metabolism affects epithelial immunity, and cellular processes, when the diet is switched from energy-rich to energy-excess status, with regard to animal production and health, have not as yet been reported. RNA-seq was applied to compare the biological processes altered by an increase of dietary concentration from 10% to 35% with those altered by an increase of dietary concentration from 35% to 65% (dietary concentrate: the non-grass component in diet, including corn, soya bean meal and additive. High concentrate diet composed of 35% grass, 55% corn, 8% soya bean meal and 2% additive). In addition to the functional analysis of enriched genes in terms of metabolism, the immune system, and cellular process, the highly correlated genes to the enriched metabolism genes were identified, and the function and signaling pathways related to the differentially expressed neighbors were compared among the groups. The variation trends of molar proportions of ruminal SCFAs and those of enriched pathways belonging to metabolism, immune system, and cellular process were altered with the change of diets. With regard to metabolism, lipid metabolism and amino acid metabolism were most affected. According to the correlation analysis, both innate and adaptive immune responses were promoted by the metabolism genes enriched under the 65% concentrate diet. However, the majority of immune responses were suppressed under the 35% concentrate diet. Moreover, the exclusive upregulation of cell growth and dysfunction of cellular transport and catabolism were induced by the metabolism genes enriched under the 65% concentrate diet. On the contrary, a balanced regulation of cellular processes was detected under the 35% concentrate diet. These results indicated that the alterations of cellular metabolism promote the alterations in cellular

High-Concentrate Diet-Induced Change of Cellular Metabolism Leads to Decreases of Immunity and Imbalance of Cellular Activities in Rumen Epithelium

Directory of Open Access Journals (Sweden)

Zhongyan Lu

2018-03-01

Full Text Available Background/Aims: In animals, the immune and cellular processes of tissue largely depend on the status of local metabolism. However, in the rumen epithelium, how the cellular metabolism affects epithelial immunity, and cellular processes, when the diet is switched from energy-rich to energy-excess status, with regard to animal production and health, have not as yet been reported. Methods: RNA-seq was applied to compare the biological processes altered by an increase of dietary concentration from 10% to 35% with those altered by an increase of dietary concentration from 35% to 65% (dietary concentrate: the non-grass component in diet, including corn, soya bean meal and additive. High concentrate diet composed of 35% grass, 55% corn, 8% soya bean meal and 2% additive. In addition to the functional analysis of enriched genes in terms of metabolism, the immune system, and cellular process, the highly correlated genes to the enriched metabolism genes were identified, and the function and signaling pathways related to the differentially expressed neighbors were compared among the groups. Results: The variation trends of molar proportions of ruminal SCFAs and those of enriched pathways belonging to metabolism, immune system, and cellular process were altered with the change of diets. With regard to metabolism, lipid metabolism and amino acid metabolism were most affected. According to the correlation analysis, both innate and adaptive immune responses were promoted by the metabolism genes enriched under the 65% concentrate diet. However, the majority of immune responses were suppressed under the 35% concentrate diet. Moreover, the exclusive upregulation of cell growth and dysfunction of cellular transport and catabolism were induced by the metabolism genes enriched under the 65% concentrate diet. On the contrary, a balanced regulation of cellular processes was detected under the 35% concentrate diet. Conclusions: These results indicated that the

Tropomodulins and tropomyosins - organizers of cellular microcompartments.

Science.gov (United States)

Fath, Thomas

2013-02-01

Eukaryotic cells show a remarkable compartmentalization into compartments such as the cell nucleus, the Golgi apparatus, the endoplasmic reticulum, and endosomes. However, organelle structures are not the only means by which specialized compartments are formed. Recent research shows a critical role for diverse actin filament populations in defining functional compartments, here referred to as microcompartments, in a wide range of cells. These microcompartments are involved in regulating fundamental cellular functions including cell motility, plasma membrane organization, and cellular morphogenesis. In this overview, the importance of two multigene families of actin-associated proteins, tropomodulins and tropomyosins, their interactions with each other, and a large number of other proteins will be discussed in the context of generating specialized actin-based microcompartments.

Cellular stress induces a protective sleep-like state in C. elegans.

Science.gov (United States)

Hill, Andrew J; Mansfield, Richard; Lopez, Jessie M N G; Raizen, David M; Van Buskirk, Cheryl

2014-10-20

Sleep is recognized to be ancient in origin, with vertebrates and invertebrates experiencing behaviorally quiescent states that are regulated by conserved genetic mechanisms. Despite its conservation throughout phylogeny, the function of sleep remains debated. Hypotheses for the purpose of sleep include nervous-system-specific functions such as modulation of synaptic strength and clearance of metabolites from the brain, as well as more generalized cellular functions such as energy conservation and macromolecule biosynthesis. These models are supported by the identification of synaptic and metabolic processes that are perturbed during prolonged wakefulness. It remains to be seen whether perturbations of cellular homeostasis in turn drive sleep. Here we show that under conditions of cellular stress, including noxious heat, cold, hypertonicity, and tissue damage, the nematode Caenorhabditis elegans engages a behavioral quiescence program. The stress-induced quiescent state displays properties of sleep and is dependent on the ALA neuron, which mediates the conserved soporific effect of epidermal growth factor (EGF) ligand overexpression. We characterize heat-induced quiescence in detail and show that it is indeed dependent on components of EGF signaling, providing physiological relevance to the behavioral effects of EGF family ligands. We find that after noxious heat exposure, quiescence-defective animals show elevated expression of cellular stress reporter genes and are impaired for survival, demonstrating the benefit of stress-induced behavioral quiescence. These data provide evidence that cellular stress can induce a protective sleep-like state in C. elegans and suggest that a deeply conserved function of sleep is to mitigate disruptions of cellular homeostasis. Copyright © 2014 Elsevier Ltd. All rights reserved.

Tissue Engineering Strategies for Myocardial Regeneration: Acellular Versus Cellular Scaffolds?

Science.gov (United States)

Domenech, Maribella; Polo-Corrales, Lilliana; Ramirez-Vick, Jaime E; Freytes, Donald O

2016-12-01

Heart disease remains one of the leading causes of death in industrialized nations with myocardial infarction (MI) contributing to at least one fifth of the reported deaths. The hypoxic environment eventually leads to cellular death and scar tissue formation. The scar tissue that forms is not mechanically functional and often leads to myocardial remodeling and eventual heart failure. Tissue engineering and regenerative medicine principles provide an alternative approach to restoring myocardial function by designing constructs that will restore the mechanical function of the heart. In this review, we will describe the cellular events that take place after an MI and describe current treatments. We will also describe how biomaterials, alone or in combination with a cellular component, have been used to engineer suitable myocardium replacement constructs and how new advanced culture systems will be required to achieve clinical success.

Retinoic acid-induced alveolar cellular growth does not improve function after right pneumonectomy.

Science.gov (United States)

Dane, D Merrill; Yan, Xiao; Tamhane, Rahul M; Johnson, Robert L; Estrera, Aaron S; Hogg, Deborah C; Hogg, Richard T; Hsia, Connie C W

2004-03-01

To determine whether all-trans retinoic acid (RA) treatment enhances lung function during compensatory lung growth in fully mature animals, adult male dogs (n = 4) received 2 mg x kg(-1) x day(-1) po RA 4 days/wk beginning the day after right pneumonectomy (R-PNX, 55-58% resection). Litter-matched male R-PNX controls (n = 4) received placebo. After 3 mo, transpulmonary pressure (TPP)-lung volume relationship, diffusing capacities for carbon monoxide and nitric oxide, cardiac output, and septal volume (V(tiss-RB)) were measured under anesthesia by a rebreathing technique at two lung volumes. Lung air and tissue volumes (V(air-CT) and V(tiss-CT)) were also measured from high-resolution computerized tomographic (CT) scans at a constant TPP. In RA-treated dogs compared with controls, TPP-lung volume relationships were similar. Diffusing capacities for carbon monoxide and nitric oxide were significantly impaired at a lower lung volume but similar at a high lung volume. Whereas V(tiss-RB) was significantly lower at both lung volumes in RA-treated animals, V(air-CT) and V(tiss-CT) were not different between groups; results suggest uneven distribution of ventilation consistent with distortion of alveolar geometry and/or altered small airway function induced by RA. We conclude that RA does not improve resting pulmonary function during the early months after R-PNX despite histological evidence of its action in enhancing alveolar cellular growth in the remaining lung.

Cellular Adhesion and Adhesion Molecules

OpenAIRE

SELLER, Zerrin

2014-01-01

In recent years, cell adhesion and cell adhesion molecules have been shown to be important for many normal biological processes, including embryonic cell migration, immune system functions and wound healing. It has also been shown that they contribute to the pathogenesis of a large number of common human disorders, such as rheumatoid arthritis and tumor cell metastasis in cancer. In this review, the basic mechanisms of cellular adhesion and the structural and functional features of adhes...

Functional and genetic deconstruction of the cellular origin in liver cancer

DEFF Research Database (Denmark)

Marquardt, Jens U; Andersen, Jesper B; Thorgeirsson, Snorri S

2015-01-01

During the past decade, research on primary liver cancers has particularly highlighted the uncommon plasticity of differentiated parenchymal liver cells (that is, hepatocytes and cholangiocytes (also known as biliary epithelial cells)), the role of liver progenitor cells in malignant transformation......, the importance of the tumour microenvironment and the molecular complexity of liver tumours. Whereas other reviews have focused on the landscape of genetic alterations that promote development and progression of primary liver cancers and the role of the tumour microenvironment, the crucial importance...... of the cellular origin of liver cancer has been much less explored. Therefore, in this Review, we emphasize the importance and complexity of the cellular origin in tumour initiation and progression, and attempt to integrate this aspect with recent discoveries in tumour genomics and the contribution...

Cellular Senescence in Postmitotic Cells: Beyond Growth Arrest.

Science.gov (United States)

Sapieha, Przemyslaw; Mallette, Frédérick A

2018-04-25

In mitotic cells, cellular senescence is a permanent state of G1 arrest, that may have evolved in parallel to apoptosis, to limit proliferation of damaged cells and oncogenesis. Recent studies have suggested that postmitotic cells are also capable of entering a state of senescence, although the repercussions of postmitotic cellular senescence (PoMiCS) on tissue health and function are currently ill-defined. In tissues made largely of post-mitotic cells, it is evolutionary advantageous to preserve cellular integrity and cellular senescence of post-mitotic cells may prevent stressor-induced tissue degeneration and promote tissue repair. Paradoxically, PoMiCS may also contribute to disease progression through the generation of inflammatory mediators, termed the senescence-associated secretory phenotype. Here, we discuss the potential roles of PoMiCS and propose to enlarge the current definition of cellular senescence to postmitotic terminally differentiated cells. Copyright © 2018 Elsevier Ltd. All rights reserved.

Cellular Basis for ADT-Induced Acceleration of Sarcopenia

Science.gov (United States)

2015-10-01

1 AWARD NUMBER: W81XWH-14-1-0454 TITLE: Cellular Basis for ADT-Induced Acceleration of Sarcopenia PRINCIPAL INVESTIGATOR: Joe V...AND SUBTITLE Cellular Basis for ADT-Induced Acceleration of Sarcopenia 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-14-1-0454 5c. PROGRAM...cell function and thereby regenerative capability contribute to the acceleration of sarcopenia observed in prostate cancer patients undergoing ADT

Dual Functional Nanocarrier for Cellular Imaging and Drug Delivery in Cancer Cells Based on π-Conjugated Core and Biodegradable Polymer Arms.

Science.gov (United States)

Kulkarni, Bhagyashree; Surnar, Bapurao; Jayakannan, Manickam

2016-03-14

Multipurpose polymer nanoscaffolds for cellular imaging and delivery of anticancer drug are urgently required for the cancer therapy. The present investigation reports a new polymer drug delivery concept based on biodegradable polycaprolactone (PCL) and highly luminescent π-conjugated fluorophore as dual functional nanocarrier for cellular imaging and delivery vehicles for anticancer drug to cancer cells. To accomplish this goal, a new substituted caprolactone monomer was designed, and it was subjected to ring opening polymerization using a blue luminescent bishydroxyloligo-phenylenevinylene (OPV) fluorophore as an initiator. A series of A-B-A triblock copolymer building blocks with a fixed OPV π-core and variable chain biodegradable PCL arm length were tailor-made. These triblocks self-assembled in organic solvents to produce well-defined helical nanofibers, whereas in water they produced spherical nanoparticles (size ∼150 nm) with blue luminescence. The hydrophobic pocket of the polymer nanoparticle was found to be an efficient host for loading water insoluble anticancer drug such as doxorubicin (DOX). The photophysical studies revealed that there was no cross-talking between the OPV and DOX chromophores, and their optical purity was retained in the nanoparticle assembly for cellular imaging. In vitro studies revealed that the biodegradable PCL arm was susceptible to enzymatic cleavage at the intracellular lysosomal esterase under physiological conditions to release the loaded drugs. The nascent nanoparticles were found to be nontoxic to cancer cells, whereas the DOX-loaded nanoparticles accomplished more than 80% killing in HeLa cells. Confocal microscopic analysis confirmed the cell penetrating ability of the blue luminescent polymer nanoparticles and their accumulation preferably in the cytoplasm. The DOX loaded red luminescent polymer nanoparticles were also taken up by the cells, and the drug was found to be accumulated at the perinuclear environment

Cellular roles of ADAM12 in health and disease

DEFF Research Database (Denmark)

Kveiborg, Marie; Albrechtsen, Reidar; Couchman, John R

2008-01-01

and it is a potential biomarker for breast cancer. It is therefore important to understand ADAM12's functions. Many cellular roles for ADAM12 have been suggested. It is an active metalloprotease, and has been implicated in insulin-like growth factor (IGF) receptor signaling, through cleavage of IGF-binding proteins......, and in epidermal growth factor receptor (EGFR) pathways, via ectodomain shedding of membrane-tethered EGFR ligands. These proteolytic events may regulate diverse cellular responses, such as altered cell differentiation, proliferation, migration, and invasion. ADAM12 may also regulate cell-cell and cell...... to or from the cell interior. These ADAM12-mediated cellular effects appear to be critical events in both biological and pathological processes. This review presents current knowledge on ADAM12 functions gained from in vitro and in vivo observations, describes ADAM12's role in both normal physiology...

Human cellular restriction factors that target HIV-1 replication

Directory of Open Access Journals (Sweden)

Jeang Kuan-Teh

2009-09-01

Full Text Available Abstract Recent findings have highlighted roles played by innate cellular factors in restricting intracellular viral replication. In this review, we discuss in brief the activities of apolipoprotein B mRNA-editing enzyme 3G (APOBEC3G, bone marrow stromal cell antigen 2 (BST-2, cyclophilin A, tripartite motif protein 5 alpha (Trim5α, and cellular microRNAs as examples of host restriction factors that target HIV-1. We point to countermeasures encoded by HIV-1 for moderating the potency of these cellular restriction functions.

78 FR 44133 - Cellular, Tissue and Gene Therapies Advisory Committee; Notice of Meeting

Science.gov (United States)

2013-07-23

...] Cellular, Tissue and Gene Therapies Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Cellular, Tissue and Gene Therapies Advisory Committee. General Function of the Committee: To provide... documents issued from the Office of Cellular, Tissue and Gene Therapies, Center for Biologics Evaluation and...

76 FR 22405 - Cellular, Tissue and Gene Therapies Advisory Committee; Notice of Meeting

Science.gov (United States)

2011-04-21

...] Cellular, Tissue and Gene Therapies Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Cellular, Tissue and Gene Therapies Advisory Committee. General Function of the Committee: To provide... June 29, 2011, the committee will discuss cellular and gene therapy products for the treatment of...

78 FR 79699 - Cellular, Tissue, and Gene Therapies Advisory Committee; Notice of Meeting

Science.gov (United States)

2013-12-31

...] Cellular, Tissue, and Gene Therapies Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Cellular, Tissue, and Gene Therapies Advisory Committee. General Function of the Committee: To provide... updates on guidance documents issued from the Office of Cellular, Tissue, and Gene Therapies, Center for...

Iron Oxide Nanoparticles Stimulates Extra-Cellular Matrix Production in Cellular Spheroids

Directory of Open Access Journals (Sweden)

Megan Casco

2017-01-01

Full Text Available Nanotechnologies have been integrated into drug delivery, and non-invasive imaging applications, into nanostructured scaffolds for the manipulation of cells. The objective of this work was to determine how the physico-chemical properties of magnetic nanoparticles (MNPs and their spatial distribution into cellular spheroids stimulated cells to produce an extracellular matrix (ECM. The MNP concentration (0.03 mg/mL, 0.1 mg/mL and 0.3 mg/mL, type (magnetoferritin, shape (nanorod—85 nm × 425 nm and incorporation method were studied to determine each of their effects on the specific stimulation of four ECM proteins (collagen I, collagen IV, elastin and fibronectin in primary rat aortic smooth muscle cell. Results demonstrated that as MNP concentration increased there was up to a 6.32-fold increase in collagen production over no MNP samples. Semi-quantitative Immunohistochemistry (IHC results demonstrated that MNP type had the greatest influence on elastin production with a 56.28% positive area stain compared to controls and MNP shape favored elastin stimulation with a 50.19% positive area stain. Finally, there are no adverse effects of MNPs on cellular contractile ability. This study provides insight on the stimulation of ECM production in cells and tissues, which is important because it plays a critical role in regulating cellular functions.

Predicting cellular growth from gene expression signatures.

Directory of Open Access Journals (Sweden)

Edoardo M Airoldi

2009-01-01

Full Text Available Maintaining balanced growth in a changing environment is a fundamental systems-level challenge for cellular physiology, particularly in microorganisms. While the complete set of regulatory and functional pathways supporting growth and cellular proliferation are not yet known, portions of them are well understood. In particular, cellular proliferation is governed by mechanisms that are highly conserved from unicellular to multicellular organisms, and the disruption of these processes in metazoans is a major factor in the development of cancer. In this paper, we develop statistical methodology to identify quantitative aspects of the regulatory mechanisms underlying cellular proliferation in Saccharomyces cerevisiae. We find that the expression levels of a small set of genes can be exploited to predict the instantaneous growth rate of any cellular culture with high accuracy. The predictions obtained in this fashion are robust to changing biological conditions, experimental methods, and technological platforms. The proposed model is also effective in predicting growth rates for the related yeast Saccharomyces bayanus and the highly diverged yeast Schizosaccharomyces pombe, suggesting that the underlying regulatory signature is conserved across a wide range of unicellular evolution. We investigate the biological significance of the gene expression signature that the predictions are based upon from multiple perspectives: by perturbing the regulatory network through the Ras/PKA pathway, observing strong upregulation of growth rate even in the absence of appropriate nutrients, and discovering putative transcription factor binding sites, observing enrichment in growth-correlated genes. More broadly, the proposed methodology enables biological insights about growth at an instantaneous time scale, inaccessible by direct experimental methods. Data and tools enabling others to apply our methods are available at http://function.princeton.edu/growthrate.

Effects of acamprosate on attentional set-shifting and cellular function in the prefrontal cortex of chronic alcohol-exposed mice

Science.gov (United States)

Hu, Wei

Background: The medial prefrontal cortex (mPFC) inhibits impulsive and compulsive behaviors that characterize drug abuse and dependence. Acamprosate is the leading medication approved for the maintenance of abstinence, shown to reduce craving and relapse in animal models and human alcoholics. Whether acamprosate can modulate executive functions that are impaired by chronic ethanol exposure is unknown. Here we explored the effects of acamprosate on an attentional set-shifting task, and tested whether these behavioral effects are correlated with modulation of glutamatergic synaptic transmission and intrinsic excitability of mPFC neurons. Methods: We induced alcohol dependence in mice via chronic intermittent ethanol (CIE) exposure in vapor chambers and measured changes in alcohol consumption in a limited access 2-bottle choice paradigm. Impairments of executive function were assessed in an attentional set-shifting task. Acamprosate was applied subchronically for 2 days during withdrawal before the final behavioral test. Alcohol-induced changes in cellular function of layer 5/6 pyramidal neurons, and the potential modulation of these changes by acamprosate, were measured using patch clamp recordings in brain slices. Results: Chronic ethanol exposure impaired cognitive flexibility in the attentional set-shifting task. Acamprosate improved overall performance and reduced perseveration. Recordings of mPFC neurons showed that chronic ethanol exposure increased use-dependent presynaptic transmitter release and enhanced postsynaptic N-methyl-D-aspartate receptor (NMDAR) function. Moreover, CIE-treatment lowered input resistance, and decreased the threshold and the afterhyperpolarization (AHP) of action potentials, suggesting chronic ethanol exposure also impacted membrane excitability of mPFC neurons. However, acamprosate treatment did not reverse these ethanol-induced changes cellular function. Conclusion: Acamprosate improved attentional control of ethanol exposed animals

Changes in Retinal Function and Cellular Remodeling Following Experimental Retinal Detachment in a Rabbit Model

Directory of Open Access Journals (Sweden)

Tilda Barliya

2017-01-01

Full Text Available Purpose. To explore functional electroretinographic (ERG changes and associated cellular remodeling following experimental retinal detachment in a rabbit model. Methods. Retinal detachment was created in ten rabbits by injecting 0.1 ml balanced salt solution under the retina. Fundus imaging was performed 0, 3, 7, 14, and 21 days postoperatively. ERGs were recorded pre- and 7 and 21 days postoperatively. Eyes were harvested on day 21 and evaluated immunohistochemically (IHC for remodeling of second- and third-order neurons. Results. Retinal reattachment occurred within two weeks following surgery. No attenuation was observed in the photopic or scotopic a- and b-waves. A secondary wavefront on the descending slope of the scotopic b-wave was the only ERG result that was attenuated in detached retinas. IHC demonstrated anatomical changes in both ON and OFF bipolar cells. Bassoon staining was observed in the remodeled dendrites. Amacrine and horizontal cells did not alter, but Muller cells were clearly reactive with marked extension. Conclusion. Retinal detachment and reattachment were associated with functional and anatomical changes. Exploring the significance of the secondary scotopic wavefront and its association with the remodeling of 2nd- and 3rd-order neurons will shade more light on functional changes and recovery of the retina.

Coordination of Heparan Sulfate Proteoglycans with Wnt Signaling To Control Cellular Migrations and Positioning in Caenorhabditis elegans.

Science.gov (United States)

Saied-Santiago, Kristian; Townley, Robert A; Attonito, John D; da Cunha, Dayse S; Díaz-Balzac, Carlos A; Tecle, Eillen; Bülow, Hannes E

2017-08-01

Heparan sulfates (HS) are linear polysaccharides with complex modification patterns, which are covalently bound via conserved attachment sites to core proteins to form heparan sulfate proteoglycans (HSPGs). HSPGs regulate many aspects of the development and function of the nervous system, including cell migration, morphology, and network connectivity. HSPGs function as cofactors for multiple signaling pathways, including the Wnt-signaling molecules and their Frizzled receptors. To investigate the functional interactions among the HSPG and Wnt networks, we conducted genetic analyses of each, and also between these networks using five cellular migrations in the nematode Caenorhabditis elegans We find that HSPG core proteins act genetically in a combinatorial fashion dependent on the cellular contexts. Double mutant analyses reveal distinct redundancies among HSPGs for different migration events, and different cellular migrations require distinct heparan sulfate modification patterns. Our studies reveal that the transmembrane HSPG SDN-1/Syndecan functions within the migrating cell to promote cellular migrations, while the GPI-linked LON-2/Glypican functions cell nonautonomously to establish the final cellular position. Genetic analyses with the Wnt-signaling system show that (1) a given HSPG can act with different Wnts and Frizzled receptors, and that (2) a given Wnt/Frizzled pair acts with different HSPGs in a context-dependent manner. Lastly, we find that distinct HSPG and Wnt/Frizzled combinations serve separate functions to promote cellular migration and establish position of specific neurons. Our studies suggest that HSPGs use structurally diverse glycans in coordination with Wnt-signaling pathways to control multiple cellular behaviors, including cellular and axonal migrations and, cellular positioning. Copyright © 2017 by the Genetics Society of America.

Chaotic behavior in the disorder cellular automata

International Nuclear Information System (INIS)

Ko, J.-Y.; Hung, Y.-C.; Ho, M.-C.; Jiang, I-M.

2008-01-01

Disordered cellular automata (DCA) represent an intermediate class between elementary cellular automata and the Kauffman network. Recently, Rule 126 of DCA has been explicated: the system can be accurately described by a discrete probability function. However, a means of extending to other rules has not been developed. In this investigation, a density map of the dynamical behavior of DCA is formulated based on Rule 22 and other totalistic rules. The numerical results reveal excellent agreement between the model and original automata. Furthermore, the inhomogeneous situation is also discussed

Virtualized cognitive network architecture for 5G cellular networks

KAUST Repository

Elsawy, Hesham

2015-07-17

Cellular networks have preserved an application agnostic and base station (BS) centric architecture1 for decades. Network functionalities (e.g. user association) are decided and performed regardless of the underlying application (e.g. automation, tactile Internet, online gaming, multimedia). Such an ossified architecture imposes several hurdles against achieving the ambitious metrics of next generation cellular systems. This article first highlights the features and drawbacks of such architectural ossification. Then the article proposes a virtualized and cognitive network architecture, wherein network functionalities are implemented via software instances in the cloud, and the underlying architecture can adapt to the application of interest as well as to changes in channels and traffic conditions. The adaptation is done in terms of the network topology by manipulating connectivities and steering traffic via different paths, so as to attain the applications\\' requirements and network design objectives. The article presents cognitive strategies to implement some of the classical network functionalities, along with their related implementation challenges. The article further presents a case study illustrating the performance improvement of the proposed architecture as compared to conventional cellular networks, both in terms of outage probability and handover rate.

Cellular Functions of the Autism Risk Factor PTCHD1 in Mice.

Science.gov (United States)

Tora, David; Gomez, Andrea M; Michaud, Jean-Francois; Yam, Patricia T; Charron, Frédéric; Scheiffele, Peter

2017-12-06

The gene patched domain containing 1 ( PTCHD1 ) is mutated in patients with autism spectrum disorders and intellectual disabilities and has been hypothesized to contribute to Sonic hedgehog (Shh) signaling and synapse formation. We identify a panel of Ptchd1-interacting proteins that include postsynaptic density proteins and the retromer complex, revealing a link to critical regulators of dendritic and postsynaptic trafficking. Ptchd1 knock-out (KO) male mice exhibit cognitive alterations, including defects in a novel object recognition task. To test whether Ptchd1 is required for Shh-dependent signaling, we examined two Shh-dependent cell populations that express high levels of Ptchd1 mRNA: cerebellar granule cell precursors and dentate granule cells in the hippocampus. We found that proliferation of these neuronal precursors was not altered significantly in Ptchd1 KO male mice. We used whole-cell electrophysiology and anatomical methods to assess synaptic function in Ptchd1-deficient dentate granule cells. In the absence of Ptchd1, we observed profound disruption in excitatory/inhibitory balance despite normal dendritic spine density on dentate granule cells. These findings support a critical role of the Ptchd1 protein in the dentate gyrus, but indicate that it is not required for structural synapse formation in dentate granule cells or for Shh-dependent neuronal precursor proliferation. SIGNIFICANCE STATEMENT The mechanisms underlying neuronal and cellular alterations resulting from patched domain containing 1 ( Ptchd1 ) gene mutations are unknown. The results from this study support an association with dendritic trafficking complexes of Ptchd1. Loss-of-function experiments do not support a role in sonic hedgehog-dependent signaling, but reveal a disruption of synaptic transmission in the mouse dentate gyrus. The findings will help to guide ongoing efforts to understand the etiology of neurodevelopmental disorders arising from Ptchd1 deficiency. Copyright �

The cellular basis of organ ageing

NARCIS (Netherlands)

Knook, D.L.

1978-01-01

Ageing is associated with declines in the functional capacities of several organs. General causes for the decline can be divided into: 1. intrinsic cellular causes and 2. extracellular causes, e.g., changes in blood circulation and distribution. For the first group of causes, there is evidence for a

The association between systemic inflammatory cellular levels and lung function: a population-based study.

Directory of Open Access Journals (Sweden)

Tricia McKeever

Full Text Available BACKGROUND: Lower lung function is associated with an elevated systemic white cell count in men. However, these observations have not been demonstrated in a representative population that includes females and may be susceptible to confounding by recent airway infections or recent cigarette smoking. We tested the hypothesis that lung function is inversely associated with systemic white cell count in a population-based study. METHODS: The study population consisted adults aged 17-90+ years who participated in the Third National Health and Nutrition Examination Survey who did not report a recent cough, cold or acute illness in a non-smoking and smoking population. RESULTS: In non-smoking adults with the highest quintile of the total white cell count had a FEV(1 125.3 ml lower than those in the lowest quintile (95% confidence interval CI: -163.1 to -87.5. Adults with the highest quintile of the total white cell count had a FVC 151.1 ml lower than those in the lowest quintile (95% confidence interval CI: -195.0 to -107.2. Similar associations were observed for granulocytes, mononuclear cells and lymphocytes. In current smokers, similar smaller associations observed for total white cell count, granulocytes and mononuclear cells. CONCLUSIONS: Systemic cellular inflammation levels are inversely associated with lung function in a population of both non-smokers and smokers without acute illnesses. This may contribute to the increased mortality observed in individuals with a higher baseline white cell count.

An Amphipathic Helix Directs Cellular Membrane Curvature Sensing and Function of the BAR Domain Protein PICK1.

Science.gov (United States)

Herlo, Rasmus; Lund, Viktor K; Lycas, Matthew D; Jansen, Anna M; Khelashvili, George; Andersen, Rita C; Bhatia, Vikram; Pedersen, Thomas S; Albornoz, Pedro B C; Johner, Niklaus; Ammendrup-Johnsen, Ina; Christensen, Nikolaj R; Erlendsson, Simon; Stoklund, Mikkel; Larsen, Jannik B; Weinstein, Harel; Kjærulff, Ole; Stamou, Dimitrios; Gether, Ulrik; Madsen, Kenneth L

2018-05-15

BAR domains are dimeric protein modules that sense, induce, and stabilize lipid membrane curvature. Here, we show that membrane curvature sensing (MCS) directs cellular localization and function of the BAR domain protein PICK1. In PICK1, and the homologous proteins ICA69 and arfaptin2, we identify an amphipathic helix N-terminal to the BAR domain that mediates MCS. Mutational disruption of the helix in PICK1 impaired MCS without affecting membrane binding per se. In insulin-producing INS-1E cells, super-resolution microscopy revealed that disruption of the helix selectively compromised PICK1 density on insulin granules of high curvature during their maturation. This was accompanied by reduced hormone storage in the INS-1E cells. In Drosophila, disruption of the helix compromised growth regulation. By demonstrating size-dependent binding on insulin granules, our finding highlights the function of MCS for BAR domain proteins in a biological context distinct from their function, e.g., at the plasma membrane during endocytosis. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Long-time tails of the velocity autocorrelation function in 2D and 3D lattice gas cellular automata: a test of mode-coupling theory

NARCIS (Netherlands)

Hoef, M.A. van der; Frenkel, D.

1990-01-01

We report simulations of the velocity autocorrelation function (VACF) of a tagged particle in two- and three-dimensional lattice-gas cellular automata, using a new technique that is about a million times more efficient than the conventional techniques. The simulations clearly show the algebraic

Cocaine and MDMA Induce Cellular and Molecular Changes in Adult Neurogenic Systems: Functional Implications

Directory of Open Access Journals (Sweden)

Vivian Capilla-Gonzalez

2011-06-01

Full Text Available The capacity of the brain to generate new adult neurons is a recent discovery that challenges the old theory of an immutable adult brain. A new and fascinating field of research now focuses on this regenerative process. The two brain systems that constantly produce new adult neurons, known as the adult neurogenic systems, are the dentate gyrus (DG of the hippocampus and the lateral ventricules/olfactory bulb system. Both systems are involved in memory and learning processes. Different drugs of abuse, such as cocaine and MDMA, have been shown to produce cellular and molecular changes that affect adult neurogenesis. This review summarizes the effects that these drugs have on the adult neurogenic systems. The functional relevance of adult neurogenesis is obscured by the functions of the systems that integrate adult neurons. Therefore, we explore the effects that cocaine and MDMA produce not only on adult neurogenesis, but also on the DG and olfactory bulbs. Finally, we discuss the possible role of new adult neurons in cocaine- and MDMA-induced impairments. We conclude that, although harmful drug effects are produced at multiple physiological and anatomical levels, the specific consequences of reduced hippocampus neurogenesis are unclear and require further exploration.

NAD(H) and NADP(H) Redox Couples and Cellular Energy Metabolism.

Science.gov (United States)

Xiao, Wusheng; Wang, Rui-Sheng; Handy, Diane E; Loscalzo, Joseph

2018-01-20

The nicotinamide adenine dinucleotide (NAD + )/reduced NAD + (NADH) and NADP + /reduced NADP + (NADPH) redox couples are essential for maintaining cellular redox homeostasis and for modulating numerous biological events, including cellular metabolism. Deficiency or imbalance of these two redox couples has been associated with many pathological disorders. Recent Advances: Newly identified biosynthetic enzymes and newly developed genetically encoded biosensors enable us to understand better how cells maintain compartmentalized NAD(H) and NADP(H) pools. The concept of redox stress (oxidative and reductive stress) reflected by changes in NAD(H)/NADP(H) has increasingly gained attention. The emerging roles of NAD + -consuming proteins in regulating cellular redox and metabolic homeostasis are active research topics. The biosynthesis and distribution of cellular NAD(H) and NADP(H) are highly compartmentalized. It is critical to understand how cells maintain the steady levels of these redox couple pools to ensure their normal functions and simultaneously avoid inducing redox stress. In addition, it is essential to understand how NAD(H)- and NADP(H)-utilizing enzymes interact with other signaling pathways, such as those regulated by hypoxia-inducible factor, to maintain cellular redox homeostasis and energy metabolism. Additional studies are needed to investigate the inter-relationships among compartmentalized NAD(H)/NADP(H) pools and how these two dinucleotide redox couples collaboratively regulate cellular redox states and cellular metabolism under normal and pathological conditions. Furthermore, recent studies suggest the utility of using pharmacological interventions or nutrient-based bioactive NAD + precursors as therapeutic interventions for metabolic diseases. Thus, a better understanding of the cellular functions of NAD(H) and NADP(H) may facilitate efforts to address a host of pathological disorders effectively. Antioxid. Redox Signal. 28, 251-272.

Molecular and Cellular Signaling

CERN Document Server

Beckerman, Martin

2005-01-01

A small number of signaling pathways, no more than a dozen or so, form a control layer that is responsible for all signaling in and between cells of the human body. The signaling proteins belonging to the control layer determine what kinds of cells are made during development and how they function during adult life. Malfunctions in the proteins belonging to the control layer are responsible for a host of human diseases ranging from neurological disorders to cancers. Most drugs target components in the control layer, and difficulties in drug design are intimately related to the architecture of the control layer. Molecular and Cellular Signaling provides an introduction to molecular and cellular signaling in biological systems with an emphasis on the underlying physical principles. The text is aimed at upper-level undergraduates, graduate students and individuals in medicine and pharmacology interested in broadening their understanding of how cells regulate and coordinate their core activities and how diseases ...

Functional DNA-containing nanomaterials: cellular applications in biosensing, imaging, and targeted therapy.

Science.gov (United States)

Liang, Hao; Zhang, Xiao-Bing; Lv, Yifan; Gong, Liang; Wang, Ruowen; Zhu, Xiaoyan; Yang, Ronghua; Tan, Weihong

2014-06-17

CONSPECTUS: DNA performs a vital function as a carrier of genetic code, but in the field of nanotechnology, DNA molecules can catalyze chemical reactions in the cell, that is, DNAzymes, or bind with target-specific ligands, that is, aptamers. These functional DNAs with different modifications have been developed for sensing, imaging, and therapeutic systems. Thus, functional DNAs hold great promise for future applications in nanotechnology and bioanalysis. However, these functional DNAs face challenges, especially in the field of biomedicine. For example, functional DNAs typically require the use of cationic transfection reagents to realize cellular uptake. Such reagents enter the cells, increasing the difficulty of performing bioassays in vivo and potentially damaging the cell's nucleus. To address this obstacle, nanomaterials, such as metallic, carbon, silica, or magnetic materials, have been utilized as DNA carriers or assistants. In this Account, we describe selected examples of functional DNA-containing nanomaterials and their applications from our recent research and those of others. As models, we have chosen to highlight DNA/nanomaterial complexes consisting of gold nanoparticles, graphene oxides, and aptamer-micelles, and we illustrate the potential of such complexes in biosensing, imaging, and medical diagnostics. Under proper conditions, multiple ligand-receptor interactions, decreased steric hindrance, and increased surface roughness can be achieved from a high density of DNA that is bound to the surface of nanomaterials, resulting in a higher affinity for complementary DNA and other targets. In addition, this high density of DNA causes a high local salt concentration and negative charge density, which can prevent DNA degradation. For example, DNAzymes assembled on gold nanoparticles can effectively catalyze chemical reactions even in living cells. And it has been confirmed that DNA-nanomaterial complexes can enter cells more easily than free single

Bioinspired Cellular Structures: Additive Manufacturing and Mechanical Properties

Science.gov (United States)

Stampfl, J.; Pettermann, H. E.; Liska, R.

Biological materials (e.g., wood, trabecular bone, marine skeletons) rely heavily on the use of cellular architecture, which provides several advantages. (1) The resulting structures can bear the variety of "real life" load spectra using a minimum of a given bulk material, featuring engineering lightweight design principles. (2) The inside of the structures is accessible to body fluids which deliver the required nutrients. (3) Furthermore, cellular architectures can grow organically by adding or removing individual struts or by changing the shape of the constituting elements. All these facts make the use of cellular architectures a reasonable choice for nature. Using additive manufacturing technologies (AMT), it is now possible to fabricate such structures for applications in engineering and biomedicine. In this chapter, we present methods that allow the 3D computational analysis of the mechanical properties of cellular structures with open porosity. Various different cellular architectures including disorder are studied. In order to quantify the influence of architecture, the apparent density is always kept constant. Furthermore, it is shown that how new advanced photopolymers can be used to tailor the mechanical and functional properties of the fabricated structures.

The functional state of cellular antioxidant defence system of shoots of Arabidopsis thaliana exposed to the chronic ionizing radiation in the Chornobyl exclusion zone

International Nuclear Information System (INIS)

Morozova, V.S.; Kashparov, V.A.; Levchuk, S.Ye.; Umanska, A.O.; Bishchuk, Ye.V.; Otreshko, L.M

2016-01-01

The functional state of the cellular antioxidant defence system of shoots of Arabidopsis thaliana plants that grow in natural conditions in the areas of the Chornobyl Exclusion Zone with the values of the external dose rate of 0.45, 0.61, 1.05, 4.81 and 6.80 .Gy/h was evaluated. The decrease of the content of thiobarbituric acid reactive compounds in the shoots of Arabidopsis thaliana was revealed under the external dose rate of 4.81 and 6.80 .Gy/h by 38 and 48 %, respectively, compared to this parameter value under the external dose rate of 0.45 .Gy/h. In the investigated samples the capacity of guaiacol peroxidase increases, catalase and ascorbate peroxidase decreases significantly with the increase of the external dose rate from 0.45 to 6.80 .Gy/h. Probably, revealed changes in the functional state of the cellular antioxidant defence system of the shoots of Arabidopsis thaliana in the conditions of radioactive contamination are adaptive in nature.

Effects of HIV-1 protease on cellular functions and their potential applications in antiretroviral therapy

Directory of Open Access Journals (Sweden)

Yang Hailiu

2012-09-01

fission yeast as a possible surrogate system to study the effects of HIV-1 protease on cellular functions and to explore its utility as a HTS system to search for new PIs to battle HIV-1 resistant strains.

FIH Regulates Cellular Metabolism through Hydroxylation of the Deubiquitinase OTUB1.

Directory of Open Access Journals (Sweden)

Carsten C Scholz

2016-01-01

Full Text Available The asparagine hydroxylase, factor inhibiting HIF (FIH, confers oxygen-dependence upon the hypoxia-inducible factor (HIF, a master regulator of the cellular adaptive response to hypoxia. Studies investigating whether asparagine hydroxylation is a general regulatory oxygen-dependent modification have identified multiple non-HIF targets for FIH. However, the functional consequences of this outside of the HIF pathway remain unclear. Here, we demonstrate that the deubiquitinase ovarian tumor domain containing ubiquitin aldehyde binding protein 1 (OTUB1 is a substrate for hydroxylation by FIH on N22. Mutation of N22 leads to a profound change in the interaction of OTUB1 with proteins important in cellular metabolism. Furthermore, in cultured cells, overexpression of N22A mutant OTUB1 impairs cellular metabolic processes when compared to wild type. Based on these data, we hypothesize that OTUB1 is a target for functional hydroxylation by FIH. Additionally, we propose that our results provide new insight into the regulation of cellular energy metabolism during hypoxic stress and the potential for targeting hydroxylases for therapeutic benefit.

Similarities of cellular receptors for interferon and cortisol

International Nuclear Information System (INIS)

Filipic, B.; Schauer, P.; Likar, M.

1977-01-01

Cellular receptors are molecules located on the cell membrane. Their function is to bind different molecules to the cell surface. These molecules can penetrate into the cytoplasm and trigger cellular changes. One kind of such bound molecules are interferons and corticosteroids. Until very recently very little was known about interferon's receptors on the cell surface, mechanisms of interferon's binding to them or about kinetics of such binding. On the basis of results published elsewhere and on the basis of experimental results, the authors suggest: receptors for interferon and cortisol are glycoproteins located on the cell surface, in analogy with PHA receptors they are chemically sialoglycoproteins, binding kinetics of cortisol and interferon is similar, interferon and cortisol compete for cellular receptors, binding of cortisol or interferon is dependent on allosteric configuration of receptor molecules. (author)

Inter-cellular transport of ran GTPase.

Directory of Open Access Journals (Sweden)

Deepak Khuperkar

Full Text Available Ran, a member of the Ras-GTPase superfamily, has a well-established role in regulating the transport of macromolecules across the nuclear envelope (NE. Ran has also been implicated in mitosis, cell cycle progression, and NE formation. Over-expression of Ran is associated with various cancers, although the molecular mechanism underlying this phenomenon is unclear. Serendipitously, we found that Ran possesses the ability to move from cell-to-cell when transiently expressed in mammalian cells. Moreover, we show that the inter-cellular transport of Ran is GTP-dependent. Importantly, Ran displays a similar distribution pattern in the recipient cells as that in the donor cell and co-localizes with the Ran binding protein Nup358 (also called RanBP2. Interestingly, leptomycin B, an inhibitor of CRM1-mediated export, or siRNA mediated depletion of CRM1, significantly impaired the inter-cellular transport of Ran, suggesting a function for CRM1 in this process. These novel findings indicate a possible role for Ran beyond nucleo-cytoplasmic transport, with potential implications in inter-cellular communication and cancers.

Cell functional enviromics: Unravelling the function of environmental factors

Directory of Open Access Journals (Sweden)

Alves Paula M

2011-06-01

Full Text Available Abstract Background While functional genomics, focused on gene functions and gene-gene interactions, has become a very active field of research in molecular biology, equivalent methodologies embracing the environment and gene-environment interactions are relatively less developed. Understanding the function of environmental factors is, however, of paramount importance given the complex, interactive nature of environmental and genetic factors across multiple time scales. Results Here, we propose a systems biology framework, where the function of environmental factors is set at its core. We set forth a "reverse" functional analysis approach, whereby cellular functions are reconstructed from the analysis of dynamic envirome data. Our results show these data sets can be mapped to less than 20 core cellular functions in a typical mammalian cell culture, while explaining over 90% of flux data variance. A functional enviromics map can be created, which provides a template for manipulating the environmental factors to induce a desired phenotypic trait. Conclusion Our results support the feasibility of cellular function reconstruction guided by the analysis and manipulation of dynamic envirome data.

Regulation of cellular communication by signaling microdomains in the blood vessel wall.

Science.gov (United States)

Billaud, Marie; Lohman, Alexander W; Johnstone, Scott R; Biwer, Lauren A; Mutchler, Stephanie; Isakson, Brant E

2014-01-01

It has become increasingly clear that the accumulation of proteins in specific regions of the plasma membrane can facilitate cellular communication. These regions, termed signaling microdomains, are found throughout the blood vessel wall where cellular communication, both within and between cell types, must be tightly regulated to maintain proper vascular function. We will define a cellular signaling microdomain and apply this definition to the plethora of means by which cellular communication has been hypothesized to occur in the blood vessel wall. To that end, we make a case for three broad areas of cellular communication where signaling microdomains could play an important role: 1) paracrine release of free radicals and gaseous molecules such as nitric oxide and reactive oxygen species; 2) role of ion channels including gap junctions and potassium channels, especially those associated with the endothelium-derived hyperpolarization mediated signaling, and lastly, 3) mechanism of exocytosis that has considerable oversight by signaling microdomains, especially those associated with the release of von Willebrand factor. When summed, we believe that it is clear that the organization and regulation of signaling microdomains is an essential component to vessel wall function.

Regulation of Cellular Communication by Signaling Microdomains in the Blood Vessel Wall

Science.gov (United States)

Billaud, Marie; Lohman, Alexander W.; Johnstone, Scott R.; Biwer, Lauren A.; Mutchler, Stephanie; Isakson, Brant E.

2014-01-01

It has become increasingly clear that the accumulation of proteins in specific regions of the plasma membrane can facilitate cellular communication. These regions, termed signaling microdomains, are found throughout the blood vessel wall where cellular communication, both within and between cell types, must be tightly regulated to maintain proper vascular function. We will define a cellular signaling microdomain and apply this definition to the plethora of means by which cellular communication has been hypothesized to occur in the blood vessel wall. To that end, we make a case for three broad areas of cellular communication where signaling microdomains could play an important role: 1) paracrine release of free radicals and gaseous molecules such as nitric oxide and reactive oxygen species; 2) role of ion channels including gap junctions and potassium channels, especially those associated with the endothelium-derived hyperpolarization mediated signaling, and lastly, 3) mechanism of exocytosis that has considerable oversight by signaling microdomains, especially those associated with the release of von Willebrand factor. When summed, we believe that it is clear that the organization and regulation of signaling microdomains is an essential component to vessel wall function. PMID:24671377

Effect of psychological intervention in the form of relaxation and guided imagery on cellular immune function in normal healthy subjects. An overview

DEFF Research Database (Denmark)

Zachariae, R; Kristensen, J S; Hokland, P

1991-01-01

The present study measured the effects of relaxation and guided imagery on cellular immune function. During a period of 10 days 10 healthy subjects were given one 1-hour relaxation procedure and one combined relaxation and guided imagery procedure, instructing the subjects to imagine their immune...... on the immune defense and could form the basis of further studies on psychological intervention and immunological status. Udgivelsesdato: 1990-null...

A Phylogenomic Census of Molecular Functions Identifies Modern Thermophilic Archaea as the Most Ancient Form of Cellular Life

Directory of Open Access Journals (Sweden)

Arshan Nasir

2014-01-01

Full Text Available The origins of diversified life remain mysterious despite considerable efforts devoted to untangling the roots of the universal tree of life. Here we reconstructed phylogenies that described the evolution of molecular functions and the evolution of species directly from a genomic census of gene ontology (GO definitions. We sampled 249 free-living genomes spanning organisms in the three superkingdoms of life, Archaea, Bacteria, and Eukarya, and used the abundance of GO terms as molecular characters to produce rooted phylogenetic trees. Results revealed an early thermophilic origin of Archaea that was followed by genome reduction events in microbial superkingdoms. Eukaryal genomes displayed extraordinary functional diversity and were enriched with hundreds of novel molecular activities not detected in the akaryotic microbial cells. Remarkably, the majority of these novel functions appeared quite late in evolution, synchronized with the diversification of the eukaryal superkingdom. The distribution of GO terms in superkingdoms confirms that Archaea appears to be the simplest and most ancient form of cellular life, while Eukarya is the most diverse and recent.

A phylogenomic census of molecular functions identifies modern thermophilic archaea as the most ancient form of cellular life.

Science.gov (United States)

Nasir, Arshan; Kim, Kyung Mo; Caetano-Anollés, Gustavo

2014-01-01

The origins of diversified life remain mysterious despite considerable efforts devoted to untangling the roots of the universal tree of life. Here we reconstructed phylogenies that described the evolution of molecular functions and the evolution of species directly from a genomic census of gene ontology (GO) definitions. We sampled 249 free-living genomes spanning organisms in the three superkingdoms of life, Archaea, Bacteria, and Eukarya, and used the abundance of GO terms as molecular characters to produce rooted phylogenetic trees. Results revealed an early thermophilic origin of Archaea that was followed by genome reduction events in microbial superkingdoms. Eukaryal genomes displayed extraordinary functional diversity and were enriched with hundreds of novel molecular activities not detected in the akaryotic microbial cells. Remarkably, the majority of these novel functions appeared quite late in evolution, synchronized with the diversification of the eukaryal superkingdom. The distribution of GO terms in superkingdoms confirms that Archaea appears to be the simplest and most ancient form of cellular life, while Eukarya is the most diverse and recent.

Effects of radiofrequency radiation emitted by cellular telephones on the cognitive functions of humans.

Science.gov (United States)

Eliyahu, Ilan; Luria, Roy; Hareuveny, Ronen; Margaliot, Menachem; Meiran, Nachshon; Shani, Gad

2006-02-01

The present study examined the effects of exposure to Electromagnetic Radiation emitted by a standard GSM phone at 890 MHz on human cognitive functions. This study attempted to establish a connection between the exposure of a specific area of the brain and the cognitive functions associated with that area. A total of 36 healthy right-handed male subjects performed four distinct cognitive tasks: spatial item recognition, verbal item recognition, and two spatial compatibility tasks. Tasks were chosen according to the brain side they are assumed to activate. All subjects performed the tasks under three exposure conditions: right side, left side, and sham exposure. The phones were controlled by a base station simulator and operated at their full power. We have recorded the reaction times (RTs) and accuracy of the responses. The experiments consisted of two sections, of 1 h each, with a 5 min break in between. The tasks and the exposure regimes were counterbalanced. The results indicated that the exposure of the left side of the brain slows down the left-hand response time, in the second-later-part of the experiment. This effect was apparent in three of the four tasks, and was highly significant in only one of the tests. The exposure intensity and its duration exceeded the common exposure of cellular phone users.

Recycling of inorganic waste in monolithic and cellular glass-based materials for structural and functional applications.

Science.gov (United States)

Rincón, Acacio; Marangoni, Mauro; Cetin, Suna; Bernardo, Enrico

2016-07-01

The stabilization of inorganic waste of various nature and origin, in glasses, has been a key strategy for environmental protection for the last decades. When properly formulated, glasses may retain many inorganic contaminants permanently, but it must be acknowledged that some criticism remains, mainly concerning costs and energy use. As a consequence, the sustainability of vitrification largely relies on the conversion of waste glasses into new, usable and marketable glass-based materials, in the form of monolithic and cellular glass-ceramics. The effective conversion in turn depends on the simultaneous control of both starting materials and manufacturing processes. While silica-rich waste favours the obtainment of glass, iron-rich wastes affect the functionalities, influencing the porosity in cellular glass-based materials as well as catalytic, magnetic, optical and electrical properties. Engineered formulations may lead to important reductions of processing times and temperatures, in the transformation of waste-derived glasses into glass-ceramics, or even bring interesting shortcuts. Direct sintering of wastes, combined with recycled glasses, as an example, has been proven as a valid low-cost alternative for glass-ceramic manufacturing, for wastes with limited hazardousness. The present paper is aimed at providing an up-to-date overview of the correlation between formulations, manufacturing technologies and properties of most recent waste-derived, glass-based materials. © 2016 The Authors. Journal of Chemical Technology & Biotechnology published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Recycling of inorganic waste in monolithic and cellular glass‐based materials for structural and functional applications

Science.gov (United States)

Rincón, Acacio; Marangoni, Mauro; Cetin, Suna

2016-01-01

Abstract The stabilization of inorganic waste of various nature and origin, in glasses, has been a key strategy for environmental protection for the last decades. When properly formulated, glasses may retain many inorganic contaminants permanently, but it must be acknowledged that some criticism remains, mainly concerning costs and energy use. As a consequence, the sustainability of vitrification largely relies on the conversion of waste glasses into new, usable and marketable glass‐based materials, in the form of monolithic and cellular glass‐ceramics. The effective conversion in turn depends on the simultaneous control of both starting materials and manufacturing processes. While silica‐rich waste favours the obtainment of glass, iron‐rich wastes affect the functionalities, influencing the porosity in cellular glass‐based materials as well as catalytic, magnetic, optical and electrical properties. Engineered formulations may lead to important reductions of processing times and temperatures, in the transformation of waste‐derived glasses into glass‐ceramics, or even bring interesting shortcuts. Direct sintering of wastes, combined with recycled glasses, as an example, has been proven as a valid low‐cost alternative for glass‐ceramic manufacturing, for wastes with limited hazardousness. The present paper is aimed at providing an up‐to‐date overview of the correlation between formulations, manufacturing technologies and properties of most recent waste‐derived, glass‐based materials. © 2016 The Authors. Journal of Chemical Technology & Biotechnology published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry. PMID:27818564

Regulation of Mitochondrial Function and Cellular Energy Metabolism by Protein Kinase C-λ/ι: A Novel Mode of Balancing Pluripotency

Science.gov (United States)

Mahato, Biraj; Home, Pratik; Rajendran, Ganeshkumar; Paul, Arindam; Saha, Biswarup; Ganguly, Avishek; Ray, Soma; Roy, Nairita; Swerdlow, Russell H.; Paul, Soumen

2014-01-01

Pluripotent stem cells (PSCs) contain functionally immature mitochondria and rely upon high rates of glycolysis for their energy requirements. Thus, altered mitochondrial function and promotion of aerobic glycolysis is key to maintain and induce pluripotency. However, signaling mechanisms that regulate mitochondrial function and reprogram metabolic preferences in self-renewing vs. differentiated PSC populations are poorly understood. Here, using murine embryonic stem cells (ESCs) as a model system, we demonstrate that atypical protein kinase C isoform, PKC lambda/iota (PKCλ/ι), is a key regulator of mitochondrial function in ESCs. Depletion of PKCλ/ι in ESCs maintains their pluripotent state as evident from germline offsprings. Interestingly, loss of PKCλ/ι in ESCs leads to impairment in mitochondrial maturation, organization and a metabolic shift toward glycolysis under differentiating condition. Our mechanistic analyses indicate that a PKCλ/ι-HIF1α-PGC1α axis regulates mitochondrial respiration and balances pluripotency in ESCs. We propose that PKCλ/ι could be a crucial regulator of mitochondrial function and energy metabolism in stem cells and other cellular contexts. PMID:25142417

Cellular concrete: a potential load-bearing insulation for cryogenic applications

International Nuclear Information System (INIS)

Richard, T.G.; Dobogai, J.A.; Gerhardt, T.D.; Young, W.C.

1975-01-01

The need for low cost, low thermal conductivity, high strength insulation suitable for cryogenic applications is becoming more evident. An investigation of the potential of cellular concretes to fulfill this function was initiated. A review of the thermal and mechanical characteristics of foamed plastics and cellular concrete is presented along with relative cost comparisons. Test data from preliminary investigations is presented to define the influence of material constituents, density, and temperature on the mechanical and thermal response of cellular concrete. Specimen densities range from 0.64 to 1.44 gr/cc. The influence of temperature variations from 22 0 C to -196 0 C is reported for selected densities

Biomolecular condensates: organizers of cellular biochemistry.

Science.gov (United States)

Banani, Salman F; Lee, Hyun O; Hyman, Anthony A; Rosen, Michael K

2017-05-01

Biomolecular condensates are micron-scale compartments in eukaryotic cells that lack surrounding membranes but function to concentrate proteins and nucleic acids. These condensates are involved in diverse processes, including RNA metabolism, ribosome biogenesis, the DNA damage response and signal transduction. Recent studies have shown that liquid-liquid phase separation driven by multivalent macromolecular interactions is an important organizing principle for biomolecular condensates. With this physical framework, it is now possible to explain how the assembly, composition, physical properties and biochemical and cellular functions of these important structures are regulated.

Cellular, molecular and functional characterisation of YAC transgenic mouse models of Friedreich ataxia.

Directory of Open Access Journals (Sweden)

Sara Anjomani Virmouni

Full Text Available Friedreich ataxia (FRDA is an autosomal recessive neurodegenerative disorder, caused by a GAA repeat expansion mutation within intron 1 of the FXN gene. We have previously established and performed preliminary characterisation of several human FXN yeast artificial chromosome (YAC transgenic FRDA mouse models containing GAA repeat expansions, Y47R (9 GAA repeats, YG8R (90 and 190 GAA repeats and YG22R (190 GAA repeats.We now report extended cellular, molecular and functional characterisation of these FXN YAC transgenic mouse models. FXN transgene copy number analysis of the FRDA mice demonstrated that the YG22R and Y47R lines each have a single copy of the FXN transgene while the YG8R line has two copies. Single integration sites of all transgenes were confirmed by fluorescence in situ hybridisation (FISH analysis of metaphase and interphase chromosomes. We identified significant functional deficits, together with a degree of glucose intolerance and insulin hypersensitivity, in YG8R and YG22R FRDA mice compared to Y47R and wild-type control mice. We also confirmed increased somatic GAA repeat instability in the cerebellum and brain of YG22R and YG8R mice, together with significantly reduced levels of FXN mRNA and protein in the brain and liver of YG8R and YG22R compared to Y47R.Together these studies provide a detailed characterisation of our GAA repeat expansion-based YAC transgenic FRDA mouse models that will help investigations of FRDA disease mechanisms and therapy.

75 FR 66381 - Cellular, Tissue and Gene Therapies Advisory Committee; Notice of Meeting

Science.gov (United States)

2010-10-28

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0001] Cellular, Tissue and Gene Therapies Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Cellular, Tissue and Gene Therapies Advisory Committee. General Function of the Committee: To provide...

76 FR 49774 - Cellular, Tissue and Gene Therapies Advisory Committee; Notice of Meeting

Science.gov (United States)

2011-08-11

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0002] Cellular, Tissue and Gene Therapies Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Cellular, Tissue and Gene Therapies Advisory Committee. General Function of the Committee: To provide...

76 FR 64951 - Cellular, Tissue and Gene Therapies Advisory Committee; Notice of Meeting

Science.gov (United States)

2011-10-19

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0002] Cellular, Tissue and Gene Therapies Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Cellular, Tissue and Gene Therapies Advisory Committee. General Function of the Committee: To provide...

78 FR 15726 - Cellular, Tissue and Gene Therapies Advisory Committee; Notice of Meeting

Science.gov (United States)

2013-03-12

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0001] Cellular, Tissue and Gene Therapies Advisory Committee; Notice of Meeting AGENCY: Food and Drug... public. Name of Committee: Cellular, Tissue and Gene Therapies Advisory Committee. General Function of...

Cellular gravity

NARCIS (Netherlands)

F.C. Gruau; J.T. Tromp (John)

1999-01-01

textabstractWe consider the problem of establishing gravity in cellular automata. In particular, when cellular automata states can be partitioned into empty, particle, and wall types, with the latter enclosing rectangular areas, we desire rules that will make the particles fall down and pile up on

Combinatorial approaches to evaluate nanodiamond uptake and induced cellular fate

Science.gov (United States)

Eldawud, Reem; Reitzig, Manuela; Opitz, Jörg; Rojansakul, Yon; Jiang, Wenjuan; Nangia, Shikha; Zoica Dinu, Cerasela

2016-02-01

Nanodiamonds (NDs) are an emerging class of engineered nanomaterials that hold great promise for the next generation of bionanotechnological products to be used for drug and gene delivery, or for bio-imaging and biosensing. Previous studies have shown that upon their cellular uptake, NDs exhibit high biocompatibility in various in vitro and in vivo set-ups. Herein we hypothesized that the increased NDs biocompatibility is a result of minimum membrane perturbations and their reduced ability to induce disruption or damage during cellular translocation. Using multi-scale combinatorial approaches that simulate ND-membrane interactions, we correlated NDs real-time cellular uptake and kinetics with the ND-induced membrane fluctuations to derive energy requirements for the uptake to occur. Our discrete and real-time analyses showed that the majority of NDs internalization occurs within 2 h of cellular exposure, however, with no effects on cellular viability, proliferation or cellular behavior. Furthermore, our simulation analyses using coarse-grained models identified key changes in the energy profile, membrane deformation and recovery time, all functions of the average ND or ND-based agglomerate size. Understanding the mechanisms responsible for ND-cell membrane interactions could possibly advance their implementation in various biomedical applications.

Combinatorial approaches to evaluate nanodiamond uptake and induced cellular fate

Science.gov (United States)

Eldawud, Reem; Reitzig, Manuela; Opitz, Jörg; Rojansakul, Yon; Jiang, Wenjuan; Nangia, Shikha; Dinu, Cerasela Zoica

2016-01-01

Nanodiamonds (NDs) are an emerging class of engineered nanomaterials that hold great promise for the next generation of bionanotechnological products to be used for drug and gene delivery, or for bio-imaging and biosensing. Previous studies have shown that upon their cellular uptake, NDs exhibit high biocompatibility in various in vitro and in vivo set-ups. Herein we hypothesized that the increased NDs biocompatibility is a result of minimum membrane perturbations and their reduced ability to induce disruption or damage during cellular translocation. Using multi-scale combinatorial approaches that simulate ND-membrane interactions, we correlated NDs real-time cellular uptake and kinetics with the ND-induced membrane fluctuations to derive energy requirements for the uptake to occur. Our discrete and real-time analyses showed that the majority of NDs internalization occurs within 2 h of cellular exposure, however, with no effects on cellular viability, proliferation or cellular behavior. Furthermore, our simulation analyses using coarse-grained models identified key changes in the energy profile, membrane deformation and recovery time, all functions of the average ND or ND-based agglomerate size. Understanding the mechanisms responsible for ND-cell membrane interactions could possibly advance their implementation in various biomedical applications. PMID:26820775

Combinatorial approaches to evaluate nanodiamond uptake and induced cellular fate

International Nuclear Information System (INIS)

Eldawud, Reem; Dinu, Cerasela Zoica; Reitzig, Manuela; Opitz, Jörg; Rojansakul, Yon; Jiang, Wenjuan; Nangia, Shikha

2016-01-01

Nanodiamonds (NDs) are an emerging class of engineered nanomaterials that hold great promise for the next generation of bionanotechnological products to be used for drug and gene delivery, or for bio-imaging and biosensing. Previous studies have shown that upon their cellular uptake, NDs exhibit high biocompatibility in various in vitro and in vivo set-ups. Herein we hypothesized that the increased NDs biocompatibility is a result of minimum membrane perturbations and their reduced ability to induce disruption or damage during cellular translocation. Using multi-scale combinatorial approaches that simulate ND-membrane interactions, we correlated NDs real-time cellular uptake and kinetics with the ND-induced membrane fluctuations to derive energy requirements for the uptake to occur. Our discrete and real-time analyses showed that the majority of NDs internalization occurs within 2 h of cellular exposure, however, with no effects on cellular viability, proliferation or cellular behavior. Furthermore, our simulation analyses using coarse-grained models identified key changes in the energy profile, membrane deformation and recovery time, all functions of the average ND or ND-based agglomerate size. Understanding the mechanisms responsible for ND-cell membrane interactions could possibly advance their implementation in various biomedical applications. (paper)

Combinatorial approaches to evaluate nanodiamond uptake and induced cellular fate.

Science.gov (United States)

Eldawud, Reem; Reitzig, Manuela; Opitz, Jörg; Rojansakul, Yon; Jiang, Wenjuan; Nangia, Shikha; Dinu, Cerasela Zoica

2016-02-26

Nanodiamonds (NDs) are an emerging class of engineered nanomaterials that hold great promise for the next generation of bionanotechnological products to be used for drug and gene delivery, or for bio-imaging and biosensing. Previous studies have shown that upon their cellular uptake, NDs exhibit high biocompatibility in various in vitro and in vivo set-ups. Herein we hypothesized that the increased NDs biocompatibility is a result of minimum membrane perturbations and their reduced ability to induce disruption or damage during cellular translocation. Using multi-scale combinatorial approaches that simulate ND-membrane interactions, we correlated NDs real-time cellular uptake and kinetics with the ND-induced membrane fluctuations to derive energy requirements for the uptake to occur. Our discrete and real-time analyses showed that the majority of NDs internalization occurs within 2 h of cellular exposure, however, with no effects on cellular viability, proliferation or cellular behavior. Furthermore, our simulation analyses using coarse-grained models identified key changes in the energy profile, membrane deformation and recovery time, all functions of the average ND or ND-based agglomerate size. Understanding the mechanisms responsible for ND-cell membrane interactions could possibly advance their implementation in various biomedical applications.

Leading research report for fiscal 1998. Research and study of 3-dimensional cell structure module engineering; 1998 nendo sendo chosa kenkyu hokokusho. Sanjigen saibo soshiki module kogaku chosa kenkyu

Energy Technology Data Exchange (ETDEWEB)

NONE

1999-03-01

For the formation of cellular tissues to replace bionic tissues, researches were conducted about technologies of forming bionic tissue modules by culturing various kinds of cells. As for the materials and methods for constructing cellular tissues, researches were conducted about the trends of research and development of 3-dimensional tissue culturing matrices and materials for micromanipulation. As for the development of technologies for the functionalization of 3-dimensionally structured cells, research and study were conducted about the technology of 3-dimensional cell structure organization through application of physical stimulation, the biochemical technology of differentiation inducing, and the differentiation inducing technology for hetero tissue culturing. As for the development of technologies for evaluation using 3-dimensionally structured cells, light CT (computer tomography), analysis and evaluation using spectroscopy and the like, feasibility of the biochemical analysis of the cell state using biosensors, technologies for measuring the secretion of carcinogenic and toxic substances, etc., were studied. In addition, the development of organic models to replace test animals, industrial evolution of 3-dimensional tissue module engineering, etc., were investigated. (NEDO)

PM - processing for manufacturing of metals with cellular structures

International Nuclear Information System (INIS)

Strobl, S.; Danninger, H.

2001-01-01

In this review the major Processes about manufacturing of metals with cellular structure are described - based on powder metallurgy, chemical deposition and some other methods (without melting techniques). It can be shown that during the last decade many interesting innovations led to new production methods to design cellular materials. Some of them are used nowadays in industry. Also characterization and properties become more important and have therefore been carried out carefully, because of their strong influence on the functions and applications of such materials. (author)

Cellular solutions for the Poisson equation in extended systems

International Nuclear Information System (INIS)

Zhang, X.; Butler, W.H.; MacLaren, J.M.; van Ek, J.

1994-01-01

The Poisson equation for the electrostatic potential in a solid is solved using three different cellular techniques. The relative merits of these different approaches are discussed for two test charge densities for which an analytic solution to the Poisson equation is known. The first approach uses full-cell multiple-scattering theory and results in the famililar structure constant and multipole moment expansion. This solution is shown to be valid everywhere inside the cell, although for points outside the muffin-tin sphere but inside the cell the sums must be performed in the correct order to yield meaningful results. A modification of the multiple-scattering-theory approach yields a second method, a Green-function cellular method, which only requires the solution of a nearest-neighbor linear system of equations. A third approach, a related variational cellular method, is also derived. The variational cellular approach is shown to be the most accurate and reliable, and to have the best convergence in angular momentum of the three methods. Coulomb energies accurate to within 10 -6 hartree are easily achieved with the variational cellular approach, demonstrating the practicality of the approach in electronic structure calculations

[Cell signaling pathways interaction in cellular proliferation: Potential target for therapeutic interventionism].

Science.gov (United States)

Valdespino-Gómez, Víctor Manuel; Valdespino-Castillo, Patricia Margarita; Valdespino-Castillo, Víctor Edmundo

2015-01-01

Nowadays, cellular physiology is best understood by analysing their interacting molecular components. Proteins are the major components of the cells. Different proteins are organised in the form of functional clusters, pathways or networks. These molecules are ordered in clusters of receptor molecules of extracellular signals, transducers, sensors and biological response effectors. The identification of these intracellular signaling pathways in different cellular types has required a long journey of experimental work. More than 300 intracellular signaling pathways have been identified in human cells. They participate in cell homeostasis processes for structural and functional maintenance. Some of them participate simultaneously or in a nearly-consecutive progression to generate a cellular phenotypic change. In this review, an analysis is performed on the main intracellular signaling pathways that take part in the cellular proliferation process, and the potential use of some components of these pathways as target for therapeutic interventionism are also underlined. Copyright © 2015 Academia Mexicana de Cirugía A.C. Published by Masson Doyma México S.A. All rights reserved.

Connecting Photosynthesis and Cellular Respiration: Preservice Teachers' Conceptions

Science.gov (United States)

Brown, Mary H.; Schwartz, Renee S.

2009-01-01

The biological processes of photosynthesis and plant cellular respiration include multiple biochemical steps, occur simultaneously within plant cells, and share common molecular components. Yet, learners often compartmentalize functions and specialization of cell organelles relevant to these two processes, without considering the interconnections…

Osmosensory mechanisms in cellular and systemic volume regulation

DEFF Research Database (Denmark)

Pedersen, Stine Helene Falsig; Kapus, András; Hoffmann, Else K

2011-01-01

Perturbations of cellular and systemic osmolarity severely challenge the function of all organisms and are consequently regulated very tightly. Here we outline current evidence on how cells sense volume perturbations, with particular focus on mechanisms relevant to the kidneys and to extracellular...

Potential cellular receptors involved in hepatitis C virus entry into cells

Directory of Open Access Journals (Sweden)

Muellhaupt Beat

2005-04-01

Full Text Available Abstract Hepatitis C virus (HCV infects hepatocytes and leads to permanent, severe liver damage. Since the genomic sequence of HCV was determined, progress has been made towards understanding the functions of the HCV-encoded proteins and identifying the cellular receptor(s responsible for adsorption and penetration of the virus particle into the target cells. Several cellular receptors for HCV have been proposed, all of which are associated with lipid and lipoprotein metabolism. This article reviews the cellular receptors for HCV and suggests a general model for HCV entry into cells, in which lipoproteins play a crucial role.

Cell-to-cell communication and cellular environment alter the somatostatin status of delta cells

Energy Technology Data Exchange (ETDEWEB)

Kelly, Catriona, E-mail: catriona.kelly@qub.ac.uk [SAAD Centre for Pharmacy and Diabetes, School of Biomedical Sciences, University of Ulster, Coleraine (United Kingdom); Flatt, Peter R.; McClenaghan, Neville H. [SAAD Centre for Pharmacy and Diabetes, School of Biomedical Sciences, University of Ulster, Coleraine (United Kingdom)

2010-08-20

Research highlights: {yields} TGP52 cells display enhanced functionality in pseudoislet form. {yields} Somatostatin content was reduced, but secretion increased in high glucose conditions. {yields} Cellular interactions and environment alter the somatostatin status of TGP52 cells. -- Abstract: Introduction: Somatostatin, released from pancreatic delta cells, is a potent paracrine inhibitor of insulin and glucagon secretion. Islet cellular interactions and glucose homeostasis are essential to maintain normal patterns of insulin secretion. However, the importance of cell-to-cell communication and cellular environment in the regulation of somatostatin release remains unclear. Methods: This study employed the somatostatin-secreting TGP52 cell line maintained in DMEM:F12 (17.5 mM glucose) or DMEM (25 mM glucose) culture media. The effect of pseudoislet formation and culture medium on somatostatin content and release in response to a variety of stimuli was measured by somatostatin EIA. In addition, the effect of pseudoislet formation on cellular viability (MTT and LDH assays) and proliferation (BrdU ELISA) was determined. Results: TGP52 cells readily formed pseudoislets and showed enhanced functionality in three-dimensional form with increased E-cadherin expression irrespective of the culture environment used. However, culture in DMEM decreased cellular somatostatin content (P < 0.01) and increased somatostatin secretion in response to a variety of stimuli including arginine, calcium and PMA (P < 0.001) when compared with cells grown in DMEM:F12. Configuration of TGP52 cells as pseudoislets reduced the proliferative rate and increased cellular cytotoxicity irrespective of culture medium used. Conclusions: Somatostatin secretion is greatly facilitated by cell-to-cell interactions and E-cadherin expression. Cellular environment and extracellular glucose also significantly influence the function of delta cells.

Cell-to-cell communication and cellular environment alter the somatostatin status of delta cells

International Nuclear Information System (INIS)

Kelly, Catriona; Flatt, Peter R.; McClenaghan, Neville H.

2010-01-01

Research highlights: → TGP52 cells display enhanced functionality in pseudoislet form. → Somatostatin content was reduced, but secretion increased in high glucose conditions. → Cellular interactions and environment alter the somatostatin status of TGP52 cells. -- Abstract: Introduction: Somatostatin, released from pancreatic delta cells, is a potent paracrine inhibitor of insulin and glucagon secretion. Islet cellular interactions and glucose homeostasis are essential to maintain normal patterns of insulin secretion. However, the importance of cell-to-cell communication and cellular environment in the regulation of somatostatin release remains unclear. Methods: This study employed the somatostatin-secreting TGP52 cell line maintained in DMEM:F12 (17.5 mM glucose) or DMEM (25 mM glucose) culture media. The effect of pseudoislet formation and culture medium on somatostatin content and release in response to a variety of stimuli was measured by somatostatin EIA. In addition, the effect of pseudoislet formation on cellular viability (MTT and LDH assays) and proliferation (BrdU ELISA) was determined. Results: TGP52 cells readily formed pseudoislets and showed enhanced functionality in three-dimensional form with increased E-cadherin expression irrespective of the culture environment used. However, culture in DMEM decreased cellular somatostatin content (P < 0.01) and increased somatostatin secretion in response to a variety of stimuli including arginine, calcium and PMA (P < 0.001) when compared with cells grown in DMEM:F12. Configuration of TGP52 cells as pseudoislets reduced the proliferative rate and increased cellular cytotoxicity irrespective of culture medium used. Conclusions: Somatostatin secretion is greatly facilitated by cell-to-cell interactions and E-cadherin expression. Cellular environment and extracellular glucose also significantly influence the function of delta cells.

Cellular commitment in the developing cerebellum

Science.gov (United States)

Marzban, Hassan; Del Bigio, Marc R.; Alizadeh, Javad; Ghavami, Saeid; Zachariah, Robby M.; Rastegar, Mojgan

2014-01-01

The mammalian cerebellum is located in the posterior cranial fossa and is critical for motor coordination and non-motor functions including cognitive and emotional processes. The anatomical structure of cerebellum is distinct with a three-layered cortex. During development, neurogenesis and fate decisions of cerebellar primordium cells are orchestrated through tightly controlled molecular events involving multiple genetic pathways. In this review, we will highlight the anatomical structure of human and mouse cerebellum, the cellular composition of developing cerebellum, and the underlying gene expression programs involved in cell fate commitments in the cerebellum. A critical evaluation of the cell death literature suggests that apoptosis occurs in ~5% of cerebellar cells, most shortly after mitosis. Apoptosis and cellular autophagy likely play significant roles in cerebellar development, we provide a comprehensive discussion of their role in cerebellar development and organization. We also address the possible function of unfolded protein response in regulation of cerebellar neurogenesis. We discuss recent advancements in understanding the epigenetic signature of cerebellar compartments and possible connections between DNA methylation, microRNAs and cerebellar neurodegeneration. Finally, we discuss genetic diseases associated with cerebellar dysfunction and their role in the aging cerebellum. PMID:25628535

Cellular Commitment in the Developing Cerebellum

Directory of Open Access Journals (Sweden)

Hassan eMarzban

2015-01-01

Full Text Available The mammalian cerebellum is located in the posterior cranial fossa and is critical for motor coordination and non-motor functions including cognitive and emotional processes. The anatomical structure of cerebellum is distinct with a three-layered cortex. During development, neurogenesis and fate decisions of cerebellar primordium cells are orchestrated through tightly controlled molecular events involving multiple genetic pathways. In this review, we will highlight the anatomical structure of human and mouse cerebellum, the cellular composition of developing cerebellum, and the underlying gene expression programs involved in cell fate commitments in the cerebellum. A critical evaluation of the cell death literature suggests that apoptosis occurs in ~5% of cerebellar cells, most shortly after mitosis. Apoptosis and cellular autophagy likely play significant roles in cerebellar development, we provide a comprehensive discussion of their role in cerebellar development and organization. We also address the possible function of unfolded protein response in regulation of cerebellar neurogenesis. We discuss recent advancements in understanding the epigenetic signature of cerebellar compartments and possible connections between DNA methylation, microRNAs and cerebellar neurodegeneration. Finally, we then discuss genetic diseases associated with cerebellar dysfunction and their role in the aging cerebellum.

Investigation of a calcium-responsive contrast agent in cellular model systems: feasibility for use as a smart molecular probe in functional MRI.

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Angelovski, Goran; Gottschalk, Sven; Milošević, Milena; Engelmann, Jörn; Hagberg, Gisela E; Kadjane, Pascal; Andjus, Pavle; Logothetis, Nikos K

2014-05-21

Responsive or smart contrast agents (SCAs) represent a promising direction for development of novel functional MRI (fMRI) methods for the eventual noninvasive assessment of brain function. In particular, SCAs that respond to Ca(2+) may allow tracking neuronal activity independent of brain vasculature, thus avoiding the characteristic limitations of current fMRI techniques. Here we report an in vitro proof-of-principle study with a Ca(2+)-sensitive, Gd(3+)-based SCA in an attempt to validate its potential use as a functional in vivo marker. First, we quantified its relaxometric response in a complex 3D cell culture model. Subsequently, we examined potential changes in the functionality of primary glial cells following administration of this SCA. Monitoring intracellular Ca(2+) showed that, despite a reduction in the Ca(2+) level, transport of Ca(2+) through the plasma membrane remained unaffected, while stimulation with ATP induced Ca(2+)-transients suggested normal cellular signaling in the presence of low millimolar SCA concentrations. SCAs merely lowered the intracellular Ca(2+) level. Finally, we estimated the longitudinal relaxation times (T1) for an idealized in vivo fMRI experiment with SCA, for extracellular Ca(2+) concentration level changes expected during intense neuronal activity which takes place upon repetitive stimulation. The values we obtained indicate changes in T1 of around 1-6%, sufficient to be robustly detectable using modern MRI methods in high field scanners. Our results encourage further attempts to develop even more potent SCAs and appropriate fMRI protocols. This would result in novel methods that allow monitoring of essential physiological processes at the cellular and molecular level.

A coarse-grained model for the simulations of biomolecular interactions in cellular environments

International Nuclear Information System (INIS)

Xie, Zhong-Ru; Chen, Jiawen; Wu, Yinghao

2014-01-01

The interactions of bio-molecules constitute the key steps of cellular functions. However, in vivo binding properties differ significantly from their in vitro measurements due to the heterogeneity of cellular environments. Here we introduce a coarse-grained model based on rigid-body representation to study how factors such as cellular crowding and membrane confinement affect molecular binding. The macroscopic parameters such as the equilibrium constant and the kinetic rate constant are calibrated by adjusting the microscopic coefficients used in the numerical simulations. By changing these model parameters that are experimentally approachable, we are able to study the kinetic and thermodynamic properties of molecular binding, as well as the effects caused by specific cellular environments. We investigate the volumetric effects of crowded intracellular space on bio-molecular diffusion and diffusion-limited reactions. Furthermore, the binding constants of membrane proteins are currently difficult to measure. We provide quantitative estimations about how the binding of membrane proteins deviates from soluble proteins under different degrees of membrane confinements. The simulation results provide biological insights to the functions of membrane receptors on cell surfaces. Overall, our studies establish a connection between the details of molecular interactions and the heterogeneity of cellular environments

Automated and Adaptable Quantification of Cellular Alignment from Microscopic Images for Tissue Engineering Applications

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Xu, Feng; Beyazoglu, Turker; Hefner, Evan; Gurkan, Umut Atakan

2011-01-01

Cellular alignment plays a critical role in functional, physical, and biological characteristics of many tissue types, such as muscle, tendon, nerve, and cornea. Current efforts toward regeneration of these tissues include replicating the cellular microenvironment by developing biomaterials that facilitate cellular alignment. To assess the functional effectiveness of the engineered microenvironments, one essential criterion is quantification of cellular alignment. Therefore, there is a need for rapid, accurate, and adaptable methodologies to quantify cellular alignment for tissue engineering applications. To address this need, we developed an automated method, binarization-based extraction of alignment score (BEAS), to determine cell orientation distribution in a wide variety of microscopic images. This method combines a sequenced application of median and band-pass filters, locally adaptive thresholding approaches and image processing techniques. Cellular alignment score is obtained by applying a robust scoring algorithm to the orientation distribution. We validated the BEAS method by comparing the results with the existing approaches reported in literature (i.e., manual, radial fast Fourier transform-radial sum, and gradient based approaches). Validation results indicated that the BEAS method resulted in statistically comparable alignment scores with the manual method (coefficient of determination R2=0.92). Therefore, the BEAS method introduced in this study could enable accurate, convenient, and adaptable evaluation of engineered tissue constructs and biomaterials in terms of cellular alignment and organization. PMID:21370940

Programmable cellular arrays. Faults testing and correcting in cellular arrays

International Nuclear Information System (INIS)

Cercel, L.

1978-03-01

A review of some recent researches about programmable cellular arrays in computing and digital processing of information systems is presented, and includes both combinational and sequential arrays, with full arbitrary behaviour, or which can realize better implementations of specialized blocks as: arithmetic units, counters, comparators, control systems, memory blocks, etc. Also, the paper presents applications of cellular arrays in microprogramming, in implementing of a specialized computer for matrix operations, in modeling of universal computing systems. The last section deals with problems of fault testing and correcting in cellular arrays. (author)

Systematic identification of cellular signals reactivating Kaposi sarcoma-associated herpesvirus.

Directory of Open Access Journals (Sweden)

Fuqu Yu

2007-03-01

Full Text Available The herpesvirus life cycle has two distinct phases: latency and lytic replication. The balance between these two phases is critical for viral pathogenesis. It is believed that cellular signals regulate the switch from latency to lytic replication. To systematically evaluate the cellular signals regulating this reactivation process in Kaposi sarcoma-associated herpesvirus, the effects of 26,000 full-length cDNA expression constructs on viral reactivation were individually assessed in primary effusion lymphoma-derived cells that harbor the latent virus. A group of diverse cellular signaling proteins were identified and validated in their effect of inducing viral lytic gene expression from the latent viral genome. The results suggest that multiple cellular signaling pathways can reactivate the virus in a genetically homogeneous cell population. Further analysis revealed that the Raf/MEK/ERK/Ets-1 pathway mediates Ras-induced reactivation. The same pathway also mediates spontaneous reactivation, which sets the first example to our knowledge of a specific cellular pathway being studied in the spontaneous reactivation process. Our study provides a functional genomic approach to systematically identify the cellular signals regulating the herpesvirus life cycle, thus facilitating better understanding of a fundamental issue in virology and identifying novel therapeutic targets.

Membrane Lipid Replacement for chronic illnesses, aging and cancer using oral glycerolphospholipid formulations with fructooligosaccharides to restore phospholipid function in cellular membranes, organelles, cells and tissues.

Science.gov (United States)

Nicolson, Garth L; Ash, Michael E

2017-09-01

Membrane Lipid Replacement is the use of functional, oral supplements containing mixtures of cell membrane glycerolphospholipids, plus fructooligosaccharides (for protection against oxidative, bile acid and enzymatic damage) and antioxidants, in order to safely replace damaged, oxidized, membrane phospholipids and restore membrane, organelle, cellular and organ function. Defects in cellular and intracellular membranes are characteristic of all chronic medical conditions, including cancer, and normal processes, such as aging. Once the replacement glycerolphospholipids have been ingested, dispersed, complexed and transported, while being protected by fructooligosaccharides and several natural mechanisms, they can be inserted into cell membranes, lipoproteins, lipid globules, lipid droplets, liposomes and other carriers. They are conveyed by the lymphatics and blood circulation to cellular sites where they are endocytosed or incorporated into or transported by cell membranes. Inside cells the glycerolphospholipids can be transferred to various intracellular membranes by lipid globules, liposomes, membrane-membrane contact or by lipid carrier transfer. Eventually they arrive at their membrane destinations due to 'bulk flow' principles, and there they can stimulate the natural removal and replacement of damaged membrane lipids while undergoing further enzymatic alterations. Clinical trials have shown the benefits of Membrane Lipid Replacement in restoring mitochondrial function and reducing fatigue in aged subjects and chronically ill patients. Recently Membrane Lipid Replacement has been used to reduce pain and other symptoms as well as removing hydrophobic chemical contaminants, suggesting that there are additional new uses for this safe, natural medicine supplement. This article is part of a Special Issue entitled: Membrane Lipid Therapy: Drugs Targeting Biomembranes edited by Pablo V. Escribá. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights

Multiple Functional Domains and Complexes of the Two Nonstructural Proteins of Human Respiratory Syncytial Virus Contribute to Interferon Suppression and Cellular Location▿

Science.gov (United States)

Swedan, Samer; Andrews, Joel; Majumdar, Tanmay; Musiyenko, Alla; Barik, Sailen

2011-01-01

Human respiratory syncytial virus (RSV), a major cause of severe respiratory diseases, efficiently suppresses cellular innate immunity, represented by type I interferon (IFN), using its two unique nonstructural proteins, NS1 and NS2. In a search for their mechanism, NS1 was previously shown to decrease levels of TRAF3 and IKKε, whereas NS2 interacted with RIG-I and decreased TRAF3 and STAT2. Here, we report on the interaction, cellular localization, and functional domains of these two proteins. We show that recombinant NS1 and NS2, expressed in lung epithelial A549 cells, can form homo- as well as heteromers. Interestingly, when expressed alone, substantial amounts of NS1 and NS2 localized to the nuclei and to the mitochondria, respectively. However, when coexpressed with NS2, as in RSV infection, NS1 could be detected in the mitochondria as well, suggesting that the NS1-NS2 heteromer localizes to the mitochondria. The C-terminal tetrapeptide sequence, DLNP, common to both NS1 and NS2, was required for some functions, but not all, whereas only the NS1 N-terminal region was important for IKKε reduction. Finally, NS1 and NS2 both interacted specifically with host microtubule-associated protein 1B (MAP1B). The contribution of MAP1B in NS1 function was not tested, but in NS2 it was essential for STAT2 destruction, suggesting a role of the novel DLNP motif in protein-protein interaction and IFN suppression. PMID:21795342

Functional Proteomics Defines the Molecular Switch Underlying FGF Receptor Trafficking and Cellular Outputs

DEFF Research Database (Denmark)

Francavilla, Chiara; Rigbolt, Kristoffer T.G.; Emdal, Kristina B

2013-01-01

The stimulation of fibroblast growth factor receptors (FGFRs) with distinct FGF ligands generates specific cellular responses. However, the mechanisms underlying this paradigm have remained elusive. Here, we show that FGF-7 stimulation leads to FGFR2b degradation and, ultimately, cell proliferation...

Comparison of blood flow and cell function in ischemic skin flaps

International Nuclear Information System (INIS)

Bean, D.; Rees, R.S.; O'Leary, J.P.; Lynch, J.B.

1984-01-01

Cellular function and blood flow in acute, steroid-treated, and surgically delayed random skin flaps have been examined. In these studies, the period following flap elevation could be divided into early (0-2 hr), intermediate (4-6 hr), and late (12 hr) periods of ischemia, based on the cutaneous blood flow and cellular function measured by thallium-201 uptake. There was a close correlation between blood flow and cellular function during the early period of ischemia which became worse with time. Blood flow studies demonstrated a significant difference between the early and intermediate periods of ischemia which was abolished by surgical delay. Improvement in cellular function was accomplished by improved blood flow in the surgically delayed flaps, while steroid-treated flaps enhanced cellular metabolism by another mechanism. Cellular function approximated blood flow during the early and immediate period of ischemia. Steroids may augment cellular function without improving blood flow, while surgical delay improves cellular function by improving blood flow

47 CFR 22.970 - Unacceptable interference to part 90 non-cellular 800 MHz licensees from cellular radiotelephone...

Science.gov (United States)

2010-10-01

...-cellular 800 MHz licensees from cellular radiotelephone or part 90-800 MHz cellular systems. 22.970 Section... MOBILE SERVICES Cellular Radiotelephone Service § 22.970 Unacceptable interference to part 90 non-cellular 800 MHz licensees from cellular radiotelephone or part 90-800 MHz cellular systems. (a) Definition...

Heterogeneous cellular networks

CERN Document Server

Hu, Rose Qingyang

2013-01-01

A timely publication providing coverage of radio resource management, mobility management and standardization in heterogeneous cellular networks The topic of heterogeneous cellular networks has gained momentum in industry and the research community, attracting the attention of standardization bodies such as 3GPP LTE and IEEE 802.16j, whose objectives are looking into increasing the capacity and coverage of the cellular networks. This book focuses on recent progresses,  covering the related topics including scenarios of heterogeneous network deployment, interference management i

The impact of peroxisomes on cellular aging and death

NARCIS (Netherlands)

Manivannan, Selvambigai; Scheckhuber, Christian Quintus; Veenhuis, Marten; Klei, Ida Johanna van der

2012-01-01

Peroxisomes are ubiquitous eukaryotic organelles, which perform a plethora of functions including hydrogen peroxide metabolism and β-oxidation of fatty acids. Reactive oxygen species produced by peroxisomes are a major contributing factor to cellular oxidative stress, which is supposed to

Geometric Modeling of Cellular Materials for Additive Manufacturing in Biomedical Field: A Review.

Science.gov (United States)

Savio, Gianpaolo; Rosso, Stefano; Meneghello, Roberto; Concheri, Gianmaria

2018-01-01

Advances in additive manufacturing technologies facilitate the fabrication of cellular materials that have tailored functional characteristics. The application of solid freeform fabrication techniques is especially exploited in designing scaffolds for tissue engineering. In this review, firstly, a classification of cellular materials from a geometric point of view is proposed; then, the main approaches on geometric modeling of cellular materials are discussed. Finally, an investigation on porous scaffolds fabricated by additive manufacturing technologies is pointed out. Perspectives in geometric modeling of scaffolds for tissue engineering are also proposed.

Cellular Kinetics of Perivascular MSC Precursors

Directory of Open Access Journals (Sweden)

William C. W. Chen

2013-01-01

Full Text Available Mesenchymal stem/stromal cells (MSCs and MSC-like multipotent stem/progenitor cells have been widely investigated for regenerative medicine and deemed promising in clinical applications. In order to further improve MSC-based stem cell therapeutics, it is important to understand the cellular kinetics and functional roles of MSCs in the dynamic regenerative processes. However, due to the heterogeneous nature of typical MSC cultures, their native identity and anatomical localization in the body have remained unclear, making it difficult to decipher the existence of distinct cell subsets within the MSC entity. Recent studies have shown that several blood-vessel-derived precursor cell populations, purified by flow cytometry from multiple human organs, give rise to bona fide MSCs, suggesting that the vasculature serves as a systemic reservoir of MSC-like stem/progenitor cells. Using individually purified MSC-like precursor cell subsets, we and other researchers have been able to investigate the differential phenotypes and regenerative capacities of these contributing cellular constituents in the MSC pool. In this review, we will discuss the identification and characterization of perivascular MSC precursors, including pericytes and adventitial cells, and focus on their cellular kinetics: cell adhesion, migration, engraftment, homing, and intercellular cross-talk during tissue repair and regeneration.

Lysine acetylation targets protein complexes and co-regulates major cellular functions

DEFF Research Database (Denmark)

Choudhary, Chuna Ram; Kumar, Chanchal; Gnad, Florian

2009-01-01

Lysine acetylation is a reversible posttranslational modification of proteins and plays a key role in regulating gene expression. Technological limitations have so far prevented a global analysis of lysine acetylation's cellular roles. We used high-resolution mass spectrometry to identify 3600......, cell cycle, splicing, nuclear transport, and actin nucleation. Acetylation impaired phosphorylation-dependent interactions of 14-3-3 and regulated the yeast cyclin-dependent kinase Cdc28. Our data demonstrate that the regulatory scope of lysine acetylation is broad and comparable with that of other...

47 CFR 22.909 - Cellular markets.

Science.gov (United States)

2010-10-01

... 47 Telecommunication 2 2010-10-01 2010-10-01 false Cellular markets. 22.909 Section 22.909... Cellular Radiotelephone Service § 22.909 Cellular markets. Cellular markets are standard geographic areas used by the FCC for administrative convenience in the licensing of cellular systems. Cellular markets...

[Fanconi anemia: cellular and molecular features].

Science.gov (United States)

Macé, G; Briot, D; Guervilly, J-H; Rosselli, F

2007-02-01

Fanconi anemia (FA) is a recessive human cancer prone syndrome featuring bone marrow failure, developmental abnormalities and hypersensitivity to DNA crosslinking agents exposure. 11 among 12 FA gene have been isolated. The biochemical functions of the FANC proteins remain poorly understood. Anyhow, to cope with DNA crosslinks a cell needs a functional FANC pathway. Moreover, the FANC proteins appear to be involved in cell protection against oxidative damage and in the control of TNF-alpha activity. In this review, we describe the current understanding of the FANC pathway and we present how it may be integrated in the complex networks of proteins involved in maintaining the cellular homeostasis.

Cellular characterization of compression induced-damage in live biological samples

Science.gov (United States)

Bo, Chiara; Balzer, Jens; Hahnel, Mark; Rankin, Sara M.; Brown, Katherine A.; Proud, William G.

2011-06-01

Understanding the dysfunctions that high-intensity compression waves induce in human tissues is critical to impact on acute-phase treatments and requires the development of experimental models of traumatic damage in biological samples. In this study we have developed an experimental system to directly assess the impact of dynamic loading conditions on cellular function at the molecular level. Here we present a confinement chamber designed to subject live cell cultures in liquid environment to compression waves in the range of tens of MPa using a split Hopkinson pressure bars system. Recording the loading history and collecting the samples post-impact without external contamination allow the definition of parameters such as pressure and duration of the stimulus that can be related to the cellular damage. The compression experiments are conducted on Mesenchymal Stem Cells from BALB/c mice and the damage analysis are compared to two control groups. Changes in Stem cell viability, phenotype and function are assessed flow cytometry and with in vitro bioassays at two different time points. Identifying the cellular and molecular mechanisms underlying the damage caused by dynamic loading in live biological samples could enable the development of new treatments for traumatic injuries.

Geometric Modeling of Cellular Materials for Additive Manufacturing in Biomedical Field: A Review

Directory of Open Access Journals (Sweden)

Gianpaolo Savio

2018-01-01

Full Text Available Advances in additive manufacturing technologies facilitate the fabrication of cellular materials that have tailored functional characteristics. The application of solid freeform fabrication techniques is especially exploited in designing scaffolds for tissue engineering. In this review, firstly, a classification of cellular materials from a geometric point of view is proposed; then, the main approaches on geometric modeling of cellular materials are discussed. Finally, an investigation on porous scaffolds fabricated by additive manufacturing technologies is pointed out. Perspectives in geometric modeling of scaffolds for tissue engineering are also proposed.

Geometric Modeling of Cellular Materials for Additive Manufacturing in Biomedical Field: A Review

Science.gov (United States)

Rosso, Stefano; Meneghello, Roberto; Concheri, Gianmaria

2018-01-01

Advances in additive manufacturing technologies facilitate the fabrication of cellular materials that have tailored functional characteristics. The application of solid freeform fabrication techniques is especially exploited in designing scaffolds for tissue engineering. In this review, firstly, a classification of cellular materials from a geometric point of view is proposed; then, the main approaches on geometric modeling of cellular materials are discussed. Finally, an investigation on porous scaffolds fabricated by additive manufacturing technologies is pointed out. Perspectives in geometric modeling of scaffolds for tissue engineering are also proposed. PMID:29487626

General formulation of the variational cellular method for molecules and crystals

International Nuclear Information System (INIS)

Ferreira, L.G.; Leite, J.R.

A variational form of the cellular method is proposed as a new model to solve the one-electron Schroedinger equation for molecules and crystals. The model keeps the good features of the traditional cellular method, as the arbitrary partition of space, and eliminates its main drawback, the slow convergency of the cellular expansion series. With the aid of a criterion of precision on the trial wave functions, we discuss the possibilities offered by the method for more accurate calculations of the electronic structures of molecules and solids. As an example of the accuracy and fast convergency of the model, computation of the energy spectrum of the hydrogen molecular ion H 2 + is presented

Sub-cellular localisation studies may spuriously detect the Yes-associated protein, YAP, in nucleoli leading to potentially invalid conclusions of its function.

Science.gov (United States)

Finch, Megan L; Passman, Adam M; Strauss, Robyn P; Yeoh, George C; Callus, Bernard A

2015-01-01

The Yes-associated protein (YAP) is a potent transcriptional co-activator that functions as a nuclear effector of the Hippo signaling pathway. YAP is oncogenic and its activity is linked to its cellular abundance and nuclear localisation. Activation of the Hippo pathway restricts YAP nuclear entry via its phosphorylation by Lats kinases and consequent cytoplasmic retention bound to 14-3-3 proteins. We examined YAP expression in liver progenitor cells (LPCs) and surprisingly found that transformed LPCs did not show an increase in YAP abundance compared to the non-transformed LPCs from which they were derived. We then sought to ascertain whether nuclear YAP was more abundant in transformed LPCs. We used an antibody that we confirmed was specific for YAP by immunoblotting to determine YAP's sub-cellular localisation by immunofluorescence. This antibody showed diffuse staining for YAP within the cytosol and nuclei, but, noticeably, it showed intense staining of the nucleoli of LPCs. This staining was non-specific, as shRNA treatment of cells abolished YAP expression to undetectable levels by Western blot yet the nucleolar staining remained. Similar spurious YAP nucleolar staining was also seen in mouse embryonic fibroblasts and mouse liver tissue, indicating that this antibody is unsuitable for immunological applications to determine YAP sub-cellular localisation in mouse cells or tissues. Interestingly nucleolar staining was not evident in D645 cells suggesting the antibody may be suitable for use in human cells. Given the large body of published work on YAP in recent years, many of which utilise this antibody, this study raises concerns regarding its use for determining sub-cellular localisation. From a broader perspective, it serves as a timely reminder of the need to perform appropriate controls to ensure the validity of published data.

Cellular membrane trafficking of mesoporous silica nanoparticles

Energy Technology Data Exchange (ETDEWEB)

Fang, I-Ju [Iowa State Univ., Ames, IA (United States)

2012-01-01

This dissertation mainly focuses on the investigation of the cellular membrane trafficking of mesoporous silica nanoparticles. We are interested in the study of endocytosis and exocytosis behaviors of mesoporous silica nanoparticles with desired surface functionality. The relationship between mesoporous silica nanoparticles and membrane trafficking of cells, either cancerous cells or normal cells was examined. Since mesoporous silica nanoparticles were applied in many drug delivery cases, the endocytotic efficiency of mesoporous silica nanoparticles needs to be investigated in more details in order to design the cellular drug delivery system in the controlled way. It is well known that cells can engulf some molecules outside of the cells through a receptor-ligand associated endocytosis. We are interested to determine if those biomolecules binding to cell surface receptors can be utilized on mesoporous silica nanoparticle materials to improve the uptake efficiency or govern the mechanism of endocytosis of mesoporous silica nanoparticles. Arginine-glycine-aspartate (RGD) is a small peptide recognized by cell integrin receptors and it was reported that avidin internalization was highly promoted by tumor lectin. Both RGD and avidin were linked to the surface of mesoporous silica nanoparticle materials to investigate the effect of receptor-associated biomolecule on cellular endocytosis efficiency. The effect of ligand types, ligand conformation and ligand density were discussed in Chapter 2 and 3. Furthermore, the exocytosis of mesoporous silica nanoparticles is very attractive for biological applications. The cellular protein sequestration study of mesoporous silica nanoparticles was examined for further information of the intracellular pathway of endocytosed mesoporous silica nanoparticle materials. The surface functionality of mesoporous silica nanoparticle materials demonstrated selectivity among the materials and cancer and normal cell lines. We aimed to determine

Cellular energy metabolism in T-lymphocytes.

Science.gov (United States)

Gaber, Timo; Strehl, Cindy; Sawitzki, Birgit; Hoff, Paula; Buttgereit, Frank

2015-01-01

Energy homeostasis is a hallmark of cell survival and maintenance of cell function. Here we focus on the impact of cellular energy metabolism on T-lymphocyte differentiation, activation, and function in health and disease. We describe the role of transcriptional and posttranscriptional regulation of lymphocyte metabolism on immune functions of T cells. We also summarize the current knowledge about T-lymphocyte adaptations to inflammation and hypoxia, and the impact on T-cell behavior of pathophysiological hypoxia (as found in tumor tissue, chronically inflamed joints in rheumatoid arthritis and during bone regeneration). A better understanding of the underlying mechanisms that control immune cell metabolism and immune response may provide therapeutic opportunities to alter the immune response under conditions of either immunosuppression or inflammation, potentially targeting infections, vaccine response, tumor surveillance, autoimmunity, and inflammatory disorders.

Biomechanics of cellular solids.

Science.gov (United States)

Gibson, Lorna J

2005-03-01

Materials with a cellular structure are widespread in nature and include wood, cork, plant parenchyma and trabecular bone. Natural cellular materials are often mechanically efficient: the honeycomb-like microstructure of wood, for instance, gives it an exceptionally high performance index for resisting bending and buckling. Here we review the mechanics of a wide range of natural cellular materials and examine their role in lightweight natural sandwich structures (e.g. iris leaves) and natural tubular structures (e.g. plant stems or animal quills). We also describe two examples of engineered biomaterials with a cellular structure, designed to replace or regenerate tissue in the body.

Sub-cellular distribution and translocation of TRP channels.

Science.gov (United States)

Toro, Carlos A; Arias, Luis A; Brauchi, Sebastian

2011-01-01

Cellular electrical activity is the result of a highly complex processes that involve the activation of ion channel proteins. Ion channels make pores on cell membranes that rapidly transit between conductive and non-conductive states, allowing different ions to flow down their electrochemical gradients across cell membranes. In the case of neuronal cells, ion channel activity orchestrates action potentials traveling through axons, enabling electrical communication between cells in distant parts of the body. Somatic sensation -our ability to feel touch, temperature and noxious stimuli- require ion channels able to sense and respond to our peripheral environment. Sensory integration involves the summing of various environmental cues and their conversion into electrical signals. Members of the Transient Receptor Potential (TRP) family of ion channels have emerged as important mediators of both cellular sensing and sensory integration. The regulation of the spatial and temporal distribution of membrane receptors is recognized as an important mechanism for controlling the magnitude of the cellular response and the time scale on which cellular signaling occurs. Several studies have shown that this mechanism is also used by TRP channels to modulate cellular response and ultimately fulfill their physiological function as sensors. However, the inner-working of this mode of control for TRP channels remains poorly understood. The question of whether TRPs intrinsically regulate their own vesicular trafficking or weather the dynamic regulation of TRP channel residence on the cell surface is caused by extrinsic changes in the rates of vesicle insertion or retrieval remain open. This review will examine the evidence that sub-cellular redistribution of TRP channels plays an important role in regulating their activity and explore the mechanisms that control the trafficking of vesicles containing TRP channels.

New multifunctional lightweight materials based on cellular metals - manufacturing, properties and applications

International Nuclear Information System (INIS)

Stephani, Guenter; Quadbeck, Peter; Andersen, Olaf

2009-01-01

Cellular metallic materials are a new class of materials which have been the focus of numerous scientific studies over the past few years. The increasing interest in cellular metals is due to the fact that the introduction of pores into the materials significantly lowers the density. These highly porous materials also possess combinations of properties which are not possible to achieve with other materials. Besides the drastic weight and material savings that arise from the cell structure, there are also other application-specific benefits such as noise and energy absorption, heat insulation, mechanical damping, filtration effects and also catalytic properties. Cellular metallic materials are hence multi-functional lightweight materials.

Cellular Reflectarray Antenna

Science.gov (United States)

Romanofsky, Robert R.

2010-01-01

The cellular reflectarray antenna is intended to replace conventional parabolic reflectors that must be physically aligned with a particular satellite in geostationary orbit. These arrays are designed for specified geographical locations, defined by latitude and longitude, each called a "cell." A particular cell occupies nominally 1,500 square miles (3,885 sq. km), but this varies according to latitude and longitude. The cellular reflectarray antenna designed for a particular cell is simply positioned to align with magnetic North, and the antenna surface is level (parallel to the ground). A given cellular reflectarray antenna will not operate in any other cell.

Cellular MYCro economics: Balancing MYC function with MYC expression.

Science.gov (United States)

Levens, David

2013-11-01

The expression levels of the MYC oncoprotein have long been recognized to be associated with the outputs of major cellular processes including proliferation, cell growth, apoptosis, differentiation, and metabolism. Therefore, to understand how MYC operates, it is important to define quantitatively the relationship between MYC input and expression output for its targets as well as the higher-order relationships between the expression levels of subnetwork components and the flow of information and materials through those networks. Two different views of MYC are considered, first as a molecular microeconomic manager orchestrating specific positive and negative responses at individual promoters in collaboration with other transcription and chromatin components, and second, as a macroeconomic czar imposing an overarching rule onto all active genes. In either case, c-myc promoter output requires multiple inputs and exploits diverse mechanisms to tune expression to the appropriate levels relative to the thresholds of expression that separate health and disease.

Circulating Cellular Adhesion Molecules and Cognitive Function: The Coronary Artery Risk Development in Young Adults Study

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Cynthia Yursun Yoon

2017-05-01

Full Text Available ObjectiveHigher circulating concentrations of cellular adhesion molecules (CAMs can be used as markers of endothelial dysfunction. Given that the brain is highly vascularized, we assessed whether endothelial function is associated with cognitive performance.MethodWithin the Coronary Artery Risk Development in Young Adults (CARDIA Study, excluding N = 54 with stroke before year 25, we studied CAMs among N = 2,690 black and white men and women in CARDIA year 7 (1992–1993, ages 25–37 and N = 2,848 in CARDIA year 15 (2000–2001, ages 33–45. We included subjects with levels of circulating soluble CAMs measured in year 7 or 15 and cognitive function testing in year 25 (2010–2011, ages 43–55. Using multiple regression analysis, we evaluated the association between CAMs and year 25 cognitive test scores: Rey Auditory Verbal Learning Test (RAVLT, memory, Digit Symbol Substitution Test (DSST, speed of processing, and the Stroop Test (executive function.ResultAll CAM concentrations were greater in year 15 vs. year 7. Adjusting for age, race, sex, education, smoking, alcohol, diet, physical activity, participants in the fourth vs. the first quartile of CARDIA year 7 of circulating intercellular adhesion molecule-1 (ICAM-1 scored worse on RAVLT, DSST, and Stroop Test (p ≤ 0.05 in CARDIA year 25. Other CAMs showed little association with cognitive test scores. Findings were similar for ICAM-1 assessed at year 15. Adjustment for possibly mediating physical factors attenuated the findings.ConclusionHigher circulating ICAM-1 at average ages 32 and 40 was associated with lower cognitive skills at average age 50. The study is consistent with the hypothesis that endothelial dysfunction is associated with worse short-term memory, speed of processing, and executive function.

Circulating Cellular Adhesion Molecules and Cognitive Function: The Coronary Artery Risk Development in Young Adults Study.

Science.gov (United States)

Yoon, Cynthia Yursun; Steffen, Lyn M; Gross, Myron D; Launer, Lenore J; Odegaard, Andrew; Reiner, Alexander; Sanchez, Otto; Yaffe, Kristine; Sidney, Stephen; Jacobs, David R

2017-01-01

Higher circulating concentrations of cellular adhesion molecules (CAMs) can be used as markers of endothelial dysfunction. Given that the brain is highly vascularized, we assessed whether endothelial function is associated with cognitive performance. Within the Coronary Artery Risk Development in Young Adults (CARDIA) Study, excluding N  = 54 with stroke before year 25, we studied CAMs among N  = 2,690 black and white men and women in CARDIA year 7 (1992-1993, ages 25-37) and N  = 2,848 in CARDIA year 15 (2000-2001, ages 33-45). We included subjects with levels of circulating soluble CAMs measured in year 7 or 15 and cognitive function testing in year 25 (2010-2011, ages 43-55). Using multiple regression analysis, we evaluated the association between CAMs and year 25 cognitive test scores: Rey Auditory Verbal Learning Test (RAVLT, memory), Digit Symbol Substitution Test (DSST, speed of processing), and the Stroop Test (executive function). All CAM concentrations were greater in year 15 vs. year 7. Adjusting for age, race, sex, education, smoking, alcohol, diet, physical activity, participants in the fourth vs. the first quartile of CARDIA year 7 of circulating intercellular adhesion molecule-1 (ICAM-1) scored worse on RAVLT, DSST, and Stroop Test ( p  ≤ 0.05) in CARDIA year 25. Other CAMs showed little association with cognitive test scores. Findings were similar for ICAM-1 assessed at year 15. Adjustment for possibly mediating physical factors attenuated the findings. Higher circulating ICAM-1 at average ages 32 and 40 was associated with lower cognitive skills at average age 50. The study is consistent with the hypothesis that endothelial dysfunction is associated with worse short-term memory, speed of processing, and executive function.

Coordination of plant mitochondrial biogenesis: keeping pace with cellular requirements

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Welchen, Elina; García, Lucila; Mansilla, Natanael; Gonzalez, Daniel H.

2014-01-01

Plant mitochondria are complex organelles that carry out numerous metabolic processes related with the generation of energy for cellular functions and the synthesis and degradation of several compounds. Mitochondria are semiautonomous and dynamic organelles changing in shape, number, and composition depending on tissue or developmental stage. The biogenesis of functional mitochondria requires the coordination of genes present both in the nucleus and the organelle. In addition, due to their central role, all processes held inside mitochondria must be finely coordinated with those in other organelles according to cellular demands. Coordination is achieved by transcriptional control of nuclear genes encoding mitochondrial proteins by specific transcription factors that recognize conserved elements in their promoter regions. In turn, the expression of most of these transcription factors is linked to developmental and environmental cues, according to the availability of nutrients, light–dark cycles, and warning signals generated in response to stress conditions. Among the signals impacting in the expression of nuclear genes, retrograde signals that originate inside mitochondria help to adjust mitochondrial biogenesis to organelle demands. Adding more complexity, several nuclear encoded proteins are dual localized to mitochondria and either chloroplasts or the nucleus. Dual targeting might establish a crosstalk between the nucleus and cell organelles to ensure a fine coordination of cellular activities. In this article, we discuss how the different levels of coordination of mitochondrial biogenesis interconnect to optimize the function of the organelle according to both internal and external demands. PMID:24409193

Coordination of plant mitochondrial biogenesis: keeping pace with cellular requirements.

Directory of Open Access Journals (Sweden)

Elina eWelchen

2014-01-01

Full Text Available Plant mitochondria are complex organelles that carry out numerous metabolic processes related with the generation of energy for cellular functions and the synthesis and degradation of several compounds. Mitochondria are semiautonomous and dynamic organelles changing in shape, number and composition depending on tissue or developmental stage. The biogenesis of functional mitochondria requires the coordination of genes present both in the nucleus and the organelle. In addition, due to their central role, all processes held inside mitochondria must be finely coordinated with those in other organelles according to cellular demands. Coordination is achieved by transcriptional control of nuclear genes encoding mitochondrial proteins by specific transcription factors that recognize conserved elements in their promoter regions. In turn, the expression of most of these transcription factors is linked to developmental and environmental cues, according to the availability of nutrients, light-dark cycles and warning signals generated in response to stress conditions. Among the signals impacting in the expression of nuclear genes, retrograde signals that originate inside mitochondria help to adjust mitochondrial biogenesis to organelle demands. Adding more complexity, several nuclear encoded proteins are dual localized to mitochondria and either chloroplasts or the nucleus. Dual targeting might establish a crosstalk between the nucleus and cell organelles to ensure a fine coordination of cellular activities. In this article, we discuss how the different levels of coordination of mitochondrial biogenesis interconnect to optimize the function of the organelle according to both internal and external demands.

Involvement of FFA1 and FFA4 in the regulation of cellular functions during tumor progression in colon cancer cells.

Science.gov (United States)

Takahashi, Kaede; Fukushima, Kaori; Onishi, Yuka; Minami, Kanako; Otagaki, Shiho; Ishimoto, Kaichi; Fukushima, Nobuyuki; Honoki, Kanya; Tsujiuchi, Toshifumi

2018-08-01

Free fatty acid receptor 1 (FFA1) and FFA4 mediate a variety of biological responses through binding of medium- and long-chain free fatty acids. The aim of this study was to investigate an involvement of FFA1 and FFA4 in the regulation of cellular functions during tumor progression in colon cancer cells. The long-term fluorouracil (5-FU) and cisplatin (CDDP) treated cells were generated from DLD1 cells (DLD-5FU and DLD-CDDP cells, respectively). FFAR1 expressions were lower in DLD-5FU and DLD-CDDP cells than in DLD1 cells. In contrast, DLD-5FU and DLD-CDDP cells showed the high FFAR4 expressions, compared with DLD1 cells. The cell motile activities of DLD-5FU and DLD-CDDP cells were reduced by GW9508 which is an agonist of FFA1 and FFA4. Moreover, GW1100, an antagonist of FFA1, inhibited the cell motile activities of DLD-5FU and DLD-CDDP cells. To evaluate whether FFA1 and FFA4 regulate the enhancement of cell motility, invasion and colony formation, highly migratory (hmDLD1) cells were established from DLD1 cells. FFAR1 expression was significantly higher in hmDLD1 cells than in DLD1 cells, but no change of FFAR4 expression was observed. The elevated cell motile and invasive activities and colony formation of hmDLD1 cells were suppressed by FFA1 inhibition. These results suggest that FFA1 and FFA4 are involved in the regulation of cellular functions during tumor progression in colon cancer DLD1 cells. Copyright © 2018 Elsevier Inc. All rights reserved.

Platinum nanozymes recover cellular ROS homeostasis in an oxidative stress-mediated disease model

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Moglianetti, Mauro; de Luca, Elisa; Pedone, Deborah; Marotta, Roberto; Catelani, Tiziano; Sartori, Barbara; Amenitsch, Heinz; Retta, Saverio Francesco; Pompa, Pier Paolo

2016-02-01

In recent years, the use of nanomaterials as biomimetic enzymes has attracted great interest. In this work, we show the potential of biocompatible platinum nanoparticles (Pt NPs) as antioxidant nanozymes, which combine abundant cellular internalization and efficient scavenging activity of cellular reactive oxygen species (ROS), thus simultaneously integrating the functions of nanocarriers and antioxidant drugs. Careful toxicity assessment and intracellular tracking of Pt NPs proved their cytocompatibility and high cellular uptake, with compartmentalization within the endo/lysosomal vesicles. We have demonstrated that Pt NPs possess strong and broad antioxidant properties, acting as superoxide dismutase, catalase, and peroxidase enzymes, with similar or even superior performance than natural enzymes, along with higher adaptability to the changes in environmental conditions. We then exploited their potent activity as radical scavenging materials in a cellular model of an oxidative stress-related disorder, namely human Cerebral Cavernous Malformation (CCM) disease, which is associated with a significant increase in intracellular ROS levels. Noteworthily, we found that Pt nanozymes can efficiently reduce ROS levels, completely restoring the cellular physiological homeostasis.In recent years, the use of nanomaterials as biomimetic enzymes has attracted great interest. In this work, we show the potential of biocompatible platinum nanoparticles (Pt NPs) as antioxidant nanozymes, which combine abundant cellular internalization and efficient scavenging activity of cellular reactive oxygen species (ROS), thus simultaneously integrating the functions of nanocarriers and antioxidant drugs. Careful toxicity assessment and intracellular tracking of Pt NPs proved their cytocompatibility and high cellular uptake, with compartmentalization within the endo/lysosomal vesicles. We have demonstrated that Pt NPs possess strong and broad antioxidant properties, acting as superoxide

The zebrafish miR-462/miR-731 cluster is induced under hypoxic stress via hypoxia-inducible factor 1α and functions in cellular adaptations.

Science.gov (United States)

Huang, Chun-Xiao; Chen, Nan; Wu, Xin-Jie; Huang, Cui-Hong; He, Yan; Tang, Rong; Wang, Wei-Min; Wang, Huan-Ling

2015-12-01

Hypoxia, a unique and essential environmental stress, evokes highly coordinated cellular responses, and hypoxia-inducible factor (HIF) 1 in the hypoxia signaling pathway, an evolutionarily conserved cellular signaling pathway, acts as a master regulator of the transcriptional response to hypoxic stress. MicroRNAs (miRNAs), a major class of posttranscriptional gene expression regulators, also play pivotal roles in orchestrating hypoxia-mediated cellular adaptations. Here, global miRNA expression profiling and quantitative real-time PCR indicated that the up-regulation of the miR-462/miR-731 cluster in zebrafish larvae is induced by hypoxia. It was further validated that miR-462 and miR-731 are up-regulated in a Hif-1α-mediated manner under hypoxia and specifically target ddx5 and ppm1da, respectively. Overexpression of miR-462 and miR-731 represses cell proliferation through blocking cell cycle progress of DNA replication, and induces apoptosis. In situ detection revealed that the miR-462/miR-731 cluster is highly expressed in a consistent and ubiquitous manner throughout the early developmental stages. Additionally, the transcripts become restricted to the notochord, pharyngeal arch, liver, and gut regions from postfertilization d 3 to 5. These data highlight a previously unidentified role of the miR-462/miR-731 cluster as a crucial signaling mediator for hypoxia-mediated cellular adaptations and provide some insights into the potential function of the cluster during embryonic development. © FASEB.

Linearizable cellular automata

International Nuclear Information System (INIS)

Nobe, Atsushi; Yura, Fumitaka

2007-01-01

The initial value problem for a class of reversible elementary cellular automata with periodic boundaries is reduced to an initial-boundary value problem for a class of linear systems on a finite commutative ring Z 2 . Moreover, a family of such linearizable cellular automata is given

Super-Resolution Microscopy: Shedding Light on the Cellular Plasma Membrane.

Science.gov (United States)

Stone, Matthew B; Shelby, Sarah A; Veatch, Sarah L

2017-06-14

Lipids and the membranes they form are fundamental building blocks of cellular life, and their geometry and chemical properties distinguish membranes from other cellular environments. Collective processes occurring within membranes strongly impact cellular behavior and biochemistry, and understanding these processes presents unique challenges due to the often complex and myriad interactions between membrane components. Super-resolution microscopy offers a significant gain in resolution over traditional optical microscopy, enabling the localization of individual molecules even in densely labeled samples and in cellular and tissue environments. These microscopy techniques have been used to examine the organization and dynamics of plasma membrane components, providing insight into the fundamental interactions that determine membrane functions. Here, we broadly introduce the structure and organization of the mammalian plasma membrane and review recent applications of super-resolution microscopy to the study of membranes. We then highlight some inherent challenges faced when using super-resolution microscopy to study membranes, and we discuss recent technical advancements that promise further improvements to super-resolution microscopy and its application to the plasma membrane.

Electromagnetic cellular interactions.

Science.gov (United States)

Cifra, Michal; Fields, Jeremy Z; Farhadi, Ashkan

2011-05-01

Chemical and electrical interaction within and between cells is well established. Just the opposite is true about cellular interactions via other physical fields. The most probable candidate for an other form of cellular interaction is the electromagnetic field. We review theories and experiments on how cells can generate and detect electromagnetic fields generally, and if the cell-generated electromagnetic field can mediate cellular interactions. We do not limit here ourselves to specialized electro-excitable cells. Rather we describe physical processes that are of a more general nature and probably present in almost every type of living cell. The spectral range included is broad; from kHz to the visible part of the electromagnetic spectrum. We show that there is a rather large number of theories on how cells can generate and detect electromagnetic fields and discuss experimental evidence on electromagnetic cellular interactions in the modern scientific literature. Although small, it is continuously accumulating. Copyright © 2010 Elsevier Ltd. All rights reserved.

The mTOR inhibitor sirolimus suppresses renal, hepatic, and cardiac tissue cellular respiration.

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Albawardi, Alia; Almarzooqi, Saeeda; Saraswathiamma, Dhanya; Abdul-Kader, Hidaya Mohammed; Souid, Abdul-Kader; Alfazari, Ali S

2015-01-01

The purpose of this in vitro study was to develop a useful biomarker (e.g., cellular respiration, or mitochondrial O2 consumption) for measuring activities of mTOR inhibitors. It measured the effects of commonly used immunosuppressants (sirolimus-rapamycin, tacrolimus, and cyclosporine) on cellular respiration in target tissues (kidney, liver, and heart) from C57BL/6 mice. The mammalian target of rapamycin (mTOR), a serine/ threonine kinase that supports nutrient-dependent cell growth and survival, is known to control energy conversion processes within the mitochondria. Consistently, inhibitors of mTOR (e.g., rapamycin, also known as sirolimus or Rapamune®) have been shown to impair mitochondrial function. Inhibitors of the calcium-dependent serine/threonine phosphatase calcineurin (e.g., tacrolimus and cyclosporine), on the other hand, strictly prevent lymphokine production leading to a reduced T-cell function. Sirolimus (10 μM) inhibited renal (22%, P=0.002), hepatic (39%, Prespiration. Tacrolimus and cyclosporine had no or minimum effects on cellular respiration in these tissues. Thus, these results clearly demonstrate that impaired cellular respiration (bioenergetics) is a sensitive biomarker of the immunosuppressants that target mTOR.

Lysosomal Re-acidification Prevents Lysosphingolipid-Induced Lysosomal Impairment and Cellular Toxicity.

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Christopher J Folts

2016-12-01

Full Text Available Neurodegenerative lysosomal storage disorders (LSDs are severe and untreatable, and mechanisms underlying cellular dysfunction are poorly understood. We found that toxic lipids relevant to three different LSDs disrupt multiple lysosomal and other cellular functions. Unbiased drug discovery revealed several structurally distinct protective compounds, approved for other uses, that prevent lysosomal and cellular toxicities of these lipids. Toxic lipids and protective agents show unexpected convergence on control of lysosomal pH and re-acidification as a critical component of toxicity and protection. In twitcher mice (a model of Krabbe disease [KD], a central nervous system (CNS-penetrant protective agent rescued myelin and oligodendrocyte (OL progenitors, improved motor behavior, and extended lifespan. Our studies reveal shared principles relevant to several LSDs, in which diverse cellular and biochemical disruptions appear to be secondary to disruption of lysosomal pH regulation by specific lipids. These studies also provide novel protective strategies that confer therapeutic benefits in a mouse model of a severe LSD.

Glutathione in Cellular Redox Homeostasis: Association with the Excitatory Amino Acid Carrier 1 (EAAC1

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Koji Aoyama

2015-05-01

Full Text Available Reactive oxygen species (ROS are by-products of the cellular metabolism of oxygen consumption, produced mainly in the mitochondria. ROS are known to be highly reactive ions or free radicals containing oxygen that impair redox homeostasis and cellular functions, leading to cell death. Under physiological conditions, a variety of antioxidant systems scavenge ROS to maintain the intracellular redox homeostasis and normal cellular functions. This review focuses on the antioxidant system’s roles in maintaining redox homeostasis. Especially, glutathione (GSH is the most important thiol-containing molecule, as it functions as a redox buffer, antioxidant, and enzyme cofactor against oxidative stress. In the brain, dysfunction of GSH synthesis leading to GSH depletion exacerbates oxidative stress, which is linked to a pathogenesis of aging-related neurodegenerative diseases. Excitatory amino acid carrier 1 (EAAC1 plays a pivotal role in neuronal GSH synthesis. The regulatory mechanism of EAAC1 is also discussed.

Biomimetic approaches to modulate cellular adhesion in biomaterials: A review.

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Rahmany, Maria B; Van Dyke, Mark

2013-03-01

Natural extracellular matrix (ECM) proteins possess critical biological characteristics that provide a platform for cellular adhesion and activation of highly regulated signaling pathways. However, ECM-based biomaterials can have several limitations, including poor mechanical properties and risk of immunogenicity. Synthetic biomaterials alleviate the risks associated with natural biomaterials but often lack the robust biological activity necessary to direct cell function beyond initial adhesion. A thorough understanding of receptor-mediated cellular adhesion to the ECM and subsequent signaling activation has facilitated development of techniques that functionalize inert biomaterials to provide a biologically active surface. Here we review a range of approaches used to modify biomaterial surfaces for optimal receptor-mediated cell interactions, as well as provide insights into specific mechanisms of downstream signaling activation. In addition to a brief overview of integrin receptor-mediated cell function, so-called "biomimetic" techniques reviewed here include (i) surface modification of biomaterials with bioadhesive ECM macromolecules or specific binding motifs, (ii) nanoscale patterning of the materials and (iii) the use of "natural-like" biomaterials. Copyright © 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Plant Abiotic Stress Proteomics: The Major Factors Determining Alterations in Cellular Proteome

Science.gov (United States)

Kosová, Klára; Vítámvás, Pavel; Urban, Milan O.; Prášil, Ilja T.; Renaut, Jenny

2018-01-01

HIGHLIGHTS: Major environmental and genetic factors determining stress-related protein abundance are discussed.Major aspects of protein biological function including protein isoforms and PTMs, cellular localization and protein interactions are discussed.Functional diversity of protein isoforms and PTMs is discussed. Abiotic stresses reveal profound impacts on plant proteomes including alterations in protein relative abundance, cellular localization, post-transcriptional and post-translational modifications (PTMs), protein interactions with other protein partners, and, finally, protein biological functions. The main aim of the present review is to discuss the major factors determining stress-related protein accumulation and their final biological functions. A dynamics of stress response including stress acclimation to altered ambient conditions and recovery after the stress treatment is discussed. The results of proteomic studies aimed at a comparison of stress response in plant genotypes differing in stress adaptability reveal constitutively enhanced levels of several stress-related proteins (protective proteins, chaperones, ROS scavenging- and detoxification-related enzymes) in the tolerant genotypes with respect to the susceptible ones. Tolerant genotypes can efficiently adjust energy metabolism to enhanced needs during stress acclimation. Stress tolerance vs. stress susceptibility are relative terms which can reflect different stress-coping strategies depending on the given stress treatment. The role of differential protein isoforms and PTMs with respect to their biological functions in different physiological constraints (cellular compartments and interacting partners) is discussed. The importance of protein functional studies following high-throughput proteome analyses is presented in a broader context of plant biology. In summary, the manuscript tries to provide an overview of the major factors which have to be considered when interpreting data from proteomic

Cellular and functional specificity among ferritin-like proteins in the multicellular cyanobacterium Nostoc punctiforme.

Science.gov (United States)

Ekman, Martin; Sandh, Gustaf; Nenninger, Anja; Oliveira, Paulo; Stensjö, Karin

2014-03-01

Ferritin-like proteins constitute a remarkably heterogeneous protein family, including ferritins, bacterioferritins and Dps proteins. The genome of the filamentous heterocyst-forming cyanobacterium Nostoc punctiforme encodes five ferritin-like proteins. In the present paper, we report a multidimensional characterization of these proteins. Our phylogenetic and bioinformatics analyses suggest both structural and physiological differences among the ferritin-like proteins. The expression of these five genes responded differently to hydrogen peroxide treatment, with a significantly higher rise in transcript level for Npun_F3730 as compared with the other four genes. A specific role for Npun_F3730 in the cells tolerance against hydrogen peroxide was also supported by the inactivation of Npun_F3730, Npun_R5701 and Npun_R6212; among these, only the ΔNpun_F3730 strain showed an increased sensitivity to hydrogen peroxide compared with wild type. Analysis of promoter-GFP reporter fusions of the ferritin-like genes indicated that Npun_F3730 and Npun_R5701 were expressed in all cell types of a diazotrophic culture, while Npun_F6212 was expressed specifically in heterocysts. Our study provides the first comprehensive analysis combining functional differentiation and cellular specificity within this important group of proteins in a multicellular cyanobacterium. © 2013 John Wiley & Sons Ltd and Society for Applied Microbiology.

Study on the enhanced cellular uptake effect of daunorubicin on leukemia cells mediated via functionalized nickel nanoparticles

Energy Technology Data Exchange (ETDEWEB)

Guo Dadong; Wu Chunhui; Hu Hongli; Wang Xuemei [State Key Lab of Bioelectronics (Chien-Shiung Wu Lab), Southeast University, Nanjing 210096 (China); Li Xiaomao [Department of Physics, University of Saarland, D-66041 Saarbruecken (Germany); Chen Baoan, E-mail: xuewang@seu.edu.c [Zhongda Hospital, School of Clinical Medical, Southeast University, Nanjing 210096 (China)

2009-04-15

The success of cancer chemotherapy is largely dependent on the efficient anticancer drug accumulation in target tumor tissues and cells so as to inhibit the proliferation of the cancer cells. Recently, some biocompatible nanomaterials have been utilized as drug target delivery systems and have shown the great potential to effectively afford the sustained drug delivery for the target cancer cells. In this study, we have explored the possibility for the bio-application of the functionalized nickel (Ni) nanoparticles and the efficiency of the functionalized Ni nanoparticles on drug permeability, and cellular uptake of leukemia K562 cells in vitro has been probed via atomic force microscopy, inverted fluorescence microscopy and confocal microscopy, electrochemical study and MTT (3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyl-tetrazolium bromide) assay. It is observed that the presence of relevant Ni nanoparticles could induce the membrane structure change of target cells and efficiently improve the permeability of the cell membrane so that the combination of these Ni nanoparticles with anticancer drug daunorubicin could have a synergistic effect on the efficient cytotoxicity suppression in leukemia cancer cells. These observations indicate the great potential of Ni nanoparticles in the future biomedical application including target cancer diagnosis and chemotherapy.

Simulation of electrochemical processes in cardiac tissue based on cellular automaton

International Nuclear Information System (INIS)

Avdeev, S A; Bogatov, N M

2014-01-01

A new class of cellular automata using special accumulative function for nonuniformity distribution is presented. Usage of this automata type for simulation of excitable media applied to electrochemical processes in human cardiac tissue is shown

Cellular Particle Dynamics simulation of biomechanical relaxation processes of multi-cellular systems

Science.gov (United States)

McCune, Matthew; Kosztin, Ioan

2013-03-01

Cellular Particle Dynamics (CPD) is a theoretical-computational-experimental framework for describing and predicting the time evolution of biomechanical relaxation processes of multi-cellular systems, such as fusion, sorting and compression. In CPD, cells are modeled as an ensemble of cellular particles (CPs) that interact via short range contact interactions, characterized by an attractive (adhesive interaction) and a repulsive (excluded volume interaction) component. The time evolution of the spatial conformation of the multicellular system is determined by following the trajectories of all CPs through numerical integration of their equations of motion. Here we present CPD simulation results for the fusion of both spherical and cylindrical multi-cellular aggregates. First, we calibrate the relevant CPD model parameters for a given cell type by comparing the CPD simulation results for the fusion of two spherical aggregates to the corresponding experimental results. Next, CPD simulations are used to predict the time evolution of the fusion of cylindrical aggregates. The latter is relevant for the formation of tubular multi-cellular structures (i.e., primitive blood vessels) created by the novel bioprinting technology. Work supported by NSF [PHY-0957914]. Computer time provided by the University of Missouri Bioinformatics Consortium.

The E-domain region of mechano-growth factor inhibits cellular apoptosis and preserves cardiac function during myocardial infarction.

Science.gov (United States)

Mavrommatis, Evangelos; Shioura, Krystyna M; Los, Tamara; Goldspink, Paul H

2013-09-01

Insulin-like growth factor-1 (IGF-1) isoforms are expressed via alternative splicing. Expression of the minor isoform IGF-1Eb [also known as mechano-growth factor (MGF)] is responsive to cell stress. Since IGF-1 isoforms differ in their E-domain regions, we are interested in determining the biological function of the MGF E-domain. To do so, a synthetic peptide analog was used to gain mechanistic insight into the actions of the E-domain. Treatment of H9c2 cells indicated a rapid cellular uptake mechanism that did not involve IGF-1 receptor activation but resulted in a nuclear localization. Peptide treatment inhibited the intrinsic apoptotic pathway in H9c2 cells subjected to cell stress with sorbitol by preventing the collapse of the mitochondrial membrane potential and inhibition of caspase-3 activation. Therefore, we administered the peptide at the time of myocardial infarction (MI) in mice. At 2 weeks post-MI cardiac function, gene expression and cell death were assayed. A significant decline in both systolic and diastolic function was evident in untreated mice based on PV loop analysis. Delivery of the E-peptide ameliorated the decline in function and resulted in significant preservation of cardiac contractility. Associated with these changes were an inhibition of pathologic hypertrophy and significantly fewer apoptotic nuclei in the viable myocardium of E-peptide-treated mice post-MI. We conclude that administration of the MGF E-domain peptide may provide a means of modulating local tissue IGF-1 autocrine/paracrine actions to preserve cardiac function, prevent cell death, and pathologic remodeling in the heart.

FY 1997 report on the survey of fundamental technologies in the field of brain neuro-biotechnology; 1997 nendo Sendo kenkyu hokokusho (noshinkei saibo kogaku kiban gijutsu no chosa kenkyu)

Energy Technology Data Exchange (ETDEWEB)

NONE

1998-03-01

In Japan with its rapidly aging society, fundamental technologies are required for the development of artificial nerves substituting for or supporting damaged ones, and ultimately constituting artificial neurons based on the knowledge of the brain functions at the molecular and cellular levels. This study defines the fundamental technologies which would be required for the development in the area, and further, evaluates the potential of the technologies to develop the novel industry. The brain function is closely related to the activity in neuronal circuits. In order to repair injured nerves and to develop the advanced technologies of electronics for helping impaired neuronal functions, the most important and urgent is to understand how to work the neuronal circuit system in the brain. Based on these viewpoints, new methodological approaches would make it possible to relieve neural impairment in the sensory input system and the motor system by the use of electronic circuits. They also would improve rehabilitation after injury, and treat neurodegenerative diseases such as Parkinson`s disease. These advances surely create the new types of industry seeds in near future. 77 refs., 29 figs., 2 tabs.

QoE-Driven D2D Media Services Distribution Scheme in Cellular Networks

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Mingkai Chen

2017-01-01

Full Text Available Device-to-device (D2D communication has been widely studied to improve network performance and considered as a potential technological component for the next generation communication. Considering the diverse users’ demand, Quality of Experience (QoE is recognized as a new degree of user’s satisfaction for media service transmissions in the wireless communication. Furthermore, we aim at promoting user’s Mean of Score (MOS value to quantify and analyze user’s QoE in the dynamic cellular networks. In this paper, we explore the heterogeneous media service distribution in D2D communications underlaying cellular networks to improve the total users’ QoE. We propose a novel media service scheme based on different QoE models that jointly solve the massive media content dissemination issue for cellular networks. Moreover, we also investigate the so-called Media Service Adaptive Update Scheme (MSAUS framework to maximize users’ QoE satisfaction and we derive the popularity and priority function of different media service QoE expression. Then, we further design Media Service Resource Allocation (MSRA algorithm to schedule limited cellular networks resource, which is based on the popularity function to optimize the total users’ QoE satisfaction and avoid D2D interference. In addition, numerical simulation results indicate that the proposed scheme is more effective in cellular network content delivery, which makes it suitable for various media service propagation.

MEMS capacitive force sensors for cellular and flight biomechanics

International Nuclear Information System (INIS)

Sun Yu; Nelson, Bradley J

2007-01-01

Microelectromechanical systems (MEMS) are playing increasingly important roles in facilitating biological studies. They are capable of providing not only qualitative but also quantitative information on the cellular, sub-cellular and organism levels, which is instrumental to understanding the fundamental elements of biological systems. MEMS force sensors with their high bandwidth and high sensitivity combined with their small size, in particular, have found a role in this domain, because of the importance of quantifying forces and their effect on the function and morphology of many biological structures. This paper describes our research in the development of MEMS capacitive force sensors that have already demonstrated their effectiveness in the areas of cell mechanics and Drosophila flight dynamics studies. (review article)

Dynamic behavior of cellular materials and cellular structures: Experiments and modeling

Science.gov (United States)

Gao, Ziyang

Cellular solids, including cellular materials and cellular structures (CMS), have attracted people's great interests because of their low densities and novel physical, mechanical, thermal, electrical and acoustic properties. They offer potential for lightweight structures, energy absorption, thermal management, etc. Therefore, the studies of cellular solids have become one of the hottest research fields nowadays. From energy absorption point of view, any plastically deformed structures can be divided into two types (called type I and type II), and the basic cells of the CMS may take the configurations of these two types of structures. Accordingly, separated discussions are presented in this thesis. First, a modified 1-D model is proposed and numerically solved for a typical type II structure. Good agreement is achieved with the previous experimental data, hence is used to simulate the dynamic behavior of a type II chain. Resulted from different load speeds, interesting collapse modes are observed, and the parameters which govern the cell's post-collapse behavior are identified through a comprehensive non-dimensional analysis on general cellular chains. Secondly, the MHS specimens are chosen as an example of type I foam materials because of their good uniformity of the cell geometry. An extensive experimental study was carried out, where more attention was paid to their responses to dynamic loadings. Great enhancement of the stress-strain curve was observed in dynamic cases, and the energy absorption capacity is found to be several times higher than that of the commercial metal foams. Based on the experimental study, finite elemental simulations and theoretical modeling are also conducted, achieving good agreements and demonstrating the validities of those models. It is believed that the experimental, numerical and analytical results obtained in the present study will certainly deepen the understanding of the unsolved fundamental issues on the mechanical behavior of

Functional anthology of intrinsic disorder. 2. Cellular components, domains, technical terms, developmental processes, and coding sequence diversities correlated with long disordered regions.

Science.gov (United States)

Vucetic, Slobodan; Xie, Hongbo; Iakoucheva, Lilia M; Oldfield, Christopher J; Dunker, A Keith; Obradovic, Zoran; Uversky, Vladimir N

2007-05-01

Biologically active proteins without stable ordered structure (i.e., intrinsically disordered proteins) are attracting increased attention. Functional repertoires of ordered and disordered proteins are very different, and the ability to differentiate whether a given function is associated with intrinsic disorder or with a well-folded protein is crucial for modern protein science. However, there is a large gap between the number of proteins experimentally confirmed to be disordered and their actual number in nature. As a result, studies of functional properties of confirmed disordered proteins, while helpful in revealing the functional diversity of protein disorder, provide only a limited view. To overcome this problem, a bioinformatics approach for comprehensive study of functional roles of protein disorder was proposed in the first paper of this series (Xie, H.; Vucetic, S.; Iakoucheva, L. M.; Oldfield, C. J.; Dunker, A. K.; Obradovic, Z.; Uversky, V. N. Functional anthology of intrinsic disorder. 1. Biological processes and functions of proteins with long disordered regions. J. Proteome Res. 2007, 5, 1882-1898). Applying this novel approach to Swiss-Prot sequences and functional keywords, we found over 238 and 302 keywords to be strongly positively or negatively correlated, respectively, with long intrinsically disordered regions. This paper describes approximately 90 Swiss-Prot keywords attributed to the cellular components, domains, technical terms, developmental processes, and coding sequence diversities possessing strong positive and negative correlation with long disordered regions.

Functional Anthology of Intrinsic Disorder. II. Cellular Components, Domains, Technical Terms, Developmental Processes and Coding Sequence Diversities Correlated with Long Disordered Regions

Science.gov (United States)

Vucetic, Slobodan; Xie, Hongbo; Iakoucheva, Lilia M.; Oldfield, Christopher J.; Dunker, A. Keith; Obradovic, Zoran; Uversky, Vladimir N.

2008-01-01

Biologically active proteins without stable ordered structure (i.e., intrinsically disordered proteins) are attracting increased attention. Functional repertoires of ordered and disordered proteins are very different, and the ability to differentiate whether a given function is associated with intrinsic disorder or with a well-folded protein is crucial for modern protein science. However, there is a large gap between the number of proteins experimentally confirmed to be disordered and their actual number in nature. As a result, studies of functional properties of confirmed disordered proteins, while helpful in revealing the functional diversity of protein disorder, provide only a limited view. To overcome this problem, a bioinformatics approach for comprehensive study of functional roles of protein disorder was proposed in the first paper of this series (Xie H., Vucetic S., Iakoucheva L.M., Oldfield C.J., Dunker A.K., Obradovic Z., Uversky V.N. (2006) Functional anthology of intrinsic disorder. I. Biological processes and functions of proteins with long disordered regions. J. Proteome Res.). Applying this novel approach to Swiss-Prot sequences and functional keywords, we found over 238 and 302 keywords to be strongly positively or negatively correlated, respectively, with long intrinsically disordered regions. This paper describes ~90 Swiss-Prot keywords attributed to the cellular components, domains, technical terms, developmental processes and coding sequence diversities possessing strong positive and negative correlation with long disordered regions. PMID:17391015

Intracellular Localization and Cellular Factors Interaction of HTLV-1 and HTLV-2 Tax Proteins: Similarities and Functional Differences

Directory of Open Access Journals (Sweden)

Maria Grazia Romanelli

2011-05-01

Full Text Available Human T-lymphotropic viruses type 1 (HTLV-1 and type 2 (HTLV-2 present very similar genomic structures but HTLV-1 is more pathogenic than HTLV-2. Is this difference due to their transactivating Tax proteins, Tax-1 and Tax-2, which are responsible for viral and cellular gene activation? Do Tax-1 and Tax-2 differ in their cellular localization and in their interaction pattern with cellular factors? In this review, we summarize Tax-1 and Tax-2 structural and phenotypic properties, their interaction with factors involved in signal transduction and their localization-related behavior within the cell. Special attention will be given to the distinctions between Tax-1 and Tax-2 that likely play an important role in their transactivation activity.

Statistical mechanics of cellular automata

International Nuclear Information System (INIS)

Wolfram, S.

1983-01-01

Cellular automata are used as simple mathematical models to investigate self-organization in statistical mechanics. A detailed analysis is given of ''elementary'' cellular automata consisting of a sequence of sites with values 0 or 1 on a line, with each site evolving deterministically in discrete time steps according to p definite rules involving the values of its nearest neighbors. With simple initial configurations, the cellular automata either tend to homogeneous states, or generate self-similar patterns with fractal dimensions approx. =1.59 or approx. =1.69. With ''random'' initial configurations, the irreversible character of the cellular automaton evolution leads to several self-organization phenomena. Statistical properties of the structures generated are found to lie in two universality classes, independent of the details of the initial state or the cellular automaton rules. More complicated cellular automata are briefly considered, and connections with dynamical systems theory and the formal theory of computation are discussed

Performance evaluation of cellular layouts : extension to DRC system contexts

NARCIS (Netherlands)

Suresh, NC; Gaalman, GJC

This study involves a comparison of the performance of functional layouts (FL) and cellular manufacturing (CM) systems in a dual-resource-constrained( DRC) system context. Past studies of FL and CM have been based mostly on single-resource-constrained( SRC) systems. Recent studies have included

Wireless Cellular Mobile Communications

OpenAIRE

Zalud, V.

2002-01-01

In this article is briefly reviewed the history of wireless cellular mobile communications, examined the progress in current second generation (2G) cellular standards and discussed their migration to the third generation (3G). The European 2G cellular standard GSM and its evolution phases GPRS and EDGE are described somewhat in detail. The third generation standard UMTS taking up on GSM/GPRS core network and equipped with a new advanced access network on the basis of code division multiple ac...

Perspectives for the treatment of sensorineural hearing loss by cellular regeneration of the inner ear.

Science.gov (United States)

Almeida-Branco, Mario S; Cabrera, Sonia; Lopez-Escamez, Jose A

2015-01-01

Sensorineural hearing loss is a caused by the loss of the cochlear hair cells with the consequent deafferentation of spiral ganglion neurons. Humans do not show endogenous cellular regeneration in the inner ear and there is no exogenous therapy that allows the replacement of the damaged hair cells. Currently, treatment is based on the use of hearing aids and cochlear implants that present different outcomes, some difficulties in auditory discrimination and a limited useful life. More advanced technology is hindered by the functional capacity of the remaining spiral ganglion neurons. The latest advances with stem cell therapy and cellular reprogramming have developed several possibilities to induce endogenous regeneration or stem cell transplantation to replace damaged inner ear hair cells and restore hearing function. With further knowledge of the cellular and molecular biology of the inner ear and its embryonic development, it will be possible to use induced stem cells as in vitro models of disease and as replacement cellular therapy. Investigation in this area is focused on generating cellular therapy with clinical use for the treatment of profound sensorineural hearing loss. Copyright © 2014 Elsevier España, S.L.U. and Sociedad Española de Otorrinolaringología y Patología Cérvico-Facial. All rights reserved.

Sexual Experience in Female Rodents: Cellular Mechanisms and Functional Consequences

Science.gov (United States)

Meisel, Robert L.; Mullins, Amanda J.

2007-01-01

The neurobiology of female sexual behavior has largely focused on mechanisms of hormone action on nerve cells and how these effects translate into the display of copulatory motor patterns. Of equal importance, though less studied, are some of the consequences of engaging in sexual behavior, including the rewarding properties of sexual interactions and how sexual experience alters copulatory efficiency. This review summarizes the effects of sexual experience on reward processes and copulation in female Syrian hamsters. Neural correlates of these sexual interactions include long-term cellular changes in dopamine transmission and postsynaptic signaling pathways related to neuronal plasticity (e.g., dendritic spine formation). Taken together, these studies suggest that sexual experience enhances the reinforcing properties of sexual behavior, which has the coincident outcome of increasing copulatory efficiency in a way that can increase reproductive success. PMID:16978593

MSAT and cellular hybrid networking

Science.gov (United States)

Baranowsky, Patrick W., II

Westinghouse Electric Corporation is developing both the Communications Ground Segment and the Series 1000 Mobile Phone for American Mobile Satellite Corporation's (AMSC's) Mobile Satellite (MSAT) system. The success of the voice services portion of this system depends, to some extent, upon the interoperability of the cellular network and the satellite communication circuit switched communication channels. This paper will describe the set of user-selectable cellular interoperable modes (cellular first/satellite second, etc.) provided by the Mobile Phone and described how they are implemented with the ground segment. Topics including roaming registration and cellular-to-satellite 'seamless' call handoff will be discussed, along with the relevant Interim Standard IS-41 Revision B Cellular Radiotelecommunications Intersystem Operations and IOS-553 Mobile Station - Land Station Compatibility Specification.

Design and evaluation of cellular power converter architectures

Science.gov (United States)

Perreault, David John

Power electronic technology plays an important role in many energy conversion and storage applications, including machine drives, power supplies, frequency changers and UPS systems. Increases in performance and reductions in cost have been achieved through the development of higher performance power semiconductor devices and integrated control devices with increased functionality. Manufacturing techniques, however, have changed little. High power is typically achieved by paralleling multiple die in a sing!e package, producing the physical equivalent of a single large device. Consequently, both the device package and the converter in which the device is used continue to require large, complex mechanical structures, and relatively sophisticated heat transfer systems. An alternative to this approach is the use of a cellular power converter architecture, which is based upon the parallel connection of a large number of quasi-autonomous converters, called cells, each of which is designed for a fraction of the system rating. The cell rating is chosen such that single-die devices in inexpensive packages can be used, and the cell fabricated with an automated assembly process. The use of quasi-autonomous cells means that system performance is not compromised by the failure of a cell. This thesis explores the design of cellular converter architectures with the objective of achieving improvements in performance, reliability, and cost over conventional converter designs. New approaches are developed and experimentally verified for highly distributed control of cellular converters, including methods for ripple cancellation and current-sharing control. The performance of these techniques are quantified, and their dynamics are analyzed. Cell topologies suitable to the cellular architecture are investigated, and their use for systems in the 5-500 kVA range is explored. The design, construction, and experimental evaluation of a 6 kW cellular switched-mode rectifier is also addressed

Cationic liposome/DNA complexes: from structure to interactions with cellular membranes.

Science.gov (United States)

Caracciolo, Giulio; Amenitsch, Heinz

2012-10-01

Gene-based therapeutic approaches are based upon the concept that, if a disease is caused by a mutation in a gene, then adding back the wild-type gene should restore regular function and attenuate the disease phenotype. To deliver the gene of interest, both viral and nonviral vectors are used. Viruses are efficient, but their application is impeded by detrimental side-effects. Among nonviral vectors, cationic liposomes are the most promising candidates for gene delivery. They form stable complexes with polyanionic DNA (lipoplexes). Despite several advantages over viral vectors, the transfection efficiency (TE) of lipoplexes is too low compared with those of engineered viral vectors. This is due to lack of knowledge about the interactions between complexes and cellular components. Rational design of efficient lipoplexes therefore requires deeper comprehension of the interactions between the vector and the DNA as well as the cellular pathways and mechanisms involved. The importance of the lipoplex structure in biological function is revealed in the application of synchrotron small-angle X-ray scattering in combination with functional TE measurements. According to current understanding, the structure of lipoplexes can change upon interaction with cellular membranes and such changes affect the delivery efficiency. Recently, a correlation between the mechanism of gene release from complexes, the structure, and the physical and chemical parameters of the complexes has been established. Studies aimed at correlating structure and activity of lipoplexes are reviewed herein. This is a fundamental step towards rational design of highly efficient lipid gene vectors.

Creating the Chemistry in Cellular Respiration Concept Inventory (CCRCI)

Science.gov (United States)

Forshee, Jay Lance, II

Students at our institution report cellular respiration to be the most difficult concept they encounter in undergraduate biology, but why students find this difficult is unknown. Students may find cellular respiration difficult because there is a large amount of steps, or because there are persistent, long-lasting misconceptions and misunderstandings surrounding their knowledge of chemistry, which affect their performance on cellular respiration assessments. Most studies of cellular respiration focus on student macro understanding of the process related to breathing, and matter and energy. To date, no studies identify which chemistry concepts are most relevant to students' development of an understanding of the process of cellular respiration or have developed an assessment to measure student understanding of them. Following the Delphi method, the researchers conducted expert interviews with faculty members from four-year, masters-, and PhD-granting institutions who teach undergraduate general biology, and are experts in their respective fields of biology. From these interviews, researchers identified twelve chemistry concepts important to understanding cellular respiration and using surveys, these twelve concepts were refined into five (electron transfer, energy transfer, thermodynamics (law/conservation), chemical reactions, and gradients). The researchers then interviewed undergraduate introductory biology students at a large Midwestern university to identify their knowledge and misconceptions of the chemistry concepts that the faculty had identified previously as important. The CCRCI was developed using the five important chemistry concepts underlying cellular respiration. The final version of the CCRCI was administered to n=160 introductory biology students during the spring 2017 semester. Reliability of the CCRCI was evaluated using Cronbach's alpha (=.7) and split-half reliability (=.769), and validity of the instrument was assessed through content validity

Multifunctional Cellular Materials Based on 2D Nanomaterials: Prospects and Challenges.

Science.gov (United States)

Qiu, Ling; He, Zijun; Li, Dan

2018-01-01

Recent advances in emerging 2D nanomaterial-based cellular materials (2D-CMs) open up new opportunities for the development of next generation cellular solids with exceptional properties. Herein, an overview of the current research status of 2D-CMs is provided and their future opportunities are highlighted. First, the unique features of 2D nanomaterials are introduced to illustrate why these nanoscale building blocks are promising for the development of novel cellular materials and what the new features of 2D nanoscale building blocks can offer when compared to their 0D and 1D counterparts. An in-depth discussion on the structure-property relationships of 2D-CMs is then provided, and the remarkable functions that can be achieved by engineering their cellular architecture are highlighted. Additionally, the use of 2D-CMs to tackle key challenges in different practical applications is demonstrated. In conclusion, a personal perspective on the challenges and future research directions of 2D-CMs is given. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Interplay between cellular activity and three-dimensional scaffold-cell constructs with different foam structure processed by electron beam melting.

Science.gov (United States)

Nune, Krishna C; Misra, R Devesh K; Gaytan, Sara M; Murr, Lawrence E

2015-05-01

The cellular activity, biological response, and consequent integration of scaffold-cell construct in the physiological system are governed by the ability of cells to adhere, proliferate, and biomineralize. In this regard, we combine cellular biology and materials science and engineering to fundamentally elucidate the interplay between cellular activity and interconnected three-dimensional foamed architecture obtained by a novel process of electron beam melting and computational tools. Furthermore, the organization of key proteins, notably, actin, vinclulin, and fibronectin, involved in cellular activity and biological functions and relationship with the structure was explored. The interconnected foamed structure with ligaments was favorable to cellular activity that includes cell attachment, proliferation, and differentiation. The primary rationale for favorable modulation of cellular functions is that the foamed structure provided a channel for migration and communication between cells leading to highly mineralized extracellular matrix (ECM) by the differentiating osteoblasts. The filopodial interaction amongst cells on the ligaments was a governing factor in the secretion of ECM, with consequent influence on maturation and mineralization. © 2014 Wiley Periodicals, Inc.

Top-down cellular pyramids

Energy Technology Data Exchange (ETDEWEB)

Wu, A Y; Rosenfeld, A

1983-10-01

A cellular pyramid is an exponentially tapering stack of arrays of processors (cells), where each cell is connected to its neighbors (siblings) on its own level, to a parent on the level above, and to its children on the level below. It is shown that in some situations, if information flows top-down only, from fathers to sons, then a cellular pyramid may be no faster than a one-level cellular array; but it may be possible to use simpler cells in the pyramid case. 23 references.

Cellular decomposition in vikalloys

International Nuclear Information System (INIS)

Belyatskaya, I.S.; Vintajkin, E.Z.; Georgieva, I.Ya.; Golikov, V.A.; Udovenko, V.A.

1981-01-01

Austenite decomposition in Fe-Co-V and Fe-Co-V-Ni alloys at 475-600 deg C is investigated. The cellular decomposition in ternary alloys results in the formation of bcc (ordered) and fcc structures, and in quaternary alloys - bcc (ordered) and 12R structures. The cellular 12R structure results from the emergence of stacking faults in the fcc lattice with irregular spacing in four layers. The cellular decomposition results in a high-dispersion structure and magnetic properties approaching the level of well-known vikalloys [ru

Mechanisms and Regulation of Intestinal Absorption of Water-soluble Vitamins: Cellular and Molecular Aspects

DEFF Research Database (Denmark)

Nexø, Ebba; Said, Hamid M

2012-01-01

The water-soluble vitamins represent a group of structurally and functionally unrelated compounds that share the common feature of being essential for normal cellular functions, growth, and development. With the exception of some endogenous production of niacin, human cells cannot synthesize...

Absorbed Power Minimization in Cellular Users with Circular Antenna Arrays

Science.gov (United States)

Christofilakis, Vasilis; Votis, Constantinos; Tatsis, Giorgos; Raptis, Vasilis; Kostarakis, Panos

2010-01-01

Nowadays electromagnetic pollution of non ionizing radiation generated by cellular phones concerns millions of people. In this paper the use of circular antenna array as a means of minimizing the absorbed power by cellular phone users is introduced. In particular, the different characteristics of radiation patterns produced by a helical conventional antenna used in mobile phones operating at 900 MHz and those produced by a circular antenna array, hypothetically used in the same mobile phones, are in detail examined. Furthermore, the percentage of decrement of the power absorbed in the head as a function of direction of arrival is estimated for the circular antenna array.

Physical Property Control on the Cellular Uptake Pathway and Spatial Distribution of Nanoparticles in Cells.

Science.gov (United States)

Ahn, Sungsook; Seo, Eunseok; Kim, Ki Hean; Lee, Sang Joon

2015-06-01

Nanoparticles have been developed in broad biomedical research in terms of effective cellular interactions to treat and visualize diseased cells. Considering the charge and polar functional groups of proteins that are embedded in cellular membranes, charged nanoparticles have been strategically developed to enhance electrostatic cellular interactions. In this study, we show that cellular uptake efficiency, pathway, and spatial distribution of gold nanoparticles in a cell are significantly modulated based on the surface condition of gold nanoparticles and human cancer cells that were tuned by controlling the pH of the medium and by introducing an electron beam. Cellular uptake efficiency is increased when electrostatic attraction is induced between the cells and the gold nanoparticles. Cell surface modification changes the cellular uptake pathways of the gold nanoparticles and concentrates the gold nanoparticles at the membrane region. Surface modification of the gold nanoparticles also contributes to deep penetration and homogeneous spatial distributions in a cell.

Lysine-functionalized nanodiamonds as gene carriers: development of stable colloidal dispersion for in vitro cellular uptake studies and siRNA delivery application

Science.gov (United States)

Alwani, Saniya; Kaur, Randeep; Michel, Deborah; Chitanda, Jackson M; Verrall, Ronald E; Karunakaran, Chithra; Badea, Ildiko

2016-01-01

Purpose Nanodiamonds (NDs) are emerging as an attractive tool for gene therapeutics. To reach their full potential for biological application, NDs should maintain their colloidal stability in biological milieu. This study describes the behavior of lysine-functionalized ND (lys-ND) in various dispersion media, with an aim to limit aggregation and improve the colloidal stability of ND-gene complexes called diamoplexes. Furthermore, cellular and macromolecular interactions of lys-NDs are also analyzed in vitro to establish the understanding of ND-mediated gene transfer in cells. Methods lys-NDs were synthesized earlier through covalent conjugation of lysine amino acid to carboxylated NDs surface generated through re-oxidation in strong oxidizing acids. In this study, dispersions of lys-NDs were prepared in various media, and the degree of sedimentation was monitored for 72 hours. Particle size distributions and zeta potential measurements were performed for a period of 25 days to characterize the physicochemical stability of lys-NDs in the medium. The interaction profile of lys-NDs with fetal bovine serum showed formation of a protein corona, which was evaluated by size and charge distribution measurements. Uptake of lys-NDs in cervical cancer cells was analyzed by scanning transmission X-ray microscopy, flow cytometry, and confocal microscopy. Cellular uptake of diamoplexes (complex of lys-NDs with small interfering RNA) was also analyzed using flow cytometry. Results Aqueous dispersion of lys-NDs showed minimum sedimentation and remained stable over a period of 25 days. Size distributions showed good stability, remaining under 100 nm throughout the testing period. A positive zeta potential of >+20 mV indicated a preservation of surface charges. Size distribution and zeta potential changed for lys-NDs after incubation with blood serum, suggesting an interaction with biomolecules, mainly proteins, and a possible formation of a protein corona. Cellular internalization

Lysine-functionalized nanodiamonds as gene carriers: development of stable colloidal dispersion for in vitro cellular uptake studies and siRNA delivery application.

Science.gov (United States)

Alwani, Saniya; Kaur, Randeep; Michel, Deborah; Chitanda, Jackson M; Verrall, Ronald E; Karunakaran, Chithra; Badea, Ildiko

2016-01-01

Nanodiamonds (NDs) are emerging as an attractive tool for gene therapeutics. To reach their full potential for biological application, NDs should maintain their colloidal stability in biological milieu. This study describes the behavior of lysine-functionalized ND (lys-ND) in various dispersion media, with an aim to limit aggregation and improve the colloidal stability of ND-gene complexes called diamoplexes. Furthermore, cellular and macromolecular interactions of lys-NDs are also analyzed in vitro to establish the understanding of ND-mediated gene transfer in cells. lys-NDs were synthesized earlier through covalent conjugation of lysine amino acid to carboxylated NDs surface generated through re-oxidation in strong oxidizing acids. In this study, dispersions of lys-NDs were prepared in various media, and the degree of sedimentation was monitored for 72 hours. Particle size distributions and zeta potential measurements were performed for a period of 25 days to characterize the physicochemical stability of lys-NDs in the medium. The interaction profile of lys-NDs with fetal bovine serum showed formation of a protein corona, which was evaluated by size and charge distribution measurements. Uptake of lys-NDs in cervical cancer cells was analyzed by scanning transmission X-ray microscopy, flow cytometry, and confocal microscopy. Cellular uptake of diamoplexes (complex of lys-NDs with small interfering RNA) was also analyzed using flow cytometry. Aqueous dispersion of lys-NDs showed minimum sedimentation and remained stable over a period of 25 days. Size distributions showed good stability, remaining under 100 nm throughout the testing period. A positive zeta potential of >+20 mV indicated a preservation of surface charges. Size distribution and zeta potential changed for lys-NDs after incubation with blood serum, suggesting an interaction with biomolecules, mainly proteins, and a possible formation of a protein corona. Cellular internalization of lys-NDs was confirmed

Mitochondria, Energetics, Epigenetics, and Cellular Responses to Stress

Science.gov (United States)

McAllister, Kimberly; Worth, Leroy; Haugen, Astrid C.; Meyer, Joel N.; Domann, Frederick E.; Van Houten, Bennett; Mostoslavsky, Raul; Bultman, Scott J.; Baccarelli, Andrea A.; Begley, Thomas J.; Sobol, Robert W.; Hirschey, Matthew D.; Ideker, Trey; Santos, Janine H.; Copeland, William C.; Tice, Raymond R.; Balshaw, David M.; Tyson, Frederick L.

2014-01-01

Background: Cells respond to environmental stressors through several key pathways, including response to reactive oxygen species (ROS), nutrient and ATP sensing, DNA damage response (DDR), and epigenetic alterations. Mitochondria play a central role in these pathways not only through energetics and ATP production but also through metabolites generated in the tricarboxylic acid cycle, as well as mitochondria–nuclear signaling related to mitochondria morphology, biogenesis, fission/fusion, mitophagy, apoptosis, and epigenetic regulation. Objectives: We investigated the concept of bidirectional interactions between mitochondria and cellular pathways in response to environmental stress with a focus on epigenetic regulation, and we examined DNA repair and DDR pathways as examples of biological processes that respond to exogenous insults through changes in homeostasis and altered mitochondrial function. Methods: The National Institute of Environmental Health Sciences sponsored the Workshop on Mitochondria, Energetics, Epigenetics, Environment, and DNA Damage Response on 25–26 March 2013. Here, we summarize key points and ideas emerging from this meeting. Discussion: A more comprehensive understanding of signaling mechanisms (cross-talk) between the mitochondria and nucleus is central to elucidating the integration of mitochondrial functions with other cellular response pathways in modulating the effects of environmental agents. Recent studies have highlighted the importance of mitochondrial functions in epigenetic regulation and DDR with environmental stress. Development and application of novel technologies, enhanced experimental models, and a systems-type research approach will help to discern how environmentally induced mitochondrial dysfunction affects key mechanistic pathways. Conclusions: Understanding mitochondria–cell signaling will provide insight into individual responses to environmental hazards, improving prediction of hazard and susceptibility to

Cellular and Molecular Basis of Cerebellar Development

Directory of Open Access Journals (Sweden)

Salvador eMartinez

2013-06-01

Full Text Available Historically, the molecular and cellular mechanisms of cerebellar development were investigated through structural descriptions and studying spontaneous mutations in animal models and humans. Advances in experimental embryology, genetic engineering and neuroimaging techniques render today the possibility to approach the analysis of molecular mechanisms underlying histogenesis and morphogenesis of the cerebellum by experimental designs. Several genes and molecules were identified to be involved in the cerebellar plate regionalization, specification and differentiation of cerebellar neurons, as well as the establishment of cellular migratory routes and the subsequent neuronal connectivity. Indeed, pattern formation of the cerebellum requires the adequate orchestration of both key morphogenetic signals, arising from distinct brain regions, and local expression of specific transcription factors. Thus, the present review wants to revisit and discuss these morphogenetic and molecular mechanisms taking place during cerebellar development in order to understand causal processes regulating cerebellar cytoarchitecture, its highly topographically ordered circuitry and its role in brain function.

Cellular and Chemical Neuroscience of Mammalian Sleep

OpenAIRE

Datta, Subimal

2010-01-01

Extraordinary strides have been made toward understanding the complexities and regulatory mechanisms of sleep over the past two decades, thanks to the help of rapidly evolving technologies. At its most basic level, mammalian sleep is a restorative process of the brain and body. Beyond its primary restorative purpose, sleep is essential for a number of vital functions. Our primary research interest is to understand the cellular and molecular mechanisms underlying the regulation of sleep and it...

A Deterministic Approach to the Synchronization of Cellular Automata

OpenAIRE

Garcia, J.; Garcia, P.

2011-01-01

In this work we introduce a deterministic scheme of synchronization of linear and nonlinear cellular automata (CA) with complex behavior, connected through a master-slave coupling. By using a definition of Boolean derivative, we use the linear approximation of the automata to determine a function of coupling that promotes synchronization without perturbing all the sites of the slave system.

Results from functional and cellular studies using an ovine model to assess response to mesenchymal stem cell therapy after induction of myocardial infarction

International Nuclear Information System (INIS)

Bailey, Elizabeth A.; Bailey, Dale L; Roach, Paul J.; Bautovich, George; Hunyor, Stephen

2009-01-01

Full text: Background: Assessing functional and cellular consequences following myocardial infarction (MI) using large animals has advantages of similarity in size, shape and coronary supply to human heart. Aim: To confirm presence of MI and detect recovery of perfusion and function following implantation of ovine bone-marrow derived mesenchymal stem cells (MSC) using intra-myocardial (1 M ) and intra-coronary (I C ) methods. Methods: Eighteen ewes (wt: 45-50 k g, LV-EDV: 80-90 m L) included, with 10 completing protocol (3=control, 4= IM , 3= IC ). MlBI MPI SPECT/CT performed at baseline, 5-7 days post induction of Ml and 6 weeks post cellular therapy with male MSCs. At completion, sheep sacrificed and heart slices reviewed microscopically to confirm Ml, assess neovascularisation and correlate with MPI findings. MPI studies reconstructed using OSEM CT-based AC and analysed using QPS/QGS software. Calculation of Recovery Difference (RD%), Recovery Ratio (RR) and relative change to baseline determined for each study and per segment per study. Results: M I confirmed in 10 of 12 studies (I showed no perfusion abnormality, another pre-existing defect), confirmed anatomically by identification of fibrous scar tissue with lymphoid aggregates, histiocytes and calcium deposits. Reduction in perfusion was 14% to 48%. No improvement in perfusion seen in control (RR=0.8, RD=-16.9) and IC (RR=0.9, RD=-7.1) studies. Significant reperfusion seen on 1 M studies, with RR=1.5, RD=1.1 and perfusion recovery 8%, around periphery of infarct zone. Conclusions: Presence of acute Ml identified on MlBl MPI SPECT/CT correlates with anatomical findings. Improvement in perfusion and function at infarct zone seen using 1 M method of MSC implantation, correlating with significant neovascularisation identified microscopically.

Targeting Cellular Calcium Homeostasis to Prevent Cytokine-Mediated Beta Cell Death.

Science.gov (United States)

Clark, Amy L; Kanekura, Kohsuke; Lavagnino, Zeno; Spears, Larry D; Abreu, Damien; Mahadevan, Jana; Yagi, Takuya; Semenkovich, Clay F; Piston, David W; Urano, Fumihiko

2017-07-17

Pro-inflammatory cytokines are important mediators of islet inflammation, leading to beta cell death in type 1 diabetes. Although alterations in both endoplasmic reticulum (ER) and cytosolic free calcium levels are known to play a role in cytokine-mediated beta cell death, there are currently no treatments targeting cellular calcium homeostasis to combat type 1 diabetes. Here we show that modulation of cellular calcium homeostasis can mitigate cytokine- and ER stress-mediated beta cell death. The calcium modulating compounds, dantrolene and sitagliptin, both prevent cytokine and ER stress-induced activation of the pro-apoptotic calcium-dependent enzyme, calpain, and partly suppress beta cell death in INS1E cells and human primary islets. These agents are also able to restore cytokine-mediated suppression of functional ER calcium release. In addition, sitagliptin preserves function of the ER calcium pump, sarco-endoplasmic reticulum Ca 2+ -ATPase (SERCA), and decreases levels of the pro-apoptotic protein thioredoxin-interacting protein (TXNIP). Supporting the role of TXNIP in cytokine-mediated cell death, knock down of TXNIP in INS1-E cells prevents cytokine-mediated beta cell death. Our findings demonstrate that modulation of dynamic cellular calcium homeostasis and TXNIP suppression present viable pharmacologic targets to prevent cytokine-mediated beta cell loss in diabetes.

Cellular automata analysis and applications

CERN Document Server

Hadeler, Karl-Peter

2017-01-01

This book focuses on a coherent representation of the main approaches to analyze the dynamics of cellular automata. Cellular automata are an inevitable tool in mathematical modeling. In contrast to classical modeling approaches as partial differential equations, cellular automata are straightforward to simulate but hard to analyze. In this book we present a review of approaches and theories that allow the reader to understand the behavior of cellular automata beyond simulations. The first part consists of an introduction of cellular automata on Cayley graphs, and their characterization via the fundamental Cutis-Hedlund-Lyndon theorems in the context of different topological concepts (Cantor, Besicovitch and Weyl topology). The second part focuses on classification results: What classification follows from topological concepts (Hurley classification), Lyapunov stability (Gilman classification), and the theory of formal languages and grammars (Kůrka classification). These classifications suggest to cluster cel...

Signaling by Cellular Protrusions: Keeping the Conversation Private.

Science.gov (United States)

Buszczak, Michael; Inaba, Mayu; Yamashita, Yukiko M

2016-07-01

Information exchange between different cells makes multicellular life possible. Signaling between cells can occur over long distances, as in the case of hormone signaling, or it can take place over short distances between immediately juxtaposed neighbors, as in the case of stem cell-niche signaling. The ability of signal-sending and -receiving cells to communicate with one another in a specific manner is of paramount importance in the proper development and function of tissues. Growing evidence indicates that different cellular protrusions help to achieve specificity in signaling that occurs between distinct cell types. Here, we focus on new roles for cellular protrusions in cell-to-cell communication, drawing special attention to how stem cells use specialized extensions to promote reception of self-renewing signals emanating from the niche. Copyright © 2016 Elsevier Ltd. All rights reserved.

Cellular vs. organ approaches to dose estimates

International Nuclear Information System (INIS)

Adelstein, S.J.; Kassis, A.I.; Sastry, K.S.R.

1986-01-01

The cellular distribution of tissue-incorporated radionuclides has generally been neglected in the dosimetry of internal emitters. Traditional dosimetry assumes homogeneous distribution of radionuclides in organs of interest, while presuming that the ranges of particulate radiations are large relative to typical cell diameters. The macroscopic distribution of dose thus calculated has generally served as a sufficient approximation for the energy deposited within radiosensitive sites. However, with the increasing utilization of intracellular agents, such as thallium-201, it has become necessary to examine the microscopic distribution of energy at the cellular level. This is particularly important in the instance of radionuclides that decay by electron capture or by internal conversion with the release of Auger and Coster-Kronig electrons. In many instances, these electrons are released as a dense shower of low-energy particles with ranges of subcellular dimensions. The high electron density in the immediate vicinity of the decaying atom produces a focal deposition of energy that far exceeds the average dose taken over several cell diameters. These studies point out the increasing need to take into account the microscopic distribution of dose on the cellular level as radionuclides distributed in cells become more commonplace, especially if the decay involves electron capture or internal conversion. As radiotracers are developed for the measurement of intracellular functions these factors should be given greater consideration. 16 references, 5 figures, 5 tables

Rapid construction of mechanically- confined multi- cellular structures using dendrimeric intercellular linker.

Science.gov (United States)

Mo, Xuejun; Li, Qiushi; Yi Lui, Lena Wai; Zheng, Baixue; Kang, Chiang Huen; Nugraha, Bramasta; Yue, Zhilian; Jia, Rui Rui; Fu, Hong Xia; Choudhury, Deepak; Arooz, Talha; Yan, Jie; Lim, Chwee Teck; Shen, Shali; Hong Tan, Choon; Yu, Hanry

2010-10-01

Tissue constructs that mimic the in vivo cell-cell and cell-matrix interactions are especially useful for applications involving the cell- dense and matrix- poor internal organs. Rapid and precise arrangement of cells into functional tissue constructs remains a challenge in tissue engineering. We demonstrate rapid assembly of C3A cells into multi- cell structures using a dendrimeric intercellular linker. The linker is composed of oleyl- polyethylene glycol (PEG) derivatives conjugated to a 16 arms- polypropylenimine hexadecaamine (DAB) dendrimer. The positively charged multivalent dendrimer concentrates the linker onto the negatively charged cell surface to facilitate efficient insertion of the hydrophobic oleyl groups into the cellular membrane. Bringing linker- treated cells into close proximity to each other via mechanical means such as centrifugation and micromanipulation enables their rapid assembly into multi- cellular structures within minutes. The cells exhibit high levels of viability, proliferation, three- dimensional (3D) cell morphology and other functions in the constructs. We constructed defined multi- cellular structures such as rings, sheets or branching rods that can serve as potential tissue building blocks to be further assembled into complex 3D tissue constructs for biomedical applications. 2010 Elsevier Ltd. All rights reserved.

Conducting polymer scaffolds for electrical control of cellular functions (Conference Presentation)

Science.gov (United States)

Inal, Sahika; Wan, Alwin M.; Williams, Tiffany V.; Giannelis, Emmanuel P.; Fischbach-Teschl, Claudia; Gourdon, Delphine; Owens, Róisín. M.; Malliaras, George G.

2016-09-01

Considering the limited physiological relevance of 2D cell culture experiments, significant effort was devoted to the development of materials that could more accurately recreate the in vivo cellular microenvironment, and support 3D cell cultures in vitro. (1) One such class of materials is conducting polymers, which are promising due to their compliant mechanical properties, compatibility with biological systems, mixed electrical and ionic conductivity, and ability to form porous structures. (2) In this work, we report the fabrication of a single component, macroporous scaffold made from poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) via an ice-templating method. (3) PEDOT:PSS scaffolds offer tunable pore size, morphology and shape through facile changes in preparation conditions, and are capable of supporting 3D cell cultures due to their biocompatibility and tissue-like elasticity. Moreover, these materials are functional: they exhibit excellent electrochemical switching behavior and significantly lower impedance compared to films. Their electrochemical activity enables their use in the active channel of a state of the art diagnostic tool in the field of bioelectronics, i.e., the organic electrochemical transistor (OECT). The inclusion of cells within the porous architecture affects the impedance of the electrically-conducting polymer network and, thus, may be used as a method to quantify cell growth. The adhesion and pro-angiogenic secretions of mouse fibroblasts cultured within the scaffolds can be controlled by switching the electrochemical state of the polymer prior to cell-seeding. In summary, these smart materials hold promise not only as extracellular matrix-mimicking structures for cell culture, but also as high-performance bioelectronic tools for diagnostic and signaling applications. References [1] M. Holzwarth, P. X. Ma, Journal of Materials Chemistry, 21, 10243-10251 (2011). [2] L. H. Jimison, J. Rivnay, R. M. Owens, in Organic

Functional aspects of cilia and tumor suppressors

NARCIS (Netherlands)

Basten, S.G.

2013-01-01

Sensing the cellular environment and responding accordingly is pivotal for tissue development and homeostasis. One cellular structure that functions almost exclusively as a sensory organelle is the nearly ubiquitously present primary cilium, that has been implicated in orchestrating cellular

EBER2 RNA-induced transcriptome changes identify cellular processes likely targeted during Epstein Barr Virus infection

Directory of Open Access Journals (Sweden)

Benecke Bernd-Joachim

2008-10-01

Full Text Available Abstract Background Little is known about the physiological role of the EBER1 and 2 nuclear RNAs during Epstein Barr viral infection. The EBERs are transcribed by cellular RNA Polymerase III and their strong expression results in 106 to 107 copies per EBV infected cell, making them reliable diagnostic markers for the presence of EBV. Although the functions of most of the proteins targeted by EBER RNAs have been studied, the role of EBERs themselves still remains elusive. Findings The cellular transcription response to EBER2 expression using the wild-type and an internal deletion mutant was determined. Significant changes in gene expression patterns were observed. A functional meta-analysis of the regulated genes points to inhibition of stress and immune responses, as well as activation of cellular growth and cytoskeletal reorganization as potential targets for EBER2 RNA. Different functions can be assigned to different parts of the RNA. Conclusion These results provide new avenues to the understanding of EBER2 and EBV biology, and set the grounds for a more in depth functional analysis of EBER2 using transcriptome activity measurements.

Effects of cryopreservation on excretory function, cellular adhesion molecules and vessel lumen formation in human umbilical vein endothelial cells.

Science.gov (United States)

Cai, Guoping; Lai, Binbin; Hong, Huaxing; Lin, Peng; Chen, Weifu; Zhu, Zhong; Chen, Haixiao

2017-07-01

Cryopreservation is widely used in regenerative medicine for tissue preservation. In the present study, the effects of cryopreservation on excretory function, cellular adhesion molecules and vessel lumen formation in human umbilical vein endothelial cells (HUVECs) were investigated. After 0, 4, 8, 12 or 24 weeks of cryopreservation in liquid nitrogen, the HUVECs were thawed. The excretory functions markers (endothelin‑1, prostaglandin E1, von Willebrand factor and nitric oxide) of HUVECs were measured by ELISA assay. The expression of intercellular adhesion molecule‑1 (ICAM‑1) in HUVECs was analyzed using flow cytometry. An angiogenesis assay was used to determine the angiogeneic capabilities of the thawed HUVECs. The results demonstrated that cryopreserved/thawed and recultivated HUVECs were unsuitable for tissue‑engineered microvascular construction. Specifically, the excretory function of the cells was significantly decreased in the post‑cryopreserved HUVECs at 24 weeks. In addition, the level of ICAM‑1 in HUVECs was significantly upregulated from the fourth week of cryopreservation. Furthermore, the tube‑like structure‑forming potential was weakened with increasing cryopreservation duration, and the numbers of lumen and the length of the pipeline were decreased in the thawed HUVECs, in a time‑dependent manner. In conclusion, the results of the present study revealed that prolonged cryopreservation may lead to HUVEC dysfunction and did not create stable cell lines for tissue‑engineered microvascular construction.

MIMO Communication for Cellular Networks

CERN Document Server

Huang, Howard; Venkatesan, Sivarama

2012-01-01

As the theoretical foundations of multiple-antenna techniques evolve and as these multiple-input multiple-output (MIMO) techniques become essential for providing high data rates in wireless systems, there is a growing need to understand the performance limits of MIMO in practical networks. To address this need, MIMO Communication for Cellular Networks presents a systematic description of MIMO technology classes and a framework for MIMO system design that takes into account the essential physical-layer features of practical cellular networks. In contrast to works that focus on the theoretical performance of abstract MIMO channels, MIMO Communication for Cellular Networks emphasizes the practical performance of realistic MIMO systems. A unified set of system simulation results highlights relative performance gains of different MIMO techniques and provides insights into how best to use multiple antennas in cellular networks under various conditions. MIMO Communication for Cellular Networks describes single-user,...

Efficient Radio Resource Allocation in a GSM and GPRS Cellular Network

Directory of Open Access Journals (Sweden)

David Vannucci

2004-10-01

Full Text Available This paper investigates the effect of various radio resource allocation strategies in a GSM/GPRS cellular network. The most efficient resource allocation is analysed as a function of the proportion of circuit switched voice and packet switched data load. The Grade of Service and average packet delay is investigated as a function of the load, packet size and call duration. Additionally, the feasibility of using voice over Internet Protocol as opposed to circuit switched voice is investigated as a means to increase subscriber capacity per base station. The work is motivated firstly by the complexity of having both circuit switched and packet switched connectivity on GSM/GPRS mobile cellular system and secondly that an exclusively packet based access on GSM/GPRS has the potential to increase the efficiency of resource utilisation by suitably varying the channel allocation to exploit the characteristics of voice and data traffic.

Nanomechanical and electrical characterization of a new cellular electret sensor-actuator

International Nuclear Information System (INIS)

Windmill, J F C; Zorab, A; Bedwell, D J; Robert, D

2008-01-01

Electrically charged cellular polymers are known to display pseudo-piezoelectric effects that endow them with interesting mechano-electrical characteristics. When a film of such a polymer is compressed, charge is generated across its thickness, and conversely, applying an oscillatory or static potential elicits mechanical motions. This dual sensor-actuator behaviour can be embedded in one material and presents distinct advantages of functional integration. A novel electroactive foam is presented here that embeds such a sensor-actuator function. The foam has a sensitivity constant (d 33 ) of 330 pC N -1 . Interestingly, the resonant behaviour of the cellular film can be altered by variation in the DC offset across the material. Such adaptive capacity could be of great advantage for tuning polymer-based mechanical devices to be either efficient sound radiators and mechanical actuators, or sensitive and coherent sensors. Possible applications in microfluidics are also discussed

Cellular telephones measure activity and lifespace in community-dwelling adults: proof of principle.

Science.gov (United States)

Schenk, Ana Katrin; Witbrodt, Bradley C; Hoarty, Carrie A; Carlson, Richard H; Goulding, Evan H; Potter, Jane F; Bonasera, Stephen J

2011-02-01

To describe a system that uses off-the-shelf sensor and telecommunication technologies to continuously measure individual lifespace and activity levels in a novel way. Proof of concept involving three field trials of 30, 30, and 21 days. Omaha, Nebraska, metropolitan and surrounding rural region. Three participants (48-year-old man, 33-year-old woman, and 27-year-old male), none with any functional limitations. Cellular telephones were used to detect in-home position and in-community location and to measure physical activity. Within the home, cellular telephones and Bluetooth transmitters (beacons) were used to locate participants at room-level resolution. Outside the home, the same cellular telephones and global positioning system (GPS) technology were used to locate participants at a community-level resolution. Physical activity was simultaneously measured using the cellular telephone accelerometer. This approach had face validity to measure activity and lifespace. More importantly, this system could measure the spatial and temporal organization of these metrics. For example, an individual's lifespace was automatically calculated across multiple time intervals. Behavioral time budgets showing how people allocate time to specific regions within the home were also automatically generated. Mobile monitoring shows much promise as an easily deployed system to quantify activity and lifespace, important indicators of function, in community-dwelling adults. © 2011, Copyright the Authors. Journal compilation © 2011, The American Geriatrics Society.

Multidimensional cellular automata and generalization of Fekete's lemma

Directory of Open Access Journals (Sweden)

Silvio Capobianco

2008-08-01

Full Text Available Fekete's lemma is a well known combinatorial result on number sequences: we extend it to functions defined on $d$-tuples of integers. As an application of the new variant, we show that nonsurjective $d$-dimensional cellular automata are characterized by loss of arbitrarily much information on finite supports, at a growth rate greater than that of the support's boundary determined by the automaton's neighbourhood index.

Cellular function reinstitution of offspring red blood cells cloned from the sickle cell disease patient blood post CRISPR genome editing

Directory of Open Access Journals (Sweden)

Jianguo Wen

2017-06-01

Full Text Available Abstract Background Sickle cell disease (SCD is a disorder of red blood cells (RBCs expressing abnormal hemoglobin-S (HbS due to genetic inheritance of homologous HbS gene. However, people with the sickle cell trait (SCT carry a single allele of HbS and do not usually suffer from SCD symptoms, thus providing a rationale to treat SCD. Methods To validate gene therapy potential, hematopoietic stem cells were isolated from the SCD patient blood and treated with CRISPR/Cas9 approach. To precisely dissect genome-editing effects, erythroid progenitor cells were cloned from single colonies of CRISPR-treated cells and then expanded for simultaneous gene, protein, and cellular function studies. Results Genotyping and sequencing analysis revealed that the genome-edited erythroid progenitor colonies were converted to SCT genotype from SCD genotype. HPLC protein assays confirmed reinstallation of normal hemoglobin at a similar level with HbS in the cloned genome-edited erythroid progenitor cells. For cell function evaluation, in vitro RBC differentiation of the cloned erythroid progenitor cells was induced. As expected, cell sickling assays indicated function reinstitution of the genome-edited offspring SCD RBCs, which became more resistant to sickling under hypoxia condition. Conclusions This study is an exploration of genome editing of SCD HSPCs.

Cellular mRNA decay factors involved in the hepatitis C virus life cycle

OpenAIRE

Mina Ibarra, Leonardo Bruno

2010-01-01

The group of positive strand RNA ((+)RNA) viruses includes numerous plant, animal and human pathogens such as the hepatitis C virus (HCV). Their viral genomes mimic cellular mRNAs, however, besides acting as messengers for translation of viral proteins, they also act as templates for viral replication. Since these two functions are mutually exclusive, a key step in the replication of all (+) RNA viruses is the regulated exit of the genomic RNAs from the cellular translation machinery to the v...

Cellular communications a comprehensive and practical guide

CERN Document Server

Tripathi, Nishith

2014-01-01

Even as newer cellular technologies and standards emerge, many of the fundamental principles and the components of the cellular network remain the same. Presenting a simple yet comprehensive view of cellular communications technologies, Cellular Communications provides an end-to-end perspective of cellular operations, ranging from physical layer details to call set-up and from the radio network to the core network. This self-contained source forpractitioners and students represents a comprehensive survey of the fundamentals of cellular communications and the landscape of commercially deployed

Magnetohydrodynamics cellular automata

International Nuclear Information System (INIS)

Hatori, Tadatsugu.

1990-02-01

There has been a renewal of interest in cellular automata, partly because they give an architecture for a special purpose computer with parallel processing optimized to solve a particular problem. The lattice gas cellular automata are briefly surveyed, which are recently developed to solve partial differential equations such as hydrodynamics or magnetohydrodynamics. A new model is given in the present paper to implement the magnetic Lorentz force in a more deterministic and local procedure than the previous one. (author)

Magnetohydrodynamic cellular automata

Energy Technology Data Exchange (ETDEWEB)

Hatori, Tadatsugu [National Inst. for Fusion Science, Nagoya (Japan)

1990-03-01

There has been a renewal of interest in cellular automata, partly because they give an architecture for a special purpose computer with parallel processing optimized to solve a particular problem. The lattice gas cellular automata are briefly surveyed, which are recently developed to solve partial differential equations such as hydrodynamics or magnetohydrodynamics. A new model is given in the present paper to implement the magnetic Lorentz force in a more deterministic and local procedure than the previous one. (author).

Magnetohydrodynamic cellular automata

International Nuclear Information System (INIS)

Hatori, Tadatsugu

1990-01-01

There has been a renewal of interest in cellular automata, partly because they give an architecture for a special purpose computer with parallel processing optimized to solve a particular problem. The lattice gas cellular automata are briefly surveyed, which are recently developed to solve partial differential equations such as hydrodynamics or magnetohydrodynamics. A new model is given in the present paper to implement the magnetic Lorentz force in a more deterministic and local procedure than the previous one. (author)

Modeling cellular systems

CERN Document Server

Matthäus, Franziska; Pahle, Jürgen

2017-01-01

This contributed volume comprises research articles and reviews on topics connected to the mathematical modeling of cellular systems. These contributions cover signaling pathways, stochastic effects, cell motility and mechanics, pattern formation processes, as well as multi-scale approaches. All authors attended the workshop on "Modeling Cellular Systems" which took place in Heidelberg in October 2014. The target audience primarily comprises researchers and experts in the field, but the book may also be beneficial for graduate students.

Cellular Angiofibroma of the Nasopharynx.

Science.gov (United States)

Erdur, Zülküf Burak; Yener, Haydar Murat; Yilmaz, Mehmet; Karaaltin, Ayşegül Batioğlu; Inan, Hakki Caner; Alaskarov, Elvin; Gozen, Emine Deniz

2017-11-01

Angiofibroma is a common tumor of the nasopharynx region but cellular type is extremely rare in head and neck. A 13-year-old boy presented with frequent epistaxis and nasal obstruction persisting for 6 months. According to the clinical symptoms and imaging studies juvenile angiofibroma was suspected. Following angiographic embolization total excision of the lesion by midfacial degloving approach was performed. Histological examination revealed that the tumor consisted of staghorn blood vessels and irregular fibrous stroma. Stellate fibroblasts with small pyknotic to large vesicular nuclei were seen in a highly cellular stroma. These findings identified cellular angiofibroma mimicking juvenile angiofibroma. This article is about a very rare patient of cellular angiofibroma of nasopharynx.

Mitochondrial dysfunction and cellular metabolic deficiency in Alzheimer's disease.

Science.gov (United States)

Gu, Xue-Mei; Huang, Han-Chang; Jiang, Zhao-Feng

2012-10-01

Alzheimer's disease (AD) is an age-related neurodegenerative disorder. The pathology of AD includes amyloid-β (Aβ) deposits in neuritic plaques and neurofibrillary tangles composed of hyperphosphorylated tau, as well as neuronal loss in specific brain regions. Increasing epidemiological and functional neuroimaging evidence indicates that global and regional disruptions in brain metabolism are involved in the pathogenesis of this disease. Aβ precursor protein is cleaved to produce both extracellular and intracellular Aβ, accumulation of which might interfere with the homeostasis of cellular metabolism. Mitochondria are highly dynamic organelles that not only supply the main energy to the cell but also regulate apoptosis. Mitochondrial dysfunction might contribute to Aβ neurotoxicity. In this review, we summarize the pathways of Aβ generation and its potential neurotoxic effects on cellular metabolism and mitochondrial dysfunction.

Research advances in cellular immunotherapy for primary hepatocellular carcinoma

Directory of Open Access Journals (Sweden)

ZHANG Ye

2014-09-01

Full Text Available The present therapy for primary hepatocellular carcinoma (HCC consists of surgery as well as local radiotherapy and chemotherapy. However, the majority of patients are susceptible to recurrence after comprehensive treatment, and the overall treatment outcome is not ideal due to the lack of effective drugs and strategies. Increasing evidence has demonstrated that the immune system is closely related to the development, progression, metastasis, and recurrence of HCC. Thus, immune therapy, especially cellular immunotherapy, could regulate immune function and induce specific antitumor immunity to achieve the goal of controlling HCC and reducing its recurrence and metastasis, which has become an essential part in the comprehensive treatment of HCC. The findings in preclinical and clinical studies on cellular immunotherapy for HCC data are reviewed, and the current problems are discussed.

Numerical calculations of effective elastic properties of two cellular structures

International Nuclear Information System (INIS)

Tuncer, Enis

2005-01-01

Young's moduli of regular two-dimensional truss-like and eye-shaped structures are simulated using the finite element method. The structures are idealizations of soft polymeric materials used in ferro-electret applications. In the simulations, the length scales of the smallest representative units are varied, which changes the dimensions of the cell walls in the structures. A power-law expression with a quadratic as the exponent term is proposed for the effective Young's moduli of the systems as a function of the solid volume fraction. The data are divided into three regions with respect to the volume fraction: low, intermediate and high. The parameters of the proposed power-law expression in each region are later represented as a function of the structural parameters, the unit-cell dimensions. The expression presented can be used to predict a structure/property relationship in materials with similar cellular structures. The contribution of the cell-wall thickness to the elastic properties becomes significant at concentrations >0.15. The cell-wall thickness is the most significant factor in predicting the effective Young's modulus of regular cellular structures at high volume fractions of solid. At lower concentrations of solid, the eye-shaped structure yields a lower Young's modulus than a truss-like structure with similar anisotropy. Comparison of the numerical results with those of experimental data for poly(propylene) show good agreement regarding the influence of cell-wall thickness on elastic properties of thin cellular films

47 CFR 22.923 - Cellular system configuration.

Science.gov (United States)

2010-10-01

... 47 Telecommunication 2 2010-10-01 2010-10-01 false Cellular system configuration. 22.923 Section... MOBILE SERVICES Cellular Radiotelephone Service § 22.923 Cellular system configuration. Mobile stations... directly or through cellular repeaters. Auxiliary test stations may communicate with base or mobile...

Ultraviolet Radiation: Cellular Antioxidant Response and the Role of Ocular Aldehyde Dehydrogenase Enzymes

Science.gov (United States)

Marchitti, Satori A.; Chen, Ying; Thompson, David C.; Vasiliou, Vasilis

2011-01-01

Solar ultraviolet radiation (UVR) exposes the human eye to near constant oxidative stress. Evidence suggests that UVR is the most important environmental insult leading to the development of a variety of ophthalmoheliosis disorders. UVR-induced reactive oxygen species are highly reactive with DNA, proteins and cellular membranes, resulting in cellular and tissue damage. Antioxidant defense systems present in ocular tissues function to combat reactive oxygen species and protect the eye from oxidative damage. Important enzymatic antioxidants are the superoxide dismutases, catalase, glutathione peroxidases, glutathione reductase and members of the aldehyde dehydrogenase (ALDH) superfamily. Glutathione, ascorbic and uric acids, α-tocopherol, NADPH and ferritin serve as small molecule, nonenzymatic antioxidants. Ocular tissues have high levels of these antioxidants which are essential for the maintenance of redox homeostasis in the eye and protection against oxidative damage. ALDH1A1 and ALDH3A1, present abundantly in the cornea and lens, have been shown to have unique roles in the defense against UVR and the downstream effects of oxidative stress. This review presents the properties and functions of ocular antioxidants that play critical roles in the cellular response to UVR exposure, including a focused discussion of the unique roles that the ALDH1A1 and ALDH3A1 enzymes have as multi-functional ocular antioxidants. PMID:21670692

Cell-Specific Establishment of Poliovirus Resistance to an Inhibitor Targeting a Cellular Protein

Science.gov (United States)

Viktorova, Ekaterina G.; Nchoutmboube, Jules; Ford-Siltz, Lauren A.

2015-01-01

ABSTRACT It is hypothesized that targeting stable cellular factors involved in viral replication instead of virus-specific proteins may raise the barrier for development of resistant mutants, which is especially important for highly adaptable small (+)RNA viruses. However, contrary to this assumption, the accumulated evidence shows that these viruses easily generate mutants resistant to the inhibitors of cellular proteins at least in some systems. We investigated here the development of poliovirus resistance to brefeldin A (BFA), an inhibitor of the cellular protein GBF1, a guanine nucleotide exchange factor for the small cellular GTPase Arf1. We found that while resistant viruses can be easily selected in HeLa cells, they do not emerge in Vero cells, in spite that in the absence of the drug both cultures support robust virus replication. Our data show that the viral replication is much more resilient to BFA than functioning of the cellular secretory pathway, suggesting that the role of GBF1 in the viral replication is independent of its Arf activating function. We demonstrate that the level of recruitment of GBF1 to the replication complexes limits the establishment and expression of a BFA resistance phenotype in both HeLa and Vero cells. Moreover, the BFA resistance phenotype of poliovirus mutants is also cell type dependent in different cells of human origin and results in a fitness loss in the form of reduced efficiency of RNA replication in the absence of the drug. Thus, a rational approach to the development of host-targeting antivirals may overcome the superior adaptability of (+)RNA viruses. IMPORTANCE Compared to the number of viral diseases, the number of available vaccines is miniscule. For some viruses vaccine development has not been successful after multiple attempts, and for many others vaccination is not a viable option. Antiviral drugs are needed for clinical practice and public health emergencies. However, viruses are highly adaptable and can

Are cellular phone blocking applications effective for novice teen drivers?

Science.gov (United States)

Creaser, Janet I; Edwards, Christopher J; Morris, Nichole L; Donath, Max

2015-09-01

Distracted driving is a significant concern for novice teen drivers. Although cellular phone bans are applied in many jurisdictions to restrict cellular phone use, teen drivers often report making calls and texts while driving. The Minnesota Teen Driver Study incorporated cellular phone blocking functions via a software application for 182 novice teen drivers in two treatment conditions. The first condition included 92 teens who ran a driver support application on a smartphone that also blocked phone usage. The second condition included 90 teens who ran the same application with phone blocking but which also reported back to parents about monitored risky behaviors (e.g., speeding). A third control group consisting of 92 novice teen drivers had the application and phone-based software installed on the phones to record cellular phone (but not block it) use while driving. The two treatment groups made significantly fewer calls and texts per mile driven compared to the control group. The control group data also demonstrated a higher propensity to text while driving rather than making calls. Software that blocks cellular phone use (except 911) while driving can be effective at mitigating calling and texting for novice teen drivers. However, subjective data indicates that some teens were motivated to find ways around the software, as well as to use another teen's phone while driving when they were unable to use theirs. Cellular phone bans for calling and texting are the first step to changing behaviors associated with texting and driving, particularly among novice teen drivers. Blocking software has the additional potential to reduce impulsive calling and texting while driving among novice teen drivers who might logically know the risks, but for whom it is difficult to ignore calling or texting while driving. Copyright © 2015 Elsevier Ltd and National Safety Council. All rights reserved.

Recursive definition of global cellular-automata mappings

International Nuclear Information System (INIS)

Feldberg, R.; Knudsen, C.; Rasmussen, S.

1994-01-01

A method for a recursive definition of global cellular-automata mappings is presented. The method is based on a graphical representation of global cellular-automata mappings. For a given cellular-automaton rule the recursive algorithm defines the change of the global cellular-automaton mapping as the number of lattice sites is incremented. A proof of lattice size invariance of global cellular-automata mappings is derived from an approximation to the exact recursive definition. The recursive definitions are applied to calculate the fractal dimension of the set of reachable states and of the set of fixed points of cellular automata on an infinite lattice

Cellular metabolic rate is influenced by life-history traits in tropical and temperate birds.

Science.gov (United States)

Jimenez, Ana Gabriela; Van Brocklyn, James; Wortman, Matthew; Williams, Joseph B

2014-01-01

In general, tropical birds have a "slow pace of life," lower rates of whole-animal metabolism and higher survival rates, than temperate species. A fundamental challenge facing physiological ecologists is the understanding of how variation in life-history at the whole-organism level might be linked to cellular function. Because tropical birds have lower rates of whole-animal metabolism, we hypothesized that cells from tropical species would also have lower rates of cellular metabolism than cells from temperate species of similar body size and common phylogenetic history. We cultured primary dermal fibroblasts from 17 tropical and 17 temperate phylogenetically-paired species of birds in a common nutritive and thermal environment and then examined basal, uncoupled, and non-mitochondrial cellular O2 consumption (OCR), proton leak, and anaerobic glycolysis (extracellular acidification rates [ECAR]), using an XF24 Seahorse Analyzer. We found that multiple measures of metabolism in cells from tropical birds were significantly lower than their temperate counterparts. Basal and uncoupled cellular metabolism were 29% and 35% lower in cells from tropical birds, respectively, a decrease closely aligned with differences in whole-animal metabolism between tropical and temperate birds. Proton leak was significantly lower in cells from tropical birds compared with cells from temperate birds. Our results offer compelling evidence that whole-animal metabolism is linked to cellular respiration as a function of an animal's life-history evolution. These findings are consistent with the idea that natural selection has uniquely fashioned cells of long-lived tropical bird species to have lower rates of metabolism than cells from shorter-lived temperate species.

Cellular metabolic rate is influenced by life-history traits in tropical and temperate birds.

Directory of Open Access Journals (Sweden)

Ana Gabriela Jimenez

Full Text Available In general, tropical birds have a "slow pace of life," lower rates of whole-animal metabolism and higher survival rates, than temperate species. A fundamental challenge facing physiological ecologists is the understanding of how variation in life-history at the whole-organism level might be linked to cellular function. Because tropical birds have lower rates of whole-animal metabolism, we hypothesized that cells from tropical species would also have lower rates of cellular metabolism than cells from temperate species of similar body size and common phylogenetic history. We cultured primary dermal fibroblasts from 17 tropical and 17 temperate phylogenetically-paired species of birds in a common nutritive and thermal environment and then examined basal, uncoupled, and non-mitochondrial cellular O2 consumption (OCR, proton leak, and anaerobic glycolysis (extracellular acidification rates [ECAR], using an XF24 Seahorse Analyzer. We found that multiple measures of metabolism in cells from tropical birds were significantly lower than their temperate counterparts. Basal and uncoupled cellular metabolism were 29% and 35% lower in cells from tropical birds, respectively, a decrease closely aligned with differences in whole-animal metabolism between tropical and temperate birds. Proton leak was significantly lower in cells from tropical birds compared with cells from temperate birds. Our results offer compelling evidence that whole-animal metabolism is linked to cellular respiration as a function of an animal's life-history evolution. These findings are consistent with the idea that natural selection has uniquely fashioned cells of long-lived tropical bird species to have lower rates of metabolism than cells from shorter-lived temperate species.

Cellular automata in cytoskeletal lattices

Energy Technology Data Exchange (ETDEWEB)

Smith, S A; Watt, R C; Hameroff, S R

1984-01-01

Cellular automata (CA) activities could mediate biological regulation and information processing via nonlinear electrodynamic effects in cytoskeletal lattice arrays. Frohlich coherent oscillations and other nonlinear mechanisms may effect discrete 10/sup -10/ to 10/sup -11/ s interval events which result in dynamic patterns in biolattices such as cylindrical protein polymers: microtubules (MT). Structural geometry and electrostatic forces of MT subunit dipole oscillations suggest neighbor rules among the hexagonally packed protein subunits. Computer simulations using these suggested rules and MT structural geometry demonstrate CA activities including dynamical and stable self-organizing patterns, oscillators, and traveling gliders. CA activities in MT and other cytoskeletal lattices may have important biological regulatory functions. 23 references, 6 figures, 1 table.

Cellular senescence and organismal aging.

Science.gov (United States)

Jeyapalan, Jessie C; Sedivy, John M

2008-01-01

Cellular senescence, first observed and defined using in vitro cell culture studies, is an irreversible cell cycle arrest which can be triggered by a variety of factors. Emerging evidence suggests that cellular senescence acts as an in vivo tumor suppression mechanism by limiting aberrant proliferation. It has also been postulated that cellular senescence can occur independently of cancer and contribute to the physiological processes of normal organismal aging. Recent data have demonstrated the in vivo accumulation of senescent cells with advancing age. Some characteristics of senescent cells, such as the ability to modify their extracellular environment, could play a role in aging and age-related pathology. In this review, we examine current evidence that links cellular senescence and organismal aging.

Generation and comprehensive analysis of an influenza virus polymerase cellular interaction network.

Science.gov (United States)

Tafforeau, Lionel; Chantier, Thibault; Pradezynski, Fabrine; Pellet, Johann; Mangeot, Philippe E; Vidalain, Pierre-Olivier; Andre, Patrice; Rabourdin-Combe, Chantal; Lotteau, Vincent

2011-12-01

The influenza virus transcribes and replicates its genome inside the nucleus of infected cells. Both activities are performed by the viral RNA-dependent RNA polymerase that is composed of the three subunits PA, PB1, and PB2, and recent studies have shown that it requires host cell factors to transcribe and replicate the viral genome. To identify these cellular partners, we generated a comprehensive physical interaction map between each polymerase subunit and the host cellular proteome. A total of 109 human interactors were identified by yeast two-hybrid screens, whereas 90 were retrieved by literature mining. We built the FluPol interactome network composed of the influenza virus polymerase (PA, PB1, and PB2) and the nucleoprotein NP and 234 human proteins that are connected through 279 viral-cellular protein interactions. Analysis of this interactome map revealed enriched cellular functions associated with the influenza virus polymerase, including host factors involved in RNA polymerase II-dependent transcription and mRNA processing. We confirmed that eight influenza virus polymerase-interacting proteins are required for virus replication and transcriptional activity of the viral polymerase. These are involved in cellular transcription (C14orf166, COPS5, MNAT1, NMI, and POLR2A), translation (EIF3S6IP), nuclear transport (NUP54), and DNA repair (FANCG). Conversely, we identified PRKRA, which acts as an inhibitor of the viral polymerase transcriptional activity and thus is required for the cellular antiviral response.

PDGF-AA-induced filamentous mitochondria benefit dermal papilla cells in cellular migration.

Science.gov (United States)

Mifude, C; Kaseda, K

2015-06-01

Human dermal papilla cells (HDPCs) play essential roles in hair follicular morphogenesis and postnatal hair growth cycles. Previous reports demonstrated that platelet-derived growth factor-AA (PDGF-AA) enhanced the formation of dermal condensates in hair follicular development. Additionally, PDGF-AA induces/maintains the anagen phase of the hair cycle. It is likely that mitochondrial morphology and functions are tightly coupled with maintenance of these energy-demanding activities. However, little is known about the mitochondrial regulation in HDPCs. Thus, we investigated the PDGF-involved mitochondrial regulation in HDPCs. The mitochondrial morphologies of HDPCs were examined in the presence or absence of PDGF-AA under a fluorescent microscope. ATP production and cellular motility were investigated. The relationship between mitochondrial morphology and the cellular functions was discussed. We observed that primary HDPCs contained mitochondria with filamentous and/or rounded morphologies. Both types of mitochondria showed similar membrane potentials. Interestingly, in the presence of PDGF-AA, but not PDGF-BB, the balance between the two morphologies shifted towards the filamentous form. Concomitantly, both mitochondrial enzymatic activity and total cellular ATP level were augmented by PDGF-AA. These two parameters were closely correlated, suggesting the mitochondrial involvement in the PDGF-augmented ATP production. Moreover, PDGF-AA accelerated the migration of HDPCs in a gap-filling assay, but did not change the rate of cellular proliferation. Notably, filamentous mitochondria dominated migrating HDPCs. PDGF-AA benefits HDPCs in the process of migration, by increasing the number of filamentous mitochondria. © 2014 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

HAVCR1 (CD365) and Its Mouse Ortholog Are Functional Hepatitis A Virus (HAV) Cellular Receptors That Mediate HAV Infection.

Science.gov (United States)

Costafreda, Maria Isabel; Kaplan, Gerardo

2018-05-01

The hepatitis A virus (HAV) cellular receptor 1 (HAVCR1), classified as CD365, was initially discovered as an HAV cellular receptor using an expression cloning strategy. Due to the lack of HAV receptor-negative replication-competent cells, it was not possible to fully prove that HAVCR1 was a functional HAV receptor. However, biochemistry, classical virology, and epidemiology studies further supported the functional role of HAVCR1 as an HAV receptor. Here, we show that an anti-HAVCR1 monoclonal antibody that protected African green monkey kidney (AGMK) cells against HAV infection only partially protected monkey Vero E6 cells and human hepatoma Huh7 cells, indicating that these two cell lines express alternative yet unidentified HAV receptors. Therefore, we focused our work on AGMK cells to further characterize the function of HAVCR1 as an HAV receptor. Advances in clustered regularly interspaced short palindromic repeat/Cas9 technology allowed us to knock out the monkey ortholog of HAVCR1 in AGMK cells. The resulting AGMK HAVCR1 knockout (KO) cells lost susceptibility to HAV infection, including HAV-free viral particles (vpHAV) and exosomes purified from HAV-infected cells (exo-HAV). Transfection of HAVCR1 cDNA into AGMK HAVCR1 KO cells restored susceptibility to vpHAV and exo-HAV infection. Furthermore, transfection of the mouse ortholog of HAVCR1, mHavcr1, also restored the susceptibility of AGMK HAVCR1 KO cells to HAV infection. Taken together, our data clearly show that HAVCR1 and mHavcr1 are functional HAV receptors that mediate HAV infection. This work paves the way for the identification of alternative HAV receptors to gain a complete understanding of their interplay with HAVCR1 in the cell entry and pathogenic processes of HAV. IMPORTANCE HAVCR1, an HAV receptor, is expressed in different cell types, including regulatory immune cells and antigen-presenting cells. How HAV evades the immune response during a long incubation period of up to 4 weeks and the

Zeno's paradox in quantum cellular automata

Energy Technology Data Exchange (ETDEWEB)

Groessing, G [Atominst. der Oesterreichischen Universitaeten, Vienna (Austria); Zeilinger, A [Inst. fuer Experimentalphysik, Univ. Innsbruck (Austria)

1991-07-01

The effect of Zeno's paradox in quantum theory is demonstrated with the aid of quantum mechanical cellular automata. It is shown that the degree of non-unitarity of the cellular automaton evolution and the frequency of consecutive measurements of cellular automaton states are operationally indistinguishable. (orig.).

Zeno's paradox in quantum cellular automata

International Nuclear Information System (INIS)

Groessing, G.; Zeilinger, A.

1991-01-01

The effect of Zeno's paradox in quantum theory is demonstrated with the aid of quantum mechanical cellular automata. It is shown that the degree of non-unitarity of the cellular automaton evolution and the frequency of consecutive measurements of cellular automaton states are operationally indistinguishable. (orig.)

Cellular Metabolic Rate Is Influenced by Life-History Traits in Tropical and Temperate Birds

OpenAIRE

Jimenez, Ana Gabriela; Van Brocklyn, James; Wortman, Matthew; Williams, Joseph B.

2014-01-01

In general, tropical birds have a "slow pace of life," lower rates of whole-animal metabolism and higher survival rates, than temperate species. A fundamental challenge facing physiological ecologists is the understanding of how variation in life-history at the whole-organism level might be linked to cellular function. Because tropical birds have lower rates of whole-animal metabolism, we hypothesized that cells from tropical species would also have lower rates of cellular metabolism than cel...

Redox Regulation of Mitochondrial Function

Science.gov (United States)

Handy, Diane E.

2012-01-01

Abstract Redox-dependent processes influence most cellular functions, such as differentiation, proliferation, and apoptosis. Mitochondria are at the center of these processes, as mitochondria both generate reactive oxygen species (ROS) that drive redox-sensitive events and respond to ROS-mediated changes in the cellular redox state. In this review, we examine the regulation of cellular ROS, their modes of production and removal, and the redox-sensitive targets that are modified by their flux. In particular, we focus on the actions of redox-sensitive targets that alter mitochondrial function and the role of these redox modifications on metabolism, mitochondrial biogenesis, receptor-mediated signaling, and apoptotic pathways. We also consider the role of mitochondria in modulating these pathways, and discuss how redox-dependent events may contribute to pathobiology by altering mitochondrial function. Antioxid. Redox Signal. 16, 1323–1367. PMID:22146081

TOR Complexes and the Maintenance of Cellular Homeostasis.

Science.gov (United States)

Eltschinger, Sandra; Loewith, Robbie

2016-02-01

The Target of Rapamycin (TOR) is a conserved serine/threonine (ser/thr) kinase that functions in two, distinct, multiprotein complexes called TORC1 and TORC2. Each complex regulates different aspects of eukaryote growth: TORC1 regulates cell volume and/or mass by influencing protein synthesis and turnover, while TORC2, as detailed in this review, regulates cell surface area by influencing lipid production and intracellular turgor. TOR complexes function in feedback loops, implying that downstream effectors are also likely to be involved in upstream regulation. In this regard, the notion that TORCs function primarily as mediators of cellular and organismal homeostasis is fundamentally different from the current, predominate view of TOR as a direct transducer of extracellular biotic and abiotic signals. Copyright © 2015 Elsevier Ltd. All rights reserved.

Validation of self-reported cellular phone use

DEFF Research Database (Denmark)

Samkange-Zeeb, Florence; Berg, Gabriele; Blettner, Maria

2004-01-01

BACKGROUND: In recent years, concern has been raised over possible adverse health effects of cellular telephone use. In epidemiological studies of cancer risk associated with the use of cellular telephones, the validity of self-reported cellular phone use has been problematic. Up to now there is ......BACKGROUND: In recent years, concern has been raised over possible adverse health effects of cellular telephone use. In epidemiological studies of cancer risk associated with the use of cellular telephones, the validity of self-reported cellular phone use has been problematic. Up to now...... there is very little information published on this subject. METHODS: We conducted a study to validate the questionnaire used in an ongoing international case-control study on cellular phone use, the "Interphone study". Self-reported cellular phone use from 68 of 104 participants who took part in our study...... was compared with information derived from the network providers over a period of 3 months (taken as the gold standard). RESULTS: Using Spearman's rank correlation, the correlation between self-reported phone use and information from the network providers for cellular phone use in terms of the number of calls...

Stability analysis for cellular neural networks with variable delays

International Nuclear Information System (INIS)

Zhang Qiang; Wei Xiaopeng; Xu Jin

2006-01-01

Some sufficient conditions for the global exponential stability of cellular neural networks with variable delay are obtained by means of a method based on delay differential inequality. The method, which does not make use of Lyapunov functionals, is simple and effective for the stability analysis of neural networks with delay. Some previously established results in the literature are shown to be special cases of the presented result

47 CFR 90.672 - Unacceptable interference to non-cellular 800 MHz licensees from 800 MHz cellular systems or part...

Science.gov (United States)

2010-10-01

... 47 Telecommunication 5 2010-10-01 2010-10-01 false Unacceptable interference to non-cellular 800 MHz licensees from 800 MHz cellular systems or part 22 Cellular Radiotelephone systems, and within the... Procedures and Process-Unacceptable Interference § 90.672 Unacceptable interference to non-cellular 800 MHz...

Modeling integrated cellular machinery using hybrid Petri-Boolean networks.

Directory of Open Access Journals (Sweden)

Natalie Berestovsky

Full Text Available The behavior and phenotypic changes of cells are governed by a cellular circuitry that represents a set of biochemical reactions. Based on biological functions, this circuitry is divided into three types of networks, each encoding for a major biological process: signal transduction, transcription regulation, and metabolism. This division has generally enabled taming computational complexity dealing with the entire system, allowed for using modeling techniques that are specific to each of the components, and achieved separation of the different time scales at which reactions in each of the three networks occur. Nonetheless, with this division comes loss of information and power needed to elucidate certain cellular phenomena. Within the cell, these three types of networks work in tandem, and each produces signals and/or substances that are used by the others to process information and operate normally. Therefore, computational techniques for modeling integrated cellular machinery are needed. In this work, we propose an integrated hybrid model (IHM that combines Petri nets and Boolean networks to model integrated cellular networks. Coupled with a stochastic simulation mechanism, the model simulates the dynamics of the integrated network, and can be perturbed to generate testable hypotheses. Our model is qualitative and is mostly built upon knowledge from the literature and requires fine-tuning of very few parameters. We validated our model on two systems: the transcriptional regulation of glucose metabolism in human cells, and cellular osmoregulation in S. cerevisiae. The model produced results that are in very good agreement with experimental data, and produces valid hypotheses. The abstract nature of our model and the ease of its construction makes it a very good candidate for modeling integrated networks from qualitative data. The results it produces can guide the practitioner to zoom into components and interconnections and investigate them

Determining the sub-cellular localization of proteins within Caenorhabditis elegans body wall muscle.

Science.gov (United States)

Meissner, Barbara; Rogalski, Teresa; Viveiros, Ryan; Warner, Adam; Plastino, Lorena; Lorch, Adam; Granger, Laure; Segalat, Laurent; Moerman, Donald G

2011-01-01

Determining the sub-cellular localization of a protein within a cell is often an essential step towards understanding its function. In Caenorhabditis elegans, the relatively large size of the body wall muscle cells and the exquisite organization of their sarcomeres offer an opportunity to identify the precise position of proteins within cell substructures. Our goal in this study is to generate a comprehensive "localizome" for C. elegans body wall muscle by GFP-tagging proteins expressed in muscle and determining their location within the cell. For this project, we focused on proteins that we know are expressed in muscle and are orthologs or at least homologs of human proteins. To date we have analyzed the expression of about 227 GFP-tagged proteins that show localized expression in the body wall muscle of this nematode (e.g. dense bodies, M-lines, myofilaments, mitochondria, cell membrane, nucleus or nucleolus). For most proteins analyzed in this study no prior data on sub-cellular localization was available. In addition to discrete sub-cellular localization we observe overlapping patterns of localization including the presence of a protein in the dense body and the nucleus, or the dense body and the M-lines. In total we discern more than 14 sub-cellular localization patterns within nematode body wall muscle. The localization of this large set of proteins within a muscle cell will serve as an invaluable resource in our investigation of muscle sarcomere assembly and function.

Understanding D-Ribose and Mitochondrial Function

Directory of Open Access Journals (Sweden)

Diane E. Mahoney

2018-02-01

Full Text Available Mitochondria are important organelles referred to as cellular powerhouses for their unique properties of cellular energy production.  With many pathologic conditions and aging, mitochondrial function declines, and there is a reduction in the production of adenosine triphosphate. The energy carrying molecule generated by cellular respiration and by pentose phosphate pathway, an alternative pathway of glucose metabolism. D-ribose is a naturally occurring monosaccharide found in the cells and particularly in the mitochondria is essential in energy production. Without sufficient energy, cells cannot maintain integrity and function. Supplemental D-ribose has been shown to improve cellular processes when there is mitochondrial dysfunction. When individuals take supplemental D-ribose, it can bypass part of the pentose pathway to produce D-ribose-5-phosphate for the production of energy. In this article, we review how energy is produced by cellular respiration, the pentose pathway, and the use of supplemental D-ribose.

Global exponential stability for nonautonomous cellular neural networks with delays

International Nuclear Information System (INIS)

Zhang Qiang; Wei Xiaopeng; Xu Jin

2006-01-01

In this Letter, by utilizing Lyapunov functional method and Halanay inequalities, we analyze global exponential stability of nonautonomous cellular neural networks with delay. Several new sufficient conditions ensuring global exponential stability of the network are obtained. The results given here extend and improve the earlier publications. An example is given to demonstrate the effectiveness of the obtained results

Origami interleaved tube cellular materials

International Nuclear Information System (INIS)

Cheung, Kenneth C; Tachi, Tomohiro; Calisch, Sam; Miura, Koryo

2014-01-01

A novel origami cellular material based on a deployable cellular origami structure is described. The structure is bi-directionally flat-foldable in two orthogonal (x and y) directions and is relatively stiff in the third orthogonal (z) direction. While such mechanical orthotropicity is well known in cellular materials with extruded two dimensional geometry, the interleaved tube geometry presented here consists of two orthogonal axes of interleaved tubes with high interfacial surface area and relative volume that changes with fold-state. In addition, the foldability still allows for fabrication by a flat lamination process, similar to methods used for conventional expanded two dimensional cellular materials. This article presents the geometric characteristics of the structure together with corresponding kinematic and mechanical modeling, explaining the orthotropic elastic behavior of the structure with classical dimensional scaling analysis. (paper)

Origami interleaved tube cellular materials

Science.gov (United States)

Cheung, Kenneth C.; Tachi, Tomohiro; Calisch, Sam; Miura, Koryo

2014-09-01

A novel origami cellular material based on a deployable cellular origami structure is described. The structure is bi-directionally flat-foldable in two orthogonal (x and y) directions and is relatively stiff in the third orthogonal (z) direction. While such mechanical orthotropicity is well known in cellular materials with extruded two dimensional geometry, the interleaved tube geometry presented here consists of two orthogonal axes of interleaved tubes with high interfacial surface area and relative volume that changes with fold-state. In addition, the foldability still allows for fabrication by a flat lamination process, similar to methods used for conventional expanded two dimensional cellular materials. This article presents the geometric characteristics of the structure together with corresponding kinematic and mechanical modeling, explaining the orthotropic elastic behavior of the structure with classical dimensional scaling analysis.

Estimating cellular network performance during hurricanes

International Nuclear Information System (INIS)

Booker, Graham; Torres, Jacob; Guikema, Seth; Sprintson, Alex; Brumbelow, Kelly

2010-01-01

Cellular networks serve a critical role during and immediately after a hurricane, allowing citizens to contact emergency services when land-line communication is lost and serving as a backup communication channel for emergency responders. However, due to their ubiquitous deployment and limited design for extreme loading events, basic network elements, such as cellular towers and antennas are prone to failures during adverse weather conditions such as hurricanes. Accordingly, a systematic and computationally feasible approach is required for assessing and improving the reliability of cellular networks during hurricanes. In this paper we develop a new multi-disciplinary approach to efficiently and accurately assess cellular network reliability during hurricanes. We show how the performance of a cellular network during and immediately after future hurricanes can be estimated based on a combination of hurricane wind field models, structural reliability analysis, Monte Carlo simulation, and cellular network models and simulation tools. We then demonstrate the use of this approach for assessing the improvement in system reliability that can be achieved with discrete topological changes in the system. Our results suggest that adding redundancy, particularly through a mesh topology or through the addition of an optical fiber ring around the perimeter of the system can be an effective way to significantly increase the reliability of some cellular systems during hurricanes.

Cellular reflectarray antenna and method of making same

Science.gov (United States)

Romanofsky, Robert R (Inventor)

2011-01-01

A method of manufacturing a cellular reflectarray antenna arranged in an m by n matrix of radiating elements for communication with a satellite includes steps of determining a delay .phi.m,n for each of said m by n matrix of elements of said cellular reflectarray antenna using sub-steps of: determining the longitude and latitude of operation, determining elevation and azimuth angles of the reflectarray with respect to the satellite and converting theta.sub.0 (.theta..sub.0) and phi.sub.0 (.phi..sub.0), determining .DELTA..beta..sub.m,n, the pointing vector correction, for a given inter-element spacing and wavelength, determining .DELTA..phi..sub.m,n, the spherical wave front correction factor, for a given radius from the central element and/or from measured data from the feed horn; and, determining a delay .phi.m,n for each of said m by n matrix of elements as a function of .DELTA..beta..sub.m,n and .DELTA..phi..sub.m,n.

Controlled cellular energy conversion in brown adipose tissue thermogenesis

Science.gov (United States)

Horowitz, J. M.; Plant, R. E.

1978-01-01

Brown adipose tissue serves as a model system for nonshivering thermogenesis (NST) since a) it has as a primary physiological function the conversion of chemical energy to heat; and b) preliminary data from other tissues involved in NST (e.g., muscle) indicate that parallel mechanisms may be involved. Now that biochemical pathways have been proposed for brown fat thermogenesis, cellular models consistent with a thermodynamic representation can be formulated. Stated concisely, the thermogenic mechanism in a brown fat cell can be considered as an energy converter involving a sequence of cellular events controlled by signals over the autonomic nervous system. A thermodynamic description for NST is developed in terms of a nonisothermal system under steady-state conditions using network thermodynamics. Pathways simulated include mitochondrial ATP synthesis, a Na+/K+ membrane pump, and ionic diffusion through the adipocyte membrane.

The application of multiple biophysical cues to engineer functional neocartilage for treatment of osteoarthritis. Part I: cellular response.

Science.gov (United States)

Brady, Mariea A; Waldman, Stephen D; Ethier, C Ross

2015-02-01

Osteoarthritis (OA) is a complex disease of the joint for which current treatments are unsatisfactory, thus motivating development of tissue engineering (TE)-based therapies. To date, TE strategies have had some success, developing replacement tissue constructs with biochemical properties approaching that of native cartilage. However, poor biomechanical properties and limited postimplantation integration with surrounding tissue are major shortcomings that need to be addressed. Functional tissue engineering strategies that apply physiologically relevant biophysical cues provide a platform to improve TE constructs before implantation. In the previous decade, new experimental and theoretical findings in cartilage biomechanics and electromechanics have emerged, resulting in an increased understanding of the complex interplay of multiple biophysical cues in the extracellular matrix of the tissue. The effect of biophysical stimulation on cartilage, and the resulting chondrocyte-mediated biosynthesis, remodeling, degradation, and repair, has, therefore, been extensively explored by the TE community. This article compares and contrasts the cellular response of chondrocytes to multiple biophysical stimuli, and may be read in conjunction with its companion paper that compares and contrasts the subsequent intracellular signal transduction cascades. Mechanical, magnetic, and electrical stimuli promote proliferation, differentiation, and maturation of chondrocytes within established dose parameters or "biological windows." This knowledge will provide a framework for ongoing studies incorporating multiple biophysical cues in TE functional neocartilage for treatment of OA.

The Die Is Cast: Precision Electrophilic Modifications Contribute to Cellular Decision Making.

Science.gov (United States)

Long, Marcus J C; Aye, Yimon

2016-10-02

This perspective sets out to critically evaluate the scope of reactive electrophilic small molecules as unique chemical signal carriers in biological information transfer cascades. We consider these electrophilic cues as a new volatile cellular currency and compare them to canonical signaling circulation such as phosphate in terms of chemical properties, biological specificity, sufficiency, and necessity. The fact that nonenzymatic redox sensing properties are found in proteins undertaking varied cellular tasks suggests that electrophile signaling is a moonlighting phenomenon manifested within a privileged set of sensor proteins. The latest interrogations into these on-target electrophilic responses set forth a new horizon in the molecular mechanism of redox signal propagation wherein direct low-occupancy electrophilic modifications on a single sensor target are biologically sufficient to drive functional redox responses with precision timing. We detail how the various mechanisms through which redox signals function could contribute to their interesting phenotypic responses, including hormesis.

The cellular memory disc of reprogrammed cells.

Science.gov (United States)

Anjamrooz, Seyed Hadi

2013-04-01

The crucial facts underlying the low efficiency of cellular reprogramming are poorly understood. Cellular reprogramming occurs in nuclear transfer, induced pluripotent stem cell (iPSC) formation, cell fusion, and lineage-switching experiments. Despite these advances, there are three fundamental problems to be addressed: (1) the majority of cells cannot be reprogrammed, (2) the efficiency of reprogramming cells is usually low, and (3) the reprogrammed cells developed from a patient's own cells activate immune responses. These shortcomings present major obstacles for using reprogramming approaches in customised cell therapy. In this Perspective, the author synthesises past and present observations in the field of cellular reprogramming to propose a theoretical picture of the cellular memory disc. The current hypothesis is that all cells undergo an endogenous and exogenous holographic memorisation such that parts of the cellular memory dramatically decrease the efficiency of reprogramming cells, act like a barrier against reprogramming in the majority of cells, and activate immune responses. Accordingly, the focus of this review is mainly to describe the cellular memory disc (CMD). Based on the present theory, cellular memory includes three parts: a reprogramming-resistance memory (RRM), a switch-promoting memory (SPM) and a culture-induced memory (CIM). The cellular memory arises genetically, epigenetically and non-genetically and affects cellular behaviours. [corrected].

Single Cell Force Spectroscopy for Quantification of Cellular Adhesion on Surfaces

Science.gov (United States)

Christenson, Wayne B.

Cell adhesion is an important aspect of many biological processes. The atomic force microscope (AFM) has made it possible to quantify the forces involved in cellular adhesion using a technique called single cell force spectroscopy (SCFS). AFM based SCFS offers versatile control over experimental conditions for probing directly the interaction between specific cell types and specific proteins, surfaces, or other cells. Transmembrane integrins are the primary proteins involved in cellular adhesion to the extra cellular matix (ECM). One of the chief integrins involved in the adhesion of leukocyte cells is alpha Mbeta2 (Mac-1). The experiments in this dissertation quantify the adhesion of Mac-1 expressing human embryonic kidney (HEK Mac-1), platelets, and neutrophils cells on substrates with different concentrations of fibrinogen and on fibrin gels and multi-layered fibrinogen coated fibrin gels. It was shown that multi-layered fibrinogen reduces the adhesion force of these cells considerably. A novel method was developed as part of this research combining total internal reflection microscopy (TIRFM) with SCFS allowing for optical microscopy of HEK Mac-1 cells interacting with bovine serum albumin (BSA) coated glass after interacting with multi-layered fibrinogen. HEK Mac-1 cells are able to remove fibrinogen molecules from the multi-layered fibrinogen matrix. An analysis methodology for quantifying the kinetic parameters of integrin-ligand interactions from SCFS experiments is proposed, and the kinetic parameters of the Mac-1 fibrinogen bond are quantified. Additional SCFS experiments quantify the adhesion of macrophages and HEK Mac-1 cells on functionalized glass surfaces and normal glass surfaces. Both cell types show highest adhesion on a novel functionalized glass surface that was prepared to induce macrophage fusion. These experiments demonstrate the versatility of AFM based SCFS, and how it can be applied to address many questions in cellular biology offering

Study of the influence of microgravity on the biological cells and molecular level; Seitai saibo bunshi level ni okeru bisho juryoku no eikyo ni kansuru kenkyu

Energy Technology Data Exchange (ETDEWEB)

NONE

1996-03-01

The shape of osteoblast, gene appearance, gene of rice blast, cellular fusion of plants, gravity acceptance mechanism of unicellular organisms, and physiological and immunity functions of mice were investigated under the microgravity condition. The influence of gravity on the vital reaction and the influence of microgravity on the crystallization of vital substances were also investigated. For the observation of osteoblast, the fluorescence dye reacted with Ca was well taken in the cells. The microgravity affected the stability of rice blast, but hardly affected the protoplast culture of mushroom. The reaction of ciliate against the gravity related to the specific gravity difference between cells and outer liquid. The level of adrenaline in blood of mice increased during the drop. The moving speed of trigger waves of chemical parallel slit formed at the BZ reaction under the microgravity became 60% to 80% of that on the ground. In the case of crystallization at the deposition agent concentration of 1% to 4%, the turbidity showing the degree of crystallization changed complicatedly. Nine processes of crystal growth were recognized. 21 refs., 55 figs., 1 tab.

Cosserat modeling of cellular solids

NARCIS (Netherlands)

Onck, P.R.

Cellular solids inherit their macroscopic mechanical properties directly from the cellular microstructure. However, the characteristic material length scale is often not small compared to macroscopic dimensions, which limits the applicability of classical continuum-type constitutive models. Cosserat

Recursive definition of global cellular-automata mappings

DEFF Research Database (Denmark)

Feldberg, Rasmus; Knudsen, Carsten; Rasmussen, Steen

1994-01-01

A method for a recursive definition of global cellular-automata mappings is presented. The method is based on a graphical representation of global cellular-automata mappings. For a given cellular-automaton rule the recursive algorithm defines the change of the global cellular-automaton mapping...... as the number of lattice sites is incremented. A proof of lattice size invariance of global cellular-automata mappings is derived from an approximation to the exact recursive definition. The recursive definitions are applied to calculate the fractal dimension of the set of reachable states and of the set...

Hepatitis C virus NS2 protein activates cellular cyclic AMP-dependent pathways

International Nuclear Information System (INIS)

Kim, Kyoung Mi; Kwon, Shi-Nae; Kang, Ju-Il; Lee, Song Hee; Jang, Sung Key; Ahn, Byung-Yoon; Kim, Yoon Ki

2007-01-01

Chronic infection of the hepatitis C virus (HCV) leads to liver cirrhosis and cancer. The mechanism leading to viral persistence and hepatocellular carcinoma, however, has not been fully understood. In this study, we show that the HCV infection activates cellular cAMP-dependent pathways. Expression of a luciferase reporter gene controlled by a basic promoter with the cAMP response element (CRE) was significantly elevated in human hepatoma Huh-7 cells infected with the HCV JFH1. Analysis with viral subgenomic replicons indicated that the HCV NS2 protein is responsible for the effect. Furthermore, the level of cellular transcripts whose stability is known to be regulated by cAMP was specifically reduced in cells harboring NS2-expressing replicons. These results allude to the HCV NS2 protein having a novel function of regulating cellular gene expression and proliferation through the cAMP-dependent pathway

Complex cellular logic computation using ribocomputing devices.

Science.gov (United States)

Green, Alexander A; Kim, Jongmin; Ma, Duo; Silver, Pamela A; Collins, James J; Yin, Peng

2017-08-03

Synthetic biology aims to develop engineering-driven approaches to the programming of cellular functions that could yield transformative technologies. Synthetic gene circuits that combine DNA, protein, and RNA components have demonstrated a range of functions such as bistability, oscillation, feedback, and logic capabilities. However, it remains challenging to scale up these circuits owing to the limited number of designable, orthogonal, high-performance parts, the empirical and often tedious composition rules, and the requirements for substantial resources for encoding and operation. Here, we report a strategy for constructing RNA-only nanodevices to evaluate complex logic in living cells. Our 'ribocomputing' systems are composed of de-novo-designed parts and operate through predictable and designable base-pairing rules, allowing the effective in silico design of computing devices with prescribed configurations and functions in complex cellular environments. These devices operate at the post-transcriptional level and use an extended RNA transcript to co-localize all circuit sensing, computation, signal transduction, and output elements in the same self-assembled molecular complex, which reduces diffusion-mediated signal losses, lowers metabolic cost, and improves circuit reliability. We demonstrate that ribocomputing devices in Escherichia coli can evaluate two-input logic with a dynamic range up to 900-fold and scale them to four-input AND, six-input OR, and a complex 12-input expression (A1 AND A2 AND NOT A1*) OR (B1 AND B2 AND NOT B2*) OR (C1 AND C2) OR (D1 AND D2) OR (E1 AND E2). Successful operation of ribocomputing devices based on programmable RNA interactions suggests that systems employing the same design principles could be implemented in other host organisms or in extracellular settings.

Progress in studies on nucleolus functions

International Nuclear Information System (INIS)

Chang Lei; Zhou Guangming

2011-01-01

Nucleoli is the sites for ribosome synthesis and processing, however, recent approaches have revealed that it is also involved in variety of cellular processes, especially the cellular stress response. As sensors, nucleoli regulate the localization of nucleolar proteins, such as (Alternate Reading Frame, ARF), and the activation of key factors, such as P53, and consequently mediate the cellular stress response.In this paper, recent progress in the studies on nucleolar functions in cellular stress response to radiation is reviewed. (authors)

Topology optimization of adaptive fluid-actuated cellular structures with arbitrary polygonal motor cells

International Nuclear Information System (INIS)

Lv, Jun; Tang, Liang; Li, Wenbo; Liu, Lei; Zhang, Hongwu

2016-01-01

This paper mainly focuses on the fast and efficient design method for plant bioinspired fluidic cellular materials and structures composed of polygonal motor cells. Here we developed a novel structural optimization method with arbitrary polygonal coarse-grid elements based on multiscale finite element frameworks. The fluidic cellular structures are meshed with irregular polygonal coarse-grid elements according to their natural size and the shape of the imbedded motor cells. The multiscale base functions of solid displacement and hydraulic pressure are then constructed to bring the small-scale information of the irregular motor cells to the large-scale simulations on the polygonal coarse-grid elements. On this basis, a new topology optimization method based on the resulting polygonal coarse-grid elements is proposed to determine the optimal distributions or number of motor cells in the smart cellular structures. Three types of optimization problems are solved according to the usages of the fluidic cellular structures. Firstly, the proposed optimization method is utilized to minimize the system compliance of the load-bearing fluidic cellular structures. Second, the method is further extended to design biomimetic compliant actuators of the fluidic cellular materials due to the fact that non-uniform volume expansions of fluid in the cells can induce elastic action. Third, the optimization problem focuses on the weight minimization of the cellular structure under the constraints for the compliance of the whole system. Several representative examples are investigated to validate the effectiveness of the proposed polygon-based topology optimization method of the smart materials. (paper)

Postischemic revascularization: from cellular and molecular mechanisms to clinical applications.

Science.gov (United States)

Silvestre, Jean-Sébastien; Smadja, David M; Lévy, Bernard I

2013-10-01

After the onset of ischemia, cardiac or skeletal muscle undergoes a continuum of molecular, cellular, and extracellular responses that determine the function and the remodeling of the ischemic tissue. Hypoxia-related pathways, immunoinflammatory balance, circulating or local vascular progenitor cells, as well as changes in hemodynamical forces within vascular wall trigger all the processes regulating vascular homeostasis, including vasculogenesis, angiogenesis, arteriogenesis, and collateral growth, which act in concert to establish a functional vascular network in ischemic zones. In patients with ischemic diseases, most of the cellular (mainly those involving bone marrow-derived cells and local stem/progenitor cells) and molecular mechanisms involved in the activation of vessel growth and vascular remodeling are markedly impaired by the deleterious microenvironment characterized by fibrosis, inflammation, hypoperfusion, and inhibition of endogenous angiogenic and regenerative programs. Furthermore, cardiovascular risk factors, including diabetes, hypercholesterolemia, hypertension, diabetes, and aging, constitute a deleterious macroenvironment that participates to the abrogation of postischemic revascularization and tissue regeneration observed in these patient populations. Thus stimulation of vessel growth and/or remodeling has emerged as a new therapeutic option in patients with ischemic diseases. Many strategies of therapeutic revascularization, based on the administration of growth factors or stem/progenitor cells from diverse sources, have been proposed and are currently tested in patients with peripheral arterial disease or cardiac diseases. This review provides an overview from our current knowledge regarding molecular and cellular mechanisms involved in postischemic revascularization, as well as advances in the clinical application of such strategies of therapeutic revascularization.

Evaluation of Structural Cellular Glass

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Adams, M. A.; Zwissler, J. G.

1984-01-01

Preliminary design information presented. First report discusses state of structural-cellular-glass programs as of June 1979. Second report gives further details of program to develop improved cellular glasses and to characterize properties of glasses and commercially available materials.

Computing by Temporal Order: Asynchronous Cellular Automata

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Michael Vielhaber

2012-08-01

Full Text Available Our concern is the behaviour of the elementary cellular automata with state set 0,1 over the cell set Z/nZ (one-dimensional finite wrap-around case, under all possible update rules (asynchronicity. Over the torus Z/nZ (n<= 11,we will see that the ECA with Wolfram rule 57 maps any v in F_2^n to any w in F_2^n, varying the update rule. We furthermore show that all even (element of the alternating group bijective functions on the set F_2^n = 0,...,2^n-1, can be computed by ECA57, by iterating it a sufficient number of times with varying update rules, at least for n <= 10. We characterize the non-bijective functions computable by asynchronous rules.

Cellular and chemical neuroscience of mammalian sleep.

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Datta, Subimal

2010-05-01

Extraordinary strides have been made toward understanding the complexities and regulatory mechanisms of sleep over the past two decades thanks to the help of rapidly evolving technologies. At its most basic level, mammalian sleep is a restorative process of the brain and body. Beyond its primary restorative purpose, sleep is essential for a number of vital functions. Our primary research interest is to understand the cellular and molecular mechanisms underlying the regulation of sleep and its cognitive functions. Here I will reflect on our own research contributions to 50 years of extraordinary advances in the neurobiology of slow-wave sleep (SWS) and rapid eye movement (REM) sleep regulation. I conclude this review by suggesting some potential future directions to further our understanding of the neurobiology of sleep. Copyright 2010 Elsevier B.V. All rights reserved.

Epigenetics and Cellular Metabolism

OpenAIRE

Wenyi Xu; Fengzhong Wang; Zhongsheng Yu; Fengjiao Xin

2016-01-01

Living eukaryotic systems evolve delicate cellular mechanisms for responding to various environmental signals. Among them, epigenetic machinery (DNA methylation, histone modifications, microRNAs, etc.) is the hub in transducing external stimuli into transcriptional response. Emerging evidence reveals the concept that epigenetic signatures are essential for the proper maintenance of cellular metabolism. On the other hand, the metabolite, a main environmental input, can also influence the proce...

Open-cellular copper structures fabricated by additive manufacturing using electron beam melting

International Nuclear Information System (INIS)

Ramirez, D.A.; Murr, L.E.; Li, S.J.; Tian, Y.X.; Martinez, E.; Martinez, J.L.; Machado, B.I.; Gaytan, S.M.; Medina, F.; Wicker, R.B.

2011-01-01

Highlights: → Relative stiffness versus relative density measurements for reticulated mesh and stochastic open cellular copper were shown to follow the Gibson-Ashby foam model. → Microstructures for the mesh struts and foam ligaments illustrated a propensity of copper oxide precipitates which provided structural hardness and strength. → These components, fabricated by electron beam melting, exhibit interesting prospects for specialized, complex heat-transfer devices. - Abstract: Cu reticulated mesh and stochastic open cellular foams were fabricated by additive manufacturing using electron beam melting. Fabricated densities ranged from 0.73 g/cm 3 to 6.67 g/cm 3 . The precursor Cu powder contained Cu 2 O precipitates and the fabricated components contained arrays of Cu 2 O precipitates and interconnected dislocation microstructures having average spacings of ∼2 μm, which provide hardness values ∼75% above commercial Cu products. Plots of stiffness (Young's modulus) versus density and relative stiffness versus relative density were in very close agreement with the Gibson-Ashby model for open cellular foams. These open cellular structure components exhibit considerable potential for novel, complex, multi-functional electrical and thermal management systems, especially complex, monolithic heat exchange devices.

Cellular Metabolic Rate Is Influenced by Life-History Traits in Tropical and Temperate Birds

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Jimenez, Ana Gabriela; Van Brocklyn, James; Wortman, Matthew; Williams, Joseph B.

2014-01-01

In general, tropical birds have a “slow pace of life,” lower rates of whole-animal metabolism and higher survival rates, than temperate species. A fundamental challenge facing physiological ecologists is the understanding of how variation in life-history at the whole-organism level might be linked to cellular function. Because tropical birds have lower rates of whole-animal metabolism, we hypothesized that cells from tropical species would also have lower rates of cellular metabolism than cells from temperate species of similar body size and common phylogenetic history. We cultured primary dermal fibroblasts from 17 tropical and 17 temperate phylogenetically-paired species of birds in a common nutritive and thermal environment and then examined basal, uncoupled, and non-mitochondrial cellular O2 consumption (OCR), proton leak, and anaerobic glycolysis (extracellular acidification rates [ECAR]), using an XF24 Seahorse Analyzer. We found that multiple measures of metabolism in cells from tropical birds were significantly lower than their temperate counterparts. Basal and uncoupled cellular metabolism were 29% and 35% lower in cells from tropical birds, respectively, a decrease closely aligned with differences in whole-animal metabolism between tropical and temperate birds. Proton leak was significantly lower in cells from tropical birds compared with cells from temperate birds. Our results offer compelling evidence that whole-animal metabolism is linked to cellular respiration as a function of an animal’s life-history evolution. These findings are consistent with the idea that natural selection has uniquely fashioned cells of long-lived tropical bird species to have lower rates of metabolism than cells from shorter-lived temperate species. PMID:24498080

From "Cellular" RNA to "Smart" RNA: Multiple Roles of RNA in Genome Stability and Beyond.

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Michelini, Flavia; Jalihal, Ameya P; Francia, Sofia; Meers, Chance; Neeb, Zachary T; Rossiello, Francesca; Gioia, Ubaldo; Aguado, Julio; Jones-Weinert, Corey; Luke, Brian; Biamonti, Giuseppe; Nowacki, Mariusz; Storici, Francesca; Carninci, Piero; Walter, Nils G; Fagagna, Fabrizio d'Adda di

2018-03-30

Coding for proteins has been considered the main function of RNA since the "central dogma" of biology was proposed. The discovery of noncoding transcripts shed light on additional roles of RNA, ranging from the support of polypeptide synthesis, to the assembly of subnuclear structures, to gene expression modulation. Cellular RNA has therefore been recognized as a central player in often unanticipated biological processes, including genomic stability. This ever-expanding list of functions inspired us to think of RNA as a "smart" phone, which has replaced the older obsolete "cellular" phone. In this review, we summarize the last two decades of advances in research on the interface between RNA biology and genome stability. We start with an account of the emergence of noncoding RNA, and then we discuss the involvement of RNA in DNA damage signaling and repair, telomere maintenance, and genomic rearrangements. We continue with the depiction of single-molecule RNA detection techniques, and we conclude by illustrating the possibilities of RNA modulation in hopes of creating or improving new therapies. The widespread biological functions of RNA have made this molecule a reoccurring theme in basic and translational research, warranting it the transcendence from classically studied "cellular" RNA to "smart" RNA.

Label-Free Analysis of Cellular Lipid Droplet Formation by Non-Linear Microscopy

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Schie, Iwan W.

Cellular lipid droplets (LD) are cellular organelles that can be found in every cell type. Recent research indicates that cellular LD are involved in a large number of cellular metabolic functions, such as lipid metabolism, protection from lipotoxicity, protein storage and degradation, and many more. LD formation is frequently associated with adverse health effects, i.e. alcoholic and non-alcoholic fatty liver disease, diabetes type-2, as well as many cardiovascular disorders. Despite their wide presence, LDs are the least studied and most poorly understood cellular organelles. Typically, LDs are investigated using fluorescence-based techniques that require staining with exogenous fluorophores. Other techniques, e.g. biochemical assays, require the destruction of cells that prohibit the analysis of living cells. Therefore, in my thesis research I developed a novel compound fast-scanning nonlinear optical microscope equipped with the ability to also acquire Raman spectra at specific image locations. This system allows us to image label-free cellular LD formation in living cells and analyze the composition of single cellular LDs. Images can be acquired at near video-rate (˜16 frames/s). Furthermore, the system has the ability to acquire very large images of tissue of up to 7.5x15 cm2 total area by stitching together scans with dimensions of 1x1 mm2 in less than 1 minute. The system also enables the user to acquire Raman spectra from points of interest in the multiphoton images and provides chemically-specific data from sample volumes as small as 1 femtoliter. In my thesis I used this setup to determine the effects of VLDL lipolysis products on primary rat hepatocytes. By analyzing the Raman spectra and comparing the peak ratios for saturated and unsaturated fatty acid it was determined that the small cellular LD are highly saturated, while large cellular LDs contain mostly unsaturated lipids. Furthermore, I established a method to determine the specific contribution

Modeling the mechanics of cancer: effect of changes in cellular and extra-cellular mechanical properties.

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Katira, Parag; Bonnecaze, Roger T; Zaman, Muhammad H

2013-01-01

Malignant transformation, though primarily driven by genetic mutations in cells, is also accompanied by specific changes in cellular and extra-cellular mechanical properties such as stiffness and adhesivity. As the transformed cells grow into tumors, they interact with their surroundings via physical contacts and the application of forces. These forces can lead to changes in the mechanical regulation of cell fate based on the mechanical properties of the cells and their surrounding environment. A comprehensive understanding of cancer progression requires the study of how specific changes in mechanical properties influences collective cell behavior during tumor growth and metastasis. Here we review some key results from computational models describing the effect of changes in cellular and extra-cellular mechanical properties and identify mechanistic pathways for cancer progression that can be targeted for the prediction, treatment, and prevention of cancer.

Design mobile satellite system architecture as an integral part of the cellular access digital network

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Chien, E. S. K.; Marinho, J. A.; Russell, J. E., Sr.

1988-01-01

The Cellular Access Digital Network (CADN) is the access vehicle through which cellular technology is brought into the mainstream of the evolving integrated telecommunications network. Beyond the integrated end-to-end digital access and per call network services provisioning of the Integrated Services Digital Network (ISDN), the CADN engenders the added capability of mobility freedom via wireless access. One key element of the CADN network architecture is the standard user to network interface that is independent of RF transmission technology. Since the Mobile Satellite System (MSS) is envisioned to not only complement but also enhance the capabilities of the terrestrial cellular telecommunications network, compatibility and interoperability between terrestrial cellular and mobile satellite systems are vitally important to provide an integrated moving telecommunications network of the future. From a network standpoint, there exist very strong commonalities between the terrestrial cellular system and the mobile satellite system. Therefore, the MSS architecture should be designed as an integral part of the CADN. This paper describes the concept of the CADN, the functional architecture of the MSS, and the user-network interface signaling protocols.

Cellular Stress Response to Engineered Nanoparticles: Effect of Size, Surface Coating, and Cellular Uptake

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CELLULAR STRESS RESPONSE TO ENGINEERED NANOPARTICLES: EFFECT OF SIZE, SURFACE COATING, AND CELLULAR UPTAKE RY Prasad 1, JK McGee2, MG Killius1 D Ackerman2, CF Blackman2 DM DeMarini2 , SO Simmons2 1 Student Services Contractor, US EPA, RTP, NC 2 US EPA, RTP, NC The num...

Cellular islet autoimmunity associates with clinical outcome of islet cell transplantation.

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Volkert A L Huurman

2008-06-01

Full Text Available Islet cell transplantation can cure type 1 diabetes (T1D, but only a minority of recipients remains insulin-independent in the following years. We tested the hypothesis that allograft rejection and recurrent autoimmunity contribute to this progressive loss of islet allograft function.Twenty-one T1D patients received cultured islet cell grafts prepared from multiple donors and transplanted under anti-thymocyte globulin (ATG induction and tacrolimus plus mycophenolate mofetil (MMF maintenance immunosuppression. Immunity against auto- and alloantigens was measured before and during one year after transplantation. Cellular auto- and alloreactivity was assessed by lymphocyte stimulation tests against autoantigens and cytotoxic T lymphocyte precursor assays, respectively. Humoral reactivity was measured by auto- and alloantibodies. Clinical outcome parameters--including time until insulin independence, insulin independence at one year, and C-peptide levels over one year--remained blinded until their correlation with immunological parameters. All patients showed significant improvement of metabolic control and 13 out of 21 became insulin-independent. Multivariate analyses showed that presence of cellular autoimmunity before and after transplantation is associated with delayed insulin-independence (p = 0.001 and p = 0.01, respectively and lower circulating C-peptide levels during the first year after transplantation (p = 0.002 and p = 0.02, respectively. Seven out of eight patients without pre-existent T-cell autoreactivity became insulin-independent, versus none of the four patients reactive to both islet autoantigens GAD and IA-2 before transplantation. Autoantibody levels and cellular alloreactivity had no significant association with outcome.In this cohort study, cellular islet-specific autoimmunity associates with clinical outcome of islet cell transplantation under ATG-tacrolimus-MMF immunosuppression. Tailored immunotherapy targeting cellular

Point process models for localization and interdependence of punctate cellular structures.

Science.gov (United States)

Li, Ying; Majarian, Timothy D; Naik, Armaghan W; Johnson, Gregory R; Murphy, Robert F

2016-07-01

Accurate representations of cellular organization for multiple eukaryotic cell types are required for creating predictive models of dynamic cellular function. To this end, we have previously developed the CellOrganizer platform, an open source system for generative modeling of cellular components from microscopy images. CellOrganizer models capture the inherent heterogeneity in the spatial distribution, size, and quantity of different components among a cell population. Furthermore, CellOrganizer can generate quantitatively realistic synthetic images that reflect the underlying cell population. A current focus of the project is to model the complex, interdependent nature of organelle localization. We built upon previous work on developing multiple non-parametric models of organelles or structures that show punctate patterns. The previous models described the relationships between the subcellular localization of puncta and the positions of cell and nuclear membranes and microtubules. We extend these models to consider the relationship to the endoplasmic reticulum (ER), and to consider the relationship between the positions of different puncta of the same type. Our results do not suggest that the punctate patterns we examined are dependent on ER position or inter- and intra-class proximity. With these results, we built classifiers to update previous assignments of proteins to one of 11 patterns in three distinct cell lines. Our generative models demonstrate the ability to construct statistically accurate representations of puncta localization from simple cellular markers in distinct cell types, capturing the complex phenomena of cellular structure interaction with little human input. This protocol represents a novel approach to vesicular protein annotation, a field that is often neglected in high-throughput microscopy. These results suggest that spatial point process models provide useful insight with respect to the spatial dependence between cellular structures. �

The major cellular sterol regulatory pathway is required for Andes virus infection.

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Josiah Petersen

2014-02-01

Full Text Available The Bunyaviridae comprise a large family of RNA viruses with worldwide distribution and includes the pathogenic New World hantavirus, Andes virus (ANDV. Host factors needed for hantavirus entry remain largely enigmatic and therapeutics are unavailable. To identify cellular requirements for ANDV infection, we performed two parallel genetic screens. Analysis of a large library of insertionally mutagenized human haploid cells and a siRNA genomic screen converged on components (SREBP-2, SCAP, S1P and S2P of the sterol regulatory pathway as critically important for infection by ANDV. The significance of this pathway was confirmed using functionally deficient cells, TALEN-mediated gene disruption, RNA interference and pharmacologic inhibition. Disruption of sterol regulatory complex function impaired ANDV internalization without affecting virus binding. Pharmacologic manipulation of cholesterol levels demonstrated that ANDV entry is sensitive to changes in cellular cholesterol and raises the possibility that clinically approved regulators of sterol synthesis may prove useful for combating ANDV infection.

The long Tramp from Cellular Pathology to Molecular Pathology

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Hans Guski

2017-05-01

Derivatives: The observation of principal identity of biological meaningful elements can be agglutinated to a ‘general theory of live’ and its manifestation. All of the investigated elements posses the same regularities, which are altered, destroyed or newly built by external influences such as disease, physical and psychological forces. Not all magnification levels that display with these elements are of the same significance. Already Virchow suggested that ‘smaller elements (molecules might be responsible for changes that are visible ‘in larger elements’ (at cellular level.  The reflection on these ideas can be associated with the implementation of molecular techniques which has been developed in the 20th century and are still ongoing today. Perspectives: Thus, cellular and molecular pathology can be integrated under one umbrella. This umbrella will lead to newly man-formed structures, such as artificial DNA and gene components or functional chip implantations.

Investigating the effects of ABC transporter-based acquired drug resistance mechanisms at the cellular and tissue scale.

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Liu, Cong; Krishnan, J; Xu, Xiao Yun

2013-03-01

In this paper we systematically investigate the effects of acquired drug resistance at the cellular and tissue scale, with a specific focus on ATP-binding cassette (ABC) transporter-based mechanisms and contrast this with other representative intracellular resistance mechanisms. This is done by developing in silico models wherein the drug resistance mechanism is overlaid on a coarse-grained description of apoptosis; these cellular models are coupled with interstitial drug transport, allowing for a transparent examination of the effect of acquired drug resistances at the tissue level. While ABC transporter-mediated resistance mechanisms counteract drug effect at the cellular level, its tissue-level effect is more complicated, revealing unexpected trends in tissue response as drug stimuli are systematically varied. Qualitatively different behaviour is observed in other drug resistance mechanisms. Overall the paper (i) provides insight into the tissue level functioning of a particular resistance mechanism, (ii) shows that this is very different from other resistance mechanisms of an apparently similar type, and (iii) demonstrates a concrete instance of how the functioning of a negative feedback based cellular adaptive mechanism can have unexpected higher scale effects.

Overexpression of the human DEK oncogene reprograms cellular metabolism and promotes glycolysis

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Watanabe, Miki; Muraleedharan, Ranjithmenon; Lambert, Paul F.; Lane, Andrew N.; Romick-Rosendale, Lindsey E.; Wells, Susanne I.

2017-01-01

The DEK oncogene is overexpressed in many human malignancies including at early tumor stages. Our reported in vitro and in vivo models of squamous cell carcinoma have demonstrated that DEK contributes functionally to cellular and tumor survival and to proliferation. However, the underlying molecular mechanisms remain poorly understood. Based on recent RNA sequencing experiments, DEK expression was necessary for the transcription of several metabolic enzymes involved in anabolic pathways. This identified a possible mechanism whereby DEK may drive cellular metabolism to enable cell proliferation. Functional metabolic Seahorse analysis demonstrated increased baseline and maximum extracellular acidification rates, a readout of glycolysis, in DEK-overexpressing keratinocytes and squamous cell carcinoma cells. DEK overexpression also increased the maximum rate of oxygen consumption and therefore increased the potential for oxidative phosphorylation (OxPhos). To detect small metabolites that participate in glycolysis and the tricarboxylic acid cycle (TCA) that supplies substrate for OxPhos, we carried out NMR-based metabolomics studies. We found that high levels of DEK significantly reprogrammed cellular metabolism and altered the abundances of amino acids, TCA cycle intermediates and the glycolytic end products lactate, alanine and NAD+. Taken together, these data support a scenario whereby overexpression of the human DEK oncogene reprograms keratinocyte metabolism to fulfill energy and macromolecule demands required to enable and sustain cancer cell growth. PMID:28558019

Overexpression of the human DEK oncogene reprograms cellular metabolism and promotes glycolysis.

Directory of Open Access Journals (Sweden)

Marie C Matrka

Full Text Available The DEK oncogene is overexpressed in many human malignancies including at early tumor stages. Our reported in vitro and in vivo models of squamous cell carcinoma have demonstrated that DEK contributes functionally to cellular and tumor survival and to proliferation. However, the underlying molecular mechanisms remain poorly understood. Based on recent RNA sequencing experiments, DEK expression was necessary for the transcription of several metabolic enzymes involved in anabolic pathways. This identified a possible mechanism whereby DEK may drive cellular metabolism to enable cell proliferation. Functional metabolic Seahorse analysis demonstrated increased baseline and maximum extracellular acidification rates, a readout of glycolysis, in DEK-overexpressing keratinocytes and squamous cell carcinoma cells. DEK overexpression also increased the maximum rate of oxygen consumption and therefore increased the potential for oxidative phosphorylation (OxPhos. To detect small metabolites that participate in glycolysis and the tricarboxylic acid cycle (TCA that supplies substrate for OxPhos, we carried out NMR-based metabolomics studies. We found that high levels of DEK significantly reprogrammed cellular metabolism and altered the abundances of amino acids, TCA cycle intermediates and the glycolytic end products lactate, alanine and NAD+. Taken together, these data support a scenario whereby overexpression of the human DEK oncogene reprograms keratinocyte metabolism to fulfill energy and macromolecule demands required to enable and sustain cancer cell growth.

Glycosaminoglycan-functionalized poly-lactide-co-glycolide nanoparticles: synthesis, characterization, cytocompatibility, and cellular uptake

Directory of Open Access Journals (Sweden)

Lamichhane SP

2015-01-01

Full Text Available Surya P Lamichhane,1 Neha Arya,1,2 Nirdesh Ojha,3 Esther Kohler,1 V Prasad Shastri1,2,41Institute for Macromolecular Chemistry, University of Freiburg, Freiburg, 2Helmholtz Virtual Institute on “Multifunctional Biomaterials for Medicine”, 3Laboratory for Process Technology, Department of Microsystems Engineering, University of Freiburg, Freiburg, 4Centre for Biological Signaling Studies (BIOSS, University of Freiburg, Freiburg, GermanyAbstract: The efficient delivery of chemotherapeutics to the tumor via nanoparticle (NP-based delivery systems remains a significant challenge. This is compounded by the fact that the tumor is highly dynamic and complex environment composed of a plurality of cell types and extracellular matrix. Since glycosaminoglycan (GAG production is altered in many diseases (or pathologies, NPs bearing GAG moieties on the surface may confer some unique advantages in interrogating the tumor microenvironment. In order to explore this premise, in the study reported here poly-lactide-co-glycolide (PLGA NPs in the range of 100–150 nm bearing various proteoglycans were synthesized by a single-step nanoprecipitation and characterized. The surface functionalization of the NPs with GAG moieties was verified using zeta potential measurements and X-ray photoelectron spectroscopy. To establish these GAG-bearing NPs as carriers of therapeutics, cellular toxicity assays were undertaken in lung epithelial adenocarcinoma (A549 cells, human pulmonary microvascular endothelial cells (HPMEC, and renal proximal tubular epithelial cells. In general NPs were well tolerated over a wide concentration range (100–600 µg/mL by all cell types and were taken up to appreciable extents without any adverse cell response in A549 cells and HPMEC. Further, GAG-functionalized PLGA NPs were taken up to different extents in A459 cells and HPMEC. In both cell systems, the uptake of heparin-modified NPs was diminished by 50%–65% in comparison to that of

Game-Theoretic Social-Aware Resource Allocation for Device-to-Device Communications Underlaying Cellular Network

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Lei Wang

2018-01-01

Full Text Available Device-to-Device communication underlaying cellular network can increase the spectrum efficiency due to direct proximity communication and frequency reuse. However, such performance improvement is influenced by the power interference caused by spectrum sharing and social characteristics in each social community jointly. In this investigation, we present a dynamic game theory with complete information based D2D resource allocation scheme for D2D communication underlaying cellular network. In this resource allocation method, we quantify both the rate influence from the power interference caused by the D2D transmitter to cellular users and rate enhancement brought by the social relationships between mobile users. Then, the utility function maximization game is formulated to optimize the overall transmission rate performance of the network, which synthetically measures the final influence from both power interference and sociality enhancement. Simultaneously, we discuss the Nash Equilibrium of the proposed utility function maximization game from a theoretical point of view and further put forward a utility priority searching algorithm based resource allocation scheme. Simulation results show that our proposed scheme attains better performance compared with the other two advanced proposals.

Decomposing Oncogenic Transcriptional Signatures to Generate Maps of Divergent Cellular States.

Science.gov (United States)

Kim, Jong Wook; Abudayyeh, Omar O; Yeerna, Huwate; Yeang, Chen-Hsiang; Stewart, Michelle; Jenkins, Russell W; Kitajima, Shunsuke; Konieczkowski, David J; Medetgul-Ernar, Kate; Cavazos, Taylor; Mah, Clarence; Ting, Stephanie; Van Allen, Eliezer M; Cohen, Ofir; Mcdermott, John; Damato, Emily; Aguirre, Andrew J; Liang, Jonathan; Liberzon, Arthur; Alexe, Gabriella; Doench, John; Ghandi, Mahmoud; Vazquez, Francisca; Weir, Barbara A; Tsherniak, Aviad; Subramanian, Aravind; Meneses-Cime, Karina; Park, Jason; Clemons, Paul; Garraway, Levi A; Thomas, David; Boehm, Jesse S; Barbie, David A; Hahn, William C; Mesirov, Jill P; Tamayo, Pablo

2017-08-23

The systematic sequencing of the cancer genome has led to the identification of numerous genetic alterations in cancer. However, a deeper understanding of the functional consequences of these alterations is necessary to guide appropriate therapeutic strategies. Here, we describe Onco-GPS (OncoGenic Positioning System), a data-driven analysis framework to organize individual tumor samples with shared oncogenic alterations onto a reference map defined by their underlying cellular states. We applied the methodology to the RAS pathway and identified nine distinct components that reflect transcriptional activities downstream of RAS and defined several functional states associated with patterns of transcriptional component activation that associates with genomic hallmarks and response to genetic and pharmacological perturbations. These results show that the Onco-GPS is an effective approach to explore the complex landscape of oncogenic cellular states across cancers, and an analytic framework to summarize knowledge, establish relationships, and generate more effective disease models for research or as part of individualized precision medicine paradigms. Copyright © 2017 Elsevier Inc. All rights reserved.

Winding through the WNT pathway during cellular development and demise.

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Li, F; Chong, Z Z; Maiese, K

2006-01-01

In slightly over a period of twenty years, our comprehension of the cellular and molecular mechanisms that govern the Wnt signaling pathway continue to unfold. The Wnt proteins were initially implicated in viral carcinogenesis experiments associated with mammary tumors, but since this period investigations focusing on the Wnt pathways and their transmembrane receptors termed Frizzled have been advanced to demonstrate the critical nature of Wnt for the development of a variety of cell populations as well as the potential of the Wnt pathway to avert apoptotic injury. In particular, Wnt signaling plays a significant role in both the cardiovascular and nervous systems during embryonic cell patterning, proliferation, differentiation, and orientation. Furthermore, modulation of Wnt signaling under specific cellular influences can either promote or prevent the early and late stages of apoptotic cellular injury in neurons, endothelial cells, vascular smooth muscle cells, and cardiomyocytes. A number of downstream signal transduction pathways can mediate the biological response of the Wnt proteins that include Dishevelled, beta-catenin, intracellular calcium, protein kinase C, Akt, and glycogen synthase kinase-3beta. Interestingly, these cellular cascades of the Wnt-Frizzled pathways can participate in several neurodegenerative, vascular, and cardiac disorders and may be closely integrated with the function of trophic factors. Identification of the critical elements that modulate the Wnt-Frizzled signaling pathway should continue to unlock the potential of Wnt pathway for the development of new therapeutic options against neurodegenerative and vascular diseases.

Cellular-based preemption system

Science.gov (United States)

Bachelder, Aaron D. (Inventor)

2011-01-01

A cellular-based preemption system that uses existing cellular infrastructure to transmit preemption related data to allow safe passage of emergency vehicles through one or more intersections. A cellular unit in an emergency vehicle is used to generate position reports that are transmitted to the one or more intersections during an emergency response. Based on this position data, the one or more intersections calculate an estimated time of arrival (ETA) of the emergency vehicle, and transmit preemption commands to traffic signals at the intersections based on the calculated ETA. Additional techniques may be used for refining the position reports, ETA calculations, and the like. Such techniques include, without limitation, statistical preemption, map-matching, dead-reckoning, augmented navigation, and/or preemption optimization techniques, all of which are described in further detail in the above-referenced patent applications.

A cellular automata model of bone formation.

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Van Scoy, Gabrielle K; George, Estee L; Opoku Asantewaa, Flora; Kerns, Lucy; Saunders, Marnie M; Prieto-Langarica, Alicia

2017-04-01

Bone remodeling is an elegantly orchestrated process by which osteocytes, osteoblasts and osteoclasts function as a syncytium to maintain or modify bone. On the microscopic level, bone consists of cells that create, destroy and monitor the bone matrix. These cells interact in a coordinated manner to maintain a tightly regulated homeostasis. It is this regulation that is responsible for the observed increase in bone gain in the dominant arm of a tennis player and the observed increase in bone loss associated with spaceflight and osteoporosis. The manner in which these cells interact to bring about a change in bone quality and quantity has yet to be fully elucidated. But efforts to understand the multicellular complexity can ultimately lead to eradication of metabolic bone diseases such as osteoporosis and improved implant longevity. Experimentally validated mathematical models that simulate functional activity and offer eventual predictive capabilities offer tremendous potential in understanding multicellular bone remodeling. Here we undertake the initial challenge to develop a mathematical model of bone formation validated with in vitro data obtained from osteoblastic bone cells induced to mineralize and quantified at 26 days of culture. A cellular automata model was constructed to simulate the in vitro characterization. Permutation tests were performed to compare the distribution of the mineralization in the cultures and the distribution of the mineralization in the mathematical models. The results of the permutation test show the distribution of mineralization from the characterization and mathematical model come from the same probability distribution, therefore validating the cellular automata model. Copyright © 2017 Elsevier Inc. All rights reserved.

Symposium cellular response to DNA damage the role of poly(ADP-ribose) poly(ADP-ribose) in the cellular response to DNA damage

International Nuclear Information System (INIS)

Berger, N.A.

1985-01-01

Poly(ADP-ribose) polymerase is a chromatin-bound enzyme which, on activation by DNA strand breaks, catalyzes the successive transfer of ADP-ribose units from NAD to nuclear proteins. Poly(ADP-ribose) synthesis is stimulated by DNA strand breaks, and the polymer may alter the structure and/or function of chromosomal proteins to facilitate the DNA repair process. Inhibitors of Poly(ADP-ribose) polymerase or deficiencies of the substrate, NAD, lead to retardation of the DNA repair process. When DNA strand breaks are extensive or when breaks fail to be repaired, the stimulus for activation of Poly(ADP-ribose) persists and the activated enzyme is capable of totaly consuming cellular pools of NAD. Depletion of NAD and consequent lowering of cellular ATP pools, due to activation of Poly(ADP-ribose) polymerase, may account for rapid cell death before DNA repair takes place and before the genetic effects of DNA damage become manifest

Probabilistic cellular automata.

Science.gov (United States)

Agapie, Alexandru; Andreica, Anca; Giuclea, Marius

2014-09-01

Cellular automata are binary lattices used for modeling complex dynamical systems. The automaton evolves iteratively from one configuration to another, using some local transition rule based on the number of ones in the neighborhood of each cell. With respect to the number of cells allowed to change per iteration, we speak of either synchronous or asynchronous automata. If randomness is involved to some degree in the transition rule, we speak of probabilistic automata, otherwise they are called deterministic. With either type of cellular automaton we are dealing with, the main theoretical challenge stays the same: starting from an arbitrary initial configuration, predict (with highest accuracy) the end configuration. If the automaton is deterministic, the outcome simplifies to one of two configurations, all zeros or all ones. If the automaton is probabilistic, the whole process is modeled by a finite homogeneous Markov chain, and the outcome is the corresponding stationary distribution. Based on our previous results for the asynchronous case-connecting the probability of a configuration in the stationary distribution to its number of zero-one borders-the article offers both numerical and theoretical insight into the long-term behavior of synchronous cellular automata.

47 CFR 32.5003 - Cellular mobile revenue.

Science.gov (United States)

2010-10-01

... 47 Telecommunication 2 2010-10-01 2010-10-01 false Cellular mobile revenue. 32.5003 Section 32... SYSTEM OF ACCOUNTS FOR TELECOMMUNICATIONS COMPANIES Instructions For Revenue Accounts § 32.5003 Cellular mobile revenue. This account shall include message revenue derived from cellular mobile...

Chronic pain, perceived stress, and cellular aging: an exploratory study

OpenAIRE

Sibille, Kimberly T; Langaee, Taimour; Burkley, Ben; Gong, Yan; Glover, Toni L; King, Chris; Riley, Joseph L; Leeuwenburgh, Christiaan; Staud, Roland; Bradley, Laurence A; Fillingim, Roger B

2012-01-01

Abstract Background Chronic pain conditions are characterized by significant individual variability complicating the identification of pathophysiological markers. Leukocyte telomere length (TL), a measure of cellular aging, is associated with age-related disease onset, psychosocial stress, and health-related functional decline. Psychosocial stress has been associated with the onset of chronic pain and chronic pain is experienced as a physical and psychosocial stressor. However, the utility of...

47 CFR 22.905 - Channels for cellular service.

Science.gov (United States)

2010-10-01

... 47 Telecommunication 2 2010-10-01 2010-10-01 false Channels for cellular service. 22.905 Section... MOBILE SERVICES Cellular Radiotelephone Service § 22.905 Channels for cellular service. The following frequency bands are allocated for assignment to service providers in the Cellular Radiotelephone Service. (a...

Lysine-functionalized nanodiamonds as gene carriers: development of stable colloidal dispersion for in vitro cellular uptake studies and siRNA delivery application

Directory of Open Access Journals (Sweden)

Alwani S

2016-02-01

Full Text Available Saniya Alwani,1 Randeep Kaur,1 Deborah Michel,1 Jackson M Chitanda,2 Ronald E Verrall,3 Chithra Karunakaran,4 Ildiko Badea1 1Drug Design and Discovery Research Group, College of Pharmacy and Nutrition, 2Department of Chemical & Biological Engineering, 3Department of Chemistry, University of Saskatchewan, 4Canadian Light Source, Saskatoon, SK, Canada Purpose: Nanodiamonds (NDs are emerging as an attractive tool for gene therapeutics. To reach their full potential for biological application, NDs should maintain their colloidal stability in biological milieu. This study describes the behavior of lysine-functionalized ND (lys-ND in various dispersion media, with an aim to limit aggregation and improve the colloidal stability of ND-gene complexes called diamoplexes. Furthermore, cellular and macromolecular interactions of lys-NDs are also analyzed in vitro to establish the understanding of ND-mediated gene transfer in cells. Methods: lys-NDs were synthesized earlier through covalent conjugation of lysine amino acid to carboxylated NDs surface generated through re-oxidation in strong oxidizing acids. In this study, dispersions of lys-NDs were prepared in various media, and the degree of sedimentation was monitored for 72 hours. Particle size distributions and zeta potential measurements were performed for a period of 25 days to characterize the physicochemical stability of lys-NDs in the medium. The interaction profile of lys-NDs with fetal bovine serum showed formation of a protein corona, which was evaluated by size and charge distribution measurements. Uptake of lys-NDs in cervical cancer cells was analyzed by scanning transmission X-ray microscopy, flow cytometry, and confocal microscopy. Cellular uptake of diamoplexes (complex of lys-NDs with small interfering RNA was also analyzed using flow cytometry. Results: Aqueous dispersion of lys-NDs showed minimum sedimentation and remained stable over a period of 25 days. Size distributions showed

Cellular imaging using biocompatible dendrimer-functionalized graphene oxide-based fluorescent probe anchored with magnetic nanoparticles

International Nuclear Information System (INIS)

Wate, Prateek S; Banerjee, Shashwat S; Mascarenhas, Russel R; Zope, Khushbu R; Khandare, Jayant; Jalota-Badhwar, Archana; Misra, R Devesh K

2012-01-01

We describe a novel multicomponent graphene nanostructured system that is biocompatible, and has strong NIR optical absorbance and superparamagnetic properties. The fabrication of the multicomponent nanostructure system involves the covalent attachment of 3 components; Fe 3 O 4 (Fe) nanoparticles, PAMAM-G4-NH 2 (G4) dendrimer and Cy5 (Cy) on a graphene oxide (GO) surface to synthesize a biologically relevant multifunctional system. The resultant GO-G4-Fe-Cy nanosystem exhibits high dispersion in an aqueous medium, and is magnetically responsive and fluorescent. In vitro experiments provide a clear indication of successful uptake of the GO-G4-Fe-Cy nanosystem by MCF-7 breast cancer cells, and it is seen to behave as a bright and stable fluorescent marker. The study also reveals varied cellular distribution kinetics profile for the GO nanostructured system compared to free Cy. Furthermore, the newly developed GO nanostructured system is observed to be non-toxic to MDA-MB-231 cell growth, in striking contrast to free G4 dendrimer and GO-G4 conjugate. The GO-G4-Fe-Cy nanostructured system characterized by multifunctionality suggests the merits of graphene for cellular bioimaging and the delivery of bioactives. (paper)

The thorny path linking cellular senescence to organismalaging

Energy Technology Data Exchange (ETDEWEB)

Patil, Christopher K.; Mian, Saira; Campisi, Judith

2005-08-09

Half a century is fast approaching since Hayflick and colleagues formally described the limited ability of normal human cells to proliferate in culture (Hayflick and Moorhead, 1961). This finding--that normal somatic cells, in contrast to cancer cells, cannot divide indefinitely--challenged the prevailing idea that cells from mortal multicellular organisms were intrinsically ''immortal'' (Carrell, 1912). It also spawned two hypotheses, essential elements of which persist today. The first held that the restricted proliferation of normal cells, now termed cellular senescence, suppresses cancer (Hayflick, 1965; Sager, 1991; Campisi, 2001). The second hypothesis, as explained in the article by Lorenzini et al., suggested that the limited proliferation of cells in culture recapitulated aspects of organismal aging (Hayflick, 1965; Martin, 1993). How well have these hypotheses weathered the ensuing decades? Before answering this question, we first consider current insights into the causes and consequences of cellular senescence. Like Lorenzini et al., we limit our discussion to mammals. We also focus on fibroblasts, the cell type studied by Lorenzini et al., but consider other types as well. We suggest that replicative capacity in culture is not a straightforward assessment, and that it correlates poorly with both longevity and body mass. We speculate this is due to the malleable and variable nature of replicative capacity, which renders it an indirect metric of qualitative and quantitative differences among cells to undergo senescence, a response that directly alters cellular phenotype and might indirectly alter tissue structure and function.

Cellular cytotoxic response induced by highly purified multi-wall carbon nanotube in human lung cells.

Science.gov (United States)

Tsukahara, Tamotsu; Haniu, Hisao

2011-06-01

Carbon nanotubes, a promising nanomaterial with unique characteristics, have applications in a variety of fields. The cytotoxic effects of carbon nanotubes are partially due to the induction of oxidative stress; however, the detailed mechanisms of nanotube cytotoxicity and their interaction with cells remain unclear. In this study, the authors focus on the acute toxicity of vapor-grown carbon fiber, HTT2800, which is one of the most highly purified multi-wall carbon nanotubes (MWCNT) by high-temperature thermal treatment. The authors exposed human bronchial epithelial cells (BEAS-2B) to HTT2800 and measured the cellular uptake, mitochondrial function, cellular LDH release, apoptotic signaling, reactive oxygen species (ROS) generation and pro-inflammatory cytokine release. The HTT2800-exposed cells showed cellular uptake of the carbon nanotube, increased cell death, enhanced DNA damage, and induced cytokine release. However, the exposed cells showed no obvious intracellular ROS generation. These cellular and molecular findings suggest that HTT2800 could cause a potentially adverse inflammatory response in BEAS-2B cells.

47 CFR 22.901 - Cellular service requirements and limitations.

Science.gov (United States)

2010-10-01

... 47 Telecommunication 2 2010-10-01 2010-10-01 false Cellular service requirements and limitations... SERVICES PUBLIC MOBILE SERVICES Cellular Radiotelephone Service § 22.901 Cellular service requirements and limitations. The licensee of each cellular system is responsible for ensuring that its cellular system...

Fibrillarin, a nucleolar protein, is required for normal nuclear morphology and cellular growth in HeLa cells

International Nuclear Information System (INIS)

Amin, Mohammed Abdullahel; Matsunaga, Sachihiro; Ma, Nan; Takata, Hideaki; Yokoyama, Masami; Uchiyama, Susumu; Fukui, Kiichi

2007-01-01

Fibrillarin is a key small nucleolar protein in eukaryotes, which has an important role in pre-rRNA processing during ribosomal biogenesis. Though several functions of fibrillarin are known, its function during the cell cycle is still unknown. In this study, we confirmed the dynamic localization of fibrillarin during the cell cycle of HeLa cells and also performed functional studies by using a combination of immunofluorescence microscopy and RNAi technique. We observed that depletion of fibrillarin has almost no effect on the nucleolar structure. However, fibrillarin-depleted cells showed abnormal nuclear morphology. Moreover, fibrillarin depletion resulted in the reduction of the cellular growth and modest accumulation of cells with 4n DNA content. Our data suggest that fibrillarin would play a critical role in the maintenance of nuclear shape and cellular growth

The impact of technological innovations on work design in a cellular manufacturing environment

NARCIS (Netherlands)

Molleman, E.; Slomp, J.

2001-01-01

The impact of developments in market and technology on grouping machinery and work design is analysed. Over time a cellular design changed into a functional system with fewer cells, fewer workers and fewer but more advanced machines. This encourages high utilisation, specialised workers and the

The impact of technological innovations on work design in a cellular manufacturing environment

NARCIS (Netherlands)

Molleman, E.; Slomp, J.

The impact of developments in market and technology on grouping machinery and work design is analysed. Over time a cellular design changed into a functional system with fewer cells, fewer workers and fewer but more advanced machines. This encourages high utilisation, specialised workers and the

Adaptive multi-channel downlink assignment for overloaded spectrum-shared multi-antenna overlaid cellular networks

KAUST Repository

Radaydeh, Redha  Mahmoud; Alouini, Mohamed-Slim; Qaraqe, Khalid

2012-01-01

setup is expected to reduce the operational power and to function satisfactorily with the existing cellular architecture. Among the possible deployments of small-cell access points is to manage many of them to serve specific spatial locations, while

A dynamic cellular vertex model of growing epithelial tissues

Science.gov (United States)

Lin, Shao-Zhen; Li, Bo; Feng, Xi-Qiao

2017-04-01

Intercellular interactions play a significant role in a wide range of biological functions and processes at both the cellular and tissue scales, for example, embryogenesis, organogenesis, and cancer invasion. In this paper, a dynamic cellular vertex model is presented to study the morphomechanics of a growing epithelial monolayer. The regulating role of stresses in soft tissue growth is revealed. It is found that the cells originating from the same parent cell in the monolayer can orchestrate into clustering patterns as the tissue grows. Collective cell migration exhibits a feature of spatial correlation across multiple cells. Dynamic intercellular interactions can engender a variety of distinct tissue behaviors in a social context. Uniform cell proliferation may render high and heterogeneous residual compressive stresses, while stress-regulated proliferation can effectively release the stresses, reducing the stress heterogeneity in the tissue. The results highlight the critical role of mechanical factors in the growth and morphogenesis of epithelial tissues and help understand the development and invasion of epithelial tumors.

Cellular phone use while driving at night.

Science.gov (United States)

Vivoda, Jonathon M; Eby, David W; St Louis, Renée M; Kostyniuk, Lidia P

2008-03-01

Use of a cellular phone has been shown to negatively affect one's attention to the driving task, leading to an increase in crash risk. At any given daylight hour, about 6% of US drivers are actively talking on a hand-held cell phone. However, previous surveys have focused only on cell phone use during the day. Driving at night has been shown to be a riskier activity than driving during the day. The purpose of the current study was to assess the rate of hand-held cellular phone use while driving at night, using specialized night vision equipment. In 2006, two statewide direct observation survey waves of nighttime cellular phone use were conducted in Indiana utilizing specialized night vision equipment. Combined results of driver hand-held cellular phone use from both waves are presented in this manuscript. The rates of nighttime cell phone use were similar to results found in previous daytime studies. The overall rate of nighttime hand-held cellular phone use was 5.8 +/- 0.6%. Cellular phone use was highest for females and for younger drivers. In fact, the highest rate observed during the study (of 11.9%) was for 16-to 29-year-old females. The high level of cellular phone use found within the young age group, coupled with the increased crash risk associated with cellular phone use, nighttime driving, and for young drivers in general, suggests that this issue may become an important transportation-related concern.

Cellular metabolic rates from primary dermal fibroblast cells isolated from birds of different body masses.

Science.gov (United States)

Jimenez, Ana Gabriela; Williams, Joseph B

2014-10-01

The rate of metabolism is the speed at which organisms use energy, an integration of energy transformations within the body; it governs biological processes that influence rates of growth and reproduction. Progress at understanding functional linkages between whole organism metabolic rate and underlying mechanisms that influence its magnitude has been slow despite the central role this issue plays in evolutionary and physiological ecology. Previous studies that have attempted to relate how cellular processes translate into whole-organism physiology have done so over a range of body masses of subjects. However, the data still remains controversial when observing metabolic rates at the cellular level. To bridge the gap between these ideas, we examined cellular metabolic rate of primary dermal fibroblasts isolated from 49 species of birds representing a 32,000-fold range in body masses to test the hypothesis that metabolic rate of cultured cells scales with body size. We used a Seahorse XF-96 Extracellular flux analyzer to measure cellular respiration in fibroblasts. Additionally, we measured fibroblast size and mitochondrial content. We found no significant correlation between cellular metabolic rate, cell size, or mitochondrial content and body mass. Additionally, there was a significant relationship between cellular basal metabolic rate and proton leak in these cells. We conclude that metabolic rate of cells isolated in culture does not scale with body mass, but cellular metabolic rate is correlated to growth rate in birds. Copyright © 2014 Elsevier Inc. All rights reserved.

Genetic variation in the cellular response of Daphnia magna (Crustacea: Cladocera) to its bacterial parasite.

Science.gov (United States)

Auld, Stuart K J R; Scholefield, Jennifer A; Little, Tom J

2010-11-07

Linking measures of immune function with infection, and ultimately, host and parasite fitness is a major goal in the field of ecological immunology. In this study, we tested for the presence and timing of a cellular immune response in the crustacean Daphnia magna following exposure to its sterilizing endoparasite Pasteuria ramosa. We found that D. magna possesses two cell types circulating in the haemolymph: a spherical one, which we call a granulocyte and an irregular-shaped amoeboid cell first described by Metchnikoff over 125 years ago. Daphnia magna mounts a strong cellular response (of the amoeboid cells) just a few hours after parasite exposure. We further tested for, and found, considerable genetic variation for the magnitude of this cellular response. These data fostered a heuristic model of resistance in this naturally coevolving host-parasite interaction. Specifically, the strongest cellular responses were found in the most susceptible hosts, indicating resistance is not always borne from a response that destroys invading parasites, but rather stems from mechanisms that prevent their initial entry. Thus, D. magna may have a two-stage defence--a genetically determined barrier to parasite establishment and a cellular response once establishment has begun.

Large-scale inference of gene function through phylogenetic annotation of Gene Ontology terms: case study of the apoptosis and autophagy cellular processes.

Science.gov (United States)

Feuermann, Marc; Gaudet, Pascale; Mi, Huaiyu; Lewis, Suzanna E; Thomas, Paul D

2016-01-01

We previously reported a paradigm for large-scale phylogenomic analysis of gene families that takes advantage of the large corpus of experimentally supported Gene Ontology (GO) annotations. This 'GO Phylogenetic Annotation' approach integrates GO annotations from evolutionarily related genes across ∼100 different organisms in the context of a gene family tree, in which curators build an explicit model of the evolution of gene functions. GO Phylogenetic Annotation models the gain and loss of functions in a gene family tree, which is used to infer the functions of uncharacterized (or incompletely characterized) gene products, even for human proteins that are relatively well studied. Here, we report our results from applying this paradigm to two well-characterized cellular processes, apoptosis and autophagy. This revealed several important observations with respect to GO annotations and how they can be used for function inference. Notably, we applied only a small fraction of the experimentally supported GO annotations to infer function in other family members. The majority of other annotations describe indirect effects, phenotypes or results from high throughput experiments. In addition, we show here how feedback from phylogenetic annotation leads to significant improvements in the PANTHER trees, the GO annotations and GO itself. Thus GO phylogenetic annotation both increases the quantity and improves the accuracy of the GO annotations provided to the research community. We expect these phylogenetically based annotations to be of broad use in gene enrichment analysis as well as other applications of GO annotations.Database URL: http://amigo.geneontology.org/amigo. © The Author(s) 2016. Published by Oxford University Press.

Increased cellular uptake of peptide-modified PEGylated gold nanoparticles.

Science.gov (United States)

He, Bo; Yang, Dan; Qin, Mengmeng; Zhang, Yuan; He, Bing; Dai, Wenbing; Wang, Xueqing; Zhang, Qiang; Zhang, Hua; Yin, Changcheng

2017-12-09

Gold nanoparticles are promising drug delivery vehicles for nucleic acids, small molecules, and proteins, allowing various modifications on the particle surface. However, the instability and low bioavailability of gold nanoparticles compromise their clinical application. Here, we functionalized gold nanoparticles with CPP fragments (CALNNPFVYLI, CALRRRRRRRR) through sulfhydryl PEG to increase their stability and bioavailability. The resulting gold nanoparticles were characterized with transmission electron microscopy (TEM), dynamic light scattering (DLS), UV-visible spectrometry and X-ray photoelectron spectroscopy (XPS), and the stability in biological solutions was evaluated. Comparing to PEGylated gold nanoparticles, CPP (CALNNPFVYLI, CALRRRRRRRR)-modified gold nanoparticles showed 46 folds increase in cellular uptake in A549 and B16 cell lines, as evidenced by the inductively coupled plasma atomic emission spectroscopy (ICP-AES). The interactions between gold nanoparticles and liposomes indicated CPP-modified gold nanoparticles bind to cell membrane more effectively than PEGylated gold nanoparticles. Surface plasmon resonance (SPR) was used to measure interactions between nanoparticles and the membrane. TEM and uptake inhibitor experiments indicated that the cellular entry of gold nanoparticles was mediated by clathrin and macropinocytosis. Other energy independent endocytosis pathways were also identified. Our work revealed a new strategy to modify gold nanoparticles with CPP and illustrated the cellular uptake pathway of CPP-modified gold nanoparticles. Copyright © 2017 Elsevier Inc. All rights reserved.

Evidence that the tri-cellular metabolism of N-acetylaspartate functions as the brain's "operating system": how NAA metabolism supports meaningful intercellular frequency-encoded communications.

Science.gov (United States)

Baslow, Morris H

2010-11-01

N-acetylaspartate (NAA), an acetylated derivative of L-aspartate (Asp), and N-acetylaspartylglutamate (NAAG), a derivative of NAA and L-glutamate (Glu), are synthesized by neurons in brain. However, neurons cannot catabolize either of these substances, and so their metabolism requires the participation of two other cell types. Neurons release both NAA and NAAG to extra-cellular fluid (ECF) upon stimulation, where astrocytes, the target cells for NAAG, hydrolyze it releasing NAA back into ECF, and oligodendrocytes, the target cells for NAA, hydrolyze it releasing Asp to ECF for recycling to neurons. This sequence is unique as it is the only known amino acid metabolic cycle in brain that requires three cell types for its completion. The results of this cycling are two-fold. First, neuronal metabolic water is transported to ECF for its removal from brain. Second, the rate of neuronal activity is coupled with focal hyperemia, providing stimulated neurons with the energy required for transmission of meaningful frequency-encoded messages. In this paper, it is proposed that the tri-cellular metabolism of NAA functions as the "operating system" of the brain, and is essential for normal cognitive and motor activities. Evidence in support of this hypothesis is provided by the outcomes of two human inborn errors in NAA metabolism.

Almost sure exponential stability of stochastic fuzzy cellular neural networks with delays

International Nuclear Information System (INIS)

Zhao Hongyong; Ding Nan; Chen Ling

2009-01-01

This paper is concerned with the problem of exponential stability analysis for fuzzy cellular neural network with delays. By constructing suitable Lyapunov functional and using stochastic analysis we present some sufficient conditions ensuring almost sure exponential stability for the network. Moreover, an example is given to demonstrate the advantages of our method.

Outer-totalistic cellular automata on graphs

International Nuclear Information System (INIS)

Marr, Carsten; Huett, Marc-Thorsten

2009-01-01

We present an intuitive formalism for implementing cellular automata on arbitrary topologies. By that means, we identify a symmetry operation in the class of elementary cellular automata. Moreover, we determine the subset of topologically sensitive elementary cellular automata and find that the overall number of complex patterns decreases under increasing neighborhood size in regular graphs. As exemplary applications, we apply the formalism to complex networks and compare the potential of scale-free graphs and metabolic networks to generate complex dynamics

Radiation, nitric oxide and cellular death

International Nuclear Information System (INIS)

Dubner, D.; Perez, M.R. Del; Michelin, S.C.; Gisone, P.A.

1997-01-01

The mechanisms of radiation induced cellular death constitute an objective of research ever since the first biological effects of radiation were first observed. The explosion of information produced in the last 20 years calls for a careful analysis due to the apparent contradictory data related to the cellular system studied and the range of doses used. This review focuses on the role of the active oxygen species, in particular the nitric oxides, in its relevance as potential mediator of radiation induced cellular death

Building bridges between cellular and molecular structural biology.

Science.gov (United States)

Patwardhan, Ardan; Brandt, Robert; Butcher, Sarah J; Collinson, Lucy; Gault, David; Grünewald, Kay; Hecksel, Corey; Huiskonen, Juha T; Iudin, Andrii; Jones, Martin L; Korir, Paul K; Koster, Abraham J; Lagerstedt, Ingvar; Lawson, Catherine L; Mastronarde, David; McCormick, Matthew; Parkinson, Helen; Rosenthal, Peter B; Saalfeld, Stephan; Saibil, Helen R; Sarntivijai, Sirarat; Solanes Valero, Irene; Subramaniam, Sriram; Swedlow, Jason R; Tudose, Ilinca; Winn, Martyn; Kleywegt, Gerard J

2017-07-06

The integration of cellular and molecular structural data is key to understanding the function of macromolecular assemblies and complexes in their in vivo context. Here we report on the outcomes of a workshop that discussed how to integrate structural data from a range of public archives. The workshop identified two main priorities: the development of tools and file formats to support segmentation (that is, the decomposition of a three-dimensional volume into regions that can be associated with defined objects), and the development of tools to support the annotation of biological structures.

Predictability in cellular automata.

Science.gov (United States)

Agapie, Alexandru; Andreica, Anca; Chira, Camelia; Giuclea, Marius

2014-01-01

Modelled as finite homogeneous Markov chains, probabilistic cellular automata with local transition probabilities in (0, 1) always posses a stationary distribution. This result alone is not very helpful when it comes to predicting the final configuration; one needs also a formula connecting the probabilities in the stationary distribution to some intrinsic feature of the lattice configuration. Previous results on the asynchronous cellular automata have showed that such feature really exists. It is the number of zero-one borders within the automaton's binary configuration. An exponential formula in the number of zero-one borders has been proved for the 1-D, 2-D and 3-D asynchronous automata with neighborhood three, five and seven, respectively. We perform computer experiments on a synchronous cellular automaton to check whether the empirical distribution obeys also that theoretical formula. The numerical results indicate a perfect fit for neighbourhood three and five, which opens the way for a rigorous proof of the formula in this new, synchronous case.

Evolution of Cellular Automata toward a LIFE-Like Rule Guided by 1/ƒ Noise

Science.gov (United States)

Ninagawa, Shigeru

There is evidence in favor of a relationship between the presence of 1/ƒ noise and computational universality in cellular automata. To confirm the relationship, we search for two-dimensional cellular automata with a 1/ƒ power spectrum by means of genetic algorithms. The power spectrum is calculated from the evolution of the state of the cell, starting from a random initial configuration. The fitness is estimated by the power spectrum with consideration of the spectral similarity to the 1/ƒ spectrum. The result shows that the rule with the highest fitness over the most runs exhibits a 1/ƒ type spectrum and its transition function and behavior are quite similar to those of the Game of Life, which is known to be a computationally universal cellular automaton. These results support the relationship between the presence of 1/ƒ noise and computational universality.

An integrated approach to elucidate the intra-viral and viral-cellular protein interaction networks of a gamma-herpesvirus.

Directory of Open Access Journals (Sweden)

Shaoying Lee

2011-10-01

Full Text Available Genome-wide yeast two-hybrid (Y2H screens were conducted to elucidate the molecular functions of open reading frames (ORFs encoded by murine γ-herpesvirus 68 (MHV-68. A library of 84 MHV-68 genes and gene fragments was generated in a Gateway entry plasmid and transferred to Y2H vectors. All possible pair-wise interactions between viral proteins were tested in the Y2H assay, resulting in the identification of 23 intra-viral protein-protein interactions (PPIs. Seventy percent of the interactions between viral proteins were confirmed by co-immunoprecipitation experiments. To systematically investigate virus-cellular protein interactions, the MHV-68 Y2H constructs were screened against a cellular cDNA library, yielding 243 viral-cellular PPIs involving 197 distinct cellar proteins. Network analyses indicated that cellular proteins targeted by MHV-68 had more partners in the cellular PPI network and were located closer to each other than expected by chance. Taking advantage of this observation, we scored the cellular proteins based on their network distances from other MHV-68-interacting proteins and segregated them into high (Y2H-HP and low priority/not-scored (Y2H-LP/NS groups. Significantly more genes from Y2H-HP altered MHV-68 replication when their expression was inhibited with siRNAs (53% of genes from Y2H-HP, 21% of genes from Y2H-LP/NS, and 16% of genes randomly chosen from the human PPI network; p<0.05. Enriched Gene Ontology (GO terms in the Y2H-HP group included regulation of apoptosis, protein kinase cascade, post-translational protein modification, transcription from RNA polymerase II promoter, and IκB kinase/NFκB cascade. Functional validation assays indicated that PCBP1, which interacted with MHV-68 ORF34, may be involved in regulating late virus gene expression in a manner consistent with the effects of its viral interacting partner. Our study integrated Y2H screening with multiple functional validation approaches to create �

Generation and Comprehensive Analysis of an Influenza Virus Polymerase Cellular Interaction Network▿†§

Science.gov (United States)

Tafforeau, Lionel; Chantier, Thibault; Pradezynski, Fabrine; Pellet, Johann; Mangeot, Philippe E.; Vidalain, Pierre-Olivier; Andre, Patrice; Rabourdin-Combe, Chantal; Lotteau, Vincent

2011-01-01

The influenza virus transcribes and replicates its genome inside the nucleus of infected cells. Both activities are performed by the viral RNA-dependent RNA polymerase that is composed of the three subunits PA, PB1, and PB2, and recent studies have shown that it requires host cell factors to transcribe and replicate the viral genome. To identify these cellular partners, we generated a comprehensive physical interaction map between each polymerase subunit and the host cellular proteome. A total of 109 human interactors were identified by yeast two-hybrid screens, whereas 90 were retrieved by literature mining. We built the FluPol interactome network composed of the influenza virus polymerase (PA, PB1, and PB2) and the nucleoprotein NP and 234 human proteins that are connected through 279 viral-cellular protein interactions. Analysis of this interactome map revealed enriched cellular functions associated with the influenza virus polymerase, including host factors involved in RNA polymerase II-dependent transcription and mRNA processing. We confirmed that eight influenza virus polymerase-interacting proteins are required for virus replication and transcriptional activity of the viral polymerase. These are involved in cellular transcription (C14orf166, COPS5, MNAT1, NMI, and POLR2A), translation (EIF3S6IP), nuclear transport (NUP54), and DNA repair (FANCG). Conversely, we identified PRKRA, which acts as an inhibitor of the viral polymerase transcriptional activity and thus is required for the cellular antiviral response. PMID:21994455

Elucidating the Function of Penetratin and a Static Magnetic Field in Cellular Uptake of Magnetic Nanoparticles

Directory of Open Access Journals (Sweden)

David Stirling

2013-02-01

Full Text Available Nanotechnology plays an increasingly important role in the biomedical arena. In particular, magnetic nanoparticles (mNPs have become important tools in molecular diagnostics, in vivo imaging and improved treatment of disease, with the ultimate aim of producing a more theranostic approach. Due to their small sizes, the nanoparticles can cross most of the biological barriers such as the blood vessels and the blood brain barrier, thus providing ubiquitous access to most tissues. In all biomedical applications maximum nanoparticle uptake into cells is required. Two promising methods employed to this end include functionalization of mNPs with cell-penetrating peptides to promote efficient translocation of cargo into the cell and the use of external magnetic fields for enhanced delivery. This study aimed to compare the effect of both penetratin and a static magnetic field with regards to the cellular uptake of 200 nm magnetic NPs and determine the route of uptake by both methods. Results demonstrated that both techniques increased particle uptake, with penetratin proving more cell specific. Clathrin- medicated endocytosis appeared to be responsible for uptake as shown via PCR and western blot, with Pitstop 2 (known to selectively block clathrin formation blocking particle uptake. Interestingly, it was further shown that a magnetic field was able to reverse or overcome the blocking, suggesting an alternative route of uptake.

Meta-Analysis of High-Throughput Datasets Reveals Cellular Responses Following Hemorrhagic Fever Virus Infection

Directory of Open Access Journals (Sweden)

Gavin C. Bowick

2011-05-01

Full Text Available The continuing use of high-throughput assays to investigate cellular responses to infection is providing a large repository of information. Due to the large number of differentially expressed transcripts, often running into the thousands, the majority of these data have not been thoroughly investigated. Advances in techniques for the downstream analysis of high-throughput datasets are providing additional methods for the generation of additional hypotheses for further investigation. The large number of experimental observations, combined with databases that correlate particular genes and proteins with canonical pathways, functions and diseases, allows for the bioinformatic exploration of functional networks that may be implicated in replication or pathogenesis. Herein, we provide an example of how analysis of published high-throughput datasets of cellular responses to hemorrhagic fever virus infection can generate additional functional data. We describe enrichment of genes involved in metabolism, post-translational modification and cardiac damage; potential roles for specific transcription factors and a conserved involvement of a pathway based around cyclooxygenase-2. We believe that these types of analyses can provide virologists with additional hypotheses for continued investigation.

Molecular and cellular mechanisms of the age-dependency of opioid analgesia and tolerance

Directory of Open Access Journals (Sweden)

Zhao Jing

2012-05-01

Full Text Available Abstract The age-dependency of opioid analgesia and tolerance has been noticed in both clinical observation and laboratory studies. Evidence shows that many molecular and cellular events that play essential roles in opioid analgesia and tolerance are actually age-dependent. For example, the expression and functions of endogenous opioid peptides, multiple types of opioid receptors, G protein subunits that couple to opioid receptors, and regulators of G protein signaling (RGS proteins change with development and age. Other signaling systems that are critical to opioid tolerance development, such as N-methyl-D-aspartic acid (NMDA receptors, also undergo age-related changes. It is plausible that the age-dependent expression and functions of molecules within and related to the opioid signaling pathways, as well as age-dependent cellular activity such as agonist-induced opioid receptor internalization and desensitization, eventually lead to significant age-dependent changes in opioid analgesia and tolerance development.

Spectral and Energy Efficiencies in mmWave Cellular Networks for Optimal Utilization

Directory of Open Access Journals (Sweden)

Abdulbaset M. Hamed

2018-01-01

Full Text Available Millimeter wave (mmWave spectrum has been proposed for use in commercial cellular networks to relieve the already severely congested microwave spectrum. Thus, the design of an efficient mmWave cellular network has gained considerable importance and has to take into account regulations imposed by government agencies with regard to global warming and sustainable development. In this paper, a dense mmWave hexagonal cellular network with each cell consisting of a number of smaller cells with their own Base Stations (BSs is presented as a solution to meet the increasing demand for a variety of high data rate services and growing number of users of cellular networks. Since spectrum and power are critical resources in the design of such a network, a framework is presented that addresses efficient utilization of these resources in mmWave cellular networks in the 28 and 73 GHz bands. These bands are already an integral part of well-known standards such as IEEE 802.15.3c, IEEE 802.11ad, and IEEE 802.16.1. In the analysis, a well-known accurate mmWave channel model for Line of Sight (LOS and Non-Line of Sight (NLOS links is used. The cellular network is analyzed in terms of spectral efficiency, bit/s, energy efficiency, bit/J, area spectral efficiency, bit/s/m2, area energy efficiency, bit/J/m2, and network latency, s/bit. These efficiency metrics are illustrated, using Monte Carlo simulation, as a function of Signal-to-Noise Ratio (SNR, channel model parameters, user distance from BS, and BS transmission power. The efficiency metrics for optimum deployment of cellular networks in 28 and 73 GHz bands are identified. Results show that 73 GHz band achieves better spectrum efficiency and the 28 GHz band is superior in terms of energy efficiency. It is observed that while the latter band is expedient for indoor networks, the former band is appropriate for outdoor networks.

New efficient five-input majority gate for quantum-dot cellular automata

International Nuclear Information System (INIS)

Farazkish, Razieh; Navi, Keivan

2012-01-01

A novel fault-tolerant five-input majority gate for quantum-dot cellular automata is presented. Quantum-dot cellular automata (QCA) is an emerging technology which is considered to be presented in future computers. Two principle logic elements in QCA are “majority gate” and “inverter.” In this paper, we propose a new approach to the design of fault-tolerant five-input majority gate by considering two-dimensional arrays of QCA cells. We analyze fault tolerance properties of such block five-input majority gate in terms of misalignment, missing, and dislocation cells. Some physical proofs are used for verifying five-input majority gate circuit layout and functionality. Our results clearly demonstrate that the redundant version of the block five-input majority gate is more robust than the standard style for this gate.

TFEB and TFE3: Linking Lysosomes to Cellular Adaptation to Stress.

Science.gov (United States)

Raben, Nina; Puertollano, Rosa

2016-10-06

In recent years, our vision of lysosomes has drastically changed. Formerly considered to be mere degradative compartments, they are now recognized as key players in many cellular processes. The ability of lysosomes to respond to different stimuli revealed a complex and coordinated regulation of lysosomal gene expression. This review discusses the participation of the transcription factors TFEB and TFE3 in the regulation of lysosomal function and biogenesis, as well as the role of the lysosomal pathway in cellular adaptation to a variety of stress conditions, including nutrient deprivation, mitochondrial dysfunction, protein misfolding, and pathogen infection. We also describe how cancer cells make use of TFEB and TFE3 to promote their own survival and highlight the potential of these transcription factors as therapeutic targets for the treatment of neurological and lysosomal diseases.

Imaging in cellular and tissue engineering

CERN Document Server

Yu, Hanry

2013-01-01

Details on specific imaging modalities for different cellular and tissue engineering applications are scattered throughout articles and chapters in the literature. Gathering this information into a single reference, Imaging in Cellular and Tissue Engineering presents both the fundamentals and state of the art in imaging methods, approaches, and applications in regenerative medicine. The book underscores the broadening scope of imaging applications in cellular and tissue engineering. It covers a wide range of optical and biological applications, including the repair or replacement of whole tiss

Anterior gradient protein-2 is a regulator of cellular adhesion in prostate cancer.

Directory of Open Access Journals (Sweden)

Diptiman Chanda

Full Text Available Anterior Gradient Protein (AGR-2 is reported to be over-expressed in many epithelial cancers and promotes metastasis. A clear-cut mechanism for its observed function(s has not been previously identified. We found significant upregulation of AGR-2 expression in a bone metastatic prostate cancer cell line, PC3, following culturing in bone marrow-conditioned medium. Substantial AGR-2 expression was also confirmed in prostate cancer tissue specimens in patients with bone lesions. By developing stable clones of PC3 cells with varying levels of AGR-2 expression, we identified that abrogation of AGR-2 significantly reduced cellular attachment to fibronectin, collagen I, collagen IV, laminin I and fibrinogen. Loss of cellular adhesion was associated with sharp decrease in the expression of α4, α5, αV, β3 and β4 integrins. Failure to undergo apoptosis following detachment is a hallmark of epithelial cancer metastasis. The AGR-2-silenced PC3 cells showed higher resistance to Tumor necrosis factor-related apoptosis- inducing ligand (TRAIL induced apoptosis in vitro. This observation was also supported by significantly reduced Caspase-3 expression in AGR-2-silenced PC3 cells, which is a key effector of both extrinsic and intrinsic death signaling pathways. These data suggest that AGR-2 influence prostate cancer metastasis by regulation of cellular adhesion and apoptosis.

Structural requirements for the assembly of LINC complexes and their function in cellular mechanical stiffness

International Nuclear Information System (INIS)

Stewart-Hutchinson, P.J.; Hale, Christopher M.; Wirtz, Denis; Hodzic, Didier

2008-01-01

The evolutionary-conserved interactions between KASH and SUN domain-containing proteins within the perinuclear space establish physical connections, called LINC complexes, between the nucleus and the cytoskeleton. Here, we show that the KASH domains of Nesprins 1, 2 and 3 interact promiscuously with luminal domains of Sun1 and Sun2. These constructs disrupt endogenous LINC complexes as indicated by the displacement of endogenous Nesprins from the nuclear envelope. We also provide evidence that KASH domains most probably fit a pocket provided by SUN domains and that post-translational modifications are dispensable for that interaction. We demonstrate that the disruption of endogenous LINC complexes affect cellular mechanical stiffness to an extent that compares to the loss of mechanical stiffness previously reported in embryonic fibroblasts derived from mouse lacking A-type lamins, a mouse model of muscular dystrophies and cardiomyopathies. These findings support a model whereby physical connections between the nucleus and the cytoskeleton are mediated by interactions between diverse combinations of Sun proteins and Nesprins through their respective evolutionary-conserved domains. Furthermore, they emphasize, for the first time, the relevance of LINC complexes in cellular mechanical stiffness suggesting a possible involvement of their disruption in various laminopathies, a group of human diseases linked to mutations of A-type lamins

Global exponential stability of fuzzy cellular neural networks with delays and reaction-diffusion terms

International Nuclear Information System (INIS)

Wang Jian; Lu Junguo

2008-01-01

In this paper, we study the global exponential stability of fuzzy cellular neural networks with delays and reaction-diffusion terms. By constructing a suitable Lyapunov functional and utilizing some inequality techniques, we obtain a sufficient condition for the uniqueness and global exponential stability of the equilibrium solution for a class of fuzzy cellular neural networks with delays and reaction-diffusion terms. The result imposes constraint conditions on the network parameters independently of the delay parameter. The result is also easy to check and plays an important role in the design and application of globally exponentially stable fuzzy neural circuits

Simulation of diffusion in a two-dimensional lattice gas cellular automaton: a test of mode-coupling theory

NARCIS (Netherlands)

Frenkel, D.; Ernst, M.H.

1989-01-01

We compute the velocity autocorrelation function of a tagged particle in a two-dimensional lattice-gas cellular automaton using a method that is about a million times more efficient than existing techniques. A t-1 algebraic tail in the tagged-particle velocity autocorrelation function is clearly

Advances in high-resolution imaging--techniques for three-dimensional imaging of cellular structures.

Science.gov (United States)

Lidke, Diane S; Lidke, Keith A

2012-06-01

A fundamental goal in biology is to determine how cellular organization is coupled to function. To achieve this goal, a better understanding of organelle composition and structure is needed. Although visualization of cellular organelles using fluorescence or electron microscopy (EM) has become a common tool for the cell biologist, recent advances are providing a clearer picture of the cell than ever before. In particular, advanced light-microscopy techniques are achieving resolutions below the diffraction limit and EM tomography provides high-resolution three-dimensional (3D) images of cellular structures. The ability to perform both fluorescence and electron microscopy on the same sample (correlative light and electron microscopy, CLEM) makes it possible to identify where a fluorescently labeled protein is located with respect to organelle structures visualized by EM. Here, we review the current state of the art in 3D biological imaging techniques with a focus on recent advances in electron microscopy and fluorescence super-resolution techniques.

Cellular response after irradiation: Cell cycle control and apoptosis

International Nuclear Information System (INIS)

Siles, E.; Valenzuela, M.T.; Nunez, M.I.; Guerrero, R.; Villalobos, M.; Ruiz de Almodovar, J.M.

1997-01-01

The importance of apoptotic death was assessed in a set of experiments, involving eight human tumour cell lines (breast cancer, bladder carcinoma, medulloblastoma). Various aspects of the quantitative study of apoptosis and methods based on the detection of DNA fragmentation (in situ tailing and comet assay) are described and discussed. Data obtained support the hypothesis that apoptosis is not crucial for cellular radiosensitivity and that the relationship between p53 functionality or clonogenic survival and apoptosis may bee cell type specific. (author)

Protein Corona Analysis of Silver Nanoparticles Links to Their Cellular Effects.

Science.gov (United States)

Juling, Sabine; Niedzwiecka, Alicia; Böhmert, Linda; Lichtenstein, Dajana; Selve, Sören; Braeuning, Albert; Thünemann, Andreas F; Krause, Eberhard; Lampen, Alfonso

2017-11-03

The breadth of applications of nanoparticles and the access to food-associated consumer products containing nanosized materials lead to oral human exposure to such particles. In biological fluids nanoparticles dynamically interact with biomolecules and form a protein corona. Knowledge about the protein corona is of great interest for understanding the molecular effects of particles as well as their fate inside the human body. We used a mass spectrometry-based toxicoproteomics approach to elucidate mechanisms of toxicity of silver nanoparticles and to comprehensively characterize the protein corona formed around silver nanoparticles in Caco-2 human intestinal epithelial cells. Results were compared with respect to the cellular function of proteins either affected by exposure to nanoparticles or present in the protein corona. A transcriptomic data set was included in the analyses in order to obtain a combined multiomics view of nanoparticle-affected cellular processes. A relationship between corona proteins and the proteomic or transcriptomic responses was revealed, showing that differentially regulated proteins or transcripts were engaged in the same cellular signaling pathways. Protein corona analyses of nanoparticles in cells might therefore help in obtaining information about the molecular consequences of nanoparticle treatment.

Movies of cellular and sub-cellular motion by digital holographic microscopy

Directory of Open Access Journals (Sweden)

Yu Lingfeng

2006-03-01

Full Text Available Abstract Background Many biological specimens, such as living cells and their intracellular components, often exhibit very little amplitude contrast, making it difficult for conventional bright field microscopes to distinguish them from their surroundings. To overcome this problem phase contrast techniques such as Zernike, Normarsky and dark-field microscopies have been developed to improve specimen visibility without chemically or physically altering them by the process of staining. These techniques have proven to be invaluable tools for studying living cells and furthering scientific understanding of fundamental cellular processes such as mitosis. However a drawback of these techniques is that direct quantitative phase imaging is not possible. Quantitative phase imaging is important because it enables determination of either the refractive index or optical thickness variations from the measured optical path length with sub-wavelength accuracy. Digital holography is an emergent phase contrast technique that offers an excellent approach in obtaining both qualitative and quantitative phase information from the hologram. A CCD camera is used to record a hologram onto a computer and numerical methods are subsequently applied to reconstruct the hologram to enable direct access to both phase and amplitude information. Another attractive feature of digital holography is the ability to focus on multiple focal planes from a single hologram, emulating the focusing control of a conventional microscope. Methods A modified Mach-Zender off-axis setup in transmission is used to record and reconstruct a number of holographic amplitude and phase images of cellular and sub-cellular features. Results Both cellular and sub-cellular features are imaged with sub-micron, diffraction-limited resolution. Movies of holographic amplitude and phase images of living microbes and cells are created from a series of holograms and reconstructed with numerically adjustable

Probing Cellular Dynamics with Mesoscopic Simulations

DEFF Research Database (Denmark)

Shillcock, Julian C.

2010-01-01

Cellular processes span a huge range of length and time scales from the molecular to the near-macroscopic. Understanding how effects on one scale influence, and are themselves influenced by, those on lower and higher scales is a critical issue for the construction of models in Systems Biology....... Advances in computing hardware and software now allow explicit simulation of some aspects of cellular dynamics close to the molecular scale. Vesicle fusion is one example of such a process. Experiments, however, typically probe cellular behavior from the molecular scale up to microns. Standard particle...... soon be coupled to Mass Action models allowing the parameters in such models to be continuously tuned according to the finer resolution simulation. This will help realize the goal of a computational cellular simulation that is able to capture the dynamics of membrane-associated processes...

Wireless Cellular Mobile Communications

Directory of Open Access Journals (Sweden)

V. Zalud

2002-12-01

Full Text Available In this article is briefly reviewed the history of wireless cellularmobile communications, examined the progress in current secondgeneration (2G cellular standards and discussed their migration to thethird generation (3G. The European 2G cellular standard GSM and itsevolution phases GPRS and EDGE are described somewhat in detail. Thethird generation standard UMTS taking up on GSM/GPRS core network andequipped with a new advanced access network on the basis of codedivision multiple access (CDMA is investigated too. A sketch of theperspective of mobile communication beyond 3G concludes this article.

Exponential convergence for a class of delayed cellular neural networks with time-varying coefficients

International Nuclear Information System (INIS)

Liu Bingwen

2008-01-01

In this Letter, we consider a class of delayed cellular neural networks with time-varying coefficients. By applying Lyapunov functional method and differential inequality techniques, we establish new results to ensure that all solutions of the networks converge exponentially to zero point

Integrated Transceivers for Millimeter Wave and Cellular Communication

OpenAIRE

TIRED, TOBIAS

2016-01-01

Abstract:This doctoral thesis is addresses two topics in integrated circuit design: multiband direct conversion cellular receivers for cellular frequencies and beam steering transmitters for millimeter wave communication for the cellular backhaul. The trend towards cellular terminals supporting ever more different frequency bands has resulted in complex radio frontends with a large number of RF inputs. Common receivers have, for performance reasons, in the past used differential RF inputs. Ho...

The Changes of Energy Interactions between Nucleus Function and Mitochondria Functions Causing Transmutation of Chronic Inflammation into Cancer Metabolism.

Science.gov (United States)

Ponizovskiy, Michail R

2016-01-01

Interactions between nucleus and mitochondria functions induce the mechanism of maintenance stability of cellular internal energy according to the first law of thermodynamics in able-bodied cells and changes the mechanisms of maintenance stability of cellular internal energy creating a transition stationary state of ablebodied cells into quasi-stationary pathologic states of acute inflammation transiting then into chronic inflammation and then transmuting into cancer metabolism. The mechanisms' influences of intruding etiologic pathologic agents (microbe, virus, etc.) lead to these changes of energy interactions between nucleus and mitochondria functions causing general acute inflammation, then passing into local chronic inflammation, and reversing into cancer metabolism transmutation. Interactions between biochemical processes and biophysical processes of cellular capacitors' operations create a supplementary mechanism of maintenance stability of cellular internal energy in the norm and in pathology. Discussion of some scientific works eliminates doubts of the authors of these works.

Probabilistic cellular automata: Some statistical mechanical considerations

International Nuclear Information System (INIS)

Lebowitz, J.L.; Maes, C.; Speer, E.R.

1990-01-01

Spin systems evolving in continuous or discrete time under the action of stochastic dynamics are used to model phenomena as diverse as the structure of alloys and the functioning of neural networks. While in some cases the dynamics are secondary, designed to produce a specific stationary measure whose properties one is interested in studying, there are other cases in which the only available information is the dynamical rule. Prime examples of the former are computer simulations, via Glauber dynamics, of equilibrium Gibbs measures with a specified interaction potential. Examples of the latter include various types of majority rule dynamics used as models for pattern recognition and for error-tolerant computations. The present note discusses ways in which techniques found useful in equilibrium statistical mechanics can be applied to a particular class of models of the latter types. These are cellular automata with noise: systems in which the spins are updated stochastically at integer times, simultaneously at all sites of some regular lattice. These models were first investigated in detail in the Soviet literature of the late sixties and early seventies. They are now generally referred to as Stochastic or Probabilistic Cellular Automata (PCA), and may be considered to include deterministic automata (CA) as special limits. 16 refs., 3 figs

Filovirus tropism: Cellular molecules for viral entry

Directory of Open Access Journals (Sweden)

Ayato eTakada

2012-02-01

Full Text Available In human and nonhuman primates, filoviruses (Ebola and Marburg viruses cause severe hemorrhagic fever．Recently, other animals such as pigs and some species of fruit bats have also been shown to be susceptible to these viruses. While having a preference for some cell types such as hepatocytes, endothelial cells, dendritic cells, monocytes, and macrophages, filoviruses are known to be pantropic in infection of primates. The envelope glycoprotein (GP is responsible for both receptor binding and fusion of the virus envelope with the host cell membrane. It has been demonstrated that filovirus GP interacts with multiple molecules for entry into host cells, whereas none of the cellular molecules so far identified as a receptor/coreceptor fully explains filovirus tissue tropism and host range. Available data suggest that the mucin-like region (MLR on GP plays an important role in attachment to the preferred target cells, whose infection is likely involved in filovirus pathogenesis, whereas the MLR is not essential for the fundamental function of the GP in viral entry into cells in vitro. Further studies elucidating the mechanisms of cellular entry of filoviruses may shed light on the development of strategies for prophylaxis and treatment of Ebola and Marburg hemorrhagic fevers.

Toxicity of pyrolysis gases from some cellular polymers

Science.gov (United States)

Hilado, C. J.; Machado, A. M.

1978-01-01

Various samples of cellular polymers were evaluated for toxicity of pyrolysis gases, using the screening test method developed at the University of San Francisco. The cellular polymer samples included polyimide, polymethacrylimide, polybismaleimide, polyurethane, polyisocyanurate, polyethylene, polychloroprene, polyvinyl chloride, polystyrene, polysiloxane, and polyphosphazene. The cellular polymers exhibited varying levels of toxicity under these test conditions. Among the rigid cellular polymers, times to death were shortest with the imide type foams and longest with polyvinyl chloride and polystyrene. Among the flexible cellular polymers, times to death were shortest with polyimide and polyester, and longest with polychloroprene and polysiloxane. Increased char yield was not necessarily associated with reduced toxicity.

A new concept for medical imaging centered on cellular phone technology.

Directory of Open Access Journals (Sweden)

Yair Granot

2008-04-01

Full Text Available According to World Health Organization reports, some three quarters of the world population does not have access to medical imaging. In addition, in developing countries over 50% of medical equipment that is available is not being used because it is too sophisticated or in disrepair or because the health personnel are not trained to use it. The goal of this study is to introduce and demonstrate the feasibility of a new concept in medical imaging that is centered on cellular phone technology and which may provide a solution to medical imaging in underserved areas. The new system replaces the conventional stand-alone medical imaging device with a new medical imaging system made of two independent components connected through cellular phone technology. The independent units are: a a data acquisition device (DAD at a remote patient site that is simple, with limited controls and no image display capability and b an advanced image reconstruction and hardware control multiserver unit at a central site. The cellular phone technology transmits unprocessed raw data from the patient site DAD and receives and displays the processed image from the central site. (This is different from conventional telemedicine where the image reconstruction and control is at the patient site and telecommunication is used to transmit processed images from the patient site. The primary goal of this study is to demonstrate that the cellular phone technology can function in the proposed mode. The feasibility of the concept is demonstrated using a new frequency division multiplexing electrical impedance tomography system, which we have developed for dynamic medical imaging, as the medical imaging modality. The system is used to image through a cellular phone a simulation of breast cancer tumors in a medical imaging diagnostic mode and to image minimally invasive tissue ablation with irreversible electroporation in a medical imaging interventional mode.

Cellular telephone use and cancer risk

DEFF Research Database (Denmark)

Schüz, Joachim; Jacobsen, Rune; Olsen, Jørgen H.

2006-01-01

BACKGROUND: The widespread use of cellular telephones has heightened concerns about possible adverse health effects. The objective of this study was to investigate cancer risk among Danish cellular telephone users who were followed for up to 21 years. METHODS: This study is an extended follow......-up of a large nationwide cohort of 420,095 persons whose first cellular telephone subscription was between 1982 and 1995 and who were followed through 2002 for cancer incidence. Standardized incidence ratios (SIRs) were calculated by dividing the number of observed cancer cases in the cohort by the number...... expected in the Danish population. RESULTS: A total of 14,249 cancers were observed (SIR = 0.95; 95% confidence interval [CI] = 0.93 to 0.97) for men and women combined. Cellular telephone use was not associated with increased risk for brain tumors (SIR = 0.97), acoustic neuromas (SIR = 0.73), salivary...

Wavefront cellular learning automata.

Science.gov (United States)

Moradabadi, Behnaz; Meybodi, Mohammad Reza

2018-02-01

This paper proposes a new cellular learning automaton, called a wavefront cellular learning automaton (WCLA). The proposed WCLA has a set of learning automata mapped to a connected structure and uses this structure to propagate the state changes of the learning automata over the structure using waves. In the WCLA, after one learning automaton chooses its action, if this chosen action is different from the previous action, it can send a wave to its neighbors and activate them. Each neighbor receiving the wave is activated and must choose a new action. This structure for the WCLA is necessary in many dynamic areas such as social networks, computer networks, grid computing, and web mining. In this paper, we introduce the WCLA framework as an optimization tool with diffusion capability, study its behavior over time using ordinary differential equation solutions, and present its accuracy using expediency analysis. To show the superiority of the proposed WCLA, we compare the proposed method with some other types of cellular learning automata using two benchmark problems.

Wavefront cellular learning automata

Science.gov (United States)

Moradabadi, Behnaz; Meybodi, Mohammad Reza

2018-02-01

This paper proposes a new cellular learning automaton, called a wavefront cellular learning automaton (WCLA). The proposed WCLA has a set of learning automata mapped to a connected structure and uses this structure to propagate the state changes of the learning automata over the structure using waves. In the WCLA, after one learning automaton chooses its action, if this chosen action is different from the previous action, it can send a wave to its neighbors and activate them. Each neighbor receiving the wave is activated and must choose a new action. This structure for the WCLA is necessary in many dynamic areas such as social networks, computer networks, grid computing, and web mining. In this paper, we introduce the WCLA framework as an optimization tool with diffusion capability, study its behavior over time using ordinary differential equation solutions, and present its accuracy using expediency analysis. To show the superiority of the proposed WCLA, we compare the proposed method with some other types of cellular learning automata using two benchmark problems.

The preventive effect of vitamin C on the cellular and functional integrity of kidney cells in rats following repeated exposure to paraquat

Directory of Open Access Journals (Sweden)

Benjamin Nnamdi Okolonkwo

2014-11-01

Full Text Available Paraquat (PQ is a bipyridylium herbicide that is applied around trees in orchards and between crop rows to control broad-leaved and grassy weeds. Its oxidation results in the formation of superoxides which causes damage to cellular components. In this study, we determined the antioxidant effect vitamin C has on the cellular integrity of kidney function in rats following repeated exposure to PQ. Ninety-six male rats, grouped twelve rats per subgroup (A, Avit.c, B, Bvit.c, C, Cvit.c, D and Dvit.c were intraperitoneally injected with different sublethal increasing doses (0, 0, 2, 2, 4, 4, 6 and 6 mg/kg body weight of PQ respectively on biweekly (14 days intervals over a period of three months (84 days. Subsequently, the subgrouped animals (Avit.c, Bvit.c, Cvit.c and Dvit.c were maintained orally with 1 g/L vitamin C, while the other subgrouped animals (A, B, C and D received drinking water with negligible vitamin content throughout the study period. At the end of each monthly (28 days treatment, four animals per subgroup were selected. Urine samples were collected from each of the selected rats, after which each of the animals were anaesthetized with gaseous isoflurane and 5 mL of blood samples were collected using cardiac puncture procedure. The animals were later decapitated and their kidneys harvested. The samples collected were analyzed for urine [specific gravity (SG, pH, protein and glucose], blood (urea, creatinine, total protein and glucose, and the histological studies on kidney slides. The dose and exposure- time dependent PQ toxicity resulted in the reduction in urinary pH, elevation in urinary SG, and the detectable presence of protein and glucose in urine. It also caused marked elevation in serum urea and creatinine levels with reduction in serum protein and glucose levels and alterations in the cellular integrity of the renal architecture, especially the glomeruli and tubular tissues. Treatments on the PQ insulted animals with vitamin

Cellular characterization of human dermal fibroblasts, focus on mitochondria and maple syrup urine disease

DEFF Research Database (Denmark)

Fernandez-Guerra, Paula

and functions are expressed in HDFs’ culture environment. Studies of molecular disease mechanisms often point to the involvement of mitochondria. Mitochondria are involved in the regulation of cell cycle and programmed cell death as well as cellular stress responses because they are the main producers...

Cellularity of certain quantum endomorphism algebras

DEFF Research Database (Denmark)

Andersen, Henning Haahr; Lehrer, G. I.; Zhang, R.

Let $\\tA=\\Z[q^{\\pm \\frac{1}{2}}][([d]!)\\inv]$ and let $\\Delta_{\\tA}(d)$ be an integral form of the Weyl module of highest weight $d \\in \\N$ of the quantised enveloping algebra $\\U_{\\tA}$ of $\\fsl_2$. We exhibit for all positive integers $r$ an explicit cellular structure for $\\End...... of endomorphism algebras, and another which relates the multiplicities of indecomposable summands to the dimensions of simple modules for an endomorphism algebra. Our cellularity result then allows us to prove that knowledge of the dimensions of the simple modules of the specialised cellular algebra above...

Influence of extra-cellular and intra-cellular acting thiol oxidants on the 45calcium uptake by the islets of Langerhans of the rat

International Nuclear Information System (INIS)

Haegele, R.G.

1981-01-01

The glucose-stimulated calcium uptake by the islets of Langerhans is dependent on the intra-cellular GSH/GSSG ratios. The inhibition of calcium uptake is not the consequence of a direct oxidation of membrane-fixed thiol groups. In contrast, direct oxidation of extra cellular thiols leads to an increase in calcium uptake when intra-cellular oxidation is simultaneously prevented. Since this effect only occurs at high intra-cellular GSH/GSSG ratios it can be assumed that the redox state of extra-cellular thiols is dependent on the redox state of the intra-cellular GSH/GSSG ratios. These findings support the theory that the oxidation of extra-cellular thiols by thiol oxidants leads to an increase in calcium uptake and that the extent of uptake is higher, the more the redox state of the extra-cellular thiols tends towards the reduced state prior to oxidation. (orig./MG) [de

Effect of adenosine cyclophosphate combined with vitamin C on cellular immune function of children with viral myocarditis

Directory of Open Access Journals (Sweden)

Xiu Chang

2016-06-01

Full Text Available Objective: To investigate the curative effect of adenosine cyclophosphate combined with vitamin C on children with viral myocarditis andon cellular immune function. Methods: A total of 96 cases of children with viral myocarditis were randomly divided into control group and observation group, 48 cases in each. The control group received routine treatment for viral myocarditis. The observation group received routine treatment for viral myocarditis as well as vitamin C and adenosine cyclophosphate. Results: The total effective rate of observation group 89.59% was higher than that of control group 64.58%, and differences were statistical significant. The electrocardiogram total effective rate of observation group 91.67% was higher than that of control group 68.75%, and differences were statistical significant. After treatment, the level of CD3+ (65.09±10.35%, the level of CD4+ (42.93±6.22%, the level of CD8+ (29.55±4.87% and the level of NK (47.37±8.52% of observation group were higher than the level of CD3+ (51.85±9.33%, the level of CD4+ (35.18±5.73%, the level of CD8+ (24.46±4.03% and the level of NK (35.64±7.72% of control group, and differences were statistical significant. After treatment, myocardial enzyme indexes lactate dehydrogenase (329.65±19.76 U/L, creatine phosphate kinase (126.36±12.92 U/L, hydroxybutyrate dehydrogenase (271.68±14.73 U/L, glutamic oxaloacetic transaminase (31.22±3.76 U/ L and creatine kinase (185.28±13.83 U/L of observation group were lower than lactate dehydrogenase (348.06±20.51 U/L, creatine phosphate kinase (163.19±13.15 U/L, hydroxybutyrate dehydrogenase (305.50±16.42 U/L, glutamic oxaloacetic transaminase (37.87±4.07 U/L and creatine kinase (202.79±15.47 U/L of control group, and differences were statistical significant. After treatment, heart function indexes CI, FS and EF levels of observation group were higher than those of control group, and differences were statistical significant

Modems for emerging digital cellular-mobile radio system

Science.gov (United States)

Feher, Kamilo

1991-01-01

Digital modem techniques for emerging digital cellular telecommunications-mobile radio system applications are described and analyzed. In particular, theoretical performance, experimental results, principles of operation, and various architectures of pi/4-QPSK (pi/4-shifted coherent or differential QPSK) modems for second-generation US digital cellular radio system applications are presented. The spectral/power efficiency and performance of the pi/4-QPSK modems (American and Japanese digital cellular emerging standards) are studied and briefly compared to GMSK (Gaussian minimum-shift keying) modems (proposed for European DECT and GSM cellular standards). Improved filtering strategies and digital pilot-aided (digital channel sounding) techniques are also considered for pi/4-QPSK and other digital modems. These techniques could significantly improve the performance of digital cellular and other digital land mobile and satellite mobile radio systems. More spectrally efficient modem trends for future cellular/mobile (land mobile) and satellite communication systems applications are also highlighted.

Molecular genetic approaches to the study of cellular senescence.

Science.gov (United States)

Goletz, T J; Smith, J R; Pereira-Smith, O M

1994-01-01

Cellular senescence is an inability of cells to synthesize DNA and divide, which results in a terminal loss of proliferation despite the maintenance of basic metabolic processes. Senescence has been proposed as a model for the study of aging at the cellular level, and the basis for this model system and its features have been summarized. Although strong experimental evidence exists to support the hypothesis that cellular senescence is a dominant active process, the mechanisms responsible for this phenomenon remain a mystery. Investigators have taken several approaches to gain a better understanding of senescence. Several groups have documented the differences between young and senescent cells, and others have identified changes that occur during the course of a cell's in vitro life span. Using molecular and biochemical approaches, important changes in gene expression and function of cell-cycle-associated products have been identified. The active production of an inhibitor of DNA synthesis has been demonstrated. This may represent the final step in a cascade of events governing senescence. The study of immortal cells which have escaped senescence has also provided useful information, particularly with regard to the genes governing the senescence program. These studies have identified four complementation groups for indefinite division, which suggests that there are at least four genes or gene pathways in the senescence program. Through the use of microcell-mediated chromosome transfer, chromosomes encoding senescence genes have been identified; efforts to clone these genes are ongoing.(ABSTRACT TRUNCATED AT 250 WORDS)

Cellular-automata supercomputers for fluid-dynamics modeling

International Nuclear Information System (INIS)

Margolus, N.; Toffoli, T.; Vichniac, G.

1986-01-01

We report recent developments in the modeling of fluid dynamics, and give experimental results (including dynamical exponents) obtained using cellular automata machines. Because of their locality and uniformity, cellular automata lend themselves to an extremely efficient physical realization; with a suitable architecture, an amount of hardware resources comparable to that of a home computer can achieve (in the simulation of cellular automata) the performance of a conventional supercomputer

A learning algorithm for oscillatory cellular neural networks.

Science.gov (United States)

Ho, C Y.; Kurokawa, H

1999-07-01

We present a cellular type oscillatory neural network for temporal segregation of stationary input patterns. The model comprises an array of locally connected neural oscillators with connections limited to a 4-connected neighborhood. The architecture is reminiscent of the well-known cellular neural network that consists of local connection for feature extraction. By means of a novel learning rule and an initialization scheme, global synchronization can be accomplished without incurring any erroneous synchrony among uncorrelated objects. Each oscillator comprises two mutually coupled neurons, and neurons share a piecewise-linear activation function characteristic. The dynamics of traditional oscillatory models is simplified by using only one plastic synapse, and the overall complexity for hardware implementation is reduced. Based on the connectedness of image segments, it is shown that global synchronization and desynchronization can be achieved by means of locally connected synapses, and this opens up a tremendous application potential for the proposed architecture. Furthermore, by using special grouping synapses it is demonstrated that temporal segregation of overlapping gray-level and color segments can also be achieved. Finally, simulation results show that the learning rule proposed circumvents the problem of component mismatches, and hence facilitates a large-scale integration.

Analysis of Human Mobility Based on Cellular Data

Science.gov (United States)

Arifiansyah, F.; Saptawati, G. A. P.

2017-01-01

Nowadays not only adult but even teenager and children have then own mobile phones. This phenomena indicates that the mobile phone becomes an important part of everyday’s life. Based on these indication, the amount of cellular data also increased rapidly. Cellular data defined as the data that records communication among mobile phone users. Cellular data is easy to obtain because the telecommunications company had made a record of the data for the billing system of the company. Billing data keeps a log of the users cellular data usage each time. We can obtained information from the data about communication between users. Through data visualization process, an interesting pattern can be seen in the raw cellular data, so that users can obtain prior knowledge to perform data analysis. Cellular data processing can be done using data mining to find out human mobility patterns and on the existing data. In this paper, we use frequent pattern mining and finding association rules to observe the relation between attributes in cellular data and then visualize them. We used weka tools for finding the rules in stage of data mining. Generally, the utilization of cellular data can provide supporting information for the decision making process and become a data support to provide solutions and information needed by the decision makers.

Terminal addition in a cellular world.

Science.gov (United States)

Torday, J S; Miller, William B

2018-07-01

Recent advances in our understanding of evolutionary development permit a reframed appraisal of Terminal Addition as a continuous historical process of cellular-environmental complementarity. Within this frame of reference, evolutionary terminal additions can be identified as environmental induction of episodic adjustments to cell-cell signaling patterns that yield the cellular-molecular pathways that lead to differing developmental forms. Phenotypes derive, thereby, through cellular mutualistic/competitive niche constructions in reciprocating responsiveness to environmental stresses and epigenetic impacts. In such terms, Terminal Addition flows according to a logic of cellular needs confronting environmental challenges over space-time. A reconciliation of evolutionary development and Terminal Addition can be achieved through a combined focus on cell-cell signaling, molecular phylogenies and a broader understanding of epigenetic phenomena among eukaryotic organisms. When understood in this manner, Terminal Addition has an important role in evolutionary development, and chronic disease might be considered as a form of 'reverse evolution' of the self-same processes. Copyright © 2017. Published by Elsevier Ltd.

Cellular modeling of fault-tolerant multicomputers

Energy Technology Data Exchange (ETDEWEB)

Morgan, G

1987-01-01

Work described was concerned with a novel method for investigation of fault tolerance in large regular networks of computers. Motivation was to provide a technique useful in rapid evaluation of highly reliable systems that exploit the low cost and ease of volume production of simple microcomputer components. First, a system model and simulator based upon cellular automata are developed. This model is characterized by its simplicity and ease of modification when adapting to new types of network. Second, in order to test and verify the predictive capabilities of the cellular system, a more-detailed simulation is performed based upon an existing computational model, that of the Transputer. An example application is used to exercise various systems designed using the cellular model. Using this simulator, experimental results are obtained both for existing well-understood configurations and for more novel types also developed here. In all cases it was found that the cellular model and simulator successfully predicted the ranking in reliability improvement of the systems studied.

Amine functionalized nanodiamond promotes cellular adhesion, proliferation and neurite outgrowth

International Nuclear Information System (INIS)

Hopper, A P; Dugan, J M; Gill, A A; Haycock, J W; Claeyssens, F; Fox, O J L; May, P W

2014-01-01

In this study, we report the production of amine functionalized nanodiamond. The amine functionalized nanodiamond forms a conformal monolayer on a negatively charged surface produced via plasma polymerization of acrylic acid. Nanodiamond terminated surfaces were studied as substrates for neuronal cell culture. NG108-15 neuroblastoma-glyoma hybrid cells were successfully cultured upon amine functionalized nanodiamond coated surfaces for between 1 and 7 d. Additionally, primary dorsal root ganglion (DRG) neurons and Schwann cells isolated from Wistar rats were also successfully cultured over a period of 21 d illustrating the potential of the coating for applications in the treatment of peripheral nerve injury. (paper)

Drosophila melanogaster cellular repressor of E1A-stimulated genes is a lysosomal protein essential for fly development

OpenAIRE

Kowalewski-Nimmerfall, Elisabeth; Sch?hs, Philipp; Maresch, Daniel; Rendic, Dubravko; Kr?mer, Helmut; Mach, Lukas

2014-01-01

Mammalian cellular repressor of E1A-stimulated genes is a lysosomal glycoprotein implicated in cellular growth and differentiation. The genome of the fruit fly Drosophila melanogaster encodes a putative orthologue (dCREG), suggesting evolutionarily conserved physiological functions of this protein. In D. melanogaster S2 cells, dCREG was found to localize in lysosomes. Further studies revealed that intracellular dCREG is subject of proteolytic maturation. Processing and turnover could be subst...

A radiation measurement study on cellular phone

International Nuclear Information System (INIS)

Mohd Yusof Mohd Ali; Rozaimah Abd Rahim; Roha Tukimin; Khairol Nizam Mohamed; Mohd Amirul Nizam Mohamad Thari; Ahmad Fadzli Ahmad Sanusi

2007-01-01

This paper will explain the radiation level produced by various selected cellular phone from various models and brands available in the market. The result obtained from this study will also recommend whether a cellular phone is safe for public usage or it might cause any effect on public health. Finally, a database of radiation measurement level produced by selected various cellular phone will also be developed and exhibited in this paper. (Author)

The role of focal adhesion kinase in the regulation of cellular mechanical properties

International Nuclear Information System (INIS)

Mierke, Claudia Tanja

2013-01-01

The regulation of mechanical properties is necessary for cell invasion into connective tissue or intra- and extravasation through the endothelium of blood or lymph vessels. Cell invasion is important for the regulation of many healthy processes such as immune response reactions and wound healing. In addition, cell invasion plays a role in disease-related processes such as tumor metastasis and autoimmune responses. Until now the role of focal adhesion kinase (FAK) in regulating mechanical properties of cells and its impact on cell invasion efficiency is still not well known. Thus, this review focuses on mechanical properties regulated by FAK in comparison to the mechano-regulating protein vinculin. Moreover, it points out the connection between cancer cell invasion and metastasis and FAK by showing that FAK regulates cellular mechanical properties required for cellular motility. Furthermore, it sheds light on the indirect interaction of FAK with vinculin by binding to paxillin, which then impairs the binding of paxillin to vinculin. In addition, this review emphasizes whether FAK fulfills regulatory functions similar to vinculin. In particular, it discusses the differences and the similarities between FAK and vinculin in regulating the biomechanical properties of cells. Finally, this paper highlights that both focal adhesion proteins, vinculin and FAK, synergize their functions to regulate the mechanical properties of cells such as stiffness and contractile forces. Subsequently, these mechanical properties determine cellular invasiveness into tissues and provide a source sink for future drug developments to inhibit excessive cell invasion and hence, metastases formation. (paper)

The role of focal adhesion kinase in the regulation of cellular mechanical properties

Science.gov (United States)

Mierke, Claudia Tanja

2013-12-01

The regulation of mechanical properties is necessary for cell invasion into connective tissue or intra- and extravasation through the endothelium of blood or lymph vessels. Cell invasion is important for the regulation of many healthy processes such as immune response reactions and wound healing. In addition, cell invasion plays a role in disease-related processes such as tumor metastasis and autoimmune responses. Until now the role of focal adhesion kinase (FAK) in regulating mechanical properties of cells and its impact on cell invasion efficiency is still not well known. Thus, this review focuses on mechanical properties regulated by FAK in comparison to the mechano-regulating protein vinculin. Moreover, it points out the connection between cancer cell invasion and metastasis and FAK by showing that FAK regulates cellular mechanical properties required for cellular motility. Furthermore, it sheds light on the indirect interaction of FAK with vinculin by binding to paxillin, which then impairs the binding of paxillin to vinculin. In addition, this review emphasizes whether FAK fulfills regulatory functions similar to vinculin. In particular, it discusses the differences and the similarities between FAK and vinculin in regulating the biomechanical properties of cells. Finally, this paper highlights that both focal adhesion proteins, vinculin and FAK, synergize their functions to regulate the mechanical properties of cells such as stiffness and contractile forces. Subsequently, these mechanical properties determine cellular invasiveness into tissues and provide a source sink for future drug developments to inhibit excessive cell invasion and hence, metastases formation.

Modeling of time dependent localized flow shear stress and its impact on cellular growth within additive manufactured titanium implants.

Science.gov (United States)

Zhang, Ziyu; Yuan, Lang; Lee, Peter D; Jones, Eric; Jones, Julian R

2014-11-01

Bone augmentation implants are porous to allow cellular growth, bone formation and fixation. However, the design of the pores is currently based on simple empirical rules, such as minimum pore and interconnects sizes. We present a three-dimensional (3D) transient model of cellular growth based on the Navier-Stokes equations that simulates the body fluid flow and stimulation of bone precursor cellular growth, attachment, and proliferation as a function of local flow shear stress. The model's effectiveness is demonstrated for two additive manufactured (AM) titanium scaffold architectures. The results demonstrate that there is a complex interaction of flow rate and strut architecture, resulting in partially randomized structures having a preferential impact on stimulating cell migration in 3D porous structures for higher flow rates. This novel result demonstrates the potential new insights that can be gained via the modeling tool developed, and how the model can be used to perform what-if simulations to design AM structures to specific functional requirements. © 2014 Wiley Periodicals, Inc.

Functional response of osteoblasts in functionally gradient titanium alloy mesh arrays processed by 3D additive manufacturing.

Science.gov (United States)

Nune, K C; Kumar, A; Misra, R D K; Li, S J; Hao, Y L; Yang, R

2017-02-01

We elucidate here the osteoblasts functions and cellular activity in 3D printed interconnected porous architecture of functionally gradient Ti-6Al-4V alloy mesh structures in terms of cell proliferation and growth, distribution of cell nuclei, synthesis of proteins (actin, vinculin, and fibronectin), and calcium deposition. Cell culture studies with pre-osteoblasts indicated that the interconnected porous architecture of functionally gradient mesh arrays was conducive to osteoblast functions. However, there were statistically significant differences in the cellular response depending on the pore size in the functionally gradient structure. The interconnected porous architecture contributed to the distribution of cells from the large pore size (G1) to the small pore size (G3), with consequent synthesis of extracellular matrix and calcium precipitation. The gradient mesh structure significantly impacted cell adhesion and influenced the proliferation stage, such that there was high distribution of cells on struts of the gradient mesh structure. Actin and vinculin showed a significant difference in normalized expression level of protein per cell, which was absent in the case of fibronectin. Osteoblasts present on mesh struts formed a confluent sheet, bridging the pores through numerous cytoplasmic extensions. The gradient mesh structure fabricated by electron beam melting was explored to obtain fundamental insights on cellular activity with respect to osteoblast functions. Copyright © 2016 Elsevier B.V. All rights reserved.

1,4-Naphthoquinones: From Oxidative Damage to Cellular and Inter-Cellular Signaling

Directory of Open Access Journals (Sweden)

Lars-Oliver Klotz

2014-09-01

Full Text Available Naphthoquinones may cause oxidative stress in exposed cells and, therefore, affect redox signaling. Here, contributions of redox cycling and alkylating properties of quinones (both natural and synthetic, such as plumbagin, juglone, lawsone, menadione, methoxy-naphthoquinones, and others to cellular and inter-cellular signaling processes are discussed: (i naphthoquinone-induced Nrf2-dependent modulation of gene expression and its potentially beneficial outcome; (ii the modulation of receptor tyrosine kinases, such as the epidermal growth factor receptor by naphthoquinones, resulting in altered gap junctional intercellular communication. Generation of reactive oxygen species and modulation of redox signaling are properties of naphthoquinones that render them interesting leads for the development of novel compounds of potential use in various therapeutic settings.

Cellular-automata method for phase unwrapping

International Nuclear Information System (INIS)

Ghiglia, D.C.; Mastin, G.A.; Romero, L.A.

1987-01-01

Research into two-dimensional phase unwrapping has uncovered interesting and troublesome inconsistencies that cause path-dependent results. Cellular automata, which are simple, discrete mathematical systems, offered promise of computation in nondirectional, parallel manner. A cellular automaton was discovered that can unwrap consistent phase data in n dimensions in a path-independent manner and can automatically accommodate noise-induced (pointlike) inconsistencies and arbitrary boundary conditions (region partitioning). For data with regional (nonpointlike) inconsistencies, no phase-unwrapping algorithm will converge, including the cellular-automata approach. However, the automata method permits more simple visualization of the regional inconsistencies. Examples of its behavior on one- and two-dimensional data are presented

Molecular and cellular endocrinology of the testis

International Nuclear Information System (INIS)

Stefanini, M.; Conti, M.; Geremia, R.; Ziparo, E.

1986-01-01

This volume contains the Proceedings of the IV European Workshop on Molecular and Cellular Endocrinology of the Testis held in Capri (Italy) between the 9th and 12th April 1986. The workshop was organized in several symposia related to some of the most relevant aspects of the regulation of testicular function. Main topics were the role of cell interactions, the mechanisms of signal transduction, gene expression and metabolic response of somatic cells as well as differentiation of germ cells. One session was devoted to prostaglandins in the male reproductive system and to brief discussions on interstitial fluid and on antispermatogenic compounds. In this book only the main lectures and some selected short papers are presented. (Auth.)

Cellular and molecular mechanisms coordinating pancreas development.

Science.gov (United States)

Bastidas-Ponce, Aimée; Scheibner, Katharina; Lickert, Heiko; Bakhti, Mostafa

2017-08-15

The pancreas is an endoderm-derived glandular organ that participates in the regulation of systemic glucose metabolism and food digestion through the function of its endocrine and exocrine compartments, respectively. While intensive research has explored the signaling pathways and transcriptional programs that govern pancreas development, much remains to be discovered regarding the cellular processes that orchestrate pancreas morphogenesis. Here, we discuss the developmental mechanisms and principles that are known to underlie pancreas development, from induction and lineage formation to morphogenesis and organogenesis. Elucidating such principles will help to identify novel candidate disease genes and unravel the pathogenesis of pancreas-related diseases, such as diabetes, pancreatitis and cancer. © 2017. Published by The Company of Biologists Ltd.

A cryptosystem based on elementary cellular automata

Science.gov (United States)

Abdo, A. A.; Lian, Shiguo; Ismail, I. A.; Amin, M.; Diab, H.

2013-01-01

Based on elementary cellular automata, a new image encryption algorithm is proposed in this paper. In this algorithm, a special kind of periodic boundary cellular automata with unity attractors is used. From the viewpoint of security, the number of cellular automata attractor states are changed with respect to the encrypted image, and different key streams are used to encrypt different plain images. The cellular neural network with chaotic properties is used as the generator of a pseudo-random key stream. Theoretical analysis and experimental results have both confirmed that the proposed algorithm possesses high security level and good performances against differential and statistical attacks. The comparison with other existing schemes is given, which shows the superiority of the proposal scheme.

Three-dimensional microscopic deformation measurements on cellular solids.

Science.gov (United States)

Genovese, K

2016-07-01

The increasing interest in small-scale problems demands novel experimental protocols providing dense sets of 3D deformation data of complex shaped microstructures. Obtaining such information is particularly significant for the study of natural and engineered cellular solids for which experimental data collected at macro scale and describing the global mechanical response provide only limited information on their function/structure relationship. Cellular solids, in fact, due their superior mechanical performances to a unique arrangement of the bulk material properties (i.e. anisotropy and heterogeneity) and cell structural features (i.e. pores shape, size and distribution) at the micro- and nano-scales. To address the need for full-field experimental data down to the cell level, this paper proposes a single-camera stereo-Digital Image Correlation (DIC) system that makes use of a wedge prism in series to a telecentric lens for performing surface shape and deformation measurements on microstructures in three dimensions. Although the system possesses a limited measurement volume (FOV~2.8×4.3mm(2), error-free DOF ~1mm), large surface areas of cellular samples can be accurately covered by employing a sequential image capturing scheme followed by an optimization-based mosaicing procedure. The basic principles of the proposed method together with the results of the benchmarking of its metrological performances and error analysis are here reported and discussed in detail. Finally, the potential utility of this method is illustrated with micro-resolution three-dimensional measurements on a 3D printed honeycomb and on a block sample of a Luffa sponge under compression. Copyright © 2016 Elsevier Ltd. All rights reserved.

Linking Cellular Mechanisms to Behavior: Entorhinal Persistent Spiking and Membrane Potential Oscillations May Underlie Path Integration, Grid Cell Firing, and Episodic Memory

Directory of Open Access Journals (Sweden)

Michael E. Hasselmo

2008-01-01

Full Text Available The entorhinal cortex plays an important role in spatial memory and episodic memory functions. These functions may result from cellular mechanisms for integration of the afferent input to entorhinal cortex. This article reviews physiological data on persistent spiking and membrane potential oscillations in entorhinal cortex then presents models showing how both these cellular mechanisms could contribute to properties observed during unit recording, including grid cell firing, and how they could underlie behavioural functions including path integration. The interaction of oscillations and persistent firing could contribute to encoding and retrieval of trajectories through space and time as a mechanism relevant to episodic memory.

Environment Aware Cellular Networks

KAUST Repository

Ghazzai, Hakim

2015-02-01

The unprecedented rise of mobile user demand over the years have led to an enormous growth of the energy consumption of wireless networks as well as the greenhouse gas emissions which are estimated currently to be around 70 million tons per year. This significant growth of energy consumption impels network companies to pay huge bills which represent around half of their operating expenditures. Therefore, many service providers, including mobile operators, are looking for new and modern green solutions to help reduce their expenses as well as the level of their CO2 emissions. Base stations are the most power greedy element in cellular networks: they drain around 80% of the total network energy consumption even during low traffic periods. Thus, there is a growing need to develop more energy-efficient techniques to enhance the green performance of future 4G/5G cellular networks. Due to the problem of traffic load fluctuations in cellular networks during different periods of the day and between different areas (shopping or business districts and residential areas), the base station sleeping strategy has been one of the main popular research topics in green communications. In this presentation, we present several practical green techniques that provide significant gains for mobile operators. Indeed, combined with the base station sleeping strategy, these techniques achieve not only a minimization of the fossil fuel consumption but also an enhancement of mobile operator profits. We start with an optimized cell planning method that considers varying spatial and temporal user densities. We then use the optimal transport theory in order to define the cell boundaries such that the network total transmit power is reduced. Afterwards, we exploit the features of the modern electrical grid, the smart grid, as a new tool of power management for cellular networks and we optimize the energy procurement from multiple energy retailers characterized by different prices and pollutant

Theoretical aspects of cellular decision-making and information-processing.

Science.gov (United States)

Kobayashi, Tetsuya J; Kamimura, Atsushi

2012-01-01

Microscopic biological processes have extraordinary complexity and variety at the sub-cellular, intra-cellular, and multi-cellular levels. In dealing with such complex phenomena, conceptual and theoretical frameworks are crucial, which enable us to understand seemingly different intra- and inter-cellular phenomena from unified viewpoints. Decision-making is one such concept that has attracted much attention recently. Since a number of cellular behavior can be regarded as processes to make specific actions in response to external stimuli, decision-making can cover and has been used to explain a broad range of different cellular phenomena [Balázsi et al. (Cell 144(6):910, 2011), Zeng et al. (Cell 141(4):682, 2010)]. Decision-making is also closely related to cellular information-processing because appropriate decisions cannot be made without exploiting the information that the external stimuli contain. Efficiency of information transduction and processing by intra-cellular networks determines the amount of information obtained, which in turn limits the efficiency of subsequent decision-making. Furthermore, information-processing itself can serve as another concept that is crucial for understanding of other biological processes than decision-making. In this work, we review recent theoretical developments on cellular decision-making and information-processing by focusing on the relation between these two concepts.

Interacting factors and cellular localization of SR protein-specific kinase Dsk1

International Nuclear Information System (INIS)

Tang, Zhaohua; Luca, Maria; Taggart-Murphy, Laura; Portillio, Jessica; Chang, Cathey; Guven, Ayse; Lin, Ren-Jang; Murray, Johanne; Carr, Antony

2012-01-01

Schizosaccharomyces pombe Dsk1 is an SR protein-specific kinase (SRPK), whose homologs have been identified in every eukaryotic organism examined. Although discovered as a mitotic regulator with protein kinase activity toward SR splicing factors, it remains largely unknown about what and how Dsk1 contributes to cell cycle and pre-mRNA splicing. In this study, we investigated the Dsk1 function by determining interacting factors and cellular localization of the kinase. Consistent with its reported functions, we found that pre-mRNA processing and cell cycle factors are prominent among the proteins co-purified with Dsk1. The identification of these factors led us to find Rsd1 as a novel Dsk1 substrate, as well as the involvement of Dsk1 in cellular distribution of poly(A) + RNA. In agreement with its role in nuclear events, we also found that Dsk1 is mainly localized in the nucleus during G 2 phase and at mitosis. Furthermore, we revealed the oscillation of Dsk1 protein in a cell cycle-dependent manner. This paper marks the first comprehensive analysis of in vivo Dsk1-associated proteins in fission yeast. Our results reflect the conserved role of SRPK family in eukaryotic organisms, and provide information about how Dsk1 functions in pre-mRNA processing and cell-division cycle.

Interacting factors and cellular localization of SR protein-specific kinase Dsk1

Energy Technology Data Exchange (ETDEWEB)

Tang, Zhaohua, E-mail: ztang@jsd.claremont.edu [W.M. Keck Science Center, The Claremont Colleges, Claremont, CA 91711 (United States); Luca, Maria; Taggart-Murphy, Laura; Portillio, Jessica; Chang, Cathey; Guven, Ayse [W.M. Keck Science Center, The Claremont Colleges, Claremont, CA 91711 (United States); Lin, Ren-Jang [Department of Molecular and Cellular Biology, Beckman Research Institute of the City of Hope, Duarte, CA 91010 (United States); Murray, Johanne; Carr, Antony [Genome Damage and Stability Center, University of Sussex, Falmer, BN1 9RQ (United Kingdom)

2012-10-01

Schizosaccharomyces pombe Dsk1 is an SR protein-specific kinase (SRPK), whose homologs have been identified in every eukaryotic organism examined. Although discovered as a mitotic regulator with protein kinase activity toward SR splicing factors, it remains largely unknown about what and how Dsk1 contributes to cell cycle and pre-mRNA splicing. In this study, we investigated the Dsk1 function by determining interacting factors and cellular localization of the kinase. Consistent with its reported functions, we found that pre-mRNA processing and cell cycle factors are prominent among the proteins co-purified with Dsk1. The identification of these factors led us to find Rsd1 as a novel Dsk1 substrate, as well as the involvement of Dsk1 in cellular distribution of poly(A){sup +} RNA. In agreement with its role in nuclear events, we also found that Dsk1 is mainly localized in the nucleus during G{sub 2} phase and at mitosis. Furthermore, we revealed the oscillation of Dsk1 protein in a cell cycle-dependent manner. This paper marks the first comprehensive analysis of in vivo Dsk1-associated proteins in fission yeast. Our results reflect the conserved role of SRPK family in eukaryotic organisms, and provide information about how Dsk1 functions in pre-mRNA processing and cell-division cycle.

Systemic evaluation of cellular reprogramming processes exploiting a novel R-tool: eegc.

Science.gov (United States)

Zhou, Xiaoyuan; Meng, Guofeng; Nardini, Christine; Mei, Hongkang

2017-08-15

Cells derived by cellular engineering, i.e. differentiation of induced pluripotent stem cells and direct lineage reprogramming, carry a tremendous potential for medical applications and in particular for regenerative therapies. These approaches consist in the definition of lineage-specific experimental protocols that, by manipulation of a limited number of biological cues-niche mimicking factors, (in)activation of transcription factors, to name a few-enforce the final expression of cell-specific (marker) molecules. To date, given the intricate complexity of biological pathways, these approaches still present imperfect reprogramming fidelity, with uncertain consequences on the functional properties of the resulting cells. We propose a novel tool eegc to evaluate cellular engineering processes, in a systemic rather than marker-based fashion, by integrating transcriptome profiling and functional analysis. Our method clusters genes into categories representing different states of (trans)differentiation and further performs functional and gene regulatory network analyses for each of the categories of the engineered cells, thus offering practical indications on the potential lack of the reprogramming protocol. eegc R package is released under the GNU General Public License within the Bioconductor project, freely available at https://bioconductor.org/packages/eegc/. christine.nardini.rsrc@gmail.com or hongkang.k.mei@gsk.com. Supplementary data are available at Bioinformatics online. © The Author(s) 2017. Published by Oxford University Press.

The cellular approach to band structure calculations

International Nuclear Information System (INIS)

Verwoerd, W.S.

1982-01-01

A short introduction to the cellular approach in band structure calculations is given. The linear cellular approach and its potantial applicability in surface structure calculations is given some consideration in particular

Simulation of earthquakes with cellular automata

Directory of Open Access Journals (Sweden)

P. G. Akishin

1998-01-01

Full Text Available The relation between cellular automata (CA models of earthquakes and the Burridge–Knopoff (BK model is studied. It is shown that the CA proposed by P. Bak and C. Tang,although they have rather realistic power spectra, do not correspond to the BK model. We present a modification of the CA which establishes the correspondence with the BK model.An analytical method of studying the evolution of the BK-like CA is proposed. By this method a functional quadratic in stress release, which can be regarded as an analog of the event energy, is constructed. The distribution of seismic events with respect to this “energy” shows rather realistic behavior, even in two dimensions. Special attention is paid to two-dimensional automata; the physical restrictions on compression and shear stiffnesses are imposed.

Adenylate kinase I does not affect cellular growth characteristics under normal and metabolic stress conditions.

NARCIS (Netherlands)

Bruin, W.C.C. de; Oerlemans, F.T.J.J.; Wieringa, B.

2004-01-01

Adenylate kinase (AK)-catalyzed phosphotransfer is essential in the maintenance of cellular energetic economy in cells of fully differentiated tissues with highly variable energy demand, such as muscle and brain. To investigate if AK isoenzymes have a comparable function in the energy-demand

The endoplasmic reticulum coat protein II transport machinery coordinates cellular lipid secretion and cholesterol biosynthesis

NARCIS (Netherlands)

Fryer, Lee G. D.; Jones, Bethan; Duncan, Emma J.; Hutchison, Claire E.; Ozkan, Tozen; Williams, Paul A.; Alder, Olivia; Nieuwdorp, Max; Townley, Anna K.; Mensenkamp, Arjen R.; Stephens, David J.; Dallinga-Thie, Geesje M.; Shoulders, Carol C.

2014-01-01

Triglycerides and cholesterol are essential for life in most organisms. Triglycerides serve as the principal energy storage depot and, where vascular systems exist, as a means of energy transport. Cholesterol is essential for the functional integrity of all cellular membrane systems. The endoplasmic

Cellular Adaptation: Culture conditions of R. opacus and bioflotation of apatite and quartz

Directory of Open Access Journals (Sweden)

Antonio Gutiérrez Merma

Full Text Available Abstract It is well known that the culture conditions of microorganisms may affect their surface properties, zeta potential and hydrophobicity via the modification of the cell wall functional groups or metabolic products. The R. opacus bacteria strain was separately adapted to the presence of apatite and quartz, after which a cellular adaptation procedure was developed by repeated sub-culturing with a successive increase in the mineral content. Zeta potential, surface tension, FTIR and microflotation studies were used to evaluate the behavior of the cells that were developed under defined culture conditions. The cellular adaptation induced a modification of the bacterial surface charge. The FTIR results showed a modification of its functional groups. The surface tension results suggested that longer growing time promoted a higher production of metabolites. The use of mineral-adapted cells promoted an improvement in the flotability of both minerals, but it was more significant for apatite flotation. Additionally, the mineral flotability remained unchanged when the cells developed under a longer culture time. Nevertheless, there was a reduction in the surface tension.

Some Properties of topological pressure on cellular automata

Directory of Open Access Journals (Sweden)

Chih-Hung Chang

2014-09-01

Full Text Available This paper investigates the ergodicity and the power rule of the topological pressure of a cellular automaton. If a cellular automaton is either leftmost or rightmost premutive (due to the terminology given by Hedlund [Math.~Syst.~Theor.~3, 320-375, 1969], then it is ergodic with respect to the uniform Bernoulli measure. More than that, the relation of topological pressure between the original cellular automaton and its power rule is expressed in a closed form. As an application, the topological pressure of a linear cellular automaton can be computed explicitly.

Cellular and molecular modifier pathways in tauopathies: the big picture from screening invertebrate models.

Science.gov (United States)

Hannan, Shabab B; Dräger, Nina M; Rasse, Tobias M; Voigt, Aaron; Jahn, Thomas R

2016-04-01

including, but not limited to, phosphorylation, cytoskeleton organization, axonal transport, regulation of cellular proteostasis, transcription, RNA metabolism, cell cycle regulation, and apoptosis. We discuss the utility and application of invertebrate models in elucidating the cellular and molecular functions of novel and uncharacterized disease modifiers identified in large-scale screens as well as for investigating the function of genes identified as risk factors in genome-wide association studies from human patients in the post-genomic era. In this review, we combined and summarized several large-scale modifier screens performed in invertebrate models to identify modifiers of tau toxicity. A summary of the screens show that diverse cellular processes are implicated in the modification of tau toxicity. Kinases and phosphatases are the most predominant class of modifiers followed by components required for cellular proteostasis and axonal transport and cytoskeleton elements. © 2016 International Society for Neurochemistry.

The Effects of Chronological Age on the Cellular Mechanics of Human Dermal Fibroblasts

Science.gov (United States)

Pan, Z.; Hung, V.; Kambhampati, S.; Ge, S. R.; Rafailovich, M.; Ghosh, K.; Clark, R.; Liu, Y. J.; Nakamura, T.; Shu, X. Z.; Prestwich, G.

2006-03-01

It is often observed that older people display diminished wound healing abilities. Understanding of this phenomenon is important for many in vivo applications of tissue engineering. In this study, the cell mechanics of dermal fibroblasts from 25, 40 and 84 years old female subjects were compared. These cells were cultured on functionalized hyaluronic acid hydrogel substrates which emulated physiological conditions in dermal tissue. The deformation of the substrate caused by cellular traction forces was detected by tracing the displacement of fluorescent beads embedded in the substrate using Digital Image Speckle Correlation. Then cellular traction forces were quantitatively determined by Finite Element Method in a linear elastic model with a high spatial resolution. These results were correlated with auxiliary measurements of substrate modulus, cell modulus and migration. We found that with increasing age, the magnitude of the cellular traction forces diminished. Similarly, the ability of the cells to adapt to changes in the mechanical properties of their environment and migrate was also impaired. The interrelationship between these factors and wound healing will be discussed. This work is supported by NSF- MRSEC program.

Mitochondrial morphology transitions and functions: implications for retrograde signaling?

Science.gov (United States)

Picard, Martin; Shirihai, Orian S.; Gentil, Benoit J.

2013-01-01

In response to cellular and environmental stresses, mitochondria undergo morphology transitions regulated by dynamic processes of membrane fusion and fission. These events of mitochondrial dynamics are central regulators of cellular activity, but the mechanisms linking mitochondrial shape to cell function remain unclear. One possibility evaluated in this review is that mitochondrial morphological transitions (from elongated to fragmented, and vice-versa) directly modify canonical aspects of the organelle's function, including susceptibility to mitochondrial permeability transition, respiratory properties of the electron transport chain, and reactive oxygen species production. Because outputs derived from mitochondrial metabolism are linked to defined cellular signaling pathways, fusion/fission morphology transitions could regulate mitochondrial function and retrograde signaling. This is hypothesized to provide a dynamic interface between the cell, its genome, and the fluctuating metabolic environment. PMID:23364527

Lipid Replacement Therapy: a Functional Food Approach with New Formulations for Reducing Cellular Oxidative Damage, Cancer-Associated Fatigue and the Adverse Effects of Cancer Therapy

Directory of Open Access Journals (Sweden)

Garth L. Nicolson

2011-04-01

Full Text Available Backgroud:Cancer-associated fatigue and the chronic adverse effects of cancer therapy can be reduced by Lipid Replacement Therapy (LRT using membrane phospholipid mixtures given as food supplements.Methods:This is a review of the published literature on LRT and its uses.Results: LRT significantly reduced fatigue in cancer patients as well as patients suffering from chronic fatiguing illnesses and other medical conditions. It also reduced the adverse effects of chemotherapy, resulting in improvements in incidence of fatigue, nausea, diarrhea, impaired taste, constipation, insomnia and other quality of life indicators. In other diseases, such as chronic fatigue syndrome, fibromyalgia syndrome and other chronic fatiguing illnesses, LRT reduced fatigue by 35.5-43.1% in different clinical trials and increased mitochondrial function.Conclusions: LRT formulations appear to be useful as non-toxic dietary supplements for direct use or placed in functional foods to reduce fatigue and restore mitochondrial and other cellular membrane functions. Formulations of LRT phospholipids are suitable for addition to variousfood products for the treatment of a variety of chronic illnesses as well as their application inanti-aging and other health supplements and products.

Role of toll-like receptors 3, 4 and 7 in cellular uptake and response to titanium dioxide nanoparticles

Directory of Open Access Journals (Sweden)

Peng Chen, Koki Kanehira and Akiyoshi Taniguchi

2013-01-01

Full Text Available Innate immune response is believed to be among the earliest provisional cellular responses, and mediates the interactions between microbes and cells. Toll-like receptors (TLRs are critical to these interactions. We hypothesize that TLRs also play an important role in interactions between nanoparticles (NPs and cells, although little information has been reported concerning such an interaction. In this study, we investigated the role of TLR3, TLR4 and TLR7 in cellular uptake of titanium dioxide NP (TiO2 NP agglomerates and the resulting inflammatory responses to these NPs. Our data indicate that TLR4 is involved in the uptake of TiO2 NPs and promotes the associated inflammatory responses. The data also suggest that TLR3, which has a subcellular location distinct from that of TLR4, inhibits the denaturation of cellular protein caused by TiO2 NPs. In contrast, the unique cellular localization of TLR7 has middle-ground functional roles in cellular response after TiO2 NP exposure. These findings are important for understanding the molecular interaction mechanisms between NPs and cells.

Micro-/nano-engineered cellular responses for soft tissue engineering and biomedical applications.

Science.gov (United States)

Tay, Chor Yong; Irvine, Scott Alexander; Boey, Freddy Y C; Tan, Lay Poh; Venkatraman, Subbu

2011-05-23

The development of biomedical devices and reconstruction of functional ex vivo tissues often requires the need to fabricate biomimetic surfaces with features of sub-micrometer precision. This can be achieved with the advancements in micro-/nano-engineering techniques, allowing researchers to manipulate a plethora of cellular behaviors at the cell-biomaterial interface. Systematic studies conducted on these 2D engineered surfaces have unraveled numerous novel findings that can potentially be integrated as part of the design consideration for future 2D and 3D biomaterials and will no doubt greatly benefit tissue engineering. In this review, recent developments detailing the use of micro-/nano-engineering techniques to direct cellular orientation and function pertinent to soft tissue engineering will be highlighted. Particularly, this article aims to provide valuable insights into distinctive cell interactions and reactions to controlled surfaces, which can be exploited to understand the mechanisms of cell growth on micro-/nano-engineered interfaces, and to harness this knowledge to optimize the performance of 3D artificial soft tissue grafts and biomedical applications. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Cellular self-assembly and biomaterials-based organoid models of development and diseases.

Science.gov (United States)

Shah, Shivem B; Singh, Ankur

2017-04-15

Organogenesis and morphogenesis have informed our understanding of physiology, pathophysiology, and avenues to create new curative and regenerative therapies. Thus far, this understanding has been hindered by the lack of a physiologically relevant yet accessible model that affords biological control. Recently, three-dimensional ex vivo cellular cultures created through cellular self-assembly under natural extracellular matrix cues or through biomaterial-based directed assembly have been shown to physically resemble and recapture some functionality of target organs. These "organoids" have garnered momentum for their applications in modeling human development and disease, drug screening, and future therapy design or even organ replacement. This review first discusses the self-organizing organoids as materials with emergent properties and their advantages and limitations. We subsequently describe biomaterials-based strategies used to afford more control of the organoid's microenvironment and ensuing cellular composition and organization. In this review, we also offer our perspective on how multifunctional biomaterials with precise spatial and temporal control could ultimately bridge the gap between in vitro organoid platforms and their in vivo counterparts. Several notable reviews have highlighted PSC-derived organoids and 3D aggregates, including embryoid bodies, from a development and cellular assembly perspective. The focus of this review is to highlight the materials-based approaches that cells, including PSCs and others, adopt for self-assembly and the controlled development of complex tissues, such as that of the brain, gut, and immune system. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Advanced 3D Printers for Cellular Solids

Science.gov (United States)

2016-06-30

06-2016 1-Aug-2014 31-Dec-2015 Final Report: Advanced 3D printers for Cellular Solids The views, opinions and/or findings contained in this report are...2211 3d printing, cellular solids REPORT DOCUMENTATION PAGE 11. SPONSOR/MONITOR’S REPORT NUMBER(S) 10. SPONSOR/MONITOR’S ACRONYM(S) ARO 8...Papers published in non peer-reviewed journals: Final Report: Advanced 3D printers for Cellular Solids Report Title Final Report for DURIP grant W911NF

On Elementary and Algebraic Cellular Automata

Science.gov (United States)

Gulak, Yuriy

In this paper we study elementary cellular automata from an algebraic viewpoint. The goal is to relate the emergent complex behavior observed in such systems with the properties of corresponding algebraic structures. We introduce algebraic cellular automata as a natural generalization of elementary ones and discuss their applications as generic models of complex systems.

Giant Thermal Expansion in 2D and 3D Cellular Materials.

Science.gov (United States)

Zhu, Hanxing; Fan, Tongxiang; Peng, Qing; Zhang, Di

2018-03-25

When temperature increases, the volume of an object changes. This property was quantified as the coefficient of thermal expansion only a few hundred years ago. Part of the reason is that the change of volume due to the variation of temperature is in general extremely small and imperceptible. Here, abnormal giant linear thermal expansions in different types of two-ingredient microstructured hierarchical and self-similar cellular materials are reported. The cellular materials can be 2D or 3D, and isotropic or anisotropic, with a positive or negative thermal expansion due to the convex or/and concave shape in their representative volume elements respectively. The magnitude of the thermal expansion coefficient can be several times larger than the highest value reported in the literature. This study suggests an innovative approach to develop temperature-sensitive functional materials and devices. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Cellular normoxic biophysical markers of hydroxyurea treatment in sickle cell disease.

Science.gov (United States)

Hosseini, Poorya; Abidi, Sabia Z; Du, E; Papageorgiou, Dimitrios P; Choi, Youngwoon; Park, YongKeun; Higgins, John M; Kato, Gregory J; Suresh, Subra; Dao, Ming; Yaqoob, Zahid; So, Peter T C

2016-08-23

Hydroxyurea (HU) has been used clinically to reduce the frequency of painful crisis and the need for blood transfusion in sickle cell disease (SCD) patients. However, the mechanisms underlying such beneficial effects of HU treatment are still not fully understood. Studies have indicated a weak correlation between clinical outcome and molecular markers, and the scientific quest to develop companion biophysical markers have mostly targeted studies of blood properties under hypoxia. Using a common-path interferometric technique, we measure biomechanical and morphological properties of individual red blood cells in SCD patients as a function of cell density, and investigate the correlation of these biophysical properties with drug intake as well as other clinically measured parameters. Our results show that patient-specific HU effects on the cellular biophysical properties are detectable at normoxia, and that these properties are strongly correlated with the clinically measured mean cellular volume rather than fetal hemoglobin level.

Protein-protein interactions within the ensemble, eukaryotic V-ATPase, and its concerted interactions with cellular machineries.

Science.gov (United States)

Balakrishna, Asha Manikkoth; Manimekalai, Malathy Sony Subramanian; Grüber, Gerhard

2015-10-01

The V1VO-ATPase (V-ATPase) is the important proton-pump in eukaryotic cells, responsible for pH-homeostasis, pH-sensing and amino acid sensing, and therefore essential for cell growths and metabolism. ATP-cleavage in the catalytic A3B3-hexamer of V1 has to be communicated via several so-called central and peripheral stalk units to the proton-pumping VO-part, which is membrane-embedded. A unique feature of V1VO-ATPase regulation is its reversible disassembly of the V1 and VO domain. Actin provides a network to hold the V1 in proximity to the VO, enabling effective V1VO-assembly to occur. Besides binding to actin, the 14-subunit V-ATPase interacts with multi-subunit machineries to form cellular sensors, which regulate the pH in cellular compartments or amino acid signaling in lysosomes. Here we describe a variety of subunit-subunit interactions within the V-ATPase enzyme during catalysis and its protein-protein assembling with key cellular machineries, essential for cellular function. Copyright © 2015 Elsevier Ltd. All rights reserved.

Passive Noise Filtering by Cellular Compartmentalization.

Science.gov (United States)

Stoeger, Thomas; Battich, Nico; Pelkmans, Lucas

2016-03-10

Chemical reactions contain an inherent element of randomness, which presents itself as noise that interferes with cellular processes and communication. Here we discuss the ability of the spatial partitioning of molecular systems to filter and, thus, remove noise, while preserving regulated and predictable differences between single living cells. In contrast to active noise filtering by network motifs, cellular compartmentalization is highly effective and easily scales to numerous systems without requiring a substantial usage of cellular energy. We will use passive noise filtering by the eukaryotic cell nucleus as an example of how this increases predictability of transcriptional output, with possible implications for the evolution of complex multicellularity. Copyright © 2016 Elsevier Inc. All rights reserved.

Mitochondrial and cellular mechanisms for managing lipid excess

Directory of Open Access Journals (Sweden)

Miguel A Aon

2014-07-01

Full Text Available Current scientific debates center on the impact of lipids and mitochondrial function on diverse aspects of human health, nutrition and disease, among them the association of lipotoxicity with the onset of insulin resistance in skeletal muscle, and with heart dysfunction in obesity and diabetes. Mitochondria play a fundamental role in aging and in prevalent acute or chronic diseases. Lipids are main mitochondrial fuels however these molecules can also behave as uncouplers and inhibitors of oxidative phosphorylation. Knowledge about the functional composition of these contradictory effects and their impact on mitochondrial-cellular energetics/redox status is incomplete.Cells store fatty acids (FAs as triacylglycerol and package them into cytoplasmic lipid droplets (LDs. New emerging data shows the LD as a highly dynamic storage pool of FAs that can be used for energy reserve. Lipid excess packaging into LDs can be seen as an adaptive response to fulfilling energy supply without hindering mitochondrial or cellular redox status and keeping low concentration of lipotoxic intermediates.Herein we review the mechanisms of action and utilization of lipids by mitochondria reported in liver, heart and skeletal muscle under relevant physiological situations, e.g. exercise. We report on perilipins, a family of proteins that associate with LDs in response to loading of cells with lipids. Evidence showing that in addition to physical contact, mitochondria and LDs exhibit metabolic interactions is presented and discussed. A hypothetical model of channeled lipid utilization by mitochondria is proposed. Direct delivery and channeled processing of lipids in mitochondria could represent a reliable and efficient way to maintain ROS within levels compatible with signaling while ensuring robust and reliable energy supply.

Effects of fexofenadine and hydroxyzine on brake reaction time during car-driving with cellular phone use.

Science.gov (United States)

Tashiro, Manabu; Horikawa, Etsuo; Mochizuki, Hideki; Sakurada, Yumiko; Kato, Motohisa; Inokuchi, Takatoshi; Ridout, Fran; Hindmarch, Ian; Yanai, Kazuhiko

2005-10-01

Antihistamines are a mainstay treatment for allergic rhinitis; however, many older agents cause adverse events, including sedation and central nervous system (CNS) impairment. Research has shown sedating effects of antihistamines on driving; currently, no known study has examined whether cellular phone usage while driving further compounds impairment in individuals administered antihistamines. The aim of this study was to examine this endpoint. In a randomized, double-blind, placebo-controlled, three-way crossover study, healthy volunteers received fexofenadine HCl 120 mg, hydroxyzine HCl 30 mg and placebo. Brake reaction time (BRT) was used to examine driving performance across four conditions: driving only; driving while completing simple calculations; complex calculations; and conversing on a cellular phone. Subjective sedation assessments were also conducted. Brake reaction time with and without cellular phone usage in fexofenadine-treated subjects did not differ significantly from placebo in any condition. In contrast, hydroxyzine-treated subjects were significantly more sedated and had slower BRTs, suggesting slower hazard recognition and brake application, compared with the fexofenadine and placebo groups in all conditions. Importantly, cellular phone operation was an additive factor, increasing BRTs in hydroxyzine-treated volunteers. Fexofenadine did not impair CNS function in subjects involved in a divided attention task of driving and cellular phone operation. Copyright (c) 2005 John Wiley & Sons, Ltd.

Amino acids and autophagy: cross-talk and co-operation to control cellular homeostasis.

Science.gov (United States)

Carroll, Bernadette; Korolchuk, Viktor I; Sarkar, Sovan

2015-10-01

Maintenance of amino acid homeostasis is important for healthy cellular function, metabolism and growth. Intracellular amino acid concentrations are dynamic; the high demand for protein synthesis must be met with constant dietary intake, followed by cellular influx, utilization and recycling of nutrients. Autophagy is a catabolic process via which superfluous or damaged proteins and organelles are delivered to the lysosome and degraded to release free amino acids into the cytoplasm. Furthermore, autophagy is specifically activated in response to amino acid starvation via two key signaling cascades: the mammalian target of rapamycin (mTOR) complex 1 (mTORC1) and the general control nonderepressible 2 (GCN2) pathways. These pathways are key regulators of the integration between anabolic (amino acid depleting) and catabolic (such as autophagy which is amino acid replenishing) processes to ensure intracellular amino acid homeostasis. Here, we discuss the key roles that amino acids, along with energy (ATP, glucose) and oxygen, are playing in cellular growth and proliferation. We further explore how sophisticated methods are employed by cells to sense intracellular amino acid concentrations, how amino acids can act as a switch to dictate the temporal and spatial activation of anabolic and catabolic processes and how autophagy contributes to the replenishment of free amino acids, all to ensure cell survival. Relevance of these molecular processes to cellular and organismal physiology and pathology is also discussed.

Functional roles for noise in genetic circuits.

Science.gov (United States)

Eldar, Avigdor; Elowitz, Michael B

2010-09-09

The genetic circuits that regulate cellular functions are subject to stochastic fluctuations, or 'noise', in the levels of their components. Noise, far from just a nuisance, has begun to be appreciated for its essential role in key cellular activities. Noise functions in both microbial and eukaryotic cells, in multicellular development, and in evolution. It enables coordination of gene expression across large regulons, as well as probabilistic differentiation strategies that function across cell populations. At the longest timescales, noise may facilitate evolutionary transitions. Here we review examples and emerging principles that connect noise, the architecture of the gene circuits in which it is present, and the biological functions it enables. We further indicate some of the important challenges and opportunities going forward.

Cellularized Cellular Solids via Freeze-Casting.

Science.gov (United States)

Christoph, Sarah; Kwiatoszynski, Julien; Coradin, Thibaud; Fernandes, Francisco M

2016-02-01

The elaboration of metabolically active cell-containing materials is a decisive step toward the successful application of cell based technologies. The present work unveils a new process allowing to simultaneously encapsulate living cells and shaping cell-containing materials into solid-state macroporous foams with precisely controlled morphology. Our strategy is based on freeze casting, an ice templating materials processing technique that has recently emerged for the structuration of colloids into macroporous materials. Our results indicate that it is possible to combine the precise structuration of the materials with cellular metabolic activity for the model organism Saccharomyces cerevisiae. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Rational Targeting of Cellular Cholesterol in Diffuse Large B-Cell Lymphoma (DLBCL) Enabled by Functional Lipoprotein Nanoparticles: A Therapeutic Strategy Dependent on Cell of Origin.

Science.gov (United States)

Rink, Jonathan S; Yang, Shuo; Cen, Osman; Taxter, Tim; McMahon, Kaylin M; Misener, Sol; Behdad, Amir; Longnecker, Richard; Gordon, Leo I; Thaxton, C Shad

2017-11-06

Cancer cells have altered metabolism and, in some cases, an increased demand for cholesterol. It is important to identify novel, rational treatments based on biology, and cellular cholesterol metabolism as a potential target for cancer is an innovative approach. Toward this end, we focused on diffuse large B-cell lymphoma (DLBCL) as a model because there is differential cholesterol biosynthesis driven by B-cell receptor (BCR) signaling in germinal center (GC) versus activated B-cell (ABC) DLBCL. To specifically target cellular cholesterol homeostasis, we employed high-density lipoprotein-like nanoparticles (HDL NP) that can generally reduce cellular cholesterol by targeting and blocking cholesterol uptake through the high-affinity HDL receptor, scavenger receptor type B-1 (SCARB1). As we previously reported, GC DLBCL are exquisitely sensitive to HDL NP as monotherapy, while ABC DLBCL are less sensitive. Herein, we report that enhanced BCR signaling and resultant de novo cholesterol synthesis in ABC DLBCL drastically reduces the ability of HDL NPs to reduce cellular cholesterol and induce cell death. Therefore, we combined HDL NP with the BCR signaling inhibitor ibrutinib and the SYK inhibitor R406. By targeting both cellular cholesterol uptake and BCR-associated de novo cholesterol synthesis, we achieved cellular cholesterol reduction and induced apoptosis in otherwise resistant ABC DLBCL cell lines. These results in lymphoma demonstrate that reduction of cellular cholesterol is a powerful mechanism to induce apoptosis. Cells rich in cholesterol require HDL NP therapy to reduce uptake and molecularly targeted agents that inhibit upstream pathways that stimulate de novo cholesterol synthesis, thus, providing a new paradigm for rationally targeting cholesterol metabolism as therapy for cancer.

Preliminary Investigation of the Role of Cellular Immunity in Estrous Cycle Modulation of Post-Resection Breast Cancer Spread

National Research Council Canada - National Science Library

Hrushesky, William

2002-01-01

It is hypothesized that the short term objectives of doing this proposal are to better understand which sex steroids and which cellular immune functions control post resection metastatic cancer spread...

Free Space Optics for Next Generation Cellular Backhaul

KAUST Repository

Zedini, Emna

2016-11-01

The exponential increase in the number of mobile users, coupled with the strong demand for high-speed data services results in a significant growth in the required cellular backhaul capacity. Optimizing the cost efficiency while increasing the capacity is becoming a key challenge to the cellular backhaul. It refers to connections between base stations and mobile switching nodes over a variety of transport technologies such as copper, optical fibers, and radio links. These traditional transmission technologies are either expensive, or cannot provide high data rates. This work is focused on the opportunities of free-space-optical (FSO) technology in next generation cellular back- haul. FSO is a cost effective and wide bandwidth solution as compared with the traditional radio-frequency (RF) transmission. Moreover, due to its ease of deployment, license-free operation, high transmission security, and insensitivity to interference, FSO links are becoming an attractive solution for next generation cellular networks. However, the widespread deployment of FSO links is hampered by the atmospheric turbulence-induced fading, weather conditions, and pointing errors. Increasing the reliability of FSO systems, while still exploiting their high data rate communications, is a key requirement in the deployment of an FSO-based backhaul. Therefore, the aim of this work is to provide different approaches to address these technical challenges. In this context, investigation of hybrid automatic repeat request (HARQ) protocols from an information-theoretic perspective is undertaken. Moreover, performance analysis of asymmetric RF/FSO dual-hop systems is studied. In such system models, multiple RF users can be multiplexed and sent over the FSO link. More specifically, the end-to-end performance metrics are presented in closed-form. This also has increased the interest to study the performance of dual-hop mixed FSO/RF systems, where the FSO link is used as a multicast channel that serves

Characterization of the functions and proteomes associated with membrane rafts in chicken sperm.

Directory of Open Access Journals (Sweden)

Ai Ushiyama

Full Text Available Cellular membranes are heterogeneous, and this has a great impact on cellular function. Despite the central role of membrane functions in multiple cellular processes in sperm, their molecular mechanisms are poorly understood. Membrane rafts are specific membrane domains enriched in cholesterol, ganglioside GM1, and functional proteins, and they are involved in the regulation of a variety of cellular functions. Studies of the functional characterization of membrane rafts in mammalian sperm have demonstrated roles in sperm-egg binding and the acrosomal reaction. Recently, our biochemical and cell biological studies showed that membrane rafts are present and might play functional roles in chicken sperm. In this study, we isolated membrane rafts from chicken sperm as a detergent-resistant membranes (DRM floating on a density gradient in the presence of 1% Triton X-100, and characterized the function and proteomes associated with these domains. Biochemical comparison of the DRM between fresh and cryopreserved sperm demonstrated that cryopreservation induces cholesterol loss specifically from membrane rafts, indicating the functional connection with reduced post-thaw fertility in chicken sperm. Furthermore, using an avidin-biotin system, we found that sperm DRM is highly enriched in a 60 KDa single protein able to bind to the inner perivitelline layer. To identify possible roles of membrane rafts, quantitative proteomics, combined with a stable isotope dimethyl labeling approach, identified 82 proteins exclusively or relatively more associated with membrane rafts. Our results demonstrate the functional distinctions between membrane domains and provide compelling evidence that membrane rafts are involved in various cellular pathways inherent to chicken sperm.

Quantifying the global cellular thiol-disulfide status

DEFF Research Database (Denmark)

Hansen, Rosa E; Roth, Doris; Winther, Jakob R

2009-01-01

It is widely accepted that the redox status of protein thiols is of central importance to protein structure and folding and that glutathione is an important low-molecular-mass redox regulator. However, the total cellular pools of thiols and disulfides and their relative abundance have never been...... determined. In this study, we have assembled a global picture of the cellular thiol-disulfide status in cultured mammalian cells. We have quantified the absolute levels of protein thiols, protein disulfides, and glutathionylated protein (PSSG) in all cellular protein, including membrane proteins. These data...... cell types. However, when cells are exposed to a sublethal dose of the thiol-specific oxidant diamide, PSSG levels increase to >15% of all protein cysteine. Glutathione is typically characterized as the "cellular redox buffer"; nevertheless, our data show that protein thiols represent a larger active...

Multidrug and toxin extrusion proteins mediate cellular transport of cadmium

International Nuclear Information System (INIS)

Yang, Hong; Guo, Dong; Obianom, Obinna N.; Su, Tong; Polli, James E.; Shu, Yan

2017-01-01

Cadmium (Cd) is an environmentally prevalent toxicant posing increasing risk to human health worldwide. As compared to the extensive research in Cd tissue accumulation, little was known about the elimination of Cd, particularly its toxic form, Cd ion (Cd 2+ ). In this study, we aimed to examine whether Cd 2+ is a substrate of multidrug and toxin extrusion proteins (MATEs) that are important in renal xenobiotic elimination. HEK-293 cells overexpressing the human MATE1 (HEK-hMATE1), human MATE2-K (HEK-hMATE2-K) and mouse Mate1 (HEK-mMate1) were used to study the cellular transport and toxicity of Cd 2+ . The cells overexpressing MATEs showed a 2–4 fold increase of Cd 2+ uptake that could be blocked by the MATE inhibitor cimetidine. A saturable transport profile was observed with the Michaelis-Menten constant (K m ) of 130 ± 15.8 μM for HEK-hMATE1; 139 ± 21.3 μM for HEK-hMATE2-K; and 88.7 ± 13.5 μM for HEK-mMate1, respectively. Cd 2+ could inhibit the uptake of metformin, a substrate of MATE transporters, with the half maximal inhibitory concentration (IC 50 ) of 97.5 ± 6.0 μM, 20.2 ± 2.6 μM, and 49.9 ± 6.9 μM in HEK-hMATE1, HEK-hMATE2-K, and HEK-mMate1 cells, respectively. In addition, hMATE1 could transport preloaded Cd 2+ out of the HEK-hMATE1 cells, thus resulting in a significant decrease of Cd 2+ -induced cytotoxicity. The present study has provided the first evidence supporting that MATEs transport Cd 2+ and may function as cellular elimination machinery in Cd intoxication. - Highlights: • Cadmium is an environmentally prevalent toxicant. • Little was known regarding the elimination and detoxification of cadmium. • Cadmium ion is here demonstrated as a substrate of MATE transporters. • MATEs may function as cellular elimination machinery in cadmium detoxification.

Experimental design for dynamics identification of cellular processes.

Science.gov (United States)

Dinh, Vu; Rundell, Ann E; Buzzard, Gregery T

2014-03-01

We address the problem of using nonlinear models to design experiments to characterize the dynamics of cellular processes by using the approach of the Maximally Informative Next Experiment (MINE), which was introduced in W. Dong et al. (PLoS ONE 3(8):e3105, 2008) and independently in M.M. Donahue et al. (IET Syst. Biol. 4:249-262, 2010). In this approach, existing data is used to define a probability distribution on the parameters; the next measurement point is the one that yields the largest model output variance with this distribution. Building upon this approach, we introduce the Expected Dynamics Estimator (EDE), which is the expected value using this distribution of the output as a function of time. We prove the consistency of this estimator (uniform convergence to true dynamics) even when the chosen experiments cluster in a finite set of points. We extend this proof of consistency to various practical assumptions on noisy data and moderate levels of model mismatch. Through the derivation and proof, we develop a relaxed version of MINE that is more computationally tractable and robust than the original formulation. The results are illustrated with numerical examples on two nonlinear ordinary differential equation models of biomolecular and cellular processes.

Managing the cellular redox hub in photosynthetic organisms.

Science.gov (United States)

Foyer, Christine H; Noctor, Graham

2012-02-01

Light-driven redox chemistry is a powerful source of redox signals that has a decisive input into transcriptional control within the cell nucleus. Like photosynthetic electron transport pathways, the respiratory electron transport chain exerts a profound control over gene function, in order to balance energy (reductant and ATP) supply with demand, while preventing excessive over-reduction or over-oxidation that would be adversely affect metabolism. Photosynthetic and respiratory redox chemistries are not merely housekeeping processes but they exert a controlling influence over every aspect of plant biology, participating in the control of gene transcription and translation, post-translational modifications and the regulation of assimilatory reactions, assimilate partitioning and export. The number of processes influenced by redox controls and signals continues to increase as do the components that are recognized participants in the associated signalling pathways. A step change in our understanding of the overall importance of the cellular redox hub to plant cells has occurred in recent years as the complexity of the management of the cellular redox hub in relation to metabolic triggers and environmental cues has been elucidated. This special issue describes aspects of redox regulation and signalling at the cutting edge of current research in this dynamic and rapidly expanding field. © 2011 Blackwell Publishing Ltd.

Cellular energy allocation in zebra mussels exposed along a pollution gradient: linking cellular effects to higher levels of biological organization

International Nuclear Information System (INIS)

Smolders, R.; Bervoets, L.; Coen, W. de; Blust, R.

2004-01-01

Organisms exposed to suboptimal environments incur a cost of dealing with stress in terms of metabolic resources. The total amount of energy available for maintenance, growth and reproduction, based on the biochemical analysis of the energy budget, may provide a sensitive measure of stress in an organism. While the concept is clear, linking cellular or biochemical responses to the individual and population or community level remains difficult. The aim of this study was to validate, under field conditions, using cellular energy budgets [i.e. changes in glycogen-, lipid- and protein-content and mitochondrial electron transport system (ETS)] as an ecologically relevant measurement of stress by comparing these responses to physiological and organismal endpoints. Therefore, a 28-day in situ bioassay with zebra mussels (Dreissena polymorpha) was performed in an effluent-dominated stream. Five locations were selected along the pollution gradient and compared with a nearby (reference) site. Cellular Energy Allocation (CEA) served as a biomarker of cellular energetics, while Scope for Growth (SFG) indicated effects on a physiological level and Tissue Condition Index and wet tissue weight/dry tissue weight ratio were used as endpoints of organismal effects. Results indicated that energy budgets at a cellular level of biological organization provided the fastest and most sensitive response and energy budgets are a relevant currency to extrapolate cellular effects to higher levels of biological organization within the exposed mussels. - Exposure of zebra mussels along a pollution gradient has adverse effects on the cellular energy allocation, and results can be linked with higher levels of biological organization

Cellular energy allocation in zebra mussels exposed along a pollution gradient: linking cellular effects to higher levels of biological organization

Energy Technology Data Exchange (ETDEWEB)

Smolders, R.; Bervoets, L.; Coen, W. de; Blust, R

2004-05-01

Organisms exposed to suboptimal environments incur a cost of dealing with stress in terms of metabolic resources. The total amount of energy available for maintenance, growth and reproduction, based on the biochemical analysis of the energy budget, may provide a sensitive measure of stress in an organism. While the concept is clear, linking cellular or biochemical responses to the individual and population or community level remains difficult. The aim of this study was to validate, under field conditions, using cellular energy budgets [i.e. changes in glycogen-, lipid- and protein-content and mitochondrial electron transport system (ETS)] as an ecologically relevant measurement of stress by comparing these responses to physiological and organismal endpoints. Therefore, a 28-day in situ bioassay with zebra mussels (Dreissena polymorpha) was performed in an effluent-dominated stream. Five locations were selected along the pollution gradient and compared with a nearby (reference) site. Cellular Energy Allocation (CEA) served as a biomarker of cellular energetics, while Scope for Growth (SFG) indicated effects on a physiological level and Tissue Condition Index and wet tissue weight/dry tissue weight ratio were used as endpoints of organismal effects. Results indicated that energy budgets at a cellular level of biological organization provided the fastest and most sensitive response and energy budgets are a relevant currency to extrapolate cellular effects to higher levels of biological organization within the exposed mussels. - Exposure of zebra mussels along a pollution gradient has adverse effects on the cellular energy allocation, and results can be linked with higher levels of biological organization.

Apolipoprotein J/Clusterin is a novel structural component of human erythrocytes and a biomarker of cellular stress and senescence.

Directory of Open Access Journals (Sweden)

Marianna H Antonelou

Full Text Available BACKGROUND: Secretory Apolipoprotein J/Clusterin (sCLU is a ubiquitously expressed chaperone that has been functionally implicated in several pathological conditions of increased oxidative injury, including aging. Nevertheless, the biological role of sCLU in red blood cells (RBCs remained largely unknown. In the current study we identified sCLU as a component of human RBCs and we undertook a detailed analysis of its cellular topology. Moreover, we studied the erythrocytic membrane sCLU content during organismal aging, in conditions of increased organismal stress and accelerated RBCs senescence, as well as during physiological in vivo cellular senescence. METHODOLOGY/PRINCIPAL FINDINGS: By using a combination of molecular, biochemical and high resolution microscopical methods we found that sCLU is a novel structural component of RBCs extra- and intracellular plasma membrane and cytosol. We observed that the RBCs membrane-associated sCLU decreases during organismal aging or exposure to acute stress (e.g. smoking, in patients with congenital hemolytic anemia, as well as during RBCs in vivo senescence. In all cases, sCLU reduction paralleled the expression of typical cellular senescence, redox imbalance and erythrophagocytosis markers which are also indicative of the senescence- and oxidative stress-mediated RBCs membrane vesiculation. CONCLUSIONS/SIGNIFICANCE: We propose that sCLU at the mature RBCs is not a silent remnant of the erythroid precursors, but an active component being functionally implicated in the signalling mechanisms of cellular senescence and oxidative stress-responses in both healthy and diseased organism. The reduced sCLU protein levels in the RBCs membrane following cell exposure to various endogenous or exogenous stressors closely correlates to the levels of cellular senescence and redox imbalance markers, suggesting the usefulness of sCLU as a sensitive biomarker of senescence and cellular stress.

Optimizing Cellular Networks Enabled with Renewal Energy via Strategic Learning.

Science.gov (United States)

Sohn, Insoo; Liu, Huaping; Ansari, Nirwan

2015-01-01

An important issue in the cellular industry is the rising energy cost and carbon footprint due to the rapid expansion of the cellular infrastructure. Greening cellular networks has thus attracted attention. Among the promising green cellular network techniques, the renewable energy-powered cellular network has drawn increasing attention as a critical element towards reducing carbon emissions due to massive energy consumption in the base stations deployed in cellular networks. Game theory is a branch of mathematics that is used to evaluate and optimize systems with multiple players with conflicting objectives and has been successfully used to solve various problems in cellular networks. In this paper, we model the green energy utilization and power consumption optimization problem of a green cellular network as a pilot power selection strategic game and propose a novel distributed algorithm based on a strategic learning method. The simulation results indicate that the proposed algorithm achieves correlated equilibrium of the pilot power selection game, resulting in optimum green energy utilization and power consumption reduction.

[Cognitive Function and Calcium. Structures and functions of Ca2+-permeable channels].

Science.gov (United States)

Kaneko, Shuji

2015-02-01

Calcium is essential for living organisms where the increase in intracellular Ca2+ concentration functions as a second messenger for many cellular processes including synaptic transmission and neural plasticity. The cytosolic concentration of Ca2+ is finely controlled by many Ca2+-permeable ion channels and transporters. The comprehensive view of their expression, function, and regulation will advance our understanding of neural and cognitive functions of Ca2+, which leads to the future drug discovery.

Gravitational Effects on Cellular Flame Structure

Science.gov (United States)

Dunsky, C. M.; Fernandez-Pello, A. C.

1991-01-01

An experimental investigation has been conducted of the effect of gravity on the structure of downwardly propagating, cellular premixed propane-oxygen-nitrogen flames anchored on a water-cooled porous-plug burner. The flame is subjected to microgravity conditions in the NASA Lewis 2.2-second drop tower, and flame characteristics are recorded on high-speed film. These are compared to flames at normal gravity conditions with the same equivalence ratio, dilution index, mixture flow rate, and ambient pressure. The results show that the cellular instability band, which is located in the rich mixture region, changes little under the absence of gravity. Lifted normal-gravity flames near the cellular/lifted limits, however, are observed to become cellular when gravity is reduced. Observations of a transient cell growth period following ignition point to heat loss as being an important mechanism in the overall flame stability, dominating the stabilizing effect of buoyancy for these downwardly-propagating burner-anchored flames. The pulsations that are observed in the plume and diffusion flame generated downstream of the premixed flame in the fuel rich cases disappear in microgravity, verifying that these fluctuations are gravity related.

THE EFFECT OF CELLULAR PHONE USE ON DRIVING PERFORMANCE

OpenAIRE

Toshiro ISHIDA

2001-01-01

Many experiments using driving simulators or real roads have shown that using a cellular phone while driving may cause an accident because it delays visual information processing by the driver. In this research, we examined the influence on driving performance of cellular phone use on a course that simulated streets. Driving conditions were driving only, listening to the car radio, hands-free cellular phone use and using a cellular phone with the left hand. Driving performance measurements in...

Global properties of cellular automata

International Nuclear Information System (INIS)

Jen, E.

1986-01-01

Cellular automata are discrete mathematical systems that generate diverse, often complicated, behavior using simple deterministic rules. Analysis of the local structure of these rules makes possible a description of the global properties of the associated automata. A class of cellular automata that generate infinitely many aperoidic temporal sequences is defined,a s is the set of rules for which inverses exist. Necessary and sufficient conditions are derived characterizing the classes of ''nearest-neighbor'' rules for which arbitrary finite initial conditions (i) evolve to a homogeneous state; (ii) generate at least one constant temporal sequence

Induction of cellular transformation by irradiation from artificial light sources

International Nuclear Information System (INIS)

Withrow, T.J.

1981-01-01

Cellular transformation in vitro has been used to test for the carcinogenic potential of chemical and physical insults including light. This report discusses the measurement of transformation, and reviews studies done on the effects of exposure to artificial light on cellular transformation or on cellular transformation by a virus. To date, cool-white lamps have been found to cause cellular transformation, while germicidal lamps and sunlamps have been found to cause cellular transformation and to enhance virally produced transformation

Microenvironment Dependent Photobiomodulation on Function-Specific Signal Transduction Pathways

Directory of Open Access Journals (Sweden)

Timon Cheng-Yi Liu

2014-01-01

Full Text Available Cellular photobiomodulation on a cellular function has been shown to be homeostatic. Its function-specific pathway mechanism would be further discussed in this paper. The signal transduction pathways maintaining a normal function in its function-specific homeostasis (FSH, resisting the activation of many other irrelative signal transduction pathways, are so sparse that it can be supposed that there may be normal function-specific signal transduction pathways (NSPs. A low level laser irradiation or monochromatic light may promote the activation of partially activated NSP and/or its redundant NSP so that it may induce the second-order phase transition of a function from its dysfunctional one far from its FSH to its normal one in a function-specific microenvironment and may also induce the first-order functional phase transition of the normal function from low level to high level.

Use of Small-Scale Wind Energy to Power Cellular Communication Equipment

Directory of Open Access Journals (Sweden)

B. Plourde

2011-12-01

Full Text Available The recent increase in cellular communication coverage and usage has been remarkable. The increase has occurred throughout the globe, in both developed and developing regions. In fact, in some regions of the world, land-line communications are being avoided altogether as countries move into primarily mobile communication technologies. In order for cellular communication to function adequately, communication towers must be built with sufficient density to provide coverage. These towers have electrical requirements which are often not met with grid-based power. This study presents a novel design of a wind turbine which is designed to be positioned atop existing communication towers in order to provide local power for the tower. These turbines have vertical axes of rotation and other features which suit them for this highly specialized application. The study carried out here shows that these turbines are able to provide the required electrical power to fully satisfy the communication-tower electronics.

Uniform and localized corrosion modelling by means of probabilistic cellular automata

International Nuclear Information System (INIS)

Perez-Brokate, Cristian

2016-01-01

Numerical modelling is complementary tool for corrosion prediction. The objective of this work is to develop a corrosion model by means of a probabilistic cellular automata approach at a mesoscopic scale. In this work, we study the morphological evolution and kinetics of corrosion. This model couples electrochemical oxidation and reduction reactions. Regarding kinetics, cellular automata models are able to describe current as a function of the applied potential for a redox reaction on an inert electrode. The inclusion of probabilities allows the description of the stochastic nature of anodic and cathodic reactions. Corrosion morphology has been studied in different context: generalised corrosion, pitting corrosion and corrosion in an occluded environment. a general tendency of two regimes is found. a first regime of uniform corrosion where the anodic and cathodic reactions occur homogeneously over the surface. a second regime of localized corrosion when there is a spatial separation of anodic and cathodic zones, with an increase of anodic reaction rate. (author) [fr

A rapid method for the preparation of ultrapure, functional lysosomes using functionalized superparamagnetic iron oxide nanoparticles.

Science.gov (United States)

Walker, Mathew W; Lloyd-Evans, Emyr

2015-01-01

Lysosomes are an emerging and increasingly important cellular organelle. With every passing year, more novel proteins and key cellular functions are associated with lysosomes. Despite this, the methodologies for their purification have largely remained unchanged since the days of their discovery. With little advancement in this area, it is no surprise that analysis of lysosomal function has been somewhat stymied, largely in part by the change in buoyant densities that occur under conditions where lysosomes accumulate macromolecules. Such phenotypes are often associated with the lysosomal storage diseases but are increasingly being observed under conditions where lysosomal proteins or, in some cases, cellular functions associated with lysosomal proteins are being manipulated. These altered lysosomes poise a problem to the classical methods to purify lysosomes that are reliant largely on their correct sedimentation by density gradient centrifugation. Building upon a technique developed by others to purify lysosomes magnetically, we have developed a unique assay using superparamagnetic iron oxide nanoparticles (SPIONs) to purify high yields of ultrapure functional lysosomes from multiple cell types including the lysosomal storage disorders. Here we describe this method in detail, including the rationale behind using SPIONs, the potential pitfalls that can be avoided and the potential functional assays these lysosomes can be used for. Finally we also summarize the other methodologies and the exact reasons why magnetic purification of lysosomes is now the method of choice for lysosomal researchers. Copyright © 2015 Elsevier Inc. All rights reserved.

Observations of cellular transformation products in nickel-base superalloys

International Nuclear Information System (INIS)

Barlow, C.Y.; Ralph, B.

1979-01-01

Transmission electron microscopy has been used to identify the products in cellularly transformed regions of alloys based on the Nimonic 80 A composition. The commercial alloy is shown to undergo a small degree of cellular transformation even after conventional heat treatments, while recrystallization is found to increase the incidence of this reaction type. Low carbon versions of this alloy demonstrate cellular precipitation over a wider range of heat treatments. It is shown that the cellular reaction may take place in these alloys under a variety of different conditions and with a range of driving forces. Reasons for this unexpected behaviour are offeredm as is a suggestion as to why the cellular reaction occurs on a local scale. (author)

A Novel Role for Keratin 17 in Coordinating Oncogenic Transformation and Cellular Adhesion in Ewing Sarcoma

Science.gov (United States)

Sankar, Savita; Tanner, Jason M.; Bell, Russell; Chaturvedi, Aashi; Randall, R. Lor; Beckerle, Mary C.

2013-01-01

Oncogenic transformation in Ewing sarcoma is caused by EWS/FLI, an aberrant transcription factor fusion oncogene. Glioma-associated oncogene homolog 1 (GLI1) is a critical target gene activated by EWS/FLI, but the mechanism by which GLI1 contributes to the transformed phenotype of Ewing sarcoma was unknown. In this work, we identify keratin 17 (KRT17) as a direct downstream target gene upregulated by GLI1. We demonstrate that KRT17 regulates cellular adhesion by activating AKT/PKB (protein kinase B) signaling. In addition, KRT17 is necessary for oncogenic transformation in Ewing sarcoma and accounts for much of the GLI1-mediated transformation function but via a mechanism independent of AKT signaling. Taken together, our data reveal previously unknown molecular functions for a cytoplasmic intermediate filament protein, KRT17, in coordinating EWS/FLI- and GLI1-mediated oncogenic transformation and cellular adhesion in Ewing sarcoma. PMID:24043308

Mechanisms by Which Different Functional States of Mitochondria Define Yeast Longevity

Science.gov (United States)

Beach, Adam; Leonov, Anna; Arlia-Ciommo, Anthony; Svistkova, Veronika; Lutchman, Vicky; Titorenko, Vladimir I.

2015-01-01

Mitochondrial functionality is vital to organismal physiology. A body of evidence supports the notion that an age-related progressive decline in mitochondrial function is a hallmark of cellular and organismal aging in evolutionarily distant eukaryotes. Studies of the baker’s yeast Saccharomyces cerevisiae, a unicellular eukaryote, have led to discoveries of genes, signaling pathways and chemical compounds that modulate longevity-defining cellular processes in eukaryotic organisms across phyla. These studies have provided deep insights into mechanistic links that exist between different traits of mitochondrial functionality and cellular aging. The molecular mechanisms underlying the essential role of mitochondria as signaling organelles in yeast aging have begun to emerge. In this review, we discuss recent progress in understanding mechanisms by which different functional states of mitochondria define yeast longevity, outline the most important unanswered questions and suggest directions for future research. PMID:25768339

Mechanisms by Which Different Functional States of Mitochondria Define Yeast Longevity

Directory of Open Access Journals (Sweden)

Adam Beach

2015-03-01

Full Text Available Mitochondrial functionality is vital to organismal physiology. A body of evidence supports the notion that an age-related progressive decline in mitochondrial function is a hallmark of cellular and organismal aging in evolutionarily distant eukaryotes. Studies of the baker’s yeast Saccharomyces cerevisiae, a unicellular eukaryote, have led to discoveries of genes, signaling pathways and chemical compounds that modulate longevity-defining cellular processes in eukaryotic organisms across phyla. These studies have provided deep insights into mechanistic links that exist between different traits of mitochondrial functionality and cellular aging. The molecular mechanisms underlying the essential role of mitochondria as signaling organelles in yeast aging have begun to emerge. In this review, we discuss recent progress in understanding mechanisms by which different functional states of mitochondria define yeast longevity, outline the most important unanswered questions and suggest directions for future research.

Dynamic cellular manufacturing system considering machine failure and workload balance

Science.gov (United States)

Rabbani, Masoud; Farrokhi-Asl, Hamed; Ravanbakhsh, Mohammad

2018-02-01

Machines are a key element in the production system and their failure causes irreparable effects in terms of cost and time. In this paper, a new multi-objective mathematical model for dynamic cellular manufacturing system (DCMS) is provided with consideration of machine reliability and alternative process routes. In this dynamic model, we attempt to resolve the problem of integrated family (part/machine cell) formation as well as the operators' assignment to the cells. The first objective minimizes the costs associated with the DCMS. The second objective optimizes the labor utilization and, finally, a minimum value of the variance of workload between different cells is obtained by the third objective function. Due to the NP-hard nature of the cellular manufacturing problem, the problem is initially validated by the GAMS software in small-sized problems, and then the model is solved by two well-known meta-heuristic methods including non-dominated sorting genetic algorithm and multi-objective particle swarm optimization in large-scaled problems. Finally, the results of the two algorithms are compared with respect to five different comparison metrics.

Production, properties, and applications of hydrocolloid cellular solids.

Science.gov (United States)

Nussinovitch, Amos

2005-02-01

Many common synthetic and edible materials are, in fact, cellular solids. When classifying the structure of cellular solids, a few variables, such as open vs. closed cells, flexible vs. brittle cell walls, cell-size distribution, cell-wall thickness, cell shape, the uniformity of the structure of the cellular solid and the different scales of length are taken into account. Compressive stress-strain relationships of most cellular solids can be easily identified according to their characteristic sigmoid shape, reflecting three deformation mechanisms: (i) elastic distortion under small strains, (ii) collapse and/or fracture of the cell walls, and (iii) densification. Various techniques are used to produce hydrocolloid (gum) cellular solids. The products of these include (i) sponges, obtained when the drying gel contains the occasionally produced gas bubbles; (ii) sponges produced by the immobilization of microorganisms; (iii) solid foams produced by drying foamed solutions or gels containing oils, and (iv) hydrocolloid sponges produced by enzymatic reactions. The porosity of the manufactured cellular solid is subject to change and depends on its composition and the processing technique. The porosity is controlled by a range of methods and the resulting surface structures can be investigated by microscopy and analyzed using fractal methods. Models used to describe stress-strain behaviors of hydrocolloid cellular solids as well as multilayered products and composites are discussed in detail in this manuscript. Hydrocolloid cellular solids have numerous purposes, simple and complex, ranging from dried texturized fruits to carriers of vitamins and other essential micronutrients. They can also be used to control the acoustic response of specific dry food products, and have a great potential for future use in countless different fields, from novel foods and packaging to medicine and medical care, daily commodities, farming and agriculture, and the environmental, chemical

On the effects of geometry, defects, and material asymmetry on the mechanical response of shape memory alloy cellular lattice structures

International Nuclear Information System (INIS)

Ravari, M R Karamooz; Kadkhodaei, M; Ghaei, A; Esfahani, S Nasr; Andani, M Taheri; Elahinia, M; Karaca, H

2016-01-01

Shape memory alloy (such as NiTi) cellular lattice structures are a new class of advanced materials with many potential applications. The cost of fabrication of these structures however is high. It is therefore necessary to develop modeling methods to predict the functional behavior of these alloys before fabrication. The main aim of the present study is to assess the effects of geometry, microstructural imperfections and material asymmetric response of dense shape memory alloys on the mechanical response of cellular structures. To this end, several cellular and dense NiTi samples are fabricated using a selective laser melting process. Both cellular and dense specimens were tested in compression in order to obtain their stress–strain response. For modeling purposes, a three -dimensional (3D) constitutive model based on microplane theory which is able to describe the material asymmetry was employed. Five finite element models based on unit cell and multi-cell methods were generated to predict the mechanical response of cellular lattices. The results show the considerable effects of the microstructural imperfections on the mechanical response of the cellular lattice structures. The asymmetric material response of the bulk material also affects the mechanical response of the corresponding cellular structure. (paper)

Cellular chain formation in Escherichia coli biofilms

DEFF Research Database (Denmark)

Vejborg, Rebecca Munk; Klemm, Per

2009-01-01

; type I fimbriae expression significantly reduced cellular chain formation, presumably by steric hindrance. Cellular chain formation did not appear to be specific to E coli K-12. Although many urinary tract infection (UTI) isolates were found to form rather homogeneous, flat biofilms, three isolates...