Comparative effect of Piper betle, Chlorella vulgaris and tocotrienol-rich fraction on antioxidant enzymes activity in cellular ageing of human diploid fibroblasts.

Science.gov (United States)

Makpol, Suzana; Yeoh, Thong Wei; Ruslam, Farah Adilah Che; Arifin, Khaizurin Tajul; Yusof, Yasmin Anum Mohd

2013-08-16

Human diploid fibroblasts (HDFs) undergo a limited number of cellular divisions in culture and progressively reach a state of irreversible growth arrest, a process termed cellular ageing. Even though beneficial effects of Piper betle, Chlorella vulgaris and tocotrienol-rich fraction (TRF) have been reported, ongoing studies in relation to ageing is of interest to determine possible protective effects that may reverse the effect of ageing. The aim of this study was to evaluate the effect of P. betle, C. vulgaris and TRF in preventing cellular ageing of HDFs by determining the activity of antioxidant enzymes viz.; catalase, superoxide dismutase (SOD) and glutathione peroxidase. Different passages of HDFs were treated with P. betle, C. vulgaris and TRF for 24 h prior to enzymes activity determination. Senescence-associated beta-galactosidase (SA β-gal) expression was assayed to validate cellular ageing. In cellular ageing of HDFs, catalase and glutathione peroxidase activities were reduced, but SOD activity was heightened during pre-senescence. P. betle exhibited the strongest antioxidant activity by reducing SA β-gal expression, catalase activities in all age groups, and SOD activity. TRF exhibited a strong antioxidant activity by reducing SA β-gal expression, and SOD activity in senescent HDFs. C. vulgaris extract managed to reduce SOD activity in senescent HDFs. P. betle, C. vulgaris, and TRF have the potential as anti-ageing entities which compensated the role of antioxidant enzymes in cellular ageing of HDFs.

Comparative effect of Piper betle, Chlorella vulgaris and tocotrienol-rich fraction on antioxidant enzymes activity in cellular ageing of human diploid fibroblasts

Science.gov (United States)

2013-01-01

Background Human diploid fibroblasts (HDFs) undergo a limited number of cellular divisions in culture and progressively reach a state of irreversible growth arrest, a process termed cellular ageing. Even though beneficial effects of Piper betle, Chlorella vulgaris and tocotrienol-rich fraction (TRF) have been reported, ongoing studies in relation to ageing is of interest to determine possible protective effects that may reverse the effect of ageing. The aim of this study was to evaluate the effect of P. betle, C. vulgaris and TRF in preventing cellular ageing of HDFs by determining the activity of antioxidant enzymes viz.; catalase, superoxide dismutase (SOD) and glutathione peroxidase. Methods Different passages of HDFs were treated with P. betle, C. vulgaris and TRF for 24 h prior to enzymes activity determination. Senescence-associated beta-galactosidase (SA β-gal) expression was assayed to validate cellular ageing. Results In cellular ageing of HDFs, catalase and glutathione peroxidase activities were reduced, but SOD activity was heightened during pre-senescence. P. betle exhibited the strongest antioxidant activity by reducing SA β-gal expression, catalase activities in all age groups, and SOD activity. TRF exhibited a strong antioxidant activity by reducing SA β-gal expression, and SOD activity in senescent HDFs. C. vulgaris extract managed to reduce SOD activity in senescent HDFs. Conclusion P. betle, C. vulgaris, and TRF have the potential as anti-ageing entities which compensated the role of antioxidant enzymes in cellular ageing of HDFs. PMID:23948056

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.

DNA supercoiling: changes during cellular differentiation and activation of chromatin transcription

International Nuclear Information System (INIS)

Luchnik, A.N.; Bakayev, V.V.; Glaser, V.M.; Moscow State Univ., USSR)

1983-01-01

In this paper it is reported that elastic DNA torsional tension has been observed in a fraction of isolated SV40 minichromosomes, which are shown to be transcriptionally active, and that the number of DNA topological (titratable superhelical) turns in closed superhelical loops of nuclear DNA decreases during cellular differentiation, which, we propose, may be responsible for the coordinate switch in transcription of genes controlling cellular proliferation. 37 references, 6 figures, 2 tables

Antiproliferative Activity and Cellular Uptake of Evodiamine and Rutaecarpine Based on 3D Tumor Models

Directory of Open Access Journals (Sweden)

Hui Guo

2016-07-01

Full Text Available Evodiamine (EVO and rutaecarpine (RUT are promising anti-tumor drug candidates. The evaluation of the anti-proliferative activity and cellular uptake of EVO and RUT in 3D multicellular spheroids of cancer cells would better recapitulate the native situation and thus better reflect an in vivo response to the treatment. Herein, we employed the 3D culture of MCF-7 and SMMC-7721 cells based on hanging drop method and evaluated the anti-proliferative activity and cellular uptake of EVO and RUT in 3D multicellular spheroids, and compared the results with those obtained from 2D monolayers. The drugs’ IC50 values were significantly increased from the range of 6.4–44.1 μM in 2D monolayers to 21.8–138.0 μM in 3D multicellular spheroids, which may be due to enhanced mass barrier and reduced drug penetration in 3D models. The fluorescence of EVO and RUT was measured via fluorescence spectroscopy and the cellular uptake of both drugs was characterized in 2D tumor models. The results showed that the cellular uptake concentrations of RUT increased with increasing drug concentrations. However, the EVO concentrations uptaken by the cells showed only a small change with increasing drug concentrations, which may be due to the different solubility of EVO and Rut in solvents. Overall, this study provided a new vision of the anti-tumor activity of EVO and RUT via 3D multicellular spheroids and cellular uptake through the fluorescence of compounds.

Active cellular sensing with quantum dots: Transitioning from research tool to reality; a review

International Nuclear Information System (INIS)

Delehanty, James B.; Susumu, Kimihiro; Manthe, Rachel L.; Algar, W. Russ; Medintz, Igor L.

2012-01-01

Highlights: ► Quantum dots (QDs) have evolved beyond mere cellular labeling reagents. ► Significant advances have been made in QD materials, surface coatings and bioconjugation. ► Cellular targeting/delivery has been achieved using polymers, peptides, proteins. ► Numerous QD-based sensing applications: extracellular, membrane, intracellular. - Abstract: The application of luminescent semiconductor quantum dots (QDs) within a wide range of biological imaging and sensing formats is now approaching its 15th year. The unique photophysical properties of these nanomaterials have long been envisioned as having the potential to revolutionize biosensing within cellular studies that rely on fluorescence. However, it is only now that these materials are making the transition towards accomplishing this goal. With the idea of understanding how to actively incorporate QDs into different types of cellular biosensing, we review the progress in many of the areas relevant to achieving this goal. This includes the synthesis of the QDs themselves, with an emphasis on minimizing potential toxicity, along with the general methods for making these nanocrystalline structures stable in aqueous media. We next survey some methods for conjugating QDs to biomolecules to allow them to participate in active biosensing. Lastly, we extensively review many of the applications where QDs have been demonstrated in an active role in cellular biosensing. These formats cover a wide range of possibilities including where the QDs have contributed to: monitoring the cell's interaction with its extracellular environment; elucidating the complex molecular interplay that characterizes the plasma membrane; understanding how cells continuously endocytose and exocytose materials across the cellular membrane; visualizing organelle trafficking; and, perhaps most importantly, monitoring the intracellular presence of target molecules such as nucleic acids, nutrients, cofactors, and ions or, alternatively

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)

Correlation between proliferative activity and cellular thickness of human mesenchymal stem cells

International Nuclear Information System (INIS)

Katsube, Yoshihiro; Hirose, Motohiro; Nakamura, Chikashi; Ohgushi, Hajime

2008-01-01

A cell's shape is known to be related to its proliferative activity. In particular, large and flat mammalian adult stem cells seem to show slow proliferation, however using quantitative analysis to prove the phenomenon is difficult. We measured the proliferation and cellular thickness of human mesenchymal stem cells (MSCs) by atomic force microscopy and found that MSCs with high proliferative activity were thick while those with low proliferative activity were thin, even though these MSCs were early passage cells. Further, low proliferative MSCs contained many senescence-associated β-galactosidase positive cells together with high senescence-associated gene expression. These findings suggest that the measurement of cellular thickness is useful for estimating the proliferative activity of human MSCs and is expected to be a practical tool for MSC applications in regenerative medicine

Activation of the hypothalamic-pituitary-adrenal stress axis induces cellular oxidative stress

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Jereme G. Spiers

2015-01-01

Full Text Available Glucocorticoids released from the adrenal gland in response to stress-induced activation of the hypothalamic-pituitary-adrenal (HPA axis induce activity in the cellular reduction-oxidation (redox system. The redox system is a ubiquitous chemical mechanism allowing the transfer of electrons between donor/acceptors and target molecules during oxidative phosphorylation while simultaneously maintaining the overall cellular environment in a reduced state. The objective of this review is to present an overview of the current literature discussing the link between HPA axis-derived glucocorticoids and increased oxidative stress, particularly focussing on the redox changes observed in the hippocampus following glucocorticoid exposure.

Human immunodeficiency virus-induced pathology favored by cellular transmission and activation

International Nuclear Information System (INIS)

Lewis, D.E.; Yoffe, B.; Bosworth, C.G.; Hollinger, F.B.; Rich, R.R.

1988-01-01

Epidemiological data suggest that transmission of human immunodeficiency virus (HIV) occurs primarily by transference of virally infected cells. However, the efficiency of lytic productive infection induced by HIV after transmission of cell-associated virus vs. free virus is difficult to assess. The present studies compare the extent of depletion of CD4+ (helper/inducer) T cells after mixing uninfected cells with either free HIV or irradiated HIV-infected allogeneic or autologous cells in vitro. Rapid CD4+ cellular depletion occurred only in cultures containing allogeneic infected cells or after addition of a nonspecific T cell activation signal to cultures with autologous infected cells. These in vitro observations strongly support the epidemiological implication that interactions between infected and uninfected cells are the most efficient means of transmission and HIV-induced cytopathology in vivo. They also provide direct support for the concept that immunological stimulation by foreign cells infected with HIV dramatically increases the likelihood of transmission. These in vitro observations suggest a model for the acquisition of HIV in vivo and the role of cellular activation in dissemination of the virus to uninfected cells in an infected individual

Profiling cellular bioenergetics, glutathione levels, and caspase activities in stomach biopsies of patients with upper gastrointestinal symptoms

Science.gov (United States)

Alfazari, Ali S; Al-Dabbagh, Bayan; Al-Dhaheri, Wafa; Taha, Mazen S; Chebli, Ahmad A; Fontagnier, Eva M; Koutoubi, Zaher; Kochiyi, Jose; Karam, Sherif M; Souid, Abdul-Kader

2015-01-01

AIM: To measure biochemical parameters in stomach biopsies and test their suitability as diagnostic biomarkers for gastritis and precancerous lesions. METHODS: Biopsies were obtained from the stomachs of two groups of patients (n = 40) undergoing fiber-optic endoscopy due to upper gastrointestinal symptoms. In the first group (n = 17), only the corpus region was examined. Biopsies were processed for microscopic examination and measurement of mitochondrial O2 consumption (cellular respiration), cellular adenosine triphosphate (ATP), glutathione (GSH), and caspase activity. In the second group of patients (n = 23), both corpus and antral regions were studied. Some biopsies were processed for microscopic examination, while the others were used for measurements of cellular respiration and GSH level. RESULTS: Microscopic examinations of gastric corpus biopsies from 17 patients revealed normal mucosae in 8 patients, superficial gastritis in 7 patients, and chronic atrophic gastritis in 1 patient. In patients with normal histology, the rate (mean ± SD) of cellular respiration was 0.17 ± 0.02 μmol/L O2 min-1 mg-1, ATP content was 487 ± 493 pmol/mg, and GSH was 469 ± 98 pmol/mg. Caspase activity was detected in 3 out of 8 specimens. The values of ATP and caspase activity were highly variable. The presence of superficial gastritis had insignificant effects on the measured biomarkers. In the patient with atrophic gastritis, cellular respiration was high and ATP was relatively low, suggesting uncoupling oxidative phosphorylation. In the second cohort of patients, the examined biopsies showed either normal or superficial gastritis. The rate of cellular respiration (O2. μmol/L min-1 mg-1) was slightly higher in the corpus than the antrum (0.18 ± 0.05 vs 0.15 ± 0.04, P = 0.019). The value of GSH was about the same in both tissues (310 ± 135 vs 322 ± 155, P = 0.692). CONCLUSION: The corpus mucosa was metabolically more active than the antrum tissue. The data in this

DNA damage and decrease of cellular oxidase activity in piglet ...

African Journals Online (AJOL)

DNA damage and decrease of cellular oxidase activity in piglet sertoli cells exposed to gossypol. Ming Zhang, Hui Yuan, Zuping He, Liyun Yuan, Jine Yi, Sijun Deng, Li Zhu, Chengzhi Guo, Yin Lu, Jing Wu, Lixin Wen, Qiang Wei, Liqun Xue ...

Multiple-channel detection of cellular activities by ion-sensitive transistors

Science.gov (United States)

Machida, Satoru; Shimada, Hideto; Motoyama, Yumi

2018-04-01

An ion-sensitive field-effect transistor to record cellular activities was demonstrated. This field-effect transistor (bio transistor) includes cultured cells on the gate insulator instead of gate electrode. The bio transistor converts a change in potential underneath the cells into variation of the drain current when ion channels open. The bio transistor has high detection sensitivity to even minute variations in potential utilizing a subthreshold swing region. To open ion channels, a reagent solution (acetylcholine) was added to a human-originating cell cultured on the bio transistor. The drain current was successfully decreased with the addition of acetylcholine. Moreover, we attempted to detect the opening of ion channels using a multiple-channel measurement circuit containing several bio transistors. As a consequence, the drain current distinctly decreased only after the addition of acetylcholine. We confirmed that this measurement system including bio transistors enables to observation of cellular activities sensitively and simultaneously.

Detection of silent cells, synchronization and modulatory activity in developing cellular networks.

NARCIS (Netherlands)

Hjorth, J.J.J.; Dawitz, J.; Kroon, T.; da Silva Dias Pires, J.H.; Dassen, V.J.; Berkhout, J.A.; Emperador Melero, J.; Nadadhur, A.G.; Alevra, M.; Toonen, R.F.G.; Heine, V.M.; Mansvelder, H.D.; Meredith, R.M.

2016-01-01

Developing networks in the immature nervous system and in cellular cultures are characterized by waves of synchronous activity in restricted clusters of cells. Synchronized activity in immature networks is proposed to regulate many different developmental processes, from neuron growth and cell

Active cellular sensing with quantum dots: Transitioning from research tool to reality; a review

Energy Technology Data Exchange (ETDEWEB)

Delehanty, James B., E-mail: james.delehanty@nrl.navy.mil [Center for Bio/Molecular Science and Engineering, Code 6900, U.S. Naval Research Laboratory, Washington, DC 20375 (United States); Susumu, Kimihiro, E-mail: susumu@ccs.nrl.navy.mil [Optical Sciences Division, Code 5611, U.S. Naval Research Laboratory, Washington, DC 20375 (United States); Manthe, Rachel L., E-mail: rmanthe@umd.edu [Center for Bio/Molecular Science and Engineering, Code 6900, U.S. Naval Research Laboratory, Washington, DC 20375 (United States); Fischell Department of Bioengineering, School of Engineering, University of Maryland College Park, College Park, MD 20742 (United States); Algar, W. Russ, E-mail: russ.algar.ctr.ca@nrl.navy.mil [Center for Bio/Molecular Science and Engineering, Code 6900, U.S. Naval Research Laboratory, Washington, DC 20375 (United States); College of Science, George Mason University, Fairfax, VA 22030 (United States); Medintz, Igor L., E-mail: igor.medintz@nrl.navy.mil [Center for Bio/Molecular Science and Engineering, Code 6900, U.S. Naval Research Laboratory, Washington, DC 20375 (United States)

2012-10-31

Highlights: Black-Right-Pointing-Pointer Quantum dots (QDs) have evolved beyond mere cellular labeling reagents. Black-Right-Pointing-Pointer Significant advances have been made in QD materials, surface coatings and bioconjugation. Black-Right-Pointing-Pointer Cellular targeting/delivery has been achieved using polymers, peptides, proteins. Black-Right-Pointing-Pointer Numerous QD-based sensing applications: extracellular, membrane, intracellular. - Abstract: The application of luminescent semiconductor quantum dots (QDs) within a wide range of biological imaging and sensing formats is now approaching its 15th year. The unique photophysical properties of these nanomaterials have long been envisioned as having the potential to revolutionize biosensing within cellular studies that rely on fluorescence. However, it is only now that these materials are making the transition towards accomplishing this goal. With the idea of understanding how to actively incorporate QDs into different types of cellular biosensing, we review the progress in many of the areas relevant to achieving this goal. This includes the synthesis of the QDs themselves, with an emphasis on minimizing potential toxicity, along with the general methods for making these nanocrystalline structures stable in aqueous media. We next survey some methods for conjugating QDs to biomolecules to allow them to participate in active biosensing. Lastly, we extensively review many of the applications where QDs have been demonstrated in an active role in cellular biosensing. These formats cover a wide range of possibilities including where the QDs have contributed to: monitoring the cell's interaction with its extracellular environment; elucidating the complex molecular interplay that characterizes the plasma membrane; understanding how cells continuously endocytose and exocytose materials across the cellular membrane; visualizing organelle trafficking; and, perhaps most importantly, monitoring the intracellular

Effects of wearing bio-active material coated fabric against γ-irradiation-induced cellular damaged in Sprague-Dawley rats

International Nuclear Information System (INIS)

Kang, Jung Ae; Kim, Hye Rim; Yoon, Sun Hye; Nam, Sang Hyun; Park, Sang Hyun; Jang, Beom Su; Go, Kyung Chan; Yang, Gwang Wung; Rho, Young Hwan; Park, Hyo Suk

2016-01-01

Ionizing radiation causes cellular damage and death through the direct damage and/or indirectly the production of ROS, which induces oxidative stress. This study was designed to evaluate the in vivo radioprotective effects of a bio-active material coated fabric (BMCF) against γ-irradiation-induced cellular damage in Sprague-Dawley (SD) rats. Healthy male SD rats wore bio-active material coated (concentrations in 10% and 30%) fabric for 7 days after 3 Gy of γ-irradiation. Radioprotective effects were evaluated by performing various biochemical assays including spleen and thymus index, WBC count, hepatic damage marker enzymes [aspartate transaminase (AST) and alanine transaminase (ALT)] in plasma, liver antioxidant enzymes, and mitochondrial activity in muscle. Exposure to γ-irradiation resulted in hepatocellular and immune systemic damage. Gamma-irradiation induced decreases in antioxidant enzymes. However, wearing the BMCF-30% decreased significantly AST and ALT activities in plasma. Furthermore, wearing the BMCF-30% increased SOD (superoxide dismutase) and mitochondrial activity. These results suggest that wearing BMCF offers effective radioprotection against γ-irradiation-induced cellular damage in SD rats

Effects of wearing bio-active material coated fabric against γ-irradiation-induced cellular damaged in Sprague-Dawley rats

Energy Technology Data Exchange (ETDEWEB)

Kang, Jung Ae; Kim, Hye Rim; Yoon, Sun Hye; Nam, Sang Hyun; Park, Sang Hyun; Jang, Beom Su [Korea Atomic Energy Research Institute, Jeongeup (Korea, Republic of); Go, Kyung Chan; Yang, Gwang Wung; Rho, Young Hwan; Park, Hyo Suk [Research and Development Center, VENTEX Co. Ltd., Seoul (Korea, Republic of)

2016-09-15

Ionizing radiation causes cellular damage and death through the direct damage and/or indirectly the production of ROS, which induces oxidative stress. This study was designed to evaluate the in vivo radioprotective effects of a bio-active material coated fabric (BMCF) against γ-irradiation-induced cellular damage in Sprague-Dawley (SD) rats. Healthy male SD rats wore bio-active material coated (concentrations in 10% and 30%) fabric for 7 days after 3 Gy of γ-irradiation. Radioprotective effects were evaluated by performing various biochemical assays including spleen and thymus index, WBC count, hepatic damage marker enzymes [aspartate transaminase (AST) and alanine transaminase (ALT)] in plasma, liver antioxidant enzymes, and mitochondrial activity in muscle. Exposure to γ-irradiation resulted in hepatocellular and immune systemic damage. Gamma-irradiation induced decreases in antioxidant enzymes. However, wearing the BMCF-30% decreased significantly AST and ALT activities in plasma. Furthermore, wearing the BMCF-30% increased SOD (superoxide dismutase) and mitochondrial activity. These results suggest that wearing BMCF offers effective radioprotection against γ-irradiation-induced cellular damage in SD rats.

The Stability, Sustained Release and Cellular Antioxidant Activity of Curcumin Nanoliposomes

Directory of Open Access Journals (Sweden)

Xing Chen

2015-08-01

Full Text Available Curcumin is a multifunctional and natural agent considered to be pharmacologically safe. However, its application in the food and medical industry is greatly limited by its poor water solubility, physicochemical instability and inadequate bioavailability. Nanoliposome encapsulation could significantly enhance the solubility and stability of curcumin. Curcumin nanoliposomes exhibited good physicochemical properties (entrapment efficiency = 57.1, particle size = 68.1 nm, polydispersity index = 0.246, and zeta potential = −3.16 mV. Compared with free curcumin, curcumin nanoliposomes exhibited good stability against alkaline pH and metal ions as well as good storage stability at 4 °C. Curcumin nanoliposomes also showed good sustained release properties. Compared with free curcumin, curcumin nanoliposomes presented an equal cellular antioxidant activity, which is mainly attributed to its lower cellular uptake as detected by fluorescence microscopy and flow cytometry. This study provide theoretical and practical guides for the further application of curcumin nanoliposomes.

Cellular studies and interaction mechanisms of extremely low frequency fields

Science.gov (United States)

Liburdy, Robert P.

1995-01-01

Worldwide interest in the biological effects of ELF (extremely low frequency, level is to identify cellular responses to ELF fields, to develop a dose threshold for such interactions, and with such information to formulate and test appropriate interaction mechanisms. This review is selective and will discuss the most recent cellular studies directed at these goals which relate to power line, sinusoidal ELF fields. In these studies an interaction site at the cell membrane is by consensus a likely candidate, since changes in ion transport, ligand-receptor events such as antibody binding, and G protein activation have been reported. These changes strongly indicate that signal transduction (ST) can be influenced. Also, ELF fields are reported to influence enzyme activation, gene expression, protein synthesis, and cell proliferation, which are triggered by earlier ST events at the cell membrane. The concept of ELF fields altering early cell membrane events and thereby influencing intracellular cell function via the ST cascade is perhaps the most plausible biological framework currently being investigated for understanding ELF effects on cells. For example, the consequence of an increase due to ELF fields in mitogenesis, the final endpoint of the ST cascade, is an overall increase in the probability of mutagenesis and consequently cancer, according to the Ames epigenetic model of carcinogenesis. Consistent with this epigenetic mechanism and the ST pathway to carcinogenesis is recent evidence that ELF fields can alter breast cancer cell proliferation and can act as a copromoter in vitro. The most important dosimetric question being addressed currently is whether the electric (E) or the magnetic (B) field, or if combinations of static B and time-varying B fields represent an exposure metric for the cell. This question relates directly to understanding fundamental interaction mechanisms and to the development of a rationale for ELF dose threshold guidelines. The weight of

Dynamic Simulation of 1D Cellular Automata in the Active aTAM.

Science.gov (United States)

Jonoska, Nataša; Karpenko, Daria; Seki, Shinnosuke

2015-07-01

The Active aTAM is a tile based model for self-assembly where tiles are able to transfer signals and change identities according to the signals received. We extend Active aTAM to include deactivation signals and thereby allow detachment of tiles. We show that the model allows a dynamic simulation of cellular automata with assemblies that do not record the entire computational history but only the current updates of the states, and thus provide a way for (a) algorithmic dynamical structural changes in the assembly and (b) reusable space in self-assembly. The simulation is such that at a given location the sequence of tiles that attach and detach corresponds precisely to the sequence of states the synchronous cellular automaton generates at that location.

Active cell-matrix coupling regulates cellular force landscapes of cohesive epithelial monolayers

Science.gov (United States)

Zhao, Tiankai; Zhang, Yao; Wei, Qiong; Shi, Xuechen; Zhao, Peng; Chen, Long-Qing; Zhang, Sulin

2018-03-01

Epithelial cells can assemble into cohesive monolayers with rich morphologies on substrates due to competition between elastic, edge, and interfacial effects. Here we present a molecularly based thermodynamic model, integrating monolayer and substrate elasticity, and force-mediated focal adhesion formation, to elucidate the active biochemical regulation over the cellular force landscapes in cohesive epithelial monolayers, corroborated by microscopy and immunofluorescence studies. The predicted extracellular traction and intercellular tension are both monolayer size and substrate stiffness dependent, suggestive of cross-talks between intercellular and extracellular activities. Our model sets a firm ground toward a versatile computational framework to uncover the molecular origins of morphogenesis and disease in multicellular epithelia.

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.

LRRK2 Kinase Activity and Biology are Not Uniformly Predicted by its Autophosphorylation and Cellular Phosphorylation Site Status

Directory of Open Access Journals (Sweden)

April eReynolds

2014-06-01

Full Text Available Missense mutations in the Leucine Rich Repeat protein Kinase 2 (LRRK2 gene are the most common genetic predisposition to develop Parkinson’s disease (PD LRRK2 is a large multi-domain phosphoprotein with a GTPase domain and a serine/threonine protein kinase domain whose activity is implicated in neuronal toxicity; however the precise mechanism is unknown. LRRK2 autophosphorylates on several serine/threonine residues across the enzyme and is found constitutively phosphorylated on Ser910, Ser935, Ser955 and Ser973, which are proposed to be regulated by upstream kinases. Here we investigate the phosphoregulation at these sites by analyzing the effects of disease-associated mutations Arg1441Cys, Arg1441Gly, Ala1442Pro, Tyr1699Cys, Ile2012Thr, Gly2019Ser, and Ile2020Thr. We also studied alanine substitutions of phosphosite serines 910, 935, 955 and 973 and specific LRRK2 inhibition on autophosphorylation of LRRK2 Ser1292, Thr1491, Thr2483 and phosphorylation at the cellular sites. We found that mutants in the Roc-COR domains, including Arg1441Cys, Arg1441His, Ala1442Pro and Tyr1699Cys, can positively enhance LRRK2 kinase activity while concomitantly inducing the dephosphorylation of the cellular sites. Mutation of the cellular sites individually did not affect LRRK2 intrinsic kinase activity; however, Ser910/935/955/973Ala mutations trended toward increased kinase activity of LRRK2. Increased cAMP levels did not lead to increased LRRK2 cellular site phosphorylation, 14-3-3 binding or kinase activity. In cells, inhibition of LRRK2 kinase activity leads to dephosphorylation of Ser1292 by Calyculin A and okadaic acid sensitive phosphatases, while the cellular sites are dephosphorylated by Calyculin A sensitive phosphatases. These findings indicate that comparative analysis of both Ser1292 and Ser910/935/955/973 phosphorylation sites will provide important and distinct measures of LRRK2 kinase and biological activity in vitro and in vivo.

Chronic innate immune activation of TBK1 suppresses mTORC1 activity and dysregulates cellular metabolism.

Science.gov (United States)

Hasan, Maroof; Gonugunta, Vijay K; Dobbs, Nicole; Ali, Aktar; Palchik, Guillermo; Calvaruso, Maria A; DeBerardinis, Ralph J; Yan, Nan

2017-01-24

Three-prime repair exonuclease 1 knockout (Trex1 -/- ) mice suffer from systemic inflammation caused largely by chronic activation of the cyclic GMP-AMP synthase-stimulator of interferon genes-TANK-binding kinase-interferon regulatory factor 3 (cGAS-STING-TBK1-IRF3) signaling pathway. We showed previously that Trex1-deficient cells have reduced mammalian target of rapamycin complex 1 (mTORC1) activity, although the underlying mechanism is unclear. Here, we performed detailed metabolic analysis in Trex1 -/- mice and cells that revealed both cellular and systemic metabolic defects, including reduced mitochondrial respiration and increased glycolysis, energy expenditure, and fat metabolism. We also genetically separated the inflammatory and metabolic phenotypes by showing that Sting deficiency rescued both inflammatory and metabolic phenotypes, whereas Irf3 deficiency only rescued inflammation on the Trex1 -/- background, and many metabolic defects persist in Trex1 -/- Irf3 -/- cells and mice. We also showed that Leptin deficiency (ob/ob) increased lipogenesis and prolonged survival of Trex1 -/- mice without dampening inflammation. Mechanistically, we identified TBK1 as a key regulator of mTORC1 activity in Trex1 -/- cells. Together, our data demonstrate that chronic innate immune activation of TBK1 suppresses mTORC1 activity, leading to dysregulated cellular metabolism.

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.

Nicotinamide phosphoribosyltransferase delays cellular senescence by upregulating SIRT1 activity and antioxidant gene expression in mouse cells.

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Khaidizar, Fiqri D; Nakahata, Yasukazu; Kume, Akira; Sumizawa, Kyosuke; Kohno, Kenji; Matsui, Takaaki; Bessho, Yasumasa

2017-12-01

Senescent cells accumulate in tissues of aged animals and deteriorate tissue functions. The elimination of senescent cells from aged mice not only attenuates progression of already established age-related disorders, but also extends median lifespan. Nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in mammalian NAD + salvage pathway, has shown a protective effect on cellular senescence of human primary cells. However, it still remains unclear how NAMPT has a protective impact on aging in vitro and in vivo. In this study, we found that primary mouse embryonic fibroblast (MEF) cells undergo progressive decline of NAMPT and NAD + contents during serial passaging before becoming senescent. Furthermore, we showed that constitutive Nampt over-expression increases cellular NAD + content and delays cellular senescence of MEF cells in vitro. We further found that constitutive Nampt over-expression increases SIRT1 activity, increases the expression of antioxidant genes, superoxide dismutase 2 and catalase and promotes resistance against oxidative stress. These findings suggest that Nampt over-expression in MEF cells delays cellular senescence by the mitigation of oxidative stress via the upregulation of superoxide dismutase 2 and catalase gene expressions by SIRT1 activation. © 2017 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.

Activated α2 -Macroglobulin Induces Mesenchymal Cellular Migration Of Raw264.7 Cells Through Low-Density Lipoprotein Receptor-Related Protein 1.

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Ferrer, Darío G; Dato, Virginia Actis; Fincati, Javier R Jaldín; Lorenc, Valeria E; Sánchez, María C; Chiabrando, Gustavo A

2017-07-01

Distinct modes of cell migration contribute to diverse types of cell movements. The mesenchymal mode is characterized by a multistep cycle of membrane protrusion, the formation of focal adhesion, and the stabilization at the leading edge associated with the degradation of extracellular matrix (ECM) components and with regulated extracellular proteolysis. Both α 2 -Macroglobulin (α 2 M) and its receptor, low density lipoprotein receptor-related protein 1 (LRP1), play important roles in inflammatory processes, by controlling the extracellular activity of several proteases. The binding of the active form of α 2 M (α 2 M*) to LRP1 can also activate different signaling pathways in macrophages, thus inducing extracellular matrix metalloproteinase-9 (MMP-9) activation and cellular proliferation. In the present study, we investigated whether the α 2 M*/LRP1 interaction induces cellular migration of the macrophage-derived cell line, Raw264.7. By using the wound-scratch migration assay and confocal microscopy, we demonstrate that α 2 M* induces LRP1-mediated mesenchymal cellular migration. This migration exhibits the production of enlarged cellular protrusions, MT1-MMP distribution to these leading edge protrusions, actin polymerization, focal adhesion formation, and increased intracellular LRP1/β1-integrin colocalization. Moreover, the presence of calphostin-C blocked the α 2 M*-stimulated cellular protrusions, suggesting that the PKC activation is involved in the cellular motility of Raw264.7 cells. These findings could constitute a therapeutic target for inflammatory processes with deleterious consequences for human health, such as rheumatoid arthritis, atherosclerosis and cancer. J. Cell. Biochem. 118: 1810-1818, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

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

Abnormalities in the cellular phase of blood fibrinolytic activity in systemic lupus erythematosus and in venous thromboembolism

International Nuclear Information System (INIS)

Moroz, L.A.; MacLean, L.D.; Langleben, D.

1986-01-01

Fibrinolytic activities of whole blood and plasma were determined by 125 I-fibrin radiometric assay in 16 normal subjects, and in 11 patients with systemic lupus erythematosus (SLE), 14 with progressive systemic sclerosis (PSS), 23 with venous thromboembolic disease, and 20 patients awaiting elective surgery. Mean whole blood and plasma activities for patients with PSS, and for those awaiting elective surgery, were similar to normal values, as was the mean plasma activity in patients with SLE. However, mean whole blood activity in SLE was significantly decreased compared with normals (p less than 0.05), with mean plasma activity accounting for 44% of mean whole blood activity (compared with 17% in normal subjects), representing a 67% decrease in mean calculated cellular phase activity in SLE, when compared with normals. Since the numbers of cells (neutrophils, monocytes) possibly involved in cellular activity were not decreased, the findings suggest a functional defect in fibrinolytic activity of one or more blood cell types in SLE. An additional finding was the participation of the cellular phase as well as the well-known plasma phase of blood in the fibrinolytic response to thromboembolism

Cellular MR Imaging

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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.

Telomerase activity and cellular aging might be positively modified by a yoga-based lifestyle intervention.

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Kumar, Shiv Basant; Yadav, Rashmi; Yadav, Raj Kumar; Tolahunase, Madhuri; Dada, Rima

2015-06-01

Recent studies showed that a brief yoga-based lifestyle intervention was efficacious in reducing levels of oxidative stress and cellular aging in obese men. The objective of this case report was to assess the efficacy of this intervention in reducing the levels of biochemical markers of cellular ageing, oxidative stress, and inflammation at baseline (day 0), at the end of active intervention (day 10), and follow-up at day 90. Single case report from a prospective ongoing study with pre-post design assessing the level of various markers of cellular aging. Integral Health Clinic, an outpatient facility conducting meditation and yoga-based lifestyle intervention programs for management of chronic diseases. A 31-year-old man with class I obesity (body-mass index, 29.5 kg/m(2)) who presented to the medicine outpatient department at All India Institute of Medical Sciences, New Delhi, India, with a history of fatigue, difficulty losing weight, and lack of motivation. He noted a marked decrease in his energy level, particularly in the afternoon. A pretested intervention program included asanas (postures), pranayama (breathing exercises), stress management, group discussions, lectures, and individualized advice. From baseline (day 0) to day 90, the activity of telomerase and levels of β-endorphins, plasma cortisol, and interleukin-6 increased, and a sustained reduction in oxidative stress markers, such as reactive oxygen species and 8-hydroxy-2-deoxy-guanosine levels. Adopting yoga/meditation-based lifestyle modification causes reversal of markers of aging, mainly oxidative stress, telomerase activity, and oxidative DNA damage. This may not only delay aging and prolong a youthful healthy life but also delay or prevent onset of several lifestyle-related diseases, of which oxidative stress and inflammation are the chief cause. This report suggests this simple lifestyle intervention may be therapeutic for oxidative DNA damage and oxidative stress.

Direct cellular vs. indirect pager communication during orthopaedic surgical procedures: a prospective study.

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Ortega, Gil R; Taksali, Sudeep; Smart, Ryan; Baumgaertner, Michael R

2009-01-01

Cellular phone use within the hospital setting has increased as physicians, nurses, and ancillary staff incorporate wireless technologies in improving efficiencies, cost, and maintaining patient safety and high quality healthcare [11]. Through the use of wireless, cellular communication, an overall improvement in communication accuracy and efficiency between intraoperative orthopaedic surgeons and floor nurses may be achieved. Both communication types occurred while the surgeon was scrubbed in the operating room (OR). Indirect communication occurred when the pager call was answered by the OR circulating nurse with communication between the surgeon, circulating nurse, and floor nurse. Direct communication consisted of cell phone and Jabra Bluetooth BT200 wireless ear piece used by the surgeon. The surgeon answered the floor nurse's cellular call by phone ring-activated automatic answering. The study was conducted during scheduled orthopaedic procedures. An independent observer measured time variables with a stop-watch while orthopaedic nurses randomly called via pager or cell phone. The nurses asked for patient caregiver confirmation and answers to 30 different patient-care questions. Sixty trials were performed with 30 cell and 30 page communications. Direct cellular communication showed a better response rate than indirect page (Cell 100%, Page 73%). Indirect page communication allowed a 27% and 33% error rate with patient problem and surgeon solution communications, respectively. There were no reported communication errors while using direct wireless, cellular communication. When compared to page communications, cellular communications showed statistically significant improvements in mean time intervals in response time (Cell = 11s, Page = 211s), correct patient identification (Cell = 5s, Page = 172s), patient problem and solution time (Cell = 13s, Page = 189s), and total communication time (Cell = 32s, Page = 250s) (s = seconds, all P < 0.001). Floor nurse

Exploring cellular memory molecules marking competent and active transcriptions

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Liu De-Pei

2007-05-01

Full Text Available Abstract Background Development in higher eukaryotes involves programmed gene expression. Cell type-specific gene expression is established during this process and is inherited in succeeding cell cycles. Higher eukaryotes have evolved elegant mechanisms by which committed gene-expression states are transmitted through numerous cell divisions. Previous studies have shown that both DNase I-sensitive sites and the basal transcription factor TFIID remain on silenced mitotic chromosomes, suggesting that certain trans-factors might act as bookmarks, maintaining the information and transmitting it to the next generation. Results We used the mouse globin gene clusters as a model system to examine the retention of active information on M-phase chromosomes and its contribution to the persistence of transcriptional competence of these gene clusters in murine erythroleukemia cells. In cells arrested in mitosis, the erythroid-specific activator NF-E2p45 remained associated with its binding sites on the globin gene loci, while the other major erythroid factor, GATA-1, was removed from chromosome. Moreover, despite mitotic chromatin condensation, the distant regulatory regions and promoters of transcriptionally competent globin gene loci are marked by a preserved histone code consisting in active histone modifications such as H3 acetylation, H3-K4 dimethylation and K79 dimethylation. Further analysis showed that other active genes are also locally marked by the preserved active histone code throughout mitotic inactivation of transcription. Conclusion Our results imply that certain kinds of specific protein factors and active histone modifications function as cellular memory markers for both competent and active genes during mitosis, and serve as a reactivated core for the resumption of transcription when the cells exit mitosis.

Ion channel signaling influences cellular proliferation and phagocyte activity during axolotl tail regeneration.

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Franklin, Brandon M; Voss, S Randal; Osborn, Jeffrey L

2017-08-01

Little is known about the potential for ion channels to regulate cellular behaviors during tissue regeneration. Here, we utilized an amphibian tail regeneration assay coupled with a chemical genetic screen to identify ion channel antagonists that altered critical cellular processes during regeneration. Inhibition of multiple ion channels either partially (anoctamin1/Tmem16a, anoctamin2/Tmem16b, K V 2.1, K V 2.2, L-type Ca V channels and H/K ATPases) or completely (GlyR, GABA A R, K V 1.5 and SERCA pumps) inhibited tail regeneration. Partial inhibition of tail regeneration by blocking the calcium activated chloride channels, anoctamin1&2, was associated with a reduction of cellular proliferation in tail muscle and mesenchymal regions. Inhibition of anoctamin 1/2 also altered the post-amputation transcriptional response of p44/42 MAPK signaling pathway genes, including decreased expression of erk1/erk2. We also found that complete inhibition via voltage gated K + channel blockade was associated with diminished phagocyte recruitment to the amputation site. The identification of H + pumps as required for axolotl tail regeneration supports findings in Xenopus and Planaria models, and more generally, the conservation of ion channels as regulators of tissue regeneration. This study provides a preliminary framework for an in-depth investigation of the mechanistic role of ion channels and their potential involvement in regulating cellular proliferation and other processes essential to wound healing, appendage regeneration, and tissue repair. Copyright © 2017 Elsevier B.V. All rights reserved.

Active Cellular Mechanics and its Consequences for Animal Development

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Noll, Nicholas B.

A central goal of developmental biology is to understand how an organism shapes itself, a process referred to as morphogenesis. While the molecular components critical to determining the initial body plan have been well characterized, the control of the subsequent dynamics of cellular rearrangements which ultimately shape the organism are far less understood. A major roadblock to a more complete picture of morphogenesis is the inability to measure tissue-scale mechanics throughout development and thus answer fundamental questions: How is the mechanical state of the cell regulated by local protein expression and global pattering? In what way does stress feedback onto the larger developmental program? In this dissertation, we begin to approach these questions through the introduction and analysis of a multi-scale model of epithelial mechanics which explicitly connects cytoskeletal protein activity to tissue-level stress. In Chapter 2, we introduce the discrete Active Tension Network (ATN) model of cellular mechanics. ATNs are tissues that satisfy two primary assumptions: that the mechanical balance of cells is dominated by cortical tension and that myosin actively remodels the actin cytoskeleton in a stress-dependent manner. Remarkably, the interplay of these features allows for angle-preserving, i.e. 'isogonal', dilations or contractions of local cell geometry that do not generate stress. Asymptotically this model is stabilized provided there is mechanical feedback on expression of myosin within the cell; we take this to be a strong prediction to be tested. The ATN model exposes a fundamental connection between equilibrium cell geometry and its underlying force network. In Chapter 3, we relax the tension-net approximation and demonstrate that at equilibrium, epithelial tissues with non-uniform pressure have non-trivial geometric constraints that imply the network is described by a weighted `dual' triangulation. We show that the dual triangulation encodes all

Case Study: The Mystery of the Seven Deaths--A Case Study in Cellular Respiration

Science.gov (United States)

Gazdik, Michaela

2014-01-01

Cellular respiration, the central component of cellular metabolism, can be a difficult concept for many students to fully understand. In this interrupted, problem-based case study, students explore the purpose of cellular respiration as they play the role of medical examiner, analyzing autopsy evidence to determine the mysterious cause of death…

Sensitivity-Enhanced Wearable Active Voiceprint Sensor Based on Cellular Polypropylene Piezoelectret.

Science.gov (United States)

Li, Wenbo; Zhao, Sheng; Wu, Nan; Zhong, Junwen; Wang, Bo; Lin, Shizhe; Chen, Shuwen; Yuan, Fang; Jiang, Hulin; Xiao, Yongjun; Hu, Bin; Zhou, Jun

2017-07-19

Wearable active sensors have extensive applications in mobile biosensing and human-machine interaction but require good flexibility, high sensitivity, excellent stability, and self-powered feature. In this work, cellular polypropylene (PP) piezoelectret was chosen as the core material of a sensitivity-enhanced wearable active voiceprint sensor (SWAVS) to realize voiceprint recognition. By virtue of the dipole orientation control method, the air layers in the piezoelectret were efficiently utilized, and the current sensitivity was enhanced (from 1.98 pA/Hz to 5.81 pA/Hz at 115 dB). The SWAVS exhibited the superiorities of high sensitivity, accurate frequency response, and excellent stability. The voiceprint recognition system could make correct reactions to human voices by judging both the password and speaker. This study presented a voiceprint sensor with potential applications in noncontact biometric recognition and safety guarantee systems, promoting the progress of wearable sensor networks.

Wavefront cellular learning automata.

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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.

Research of the method of pseudo-random number generation based on asynchronous cellular automata with several active cells

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Bilan Stepan

2017-01-01

Full Text Available To date, there are many tasks that are aimed at studying the dynamic changes in physical processes. These tasks do not give advance known result. The solution of such problems is based on the construction of a dynamic model of the object. Successful structural and functional implementation of the object model can give a positive result in time. This approach uses the task of constructing artificial biological objects. To solve such problems, pseudo-random number generators are used, which also find wide application for information protection tasks. Such generators should have good statistical properties and give a long repetition period of the generated pseudo-random bit sequence. This work is aimed at improving these characteristics. The paper considers the method of forming pseudo-random sequences of numbers on the basis of aperiodic cellular automata with two active cells. A pseudo-random number generator is proposed that generates three bit sequences. The first two bit sequences are formed by the corresponding two active cells in the cellular automaton. The third bit sequence is the result of executing the XOR function over the bits of the first two sequences and it has better characteristics compared to them. The use of cellular automata with two active cells allowed to improve the statistical properties of the formed bit sequence, as well as its repetition period. This is proved by using graphical tests for generators built based on cellular automata using the neighborhoods of von Neumann and Moore. The tests showed high efficiency of the generator based on an asynchronous cellular automaton with the neighborhood of Moore. The proposed pseudo-random number generators have good statistical properties, which makes it possible to use them in information security systems, as well as for simulation tasks of various dynamic processes.

Different cellular effects of four anti-inflammatory eye drops on human corneal epithelial cells: independent in active components.

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Qu, Mingli; Wang, Yao; Yang, Lingling; Zhou, Qingjun

2011-01-01

To evaluate and compare the cellular effects of four commercially available anti-inflammatory eye drops and their active components on human corneal epithelial cells (HCECs) in vitro. The cellular effects of four eye drops (Bromfenac Sodium Hydrate Eye Drops, Pranoprofen Eye Drops, Diclofenac Sodium Eye Drops, and Tobramycin & Dex Eye Drops) and their corresponding active components were evaluated in an HCEC line with five in vitro assays. Cell proliferation and migration were measured using 3-(4,5)-dimethylthiahiazo (-z-y1)-3 5-di-phenytetrazoliumromide (MTT) assay and transwell migration assay. Cell damage was determined with the lactate dehydrogenase (LDH) assay. Cell viability and median lethal time (LT₅₀) were measured by 7-amino-actinomycin D (7-AAD) staining and flow cytometry analysis. Cellular effects after exposure of HCECs to the four anti-inflammatory eye drops were concentration dependent. The differences of cellular toxicity on cell proliferation became significant at lower concentrations (Eye Drops showed significant increasing effects on cell damage and viability when compared with the other three solutions. Tobramycin & Dex Eye Drops inhibited the migration of HCECs significantly. Tobramycin & Dex Eye Drops showed the quickest effect on cell viability: the LT₅₀ was 3.28, 9.23, 10.38, and 23.80 min for Tobramycin & Dex Eye Drops, Diclofenac Sodium Eye Drops, Pranoprofen Eye Drops, and Bromfenac Sodium Hydrate Eye Drops, respectively. However, the comparisons of cellular toxicity revealed significant differences between the eye drops and their active components under the same concentration. The corneal epithelial toxicity differences among the active components of the four eye drops became significant as higher concentration (>0.020%). The four anti-inflammatory eye drops showed different cellular effects on HCECs, and the toxicity was not related with their active components, which provides new reference for the clinical application and drug

Cellular signaling identifiability analysis: a case study.

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Roper, Ryan T; Pia Saccomani, Maria; Vicini, Paolo

2010-05-21

Two primary purposes for mathematical modeling in cell biology are (1) simulation for making predictions of experimental outcomes and (2) parameter estimation for drawing inferences from experimental data about unobserved aspects of biological systems. While the former purpose has become common in the biological sciences, the latter is less common, particularly when studying cellular and subcellular phenomena such as signaling-the focus of the current study. Data are difficult to obtain at this level. Therefore, even models of only modest complexity can contain parameters for which the available data are insufficient for estimation. In the present study, we use a set of published cellular signaling models to address issues related to global parameter identifiability. That is, we address the following question: assuming known time courses for some model variables, which parameters is it theoretically impossible to estimate, even with continuous, noise-free data? Following an introduction to this problem and its relevance, we perform a full identifiability analysis on a set of cellular signaling models using DAISY (Differential Algebra for the Identifiability of SYstems). We use our analysis to bring to light important issues related to parameter identifiability in ordinary differential equation (ODE) models. We contend that this is, as of yet, an under-appreciated issue in biological modeling and, more particularly, cell biology. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Dermal quercetin smartCrystals®: Formulation development, antioxidant activity and cellular safety.

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Hatahet, T; Morille, M; Hommoss, A; Dorandeu, C; Müller, R H; Bégu, S

2016-05-01

Flavonoids are natural plant pigments, which possess high antioxidative and antiradical activities. However, their poor water solubility led to a limited bioavailability. To overcome this major hurdle, quercetin nanocrystals were produced implementing smartCrystals® technology. This process combines bead milling and subsequent high-pressure homogenization at relatively low pressure (300bar). To test the possibility to develop a dermal formulation from quercetin smartCrystals®, quercetin nanosuspensions were admixed to Lutrol® F127 and hydroxythylcellulose nonionic gels. The physicochemical properties (morphology, size and charge), saturation solubility, dissolution velocity and the antioxidant properties (DPPH assay) as well as the cellular interaction of the produced quercetin smartCrystals® were studied and compared to crude quercetin powder. Quercetin smartCrystals® showed a strong increase in the saturation solubility and the dissolution velocity (7.6 fold). SmartCrystals® loaded or not into gels proved to be physically stable over a period of three months at 25°C. Interestingly, in vitro DPPH assay confirmed the preservation of quercetin antioxidative properties after nanonization. In parallel, the nanocrystalline form did not display cellular toxicity, even at high concentration (50μg/ml), as assayed on an epithelial cell line (VERO cells). In addition, the nanocrystalline form confirmed a protective activity for VERO cells against hydrogen peroxide induced toxicity in vitro. This new formulation presents a promising approach to deliver quercetin efficiently to skin in well-tolerated formulations. Copyright © 2016 Elsevier B.V. All rights reserved.

Comparison of home and away-from-home physical activity using accelerometers and cellular network-based tracking devices.

Science.gov (United States)

Ramulu, Pradeep Y; Chan, Emilie S; Loyd, Tara L; Ferrucci, Luigi; Friedman, David S

2012-08-01

Measuring physical at home and away from home is essential for assessing health and well-being, and could help design interventions to increase physical activity. Here, we describe how physical activity at home and away from home can be quantified by combining information from cellular network-based tracking devices and accelerometers. Thirty-five working adults wore a cellular network-based tracking device and an accelerometer for 6 consecutive days and logged their travel away from home. Performance of the tracking device was determined using the travel log for reference. Tracking device and accelerometer data were merged to compare physical activity at home and away from home. The tracking device detected 98.6% of all away-from-home excursions, accurately measured time away from home and demonstrated few prolonged signal drop-out periods. Most physical activity took place away from home on weekdays, but not on weekends. Subjects were more physically active per unit of time while away from home, particularly on weekends. Cellular network-based tracking devices represent an alternative to global positioning systems for tracking location, and provide information easily integrated with accelerometers to determine where physical activity takes place. Promoting greater time spent away from home may increase physical activity.

Effect of Cellular Location of Human Carboxylesterase 2 on CPT-11 Hydrolysis and Anticancer Activity.

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Yuan-Ting Hsieh

Full Text Available CPT-11 is an anticancer prodrug that is clinically used for the treatment of metastatic colorectal cancer. Hydrolysis of CPT-11 by human carboxylesterase 2 (CE2 generates SN-38, a topoisomerase I inhibitor that is the active anti-tumor agent. Expression of CE2 in cancer cells is under investigation for the tumor-localized activation of CPT-11. CE2 is normally expressed in the endoplasmic reticulum of cells but can be engineered to direct expression of active enzyme on the plasma membrane or as a secreted form. Although previous studies have investigated different locations of CE2 expression in cancer cells, it remains unclear if CE2 cellular location affects CPT-11 anticancer activity. In the present study, we directly compared the influence of CE2 cellular location on substrate hydrolysis and CPT-11 cytotoxicity. We linked expression of CE2 and enhanced green fluorescence protein (eGFP via a foot-and-mouth disease virus 2A (F2A peptide to facilitate fluorescence-activated cell sorting to achieve similar expression levels of ER-located, secreted or membrane-anchored CE2. Soluble CE2 was detected in the medium of cells that expressed secreted and membrane-anchored CE2, but not in cells that expressed ER-retained CE2. Cancer cells that expressed all three forms of CE2 were more sensitive to CPT-11 as compared to unmodified cancer cells, but the membrane-anchored and ER-retained forms of CE2 were consistently more effective than secreted CE2. We conclude that expression of CE2 in the ER or on the membrane of cancer cells is suitable for enhancing CPT-11 anticancer activity.

The Na{sup +}/K{sup +} -pump in rat peritoneal mast cells: Some aspects of regulatio of activity and cellular fusion

Energy Technology Data Exchange (ETDEWEB)

Knudsen, T. [Odense Univ., Dept. of Pharmacology, Inst. of Medical Biology, The Faculty of Health Scineces (Denmark)

1995-12-31

The mast cell contains potent mediators of inflammation which are released after IgE-directed and non-IgE-directed stimulation of the cell. This highly specialized cell is therefore ascribed a role in the pathogenesis of disease states in which the inflammatory response plays a role for the development of the clinical symptoms. Thus, besides being of interest in basic research, studies of the cellular processes leading to release of inflammatory mediators from the mast cell also also have important clinical implications. The aim of the present work has been to document the existence of the Na{sup +}/K{sup +}-pump in rat peritoneal mast cells, to investigate the regulation of the pump activity and to explore whether modulation of the pump activity interferes with the cellular stimulus/secretion coupling mechanism. The Na{sup +}/K{sup +}-pump activity following stimulation of the mast cell was also investigated. The pump activity was assessed as the ouabain-sensitive cellular potassium uptake with {sup 86}Rb{sup +} as a tracer for potassium. The histamine release from the mast cell following IgE-directed and non-IgE-directed stimulation of the cell was used as a parameter of cellular degranulation. Histamine was measured by spectrofluorometry. Besides describing aspects of the function and regulation of the Na{sup +}/K{sup +}-pump in the rat peritoneal mast cell, this thesis points to the potential role of sodium transport mechanisms in mast cell physiology. Pharmacological manipulations of such transport mechanisms might in the future add to the treatment of allergic diseases. (au) 253 refs.

Numerical Study on Critical Wedge Angle of Cellular Detonation Reflections

International Nuclear Information System (INIS)

Gang, Wang; Kai-Xin, Liu; De-Liang, Zhang

2010-01-01

The critical wedge angle (CWA) for the transition from regular reflection (RR) to Mach reflection (MR) of a cellular detonation wave is studied numerically by an improved space-time conservation element and solution element method together with a two-step chemical reaction model. The accuracy of that numerical way is verified by simulating cellular detonation reflections at a 19.3° wedge. The planar and cellular detonation reflections over 45°–55° wedges are also simulated. When the cellular detonation wave is over a 50° wedge, numerical results show a new phenomenon that RR and MR occur alternately. The transition process between RR and MR is investigated with the local pressure contours. Numerical analysis shows that the cellular structure is the essential reason for the new phenomenon and the CWA of detonation reflection is not a certain angle but an angle range. (fundamental areas of phenomenology(including applications))

Different cellular effects of four anti-inflammatory eye drops on human corneal epithelial cells: independent in active components

OpenAIRE

Qu, Mingli; Wang, Yao; Yang, Lingling; Zhou, Qingjun

2011-01-01

Purpose To evaluate and compare the cellular effects of four commercially available anti-inflammatory eye drops and their active components on human corneal epithelial cells (HCECs) in vitro. Methods The cellular effects of four eye drops (Bromfenac Sodium Hydrate Eye Drops, Pranoprofen Eye Drops, Diclofenac Sodium Eye Drops, and Tobramycin & Dex Eye Drops) and their corresponding active components were evaluated in an HCEC line with five in vitro assays. Cell proliferation and migration were...

Study of Electromagnetic Fields on Cellular Systems Study of Electromagnetic Fields on Cellular Systems

Directory of Open Access Journals (Sweden)

Sergio Solorio-Meza

2012-02-01

Full Text Available Durante las últimas décadas, el interés por explicar el efecto de la radiación no ionizante, como es el caso de los campos electromagnéticos (CEM sobre sistemas celulares ha aumentado considerablemente. En este artículo se describe la interacción que existe entre los CEM y sistemas biológicos. Se discute el efecto de la estimulación electromagnética a diferentes frecuencias e intensidades en cultivos celulares. Resultados preliminares al estimular células de neuroblastomas SK-NSH con campos electromagnéticos de extra baja frecuencia (CEM-EBF, CEM que van del rango de 3 a 30 Hz, indican que se induce un estrés celularque se refleja en variaciones en la expresión de proteínas respecto al grupo de células no estimuladas. En particular, la expresión de las proteínas muestra que los CEM-EBF producen cambios en las proteínas presentes en condiciones normales o basales en las células, es decir, aparecen nuevas proteínas o existe un aumento en la cantidad de ellas.In the last decades the interest to study the effect of non-ionizing radiation, such as the electromagnetic fields (EMF on cellular systems has increased. In this article the interaction between EMF and biological systems is described. An analysis of the effect of the electromagnetic stimulation at different frequencies and intensities on cell cultures is performed. Preliminary results show that the stimulation with extremely low frequency electromagnetic fields (ELF-EMF, EMF from 3 to 30 Hz, on the cellular line of neuroblastomaSK-NSH induces cellular stress. This is reflected by a variation in the proteins expression in comparison with the group of cells no stimulated. In particular, the proteins expression shows that the ELF-EMF produce changes in the current proteins in normal or basal conditionsin the cells, that is, new proteins appear or there is evidence of an increasing in theamount of them.

Modulation of hyaluronan synthase activity in cellular membrane fractions.

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Vigetti, Davide; Genasetti, Anna; Karousou, Evgenia; Viola, Manuela; Clerici, Moira; Bartolini, Barbara; Moretto, Paola; De Luca, Giancarlo; Hascall, Vincent C; Passi, Alberto

2009-10-30

Hyaluronan (HA), the only non-sulfated glycosaminoglycan, is involved in morphogenesis, wound healing, inflammation, angiogenesis, and cancer. In mammals, HA is synthesized by three homologous HA synthases, HAS1, HAS2, and HAS3, that polymerize the HA chain using UDP-glucuronic acid and UDP-N-acetylglucosamine as precursors. Since the amount of HA is critical in several pathophysiological conditions, we developed a non-radioactive assay for measuring the activity of HA synthases (HASs) in eukaryotic cells and addressed the question of HAS activity during intracellular protein trafficking. We prepared three cellular fractions: plasma membrane, cytosol (containing membrane proteins mainly from the endoplasmic reticulum and Golgi), and nuclei. After incubation with UDP-sugar precursors, newly synthesized HA was quantified by polyacrylamide gel electrophoresis of fluorophore-labeled saccharides and high performance liquid chromatography. This new method measured HAS activity not only in the plasma membrane fraction but also in the cytosolic membranes. This new technique was used to evaluate the effects of 4-methylumbeliferone, phorbol 12-myristate 13-acetate, interleukin 1beta, platelet-derived growth factor BB, and tunicamycin on HAS activities. We found that HAS activity can be modulated by post-translational modification, such as phosphorylation and N-glycosylation. Interestingly, we detected a significant increase in HAS activity in the cytosolic membrane fraction after tunicamycin treatment. Since this compound is known to induce HA cable structures, this result links HAS activity alteration with the capability of the cell to promote HA cable formation.

Mapping whole-brain activity with cellular resolution by light-sheet microscopy and high-throughput image analysis (Conference Presentation)

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Silvestri, Ludovico; Rudinskiy, Nikita; Paciscopi, Marco; Müllenbroich, Marie Caroline; Costantini, Irene; Sacconi, Leonardo; Frasconi, Paolo; Hyman, Bradley T.; Pavone, Francesco S.

2016-03-01

Mapping neuronal activity patterns across the whole brain with cellular resolution is a challenging task for state-of-the-art imaging methods. Indeed, despite a number of technological efforts, quantitative cellular-resolution activation maps of the whole brain have not yet been obtained. Many techniques are limited by coarse resolution or by a narrow field of view. High-throughput imaging methods, such as light sheet microscopy, can be used to image large specimens with high resolution and in reasonable times. However, the bottleneck is then moved from image acquisition to image analysis, since many TeraBytes of data have to be processed to extract meaningful information. Here, we present a full experimental pipeline to quantify neuronal activity in the entire mouse brain with cellular resolution, based on a combination of genetics, optics and computer science. We used a transgenic mouse strain (Arc-dVenus mouse) in which neurons which have been active in the last hours before brain fixation are fluorescently labelled. Samples were cleared with CLARITY and imaged with a custom-made confocal light sheet microscope. To perform an automatic localization of fluorescent cells on the large images produced, we used a novel computational approach called semantic deconvolution. The combined approach presented here allows quantifying the amount of Arc-expressing neurons throughout the whole mouse brain. When applied to cohorts of mice subject to different stimuli and/or environmental conditions, this method helps finding correlations in activity between different neuronal populations, opening the possibility to infer a sort of brain-wide 'functional connectivity' with cellular resolution.

Insulin-like growth factor-I, physical activity, and control of cellular anabolism.

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Nindl, Bradley C

2010-01-01

The underlying mechanisms responsible for mediating the beneficial outcomes of exercise undoubtedly are many, but the insulin-like growth factor-I (IGF-I) system is emerging as an important and central hormonal axis that plays a significant role concerning cellular anabolism. This introductory article summarizes the intent and the content for papers presented as part of a 2008 American College of Sports Medicine national symposium entitled "Insulin-like Growth Factor-I, Physical Activity, and Control of Cellular Anabolism." The individual authors and their papers are as follows: Jan Frystyk authoring "The relationship between exercise and the growth hormone/insulin-like growth factor-I axis," Greg Adams authoring "IGF-I signaling in skeletal muscle and the potential for cytokine interactions," and Brad Nindl authoring "Insulin-like growth factor-I as a biomarker of health, fitness, and training status." These papers focus on 1) different assay methodologies for IGF-I within the paradigm of exercise studies, 2) research demonstrating that intracellular signaling components associated with several proinflammatory cytokines have the potential to interact with anabolic signaling processes in skeletal muscle, and 3) an overview of IGF-I as a biomarker related to exercise training, muscle and bone remodeling, body composition, cognition, and cancer. When summed in total, the contribution that these papers will make will undoubtedly involve bringing attention to the vast regulatory complexity of the IGF-I system and will hopefully convince the reader that the IGF-I system warrants further detailed scientific inquiry to resolve many unanswered questions and paradoxical experimental findings. The IGF-I system remains one of the most intriguing and captivating marvels of human physiology that seems central in mediating numerous adaptations from physical activity.

Restriction on an energy-dense diet improves markers of metabolic health and cellular aging in mice through decreasing hepatic mTOR activity.

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Schloesser, Anke; Campbell, Graeme; Glüer, Claus-Christian; Rimbach, Gerald; Huebbe, Patricia

2015-02-01

Dietary restriction (DR) on a normal low-fat diet improves metabolic health and may prolong life span. However, it is still uncertain whether restriction of an energy-dense, high-fat diet would also be beneficial and mitigate age-related processes. In the present study, we determined biomarkers of metabolic health, energy metabolism, and cellular aging in obesity-prone mice subjected to 30% DR on a high-fat diet for 6 months. Dietary-restricted mice had significantly lower body weights, less adipose tissue, lower energy expenditure, and altered substrate oxidation compared to their ad libitum-fed counterparts. Hepatic major urinary proteins (Mup) expression, which is linked to glucose and energy metabolism, and biomarkers of metabolic health, including insulin, glucose, cholesterol, and leptin/adiponectin ratio, were likewise reduced in high-fat, dietary-restricted mice. Hallmarks of cellular senescence such as Lamp2a and Hsc70 that mediate chaperone-mediated autophagy were induced and mechanistic target of rapamycin (mTOR) signaling mitigated upon high-fat DR. In contrast to DR applied in low-fat diets, anti-oxidant gene expression, proteasome activity, as well as 5'-adenosine monophosphate-activated protein kinase (AMPK) activation were not changed, suggesting that high-fat DR may attenuate some processes associated with cellular aging without the induction of cellular stress response or energy deprivation.

A comparative study on fluorescent cholesterol analogs as versatile cellular reporters

DEFF Research Database (Denmark)

Sezgin, Erdinc; Betul Can, Fatma; Schneider, Falk

2016-01-01

Cholesterol is a crucial component of cellular membranes, but knowledge of its intracellular dynamics is scarce. Thus, it is of utmost interest to develop tools for visualization of cholesterol organization and dynamics in cells and tissues. For this purpose, many studies make use of fluorescently...... for their performance in cellular assays: 1) plasma membrane incorporation, specifically the preference for more ordered membrane environments in phase separated giant unilamellar vesicles (GUVs) and giant plasma membrane vesicles (GPMVs); 2) cellular trafficking, specifically subcellular localization in Niemann-Pick C...... in the intracellular trafficking assay. However, none showed positive performance in all assays. Our results constitute a concise guide for the careful use of fluorescent cholesterol analogs in visualizing cellular cholesterol dynamics....

Cellular and Animal Studies: Insights into Pathophysiology and Therapy of PCOS.

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Indran, Inthrani Raja; Lee, Bao Hui; Yong, Eu-Leong

2016-11-01

Basic science studies have advanced our understanding of the role of key enzymes in the steroidogenesis pathway and those that affect the pathophysiology of PCOS. Studies with ovarian theca cells taken from women with PCOS have demonstrated increased androgen production due to increased CYP17A1 and HSD3B2 enzyme activities. Furthermore, overexpression of DENND1A variant 2 in normal theca cells resulted in a PCOS phenotype with increased androgen production. Notably, cellular steroidogenesis models have facilitated the understanding of the mechanistic effects of pharmacotherapies, including insulin sensitizers (e.g., pioglitazone and metformin) used for the treatment of insulin resistance in PCOS, on androgen production. In addition, animal models of PCOS have provided a critical platform to study the effects of therapeutic agents in a manner closer to the physiological state. Indeed, recent breakthroughs have demonstrated that natural derivatives such as the dietary medium-chain fatty acid decanoic acid (DA) can restore estrous cyclicity and lower androgen levels in an animal model of PCOS, thus laying the platform for novel therapeutic developments in PCOS. This chapter reviews the current understanding on the pathways modulating androgen biosynthesis, and the cellular and animal models that form the basis for preclinical research in PCOS, and sets the stage for clinical research. Copyright © 2016. Published by Elsevier Ltd.

Activation of the cellular unfolded protein response by recombinant adeno-associated virus vectors.

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Balaji Balakrishnan

Full Text Available The unfolded protein response (UPR is a stress-induced cyto-protective mechanism elicited towards an influx of large amount of proteins in the endoplasmic reticulum (ER. In the present study, we evaluated if AAV manipulates the UPR pathways during its infection. We first examined the role of the three major UPR axes, namely, endoribonuclease inositol-requiring enzyme-1 (IRE1α, activating transcription factor 6 (ATF6 and PKR-like ER kinase (PERK in AAV infected cells. Total RNA from mock or AAV infected HeLa cells were used to determine the levels of 8 different ER-stress responsive transcripts from these pathways. We observed a significant up-regulation of IRE1α (up to 11 fold and PERK (up to 8 fold genes 12-48 hours after infection with self-complementary (scAAV2 but less prominent with single-stranded (ssAAV2 vectors. Further studies demonstrated that scAAV1 and scAAV6 also induce cellular UPR in vitro, with AAV1 vectors activating the PERK pathway (3 fold while AAV6 vectors induced a significant increase on all the three major UPR pathways [6-16 fold]. These data suggest that the type and strength of UPR activation is dependent on the viral capsid. We then examined if transient inhibition of UPR pathways by RNA interference has an effect on AAV transduction. siRNA mediated silencing of PERK and IRE1α had a modest effect on AAV2 and AAV6 mediated gene expression (∼1.5-2 fold in vitro. Furthermore, hepatic gene transfer of scAAV2 vectors in vivo, strongly elevated IRE1α and PERK pathways (2 and 3.5 fold, respectively. However, when animals were pre-treated with a pharmacological UPR inhibitor (metformin during scAAV2 gene transfer, the UPR signalling and its subsequent inflammatory response was attenuated concomitant to a modest 2.8 fold increase in transgene expression. Collectively, these data suggest that AAV vectors activate the cellular UPR pathways and their selective inhibition may be beneficial during AAV mediated gene transfer.

Controlling cellular P-TEFb activity by the HIV-1 transcriptional transactivator Tat.

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Lisa Muniz

Full Text Available The human immunodeficiency virus 1 (HIV-1 transcriptional transactivator (Tat is essential for synthesis of full-length transcripts from the integrated viral genome by RNA polymerase II (Pol II. Tat recruits the host positive transcription elongation factor b (P-TEFb to the HIV-1 promoter through binding to the transactivator RNA (TAR at the 5'-end of the nascent HIV transcript. P-TEFb is a general Pol II transcription factor; its cellular activity is controlled by the 7SK small nuclear RNA (snRNA and the HEXIM1 protein, which sequester P-TEFb into transcriptionally inactive 7SK/HEXIM/P-TEFb snRNP. Besides targeting P-TEFb to HIV transcription, Tat also increases the nuclear level of active P-TEFb through promoting its dissociation from the 7SK/HEXIM/P-TEFb RNP by an unclear mechanism. In this study, by using in vitro and in vivo RNA-protein binding assays, we demonstrate that HIV-1 Tat binds with high specificity and efficiency to an evolutionarily highly conserved stem-bulge-stem motif of the 5'-hairpin of human 7SK snRNA. The newly discovered Tat-binding motif of 7SK is structurally and functionally indistinguishable from the extensively characterized Tat-binding site of HIV TAR and importantly, it is imbedded in the HEXIM-binding elements of 7SK snRNA. We show that Tat efficiently replaces HEXIM1 on the 7SK snRNA in vivo and therefore, it promotes the disassembly of the 7SK/HEXIM/P-TEFb negative transcriptional regulatory snRNP to augment the nuclear level of active P-TEFb. This is the first demonstration that HIV-1 specifically targets an important cellular regulatory RNA, most probably to promote viral transcription and replication. Demonstration that the human 7SK snRNA carries a TAR RNA-like Tat-binding element that is essential for the normal transcriptional regulatory function of 7SK questions the viability of HIV therapeutic approaches based on small drugs blocking the Tat-binding site of HIV TAR.

The yeast mitogen-activated protein kinase Slt2 is involved in the cellular response to genotoxic stress

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Soriano-Carot María

2012-02-01

Full Text Available Abstract Background The maintenance of genomic integrity is essential for cell viability. Complex signalling pathways (DNA integrity checkpoints mediate the response to genotoxic stresses. Identifying new functions involved in the cellular response to DNA-damage is crucial. The Saccharomyces cerevisiae SLT2 gene encodes a member of the mitogen-activated protein kinase (MAPK cascade whose main function is the maintenance of the cell wall integrity. However, different observations suggest that SLT2 may also have a role related to DNA metabolism. Results This work consisted in a comprehensive study to connect the Slt2 protein to genome integrity maintenance in response to genotoxic stresses. The slt2 mutant strain was hypersensitive to a variety of genotoxic treatments, including incubation with hydroxyurea (HU, methylmetanosulfonate (MMS, phleomycin or UV irradiation. Furthermore, Slt2 was activated by all these treatments, which suggests that Slt2 plays a central role in the cellular response to genotoxic stresses. Activation of Slt2 was not dependent on the DNA integrity checkpoint. For MMS and UV, Slt2 activation required progression through the cell cycle. In contrast, HU also activated Slt2 in nocodazol-arrested cells, which suggests that Slt2 may respond to dNTP pools alterations. However, neither the protein level of the distinct ribonucleotide reductase subunits nor the dNTP pools were affected in a slt2 mutant strain. An analysis of the checkpoint function revealed that Slt2 was not required for either cell cycle arrest or the activation of the Rad53 checkpoint kinase in response to DNA damage. However, slt2 mutant cells showed an elongated bud and partially impaired Swe1 degradation after replicative stress, indicating that Slt2 could contribute, in parallel with Rad53, to bud morphogenesis control after genotoxic stresses. Conclusions Slt2 is activated by several genotoxic treatments and is required to properly cope with DNA damage. Slt

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

Sub-cellular distribution and translocation of TRP channels.

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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.

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...

The cellular memory disc of reprogrammed cells.

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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].

Impaired CK1 delta activity attenuates SV40-induced cellular transformation in vitro and mouse mammary carcinogenesis in vivo.

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Heidrun Hirner

Full Text Available Simian virus 40 (SV40 is a powerful tool to study cellular transformation in vitro, as well as tumor development and progression in vivo. Various cellular kinases, among them members of the CK1 family, play an important role in modulating the transforming activity of SV40, including the transforming activity of T-Ag, the major transforming protein of SV40, itself. Here we characterized the effects of mutant CK1δ variants with impaired kinase activity on SV40-induced cell transformation in vitro, and on SV40-induced mammary carcinogenesis in vivo in a transgenic/bi-transgenic mouse model. CK1δ mutants exhibited a reduced kinase activity compared to wtCK1δ in in vitro kinase assays. Molecular modeling studies suggested that mutation N172D, located within the substrate binding region, is mainly responsible for impaired mutCK1δ activity. When stably over-expressed in maximal transformed SV-52 cells, CK1δ mutants induced reversion to a minimal transformed phenotype by dominant-negative interference with endogenous wtCK1δ. To characterize the effects of CK1δ on SV40-induced mammary carcinogenesis, we generated transgenic mice expressing mutant CK1δ under the control of the whey acidic protein (WAP gene promoter, and crossed them with SV40 transgenic WAP-T-antigen (WAP-T mice. Both WAP-T mice as well as WAP-mutCK1δ/WAP-T bi-transgenic mice developed breast cancer. However, tumor incidence was lower and life span was significantly longer in WAP-mutCK1δ/WAP-T bi-transgenic animals. The reduced CK1δ activity did not affect early lesion formation during tumorigenesis, suggesting that impaired CK1δ activity reduces the probability for outgrowth of in situ carcinomas to invasive carcinomas. The different tumorigenic potential of SV40 in WAP-T and WAP-mutCK1δ/WAP-T tumors was also reflected by a significantly different expression of various genes known to be involved in tumor progression, specifically of those involved in wnt-signaling and DNA

Cellular recovery kinetic studies relevant to combined-modality research and therapy

International Nuclear Information System (INIS)

Dethlefsen, L.A.

1979-01-01

The relevance of cellular recovery kinetics to combined-modality therapy is evaluated within the framework of an idealized experimental flow chart and published adriamycin data. Within this context, limitations for both experimental design and data interpretations are discussed. The effects of adriamycin have been documented extensively at the molecular and cellular level and its interactions with x-irradiation have been studied, both in vitro and in vivo. The limited in vivo results suggest that the end results of a given protocol correlate with cellular recovery kinetics; however, definitive experiments simply have not been done. For example, no one has used single-dose drug and irradiation data to predict the outcome and then confirm or refute the prediction even in a relatively simple 2-dose drug + 2-dose drug + 2-dose x-ray protocol. Thus, at this time, the extent of the correlations between cellular recovery kinetics and clinical response for either normal or malignant tissues is not known and the possible relevance of such studies cannot be discounted

A cardiac electrical activity model based on a cellular automata system in comparison with neural network model.

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Khan, Muhammad Sadiq Ali; Yousuf, Sidrah

2016-03-01

Cardiac Electrical Activity is commonly distributed into three dimensions of Cardiac Tissue (Myocardium) and evolves with duration of time. The indicator of heart diseases can occur randomly at any time of a day. Heart rate, conduction and each electrical activity during cardiac cycle should be monitor non-invasively for the assessment of "Action Potential" (regular) and "Arrhythmia" (irregular) rhythms. Many heart diseases can easily be examined through Automata model like Cellular Automata concepts. This paper deals with the different states of cardiac rhythms using cellular automata with the comparison of neural network also provides fast and highly effective stimulation for the contraction of cardiac muscles on the Atria in the result of genesis of electrical spark or wave. The specific formulated model named as "States of automaton Proposed Model for CEA (Cardiac Electrical Activity)" by using Cellular Automata Methodology is commonly shows the three states of cardiac tissues conduction phenomena (i) Resting (Relax and Excitable state), (ii) ARP (Excited but Absolutely refractory Phase i.e. Excited but not able to excite neighboring cells) (iii) RRP (Excited but Relatively Refractory Phase i.e. Excited and able to excite neighboring cells). The result indicates most efficient modeling with few burden of computation and it is Action Potential during the pumping of blood in cardiac cycle.

Novel cellular bouton structure activated by ATP in the vascular wall of porcine retinal arterioles.

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Misfeldt, Mikkel Wölck; Aalkjaer, Christian; Simonsen, Ulf; Bek, Toke

2010-12-01

The retinal blood flow is regulated by the tone of resistance arterioles, which is influenced by purinergic compounds such as adenosine and adenosine 5'-triphosphate (ATP) released from the retinal tissue. However, it is unknown what cellular elements in the perivascular retina are responsible for the effect of purines on the tone of retinal arterioles. Porcine retinal arterioles were loaded with the calcium-sensitive fluorophore Oregon green. The vessels were mounted in a confocal myograph for simultaneous recordings of tone and calcium activity in cells of the vascular wall during stimulation with ATP and adenosine, with and without modifiers of these compounds. Additionally, immunohistochemistry was used to localize elements with calcium activity in the vascular wall. Hyperfluorescence indicating calcium activity was recorded in a population of abundant round boutons interspersed in a network of vimentin-positive processes located immediately external to the smooth muscle cell layer but internal to the perivascular glial cells. These structures showed calcium activity when the vessel was relaxed with ATP but not when it was relaxed with adenosine. Ryanodine reduced calcium activity in the boutons, whereas the ATP antagonist adenosine-5'-O-(α, β- methylene diphosphate) reduced calcium activity in both the boutons and vascular tone. The vasodilating effect of purines in porcine retinal tissue involves ATP-dependent calcium activity in a layer of cellular boutons located external to the vascular smooth muscle cells and internal to the perivascular glial cells.

Dual fluorescent molecular substrates selectively report the activation, sustainability and reversibility of cellular PKB/Akt activity.

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Shen, Duanwen; Bai, Mingfeng; Tang, Rui; Xu, Baogang; Ju, Xiaoming; Pestell, Richard G; Achilefu, Samuel

2013-01-01

Using a newly developed near-infrared (NIR) dye that fluoresces at two different wavelengths (dichromic fluorescence, DCF), we discovered a new fluorescent substrate for Akt, also known as protein kinase B, and a method to quantitatively report this enzyme's activity in real time. Upon insulin activation of cellular Akt, the enzyme multi-phosphorylated a single serine residue of a diserine DCF substrate in a time-dependent manner, culminating in monophospho- to triphospho-serine products. The NIR DCF probe was highly selective for the Akt1 isoform, which was demonstrated using Akt1 knockout cells derived from MMTV-ErbB2 transgenic mice. The DCF mechanism provides unparalleled potential to assess the stimulation, sustainability, and reversibility of Akt activation longitudinally. Importantly, NIR fluorescence provides a pathway to translate findings from cells to living organisms, a condition that could eventually facilitate the use of these probes in humans.

Influence of corona charging in cellular polyethylene film

International Nuclear Information System (INIS)

Ortega Brana, Gustavo; Magraner, Francisco; Quijano, Alfredo; Llovera Segovia, Pedro

2011-01-01

Cellular polymers have recently attracted attention for their property of exhibiting a piezoelectric constant when they are electrically charged. The electrostatic charge generated in the voids by the internal discharges creates and internal macrodipole which is responsible for the piezoelectric effect. Charging by corona discharge is the most used method for cellular polymers. Many works has been published on polypropylene and polyethylene films mainly focused on the required expansion process or on the results obtained for raw cellular materials electrically activated. Our work is based on commercial polyethylene cellular films which have been physically characterized and electrically activated. The effect of thermal treatment, physical uniaxial or biaxial stretching and corona charging was investigated. The new method of corona charging improved the piezoelectric constant under other activation conditions.

Influence of corona charging in cellular polyethylene film

Energy Technology Data Exchange (ETDEWEB)

Ortega Brana, Gustavo; Magraner, Francisco; Quijano, Alfredo [Instituto Tecnologico de la Energia (ITE), Av. Juan de la Cierva 24, Parque Tecnologico de Valencia, 46980 Paterna-Valencia (Spain); Llovera Segovia, Pedro, E-mail: gustavo.ortega@ite.es [Instituto de TecnologIa Electrica - Universitat Politecnica de Valencia, Camino de Vera s/n 46022-Valencia (Spain)

2011-06-23

Cellular polymers have recently attracted attention for their property of exhibiting a piezoelectric constant when they are electrically charged. The electrostatic charge generated in the voids by the internal discharges creates and internal macrodipole which is responsible for the piezoelectric effect. Charging by corona discharge is the most used method for cellular polymers. Many works has been published on polypropylene and polyethylene films mainly focused on the required expansion process or on the results obtained for raw cellular materials electrically activated. Our work is based on commercial polyethylene cellular films which have been physically characterized and electrically activated. The effect of thermal treatment, physical uniaxial or biaxial stretching and corona charging was investigated. The new method of corona charging improved the piezoelectric constant under other activation conditions.

Modeling and cellular studies

International Nuclear Information System (INIS)

Anon.

1982-01-01

Testing the applicability of mathematical models with carefully designed experiments is a powerful tool in the investigations of the effects of ionizing radiation on cells. The modeling and cellular studies complement each other, for modeling provides guidance for designing critical experiments which must provide definitive results, while the experiments themselves provide new input to the model. Based on previous experimental results the model for the accumulation of damage in Chlamydomonas reinhardi has been extended to include various multiple two-event combinations. Split dose survival experiments have shown that models tested to date predict most but not all the observed behavior. Stationary-phase mammalian cells, required for tests of other aspects of the model, have been shown to be at different points in the cell cycle depending on how they were forced to stop proliferating. These cultures also demonstrate different capacities for repair of sublethal radiation damage

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.

A Giant Vulvar Mass: A Case Study of Cellular Angiofibroma

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Aydın, Ümit; Terzi, Hasan; Turkay, Ünal; Eruyar, Ahmet Tuğrul; Kale, Ahmet

2016-01-01

Cellular angiofibroma is a mesenchymal tumor that affects both genders. Nucci et al. first described it in 1997. Cellular angiofibroma is generally a small and asymptomatic mass that primarily arises in the vulvar-vaginal region, although rare cases have been reported in the pelvic and extrapelvic regions. It affects women most often during the fifth decade of life. The treatment requires simple local excision due to low local recurrence and no chance of metastasization. The current study presents a case of angiofibroma in the vulvar region that measured approximately 20 cm. PMID:27293929

A Giant Vulvar Mass: A Case Study of Cellular Angiofibroma

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Ümit Aydın

2016-01-01

Full Text Available Cellular angiofibroma is a mesenchymal tumor that affects both genders. Nucci et al. first described it in 1997. Cellular angiofibroma is generally a small and asymptomatic mass that primarily arises in the vulvar-vaginal region, although rare cases have been reported in the pelvic and extrapelvic regions. It affects women most often during the fifth decade of life. The treatment requires simple local excision due to low local recurrence and no chance of metastasization. The current study presents a case of angiofibroma in the vulvar region that measured approximately 20 cm.

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

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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

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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

Reconstitution of the cellular response to DNA damage in vitro using damage-activated extracts from mammalian cells

International Nuclear Information System (INIS)

Roper, Katherine; Coverley, Dawn

2012-01-01

In proliferating mammalian cells, DNA damage is detected by sensors that elicit a cellular response which arrests the cell cycle and repairs the damage. As part of the DNA damage response, DNA replication is inhibited and, within seconds, histone H2AX is phosphorylated. Here we describe a cell-free system that reconstitutes the cellular response to DNA double strand breaks using damage-activated cell extracts and naïve nuclei. Using this system the effect of damage signalling on nuclei that do not contain DNA lesions can be studied, thereby uncoupling signalling and repair. Soluble extracts from G1/S phase cells that were treated with etoposide before isolation, or pre-incubated with nuclei from etoposide-treated cells during an in vitro activation reaction, restrain both initiation and elongation of DNA replication in naïve nuclei. At the same time, H2AX is phosphorylated in naïve nuclei in a manner that is dependent upon the phosphatidylinositol 3-kinase-like protein kinases. Notably, phosphorylated H2AX is not focal in naïve nuclei, but is evident throughout the nucleus suggesting that in the absence of DNA lesions the signal is not amplified such that discrete foci can be detected. This system offers a novel screening approach for inhibitors of DNA damage response kinases, which we demonstrate using the inhibitors wortmannin and LY294002. -- Highlights: ► A cell free system that reconstitutes the response to DNA damage in the absence of DNA lesions. ► Damage-activated extracts impose the cellular response to DNA damage on naïve nuclei. ► PIKK-dependent response impacts positively and negatively on two separate fluorescent outputs. ► Can be used to screen for inhibitors that impact on the response to damage but not on DNA repair. ► LY294002 and wortmannin demonstrate the system's potential as a pathway focused screening approach.

Role of excision repair in postradiation recovery of biological activity of cellular DNA Bacillus subtilis

International Nuclear Information System (INIS)

Filippov, V.D.

1976-01-01

DNA extracted from UV-irradiated prototroph cells of Bacillus subtilis uvr + (45 sec. of UV light, 20% survivals) has a lowered transforming activity (TA) of markers purB and metB, and a lowered ratio TA pur/TA met. During the subsequent incubation of uvr + cells in glucose-salt medium free of nitrogen sources the TA of markers and the ratio between them increase. No increase is observed during the postradiation incubation under the same conditions or in a nutrition medium of uvr cells, deficient in escision of pyrimidine dimers. The increment of DNA begins approsimately in 30 min. after the beginning of incubation of irradiated uvr cells in nutrition medium. On the basis of these facts it is concluded that neither the replication of damaged DNA nor the postreplication repair, but only excision repair, can provide the recovery of biological (transforming) activity of cellular DNA in Bac. subtilis. The system given might be a suitable model for testing compounds which affect the activity of this process. The well-known inhibitors of dark repair, caffeine, proflavine to inhibit reversibly the initial steps of the process/ and especially acriflavine, delay the recovery of markers of cellular DNA in irradiated uvr + cells. Caffeine is proved to inhibit reversibly the initial steps of the process

Cellular toxicity of calf blood extract on human corneal epithelial cells in vitro.

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Park, Young Min; Kim, Su Jin; Han, Young Sang; Lee, Jong Soo

2015-01-01

To investigate the biologic effects of the calf blood extract on corneal epithelial cells in vitro. The effects on corneal epithelial cells were evaluated after 1, 4, 12, and 24 h of exposure to various concentrations of calf blood extract (3, 5, 8 and 16%). The MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) assay was performed to measure levels of cellular metabolic activity. The lactate dehydrogenase (LDH) assay was performed to determine the extent of cellular damage. Cellular morphology was examined using phase-contrast microscopy. The scratch wound assay was performed to quantify the migration of corneal epithelial cells. At the 3 and 5% concentrations of calf blood extract, MTT values were similar to those observed in the control group. However, at a concentration of 8 and 16%, cellular metabolic activity was significantly decreased after 4 h of exposure to calf blood extract. After 12 h of exposure to 8 and 16% concentrations of calf blood extract, LDH activity and cellular morphological damage to the corneal epithelial cells were significantly increased. There was no evidence of cellular migration after 12 h exposure to 5% or higher concentration of calf blood extract because of cellular toxicity. Compared with normal corneal epithelial cells, the cellular activity was decreased, and toxicity was increased after over 12 h of exposure to more than 5% concentration of calf blood extract. Further clinical studies will be necessary to determine the optimal concentration and exposure time for the topical application of eye drops containing calf blood extract.

Determining antioxidant activities of lactobacilli cell-free supernatants by cellular antioxidant assay: a comparison with traditional methods.

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Jiali Xing

Full Text Available Antioxidant activity of lactic acid bacteria is associated with multiple health-protective effects. Traditional indexes of chemical antioxidant activities poorly reflect the antioxidant effects of these bacteria in vivo. Cellular antioxidant activity (CAA assay was used in this study to determine the antioxidant activity of cell-free supernatants (CFSs of 10 Lactobacillus strains. The performance of the CAA assay was compared with that of four chemical antioxidant activity assays, namely, DPPH radical scavenging, hydroxyl radical scavenging (HRS, reducing power (RP, and inhibition of linoleic acid peroxidation (ILAP. Results of the CAA assay were associated with those of DPPH and ILAP assays, but not with those of RP and HRS assays. The inter- and intra-specific antioxidant activities of CFS were characterized by chemical and CAA assays. L. rhamnosus CCFM 1107 displayed a high antioxidative effect similar to positive control L. rhamnosus GG ATCC 53103 in all of the assays. The CAA assay is a potential method for the detection of antioxidant activities of lactobacilli CFSs.

Force control for mechanoinduction of impedance variation in cellular organisms

International Nuclear Information System (INIS)

Nam, Joo Hoo; Chen, Peter C Y; Lu, Zhe; Luo, Hong; Lin, Wei; Ge, Ruowen

2010-01-01

Constantly exposed to various forms of mechanical forces inherent in their physical environment (such as gravity, stress induced by fluid flow or cell–cell interactions, etc), cellular organisms sense such forces and convert them into biochemical signals through the processes of mechanosensing and mechanotransduction that eventually lead to biological changes. The effect of external forces on the internal structures and activities in a cellular organism may manifest in changes its physical properties, such as impedance. Studying variation in the impedance of a cellular organism induced by the application of an external mechanical force represents a meaningful endeavor (from a biosystems perspective) in exploring the complex mechanosensing and mechanotransduction mechanisms that govern the behavior of a cellular organism under the influence of external mechanical stimuli. In this paper we describe the development of an explicit force-feedback control system for exerting an indentation force on a cellular organism while simultaneously measuring its impedance. To demonstrate the effectiveness of this force-control system, we have conducted experiments using zebrafish embryos as a test model of a cellular organism. We report experimental results demonstrating that the application of a properly controlled external force leads to a significant change in the impedance of a zebrafish embryo. These results offer support for a plausible explanation that activities of pore canals in the chorion are responsible for the observed change in impedance.

Sirtuin 7 promotes cellular survival following genomic stress by attenuation of DNA damage, SAPK activation and p53 response

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Kiran, Shashi; Oddi, Vineesha [Laboratory of Cancer Biology, Centre for DNA Fingerprinting and Diagnostics, Hyderabad, Telangana, 500001 (India); Ramakrishna, Gayatri, E-mail: gayatrirama1@gmail.com [Laboratory of Cancer Biology, Centre for DNA Fingerprinting and Diagnostics, Hyderabad, Telangana, 500001 (India); Laboratory of Cancer Cell Biology, Department of Research, Institute of Liver and Biliary Sciences, Delhi 110070 (India)

2015-02-01

Maintaining the genomic integrity is a constant challenge in proliferating cells. Amongst various proteins involved in this process, Sirtuins play a key role in DNA damage repair mechanisms in yeast as well as mammals. In the present work we report the role of one of the least explored Sirtuin viz., SIRT7, under conditions of genomic stress when treated with doxorubicin. Knockdown of SIRT7 sensitized osteosarcoma (U2OS) cells to DNA damage induced cell death by doxorubicin. SIRT7 overexpression in NIH3T3 delayed cell cycle progression by causing delay in G1 to S transition. SIRT7 overexpressing cells when treated with low dose of doxorubicin (0.25 µM) showed delayed onset of senescence, lesser accumulation of DNA damage marker γH2AX and lowered levels of growth arrest markers viz., p53 and p21 when compared to doxorubicin treated control GFP expressing cells. Resistance to DNA damage following SIRT7 overexpression was also evident by EdU incorporation studies where cellular growth arrest was significantly delayed. When treated with higher dose of doxorubicin (>1 µM), SIRT7 conferred resistance to apoptosis by attenuating stress activated kinases (SAPK viz., p38 and JNK) and p53 response thereby shifting the cellular fate towards senescence. Interestingly, relocalization of SIRT7 from nucleolus to nucleoplasm together with its co-localization with SAPK was an important feature associated with DNA damage. SIRT7 mediated resistance to doxorubicin induced apoptosis and senescence was lost when p53 level was restored by nutlin treatment. Overall, we propose SIRT7 attenuates DNA damage, SAPK activation and p53 response thereby promoting cellular survival under conditions of genomic stress. - Highlights: • Knockdown of SIRT7 sensitized cells to DNA damage induced apoptosis. • SIRT7 delayed onset of premature senescence by attenuating DNA damage response. • Overexpression of SIRT7 delayed cell cycle progression by delaying G1/S transition. • Upon DNA damage SIRT

Probiotic Properties and Cellular Antioxidant Activity of Lactobacillus plantarum MA2 Isolated from Tibetan Kefir Grains.

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Tang, Wei; Li, Chao; He, Zengguo; Pan, Fen; Pan, Shuo; Wang, Yanping

2017-11-20

Lactobacillus plantarum MA2 was isolated from traditional Chinese Tibetan kefir grains. Its antioxidant properties had been demonstrated in vitro and in vivo previously. In the present study, the probiotic characteristics of this strain were further evaluated by investigating its acid and bile salt tolerances, cell surface hydrophobicity, and autoaggregation, respectively. In addition, the cellular antioxidant activity (CAA) assay was applied to test the antioxidant capacity of the isolate in different growth phases. Same method was also used to evaluate the antioxidant capacity of its fermentation supernatant, cell-free extract, and intact cell quantitatively. The results of probiotic characteristic tests showed that MA2 could survive at pH 2.5 and 0.3% bile salt. Meanwhile, the measurements of cell surface hydrophobicity and autoaggregation were 45.29 ± 2.15 and 6.30 ± 0.34%, respectively. The results of cellular antioxidant activity tests indicated that MA2 had high antioxidant potential. The CAA value of logarithmic phase cell-free extract of MA2 (39,450.00 ± 424.05 μmol quercetin equivalents/100 g sample) was significantly higher than that in stationary phase cell-free extract (3395.98 ± 126.06 μmol quercetin equivalents/100 g sample) and that of fermentation supernatant in logarithmic phase (2174.41 ± 224.47 μmol quercetin equivalents/100 g sample) (p < 0.05). The CAA method was successively applied to evaluate the antioxidant capacity of MA2 in this study, which suggests that it could be used as a useful method for lactic acid bacteria antioxidant potential evaluation.

Ectopic AP4 expression induces cellular senescence via activation of p53 in long-term confluent retinal pigment epithelial cells.

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Wang, Yiping; Wong, Matthew Man-Kin; Zhang, Xiaojian; Chiu, Sung-Kay

2015-11-15

When cells are grown to confluence, cell-cell contact inhibition occurs and drives the cells to enter reversible quiescence rather than senescence. Confluent retinal pigment epithelial (RPE) cells exhibiting contact inhibition was used as a model in this study to examine the role of overexpression of transcription factor AP4, a highly expressed transcription factor in many types of cancer, in these cells during long-term culture. We generated stable inducible RPE cell clones expressing AP4 or AP4 without the DNA binding domain (DN-AP4) and observed that, when cultured for 24 days, RPE cells with a high level of AP4 exhibit a large, flattened morphology and even cease proliferating; these changes were not observed in DN-AP4-expressing cells or non-induced cells. In addition, AP4-expressing cells exhibited senescence-associated β-galactosidase activity and the senescence-associated secretory phenotype. We demonstrated that the induced cellular senescence was mediated by enhanced p53 expression and that AP4 regulates the p53 gene by binding directly to two of the three E-boxes present on the promoter of the p53 gene. Moreover, we showed that serum is essential for AP4 in inducing p53-associated cellular senescence. Collectively, we showed that overexpression of AP4 mediates cellular senescence involving in activation of p53 in long-term post-confluent RPE cells. Copyright © 2015 Elsevier Inc. All rights reserved.

Metavanadate causes cellular accumulation of copper and decreased lysyl oxidase activity

International Nuclear Information System (INIS)

Cui, Changtai T.; Uriu-Adams, Janet Y.; Tchaparian, Eskouhie H.; Keen, Carl L.; Rucker, Robert B.

2004-01-01

Selected indices of copper metabolism in weanling rats and fibroblast cultures were progressively altered in response to increased levels of sodium metavanadate. In diets, vanadium was added in amounts ranging from 0 to 80 μg V/g of diet, that is, 0-1.6 μmol V/g of diet. In fibroblast cultures, vanadium ranged from 0 to 400 nmol V/ml. The inhibition of P-ATPase-7A activity by metavanadate, important to copper egress from cells, was a primary focus. In skin, and tendon, the copper concentration was increased in response to increased dietary levels of metavanadate, whereas lysyl oxidase activity, a secreted cuproprotein, was reduced. The reduction in lysyl oxidase activity was also accompanied by reduced redox cycling potential of isolated fractions of lysyl oxidase, presumably due to reduced lysyltyrosyl quinone (LTQ) formation at the active site of lysyl oxidase. In contrast, liver copper concentrations and plasma ceruloplasmin activity were not affected by metavanadate exposure. However, semicarbazide-sensitive benzylamine oxidase (SCBO) activity, which was taken as an indirect measure of vascular adhesive protein-1 (VAP-1), was increased. In cultured fibroblasts, cellular copper was also increased and lysyl oxidase decreased in response to metavanadate. Moreover, the steady-state levels of atp7a and lysyl oxidase mRNAs were not affected by addition of metavanadate to culture medium up to 200 nmol/ml. Taken together, these data suggest that pathways involving copper egress and lysyl oxidase activation are particularly sensitive to metavanadate exposure through processes that are predominately posttranslational

Time-resolved spectroscopic imaging reveals the fundamentals of cellular NADH fluorescence.

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Li, Dong; Zheng, Wei; Qu, Jianan Y

2008-10-15

A time-resolved spectroscopic imaging system is built to study the fluorescence characteristics of nicotinamide adenine dinucleotide (NADH), an important metabolic coenzyme and endogenous fluorophore in cells. The system provides a unique approach to measure fluorescence signals in different cellular organelles and cytoplasm. The ratios of free over protein-bound NADH signals in cytosol and nucleus are slightly higher than those in mitochondria. The mitochondrial fluorescence contributes about 70% of overall cellular fluorescence and is not a completely dominant signal. Furthermore, NADH signals in mitochondria, cytosol, and the nucleus respond to the changes of cellular activity differently, suggesting that cytosolic and nuclear fluorescence may complicate the well-known relationship between mitochondrial fluorescence and cellular metabolism.

A perillyl alcohol-conjugated analog of 3-bromopyruvate without cellular uptake dependency on monocarboxylate transporter 1 and with activity in 3-BP-resistant tumor cells.

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Chen, Thomas C; Yu, Jiali; Nouri Nigjeh, Eslam; Wang, Weijun; Myint, Phyo Thazin; Zandi, Ebrahim; Hofman, Florence M; Schönthal, Axel H

2017-08-01

The anticancer agent 3-bromopyruvate (3-BP) is viewed as a glycolytic inhibitor that preferentially kills glycolytic cancer cells through energy depletion. However, its cytotoxic activity is dependent on cellular drug import through transmembrane monocarboxylate transporter 1 (MCT-1), which restricts its anticancer potential to MCT-1-positive tumor cells. We created and characterized an MCT-1-independent analog of 3-BP, called NEO218. NEO218 was synthesized by covalently conjugating 3-BP to perillyl alcohol (POH), a natural monoterpene. The responses of various tumor cell lines to treatment with either compound were characterized in the presence or absence of supplemental pyruvate or antioxidants N-acetyl-cysteine (NAC) and glutathione (GSH). Drug effects on glyceraldehyde 3-phosphate dehydrogenase (GAPDH) enzyme activity were investigated by mass spectrometric analysis. The development of 3-BP resistance was investigated in MCT-1-positive HCT116 colon carcinoma cells in vitro. Our results show that NEO218: (i) pyruvylated GAPDH on all 4 of its cysteine residues and shut down enzymatic activity; (ii) severely lowered cellular ATP content below life-sustaining levels, and (iii) triggered rapid necrosis. Intriguingly, supplemental antioxidants effectively prevented cytotoxic activity of NEO218 as well as 3-BP, but supplemental pyruvate powerfully protected cells only from 3-BP, not from NEO218. Unlike 3-BP, NEO218 exerted its potent cytotoxic activity irrespective of cellular MCT-1 status. Treatment of HCT116 cells with 3-BP resulted in prompt development of resistance, based on the emergence of MCT-1-negative cells. This was not the case with NEO218, and highly 3-BP-resistant cells remained exquisitely sensitive to NEO218. Thus, our study identifies a mechanism by which tumor cells develop rapid resistance to 3-BP, and presents NEO218 as a superior agent not subject to this cellular defense. Furthermore, our results offer alternative interpretations of previously

Study of cellular retention of HMPAO and ECD in a model simulating the blood-brain barrier

International Nuclear Information System (INIS)

Ponce, C.; Pittet, N.; Slosman, D.O.

1997-01-01

The HMPAO and ECD are two technetium-labelled lipophilic agents clinically used in the imagery of cerebral perfusion. These molecules cross the membranes and are retained inside the cell after being converted to a hydrophilic form. The aim of this study is to establish the distribution of this retention at the level of blood-brain barrier (BBB) and nerve cells. The incorporation of HMPAO or ECD was studied on a model of co-culture simulating the BBB by means of a T84 single-cell layer of tight junction separated from another layer of U373 astrocyte cells. The cell quality and tight junction permeability were evaluated by the cellular retention of 111-indium chloride and by para-cellular diffusion of 14 C mannitol,d-1. The values reported below were obtained at 180 minutes when the radiotracers were added near the 'T84 layer'. The cell quality is validated by the low cellular retention of the indium chloride(2.3±0.3 μg -1 for the T84 cells and 8.2±5.8 μg -1 for the U373 cells). The activity of 14 C mannitol,d-1 diminishes by 23 ± 5 % in the added compartment. The retention of ECD by the U373 cells is significantly higher (20.7 ±4.5 g -1 ) than that of T84 cells (2.9 ± 0.2 μg -1 ). For HMPAO a non-significant tendency could be observed (49 ± 34 μg -1 for the U373 cells and 38 ± 25 μg -1 for the T84 cells)> The results of cellular retention of indium by HMPAO or ECD when added near 'U373 layer' are not significantly different.In conclusion, independently of the side exposed to the radiotracers, one observes an enhanced incorporation of the U373 cells. The ensemble of these results represent additional arguments in favour of a specific cellular incorporation of the radiotracers, independent of the BBB permittivity

Identification of microbes from the surfaces of food-processing lines based on the flow cytometric evaluation of cellular metabolic activity combined with cell sorting.

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Juzwa, W; Duber, A; Myszka, K; Białas, W; Czaczyk, K

2016-09-01

In this study the design of a flow cytometry-based procedure to facilitate the detection of adherent bacteria from food-processing surfaces was evaluated. The measurement of the cellular redox potential (CRP) of microbial cells was combined with cell sorting for the identification of microorganisms. The procedure enhanced live/dead cell discrimination owing to the measurement of the cell physiology. The microbial contamination of the surface of a stainless steel conveyor used to process button mushrooms was evaluated in three independent experiments. The flow cytometry procedure provided a step towards monitoring of contamination and enabled the assessment of microbial food safety hazards by the discrimination of active, mid-active and non-active bacterial sub-populations based on determination of their cellular vitality and subsequently single cell sorting to isolate microbial strains from discriminated sub-populations. There was a significant correlation (r = 0.97; p vitality and the identification of species from defined sub-populations, although the identified microbes were limited to culturable cells.

Extracellular cystatin SN and cathepsin B prevent cellular senescence by inhibiting abnormal glycogen accumulation.

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Oh, Sang-Seok; Park, Soojong; Lee, Ki-Won; Madhi, Hamadi; Park, Sae Gwang; Lee, Hee Gu; Cho, Yong-Yeon; Yoo, Jiyun; Dong Kim, Kwang

2017-04-06

Cystatin SN (CST1), a known inhibitor of cathepsin B (CatB), has important roles in tumor development. Paradoxically, CatB is a member of the cysteine cathepsin family that acts in cellular processes, such as tumor development and invasion. However, the relationship between CST1 and CatB, and their roles in tumor development are poorly understood. In this study, we observed that the knockdown of CST1 induced the activity of senescence-associated β-galactosidase, a marker of cellular senescence, and expression of senescence-associated secretory phenotype genes, including interleukin-6 and chemokine (C-C motif) ligand 20, in MDA-MB-231 and SW480 cancer cells. Furthermore, CST1 knockdown decreased extracellular CatB activity, and direct CatB inhibition, using specific inhibitors or shCatB, induced cellular senescence. Reconstitution of CST1 restored CatB activity and inhibited cellular senescence in CST1 knockdown cells. CST1 knockdown or CatB inhibition increased glycogen synthase (GS) kinase 3β phosphorylation at serine 9, resulting in the activation of GS and the induction of glycogen accumulation associated with cellular senescence. Importantly, CST1 knockdown suppressed cancer cell proliferation, soft agar colony growth and tumor growth in a xenograft model. These results indicate that CST1-mediated extracellular CatB activity enhances tumor development by preventing cellular senescence. Our findings suggest that antagonists of CST1 or inhibitors of CatB are potential anticancer agents.

Ebselen impairs cellular oxidative state and induces endoplasmic reticulum stress and activation of crucial mitogen-activated protein kinases in pancreatic tumour AR42J cells.

Science.gov (United States)

Santofimia-Castaño, Patricia; Izquierdo-Alvarez, Alicia; Plaza-Davila, María; Martinez-Ruiz, Antonio; Fernandez-Bermejo, Miguel; Mateos-Rodriguez, Jose M; Salido, Gines M; Gonzalez, Antonio

2018-01-01

Ebselen (2-phenyl-1,2-benzisoselenazol-3(2H)-one) is an organoselenium radical scavenger compound, which has strong antioxidant and anti-inflammatory effects. However, evidence suggests that this compound could exert deleterious actions on cell physiology. In this study, we have analyzed the effect of ebselen on rat pancreatic AR42J cells. Cytosolic free-Ca 2+ concentration ([Ca 2+ ] c ), cellular oxidative status, setting of endoplasmic reticulum stress, and phosphorylation of major mitogen-activated protein kinases were analyzed. Our results show that ebselen evoked a concentration-dependent increase in [Ca 2+ ] c . The compound induced an increase in the generation of reactive oxygen species in the mitochondria. We also observed an increase in global cysteine oxidation in the presence of ebselen. In the presence of ebselen an impairment of cholecystokinin-evoked amylase release was noted. Moreover, involvement of the unfolded protein response markers, ER chaperone and signaling regulator GRP78/BiP, eukaryotic translation initiation factor 2α and X-box binding protein 1 was detected. Finally, increases in the phosphorylation of SAPK/JNK, p38 MAPK, and p44/42 MAPK in the presence of ebselen were also observed. Our results provide evidences for an impairment of cellular oxidative state and enzyme secretion, the induction of endoplasmic reticulum stress and the activation of crucial mitogen-activated protein kinases in the presence of ebselen. As a consequence ebselen exerts a potential toxic effect on AR42J cells. © 2017 Wiley Periodicals, Inc.

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

Quality Dimensions, Value, Service Cost and Recommendation Behaviour: Evidence from the Nigerian Cellular Industry

Directory of Open Access Journals (Sweden)

Abolaji Joachim Abiodun

2014-09-01

Full Text Available The present study proposed and test a model that connects both affective and cognitive factors in cellular service to customers’ recommendation behavior. Results of the analysis of data collected through questionnaire from 293 respondents with cellular phones and active account in the Nigerian cellular industry indicate that core cellular service dimensions, service cost (price and hedonic values are significant determinants of customers’ recommendation behavior. In addition, the study found that customer service and utilitarian value exert negative effect on recommendation behavior. It seems that strengthening the performance of service providers on core service attributes, service cost (price and the entertainment and emotion evoking aspects of cellular service is of more value in partnering with customer to enlarge customer base through recommendation

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.

Mechanisms and circumvention of cellular resistance to cisplatin.

NARCIS (Netherlands)

Hospers, Geesiena Alberdina Petronella

1989-01-01

Cisplatin (CDDP) is an active cytostatic agent. A limitation to its effectiveness initially or appearing during cystatic treatment is the occurrence of resistance. This thesis describes mechanisms wich are responsible for acquired cellular CDDP resistance. To investigate cellular CDDP resistance, a

Opportunistic activation of TRP receptors by endogenous lipids: exploiting lipidomics to understand TRP receptor cellular communication.

Science.gov (United States)

Bradshaw, Heather B; Raboune, Siham; Hollis, Jennifer L

2013-03-19

Transient receptor potential channels (TRPs) form a large family of ubiquitous non-selective cation channels that function as cellular sensors and in many cases regulate intracellular calcium. Identification of the endogenous ligands that activate these TRP receptors is still under intense investigation with the majority of these channels still remaining "orphans." That these channels respond to a variety of external stimuli (e.g. plant-derived lipids, changes in temperature, and changes in pH) provides a framework for their abilities as cellular sensors, however, the mechanism of direct activation is still under much debate and research. In the cases where endogenous ligands (predominately lipids) have shown direct activation of a channel, multiple ligands have been shown to activate the same channel suggesting that these receptors are "promiscuous" in nature. Lipidomics of a growing class of endogenous lipids, N-acyl amides, the most famous of which is N-arachidonoyl ethanolamine (the endogenous cannabinoid, Anandamide) is providing a novel set of ligands that have been shown to activate some members of the TRP family and have the potential to deorphanize many more. Here it is argued that activation of TRPV receptors, a subset of the larger family of TRPs, by multiple endogenous lipids that are structurally analogous is a model system to drive our understanding that many TRP receptors are not promiscuous, but are more characteristically "opportunistic" in nature; exploiting the structural similarity and biosynthesis of a narrow range of analogous endogenous lipids. In addition, this manuscript will compare the activation properties of TRPC5 to the activity profile of an "orphan" lipid, N-palmitoyl glycine; further demonstrating that lipidomics aimed at expanding our knowledge of the family of N-acyl amides has the potential to provide novel avenues of research for TRP receptors. Copyright © 2012 Elsevier Inc. All rights reserved.

Cellular Factors Shape 3D Genome Landscape

Science.gov (United States)

Researchers, using novel large-scale imaging technology, have mapped the spatial location of individual genes in the nucleus of human cells and identified 50 cellular factors required for the proper 3D positioning of genes. These spatial locations play important roles in gene expression, DNA repair, genome stability, and other cellular activities.

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...

Defining the action spectrum of potential PGC-1α activators on a mitochondrial and cellular level in vivo.

Science.gov (United States)

Hofer, Annette; Noe, Natalie; Tischner, Christin; Kladt, Nikolay; Lellek, Veronika; Schauß, Astrid; Wenz, Tina

2014-05-01

Previous studies have demonstrated a therapeutic benefit of pharmaceutical PGC-1α activation in cellular and murine model of disorders linked to mitochondrial dysfunction. While in some cases, this effect seems to be clearly associated with boosting of mitochondrial function, additional alterations as well as tissue- and cell-type-specific effects might play an important role. We initiated a comprehensive analysis of the effects of potential PGC-1α-activating drugs and pharmaceutically targeted the PPAR (bezafibrate, rosiglitazone), AMPK (AICAR, metformin) and Sirt1 (resveratrol) pathways in HeLa cells, neuronal cells and PGC-1α-deficient MEFs to get insight into cell type specificity and PGC-1α dependence of their working action. We used bezafibrate as a model drug to assess the effect on a tissue-specific level in a murine model. Not all analyzed drugs activate the PGC pathway or alter mitochondrial protein levels. However, they all affect supramolecular assembly of OXPHOS complexes and OXPHOS protein stability. In addition, a clear drug- and cell-type-specific influence on several cellular stress pathways as well as on post-translational modifications could be demonstrated, which might be relevant to fully understand the action of the analyzed drugs in the disease state. Importantly, the effect on the activation of mitochondrial biogenesis and stress response program upon drug treatment is PGC-1α dependent in MEFs demonstrating not only the pleiotropic effects of this molecule but points also to the working mechanism of the analyzed drugs. The definition of the action spectrum of the different drugs forms the basis for a defect-specific compensation strategy and a future personalized therapeutic approach.

Universality of two-dimensional critical cellular automata

OpenAIRE

Bollobás, Béla; Duminil-Copin, Hugo; Morris, Robert; Smith, Paul

2014-01-01

We study the class of monotone, two-state, deterministic cellular automata, in which sites are activated (or `infected') by certain configurations of nearby infected sites. These models have close connections to statistical physics, and several specific examples have been extensively studied in recent years by both mathematicians and physicists. This general setting was first studied only recently, however, by Bollob\\'as, Smith and Uzzell, who showed that the family of all such `bootstrap per...

AFM studies of environmental effects on nanomechanical properties and cellular structure of human hair

International Nuclear Information System (INIS)

Bhushan, Bharat; Chen, Nianhuan

2006-01-01

Characterization of cellular structure and physical and mechanical properties of hair are essential to develop better cosmetic products and advance biological and cosmetic science. Although the morphology of the cellular structure of human hair has been traditionally investigated using scanning electron microscopy and transmission electron microscopy, these techniques provide limited capability to in situ study of the physical and mechanical properties of human hair in various environments. Atomic force microscopy (AFM) overcomes these problems and can be used for characterization in ambient conditions without requiring specific sample preparations and surface treatment. In this study, film thickness, adhesive forces and effective Young's modulus of various hair surfaces were measured at different environments (humidity and temperature) using force calibration plot technique with an AFM. Torsional resonance mode phase contrast images were also taken in order to characterize the morphology and cellular structure changes of human hair at different humidity. The correlation between the nanomechanical properties and the cellular structure of hair is discussed

A Cellular Perspective on Brain Energy Metabolism and Functional Imaging

KAUST Repository

Magistretti, Pierre J.

2015-05-01

The energy demands of the brain are high: they account for at least 20% of the body\\'s energy consumption. Evolutionary studies indicate that the emergence of higher cognitive functions in humans is associated with an increased glucose utilization and expression of energy metabolism genes. Functional brain imaging techniques such as fMRI and PET, which are widely used in human neuroscience studies, detect signals that monitor energy delivery and use in register with neuronal activity. Recent technological advances in metabolic studies with cellular resolution have afforded decisive insights into the understanding of the cellular and molecular bases of the coupling between neuronal activity and energy metabolism and pointat a key role of neuron-astrocyte metabolic interactions. This article reviews some of the most salient features emerging from recent studies and aims at providing an integration of brain energy metabolism across resolution scales. © 2015 Elsevier Inc.

Continuous DC-CIK infusions restore CD8+ cellular immunity, physical activity and improve clinical efficacy in advanced cancer patients unresponsive to conventional treatments.

Science.gov (United States)

Zhao, Yan-Jie; Jiang, Ni; Song, Qing-Kun; Wu, Jiang-Ping; Song, Yu-Guang; Zhang, Hong-Mei; Chen, Feng; Zhou, Lei; Wang, Xiao-Li; Zhou, Xin-Na; Yang, Hua-Bing; Ren, Jun; Lyerly, Herbert Kim

2015-01-01

There are few choices for treatment of advanced cancer patients who do not respond to or tolerate conventional anti-cancer treatments. Therefore this study aimed to deploy the benefits and clinical efficacy of continuous dendritic cell-cytokine induced killer cell infusions in such patients. A total of 381 infusions (from 67 advanced cases recruited) were included in this study. All patients underwent peripheral blood mononuclear cell apheresis for the following cellular therapy and dendritic cells-cytokine induced killer cells were expanded in vitro. Peripheral blood T lymphocyte subsets were quantified through flow cytometry to address the cellular immunity status. Clinical efficacy and physical activities were evaluated by RECIST criteria and Eastern Cooperative Oncology Group scores respectively. Logistic regression model was used to estimate the association between cellular infusions and clinical benefits. An average of 5.7±2.94x10(9) induced cells were infused each time and patients were exposed to 6 infusions. Cellular immunity was improved in that cytotoxic CD8+CD28+T lymphocytes were increased by 74% and suppressive CD8+CD28-T lymphocytes were elevated by 16% (p<0.05). Continuous infusion of dendritic cells-cytokine induced killer cells was associated with improvement of both patient status and cellular immunity. A median of six infusions were capable of reducing risk of progression by 70% (95%CI 0.10-0.91). Every elevation of one ECOG score corresponded to a 3.90-fold higher progression risk (p<0.05) and 1% increase of CD8+CD28- T cell proportion reflecting a 5% higher risk of progression (p<0.05). In advanced cancer patients, continuous dendritic cell-cytokine induced killer cell infusions are capable of recovering cellular immunity, improving patient status and quality of life in those who are unresponsive to conventional cancer treatment.

Cellular Responses to Beta Blocker Exposures in Marine ...

Science.gov (United States)

β blockers are prescription drugs used for medical treatment of hypertension and arrhythmias. They prevent activation of adenylate cyclase and increases in blood pressure by limiting cAMP production and protein kinase A activation. After being taken therapeutically, β blockers may make their way to coastal habitats via discharge from waste water treatment plants, posing a potential risk to aquatic organisms. The aim of our research is to evaluate cellular biomarkers of β blocker exposure using two drugs, propranolol and metoprolol, in three commercially important marine bivalves -Crassostrea virginica, Mytilus edulis and Mercenaria mercenaria. Bivalves were obtained from Narragansett Bay (Rhode Island, USA) and acclimated in the laboratory. Following acclimation, gills and hepatopancreas tissues were harvested and separately exposed to 0, 1, 10, 100 and 1000 ng/l of each drug for 24 hours. Samples were preserved for cellular biomarker assays. Elevated cellular damage and changes in enzymatic activities were noted at environmentally relevant concentrations, and M. mercenaria was found to be the most sensitive bivalve out of the three species tested. These studies enhance our understanding of the potential impacts of commonly used prescription medication on organisms in coastal ecosystems, and demonstrate that filter feeders such as marine bivalves may serve as good model organisms to examine the effects of water soluble drugs. Evaluating a suite of biomarkers

Scavenger receptor B1 facilitates macrophage uptake of silver nanoparticles and cellular activation

Energy Technology Data Exchange (ETDEWEB)

Aldossari, Abdullah A.; Shannahan, Jonathan H. [The University of Colorado Anschutz Medical Campus, Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences (United States); Podila, Ramakrishna [Clemson University, Department of Physics and Astronomy (United States); Brown, Jared M., E-mail: jared.brown@ucdenver.edu [The University of Colorado Anschutz Medical Campus, Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences (United States)

2015-07-15

Due to increased use of silver nanoparticles (AgNPs) for their antimicrobial activity, concerns have risen regarding potential adverse human health effects. Scavenger receptor B1 (SR-B1), a major receptor for high-density lipoprotein (HDL), is expressed by macrophages and has also been reported to play a role in recognition of negatively charged particles. We, therefore, hypothesized that SR-B1 mediates macrophage uptake of AgNPs and inflammatory activation. To test this hypothesis, we exposed a mouse macrophage cell line RAW264.7 (RAW) and bone marrow-derived macrophages (BMDM) to 20 nm citrate-suspended AgNPs. To verify the role of the SR-B1 receptor, we utilized a SR-B1 inhibitor (Blt2). In vitro studies demonstrated uptake of AgNPs and HDL-coated AgNPs by macrophages which were significantly reduced following pretreatment with Blt2. Inflammatory cytokine arrays revealed that macrophages exposed to AgNPs up-regulated expression of Tnf-α, Oncostatin m (OSM), Ccl4, Il17f, Ccl7, and Ccl2, whereas Il16 was found to be down-regulated. Macrophage activation was observed following AgNP and HDL-coated AgNP exposure as measured by OSM protein production and increased surface expression of CD86. These markers of activation were reduced with Blt2 pretreatment. The in vitro findings were confirmed in vivo through pulmonary instillation of AgNPs in mice. Pulmonary instillation of AgNPs resulted in a recruitment of inflammatory cells that were reduced in SR-B1-deficient mice or following Blt2 pretreatment. This study suggests that SR-B1 plays a major role in cellular recognition of AgNPs and the induction of cell responses that could contribute to inflammation caused by AgNP exposure.

Scavenger receptor B1 facilitates macrophage uptake of silver nanoparticles and cellular activation

Science.gov (United States)

Aldossari, Abdullah A.; Shannahan, Jonathan H.; Podila, Ramakrishna; Brown, Jared M.

2015-07-01

Due to increased use of silver nanoparticles (AgNPs) for their antimicrobial activity, concerns have risen regarding potential adverse human health effects. Scavenger receptor B1 (SR-B1), a major receptor for high-density lipoprotein (HDL), is expressed by macrophages and has also been reported to play a role in recognition of negatively charged particles. We, therefore, hypothesized that SR-B1 mediates macrophage uptake of AgNPs and inflammatory activation. To test this hypothesis, we exposed a mouse macrophage cell line RAW264.7 (RAW) and bone marrow-derived macrophages (BMDM) to 20 nm citrate-suspended AgNPs. To verify the role of the SR-B1 receptor, we utilized a SR-B1 inhibitor (Blt2). In vitro studies demonstrated uptake of AgNPs and HDL-coated AgNPs by macrophages which were significantly reduced following pretreatment with Blt2. Inflammatory cytokine arrays revealed that macrophages exposed to AgNPs up-regulated expression of Tnf- α, Oncostatin m (OSM), Ccl4, Il17f, Ccl7, and Ccl2, whereas Il16 was found to be down-regulated. Macrophage activation was observed following AgNP and HDL-coated AgNP exposure as measured by OSM protein production and increased surface expression of CD86. These markers of activation were reduced with Blt2 pretreatment. The in vitro findings were confirmed in vivo through pulmonary instillation of AgNPs in mice. Pulmonary instillation of AgNPs resulted in a recruitment of inflammatory cells that were reduced in SR-B1-deficient mice or following Blt2 pretreatment. This study suggests that SR-B1 plays a major role in cellular recognition of AgNPs and the induction of cell responses that could contribute to inflammation caused by AgNP exposure.

The ROS-mediated activation of IL-6/STAT3 signaling pathway is involved in the 27-hydroxycholesterol-induced cellular senescence in nerve cells.

Science.gov (United States)

Liu, Jiao; Liu, Yun; Chen, Juan; Hu, Chunyan; Teng, Mengying; Jiao, Kailin; Shen, Zhaoxia; Zhu, Dongmei; Yue, Jia; Li, Zhong; Li, Yuan

2017-12-01

The oxysterol 27-hydroxycholesterol (27HC) is a selective estrogen receptor modulator (SERMs), which like endogenous estrogen 17β-estradiol (E 2 ) induces the proliferation of ER-positive breast cancer cells in vitro. Interestingly, the observation that 27HC induces adverse effects in neural system, distinguishing it from E 2 . It has been suggested that high levels of circulating cholesterol increase the entry of 27HC into the brain, which may induce learning and memory impairment. Based on this evidence, 27HC may be associated with neurodegenerative processes and interrupted cholesterol homeostasis in the brain. However, the biological events that participate in this process remain largely elusive. In the present study, we demonstrated that 27HC induced apparent cellular senescence in nerve cells. Senescence-associated β-galactosidase (SA-β-Gal) assay revealed that 27HC induced senescence in both BV2 cells and PC12 cells. Furthermore, we demonstrated that 27HC promoted the accumulation of cellular reactive oxygen species (ROS) in nerve cells and subsequently activation of IL-6/STAT3 signaling pathway. Notably, treatment with the ROS scavenger N-acetylcysteine (NAC) markedly blocked 27HC-induced ROS production and activation of IL-6/STAT3 signaling pathway. Either blocking the generation of ROS or inhibition of IL-6/STAT3 both attenuated 27HC-induced cellular senescence. In sum, these findings not only suggested a mechanism whereby 27HC induced cellular senescence in nerve cells, but also helped to recognize the 27HC as a novel harmful factor in neurodegenerative diseases. Copyright © 2017. Published by Elsevier Ltd.

Various cellular stress components change as the rat ages: An insight into the putative overall age-related cellular stress network.

Science.gov (United States)

Cueno, Marni E; Imai, Kenichi

2018-02-01

Cellular stress is mainly comprised of oxidative, nitrosative, and endoplasmic reticulum stresses and has long been correlated to the ageing process. Surprisingly, the age-related difference among the various components in each independent stress pathway and the possible significance of these components in relation to the overall cellular stress network remain to be clearly elucidated. In this study, we obtained blood from ageing rats upon reaching 20-, 40-, and 72-wk.-old. Subsequently, we measured representative cellular stress-linked biomolecules (H 2 O 2 , glutathione reductase, heme, NADPH, NADP, nitric oxide, GADD153) and cell signals [substance P (SP), free fatty acid, calcium, NF-κB] in either or both blood serum and cytosol. Subsequently, network analysis of the overall cellular stress network was performed. Our results show that there are changes affecting stress-linked biomolecules and cell signals as the rat ages. Additionally, based on our network analysis data, we postulate that NADPH, H 2 O 2 , GADD153, and SP are the key components and the interactions between these components are central to the overall age-related cellular stress network in the rat blood. Thus, we propose that the main pathway affecting the overall age-related cellular stress network in the rat blood would entail NADPH-related oxidative stress (involving H 2 O 2 ) triggering GADD153 activation leading to SP induction which in-turn affects other cell signals. Copyright © 2017 Elsevier Inc. All rights reserved.

Antioxidant activity of puha (Sonchus oleraceus L.) as assessed by the cellular antioxidant activity (CAA) assay.

Science.gov (United States)

McDowell, Arlene; Thompson, Scott; Stark, Mirjam; Ou, Zong-Quan; Gould, Kevin S

2011-12-01

There is considerable interest in antioxidant dietary components that can be protective against degenerative diseases in humans. Puha (Sonchus oleraceus L.) is a rich source of polyphenols, and exhibits strong antioxidant activity as measured by the 2,2-diphenylpicrylhydrazyl (DPPH) assay. However, the potential of puha to protect against degenerative diseases requires that low molecular weight antioxidants (LMWA) are absorbed by, and active in, human cells. The cellular antioxidant activity (CAA) assay was used to investigate the antioxidant activity of puha leaf extracts. Preparation methods of freezing and freeze-drying reduced the total polyphenolic content compared with fresh puha, but did not affect the LMWA potential as determined by the DPPH assay. The IC(50) values were 0.012 ± 0.003 mg/mL and 0.010 ± 0.005 mg/mL for freeze-dried and fresh puha leaves, respectively. Using the CAA assay, it was shown that LMWAs from foliar extracts of puha were effectively absorbed into HepG2 cells, and exerted antioxidant activity at levels comparable to those of extracts from blueberry fruits, the much-touted antioxidant superfood. Methylene blue staining of HepG2 cells indicated that puha extracts were not cytotoxic at concentrations below 100 mg DW/mL. The data indicate the potential of puha as a nutraceutical supplement for human health. Copyright © 2011 John Wiley & Sons, Ltd.

Epidemiological Safety Surveillance of Cellular Telephones in the US (invited paper)

International Nuclear Information System (INIS)

Dreyer, N.A.; Loughlin, J.E.; Rothman, K.J.

1999-01-01

In 1994 a surveillance programme was initiated to monitor the effects of exposure to the human head from radiofrequency waves, such as those emitted from handheld cellular telephones. Cellular carriers contributed information about 1.5 million telephone account holders, their phones and two months of data on minutes used and number of calls. Cellular telephone manufacturers provided data that allowed classification of phones as analogue or digital and a handheld or mobile (car or bag) for 67% of the phones. Thus far 1,021,767 individuals have been identified who had at least one active cellular telephone account in 1994 and/or 1995 and who used either a handheld (41%) or a mobile (59%) phone during the study period, but not both. Seventy-four per cent of the cohort had used their cellular phone for ≥2 years, and 30% for ≥3 years. (author)

The cellular distribution of extracellular superoxide dismutase in macrophages is altered by cellular activation but unaffected by the natural occurring R213G substitution

DEFF Research Database (Denmark)

Gottfredsen, Randi Heidemann; Goldstrohm, David; Hartney, John

2014-01-01

and associated with the cell surface via the extracellular matrix (ECM)-binding region. Upon cellular activation induced by lipopolysaccharide, EC-SOD is relocated and detected both in the cell culture medium and in lipid raft structures. Although the secreted material presented a significantly reduced ligand......-binding capacity, this could not be correlated to proteolytic removal of the ECM-binding region, because the integrity of the material recovered from the medium was comparable to that of the cell surface-associated protein. The naturally occurring R213G amino acid substitution located in the ECM-binding region...

Discovery of novel, high potent, ABC type PTP1B inhibitors with TCPTP selectivity and cellular activity.

Science.gov (United States)

Liu, Peihong; Du, Yongli; Song, Lianhua; Shen, Jingkang; Li, Qunyi

2016-08-08

Protein tyrosine phosphatase 1B (PTP1B) as a key negative regulator of both insulin and leptin receptor pathways has been an attractive therapeutic target for the treatment of type 2 diabetes mellitus (T2DM) and obesity. With the goal of enhancing potency and selectivity of the PTP1B inhibitors, a series of methyl salicylate derivatives as ABC type PTP1B inhibitors (P1-P7) were discovered. More importantly, compound P6 exhibited high potent inhibitory activity (IC50 = 50 nM) for PTP1B with 15-fold selectivity over T-cell PTPase (TCPTP). Further studies on cellular activities revealed that compound P6 could enhance insulin-mediated insulin receptor β (IRβ) phosphorylation and insulin-stimulated glucose uptake. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Sordaria macrospora, a model organism to study fungal cellular development.

Science.gov (United States)

Engh, Ines; Nowrousian, Minou; Kück, Ulrich

2010-12-01

During the development of multicellular eukaryotes, the processes of cellular growth and organogenesis are tightly coordinated. Since the 1940s, filamentous fungi have served as genetic model organisms to decipher basic mechanisms underlying eukaryotic cell differentiation. Here, we focus on Sordaria macrospora, a homothallic ascomycete and important model organism for developmental biology. During its sexual life cycle, S. macrospora forms three-dimensional fruiting bodies, a complex process involving the formation of different cell types. S. macrospora can be used for genetic, biochemical and cellular experimental approaches since diverse tools, including fluorescence microscopy, a marker recycling system and gene libraries, are available. Moreover, the genome of S. macrospora has been sequenced and allows functional genomics analyses. Over the past years, our group has generated and analysed a number of developmental mutants which has greatly enhanced our fundamental understanding about fungal morphogenesis. In addition, our recent research activities have established a link between developmental proteins and conserved signalling cascades, ultimately leading to a regulatory network controlling differentiation processes in a eukaryotic model organism. This review summarizes the results of our recent findings, thus advancing current knowledge of the general principles and paradigms underpinning eukaryotic cell differentiation and development. Copyright © 2010 Elsevier GmbH. All rights reserved.

Application of spectral hole burning to the study of in vitro cellular systems

Energy Technology Data Exchange (ETDEWEB)

Milanovich, Nebojsa [Iowa State Univ., Ames, IA (United States)

1999-11-08

Chapter 1 of this thesis describes the various stages of tumor development and a multitude of diagnostic techniques used to detect cancer. Chapter 2 gives an overview of the aspects of hole burning spectroscopy important for its application to the study of cellular systems. Chapter 3 gives general descriptions of cellular organelles, structures, and physical properties that can serve as possible markers for the differentiation of normal and cancerous cells. Also described in Chapter 3 are the principles of cryobiology important for low temperature spectroscopy of cells, characterization of MCF-10F (normal) and MCF-7 (cancer) cells lines which will serve as model systems, and cellular characteristics of aluminum phthalocyanine tetrasulfonate (APT), which was used as the test probe. Chapters 4 and 5 are previously published papers by the author pertaining to the results obtained from the application of hole burning to the study of cellular systems. Chapter 4 presents the first results obtained by spectral hole burning of cellular systems and Chapter 5 gives results for the differentiation of MCF-10F and MCF-7 cells stained with APT by an external applied electric (Stark) field. A general conclusion is presented in Chapter 6. Appendices A and B provide additional characterization of the cell/probe model systems. Appendix A describes the uptake and subcellular distribution of APT in MCF-10F and MCF-7 cells and Appendix B compares the hole burning characteristics of APT in cells when the cells are in suspension and when they are examined while adhering to a glass coverslip. Appendix C presents preliminary results for a novel probe molecule, referred to as a molecular thumbtack, designed by the authors for use in future hole burning applications to cellular systems.

Cucurbitacin IIb exhibits anti-inflammatory activity through modulating multiple cellular behaviors of mouse lymphocytes.

Directory of Open Access Journals (Sweden)

Yao Wang

Full Text Available Cucurbitacin IIb (CuIIb is one of the major active compounds in Hemsleyadine tablets which have been used for clinical treatment of bacillary dysentery, enteritis and acute tonsilitis. However, its action mechanism has not been completely understood. This study aimed to explore the anti-inflammatory activity of CuIIb and its underlying mechanism in mitogen-activated lymphocytes isolated from mouse mesenteric lymph nodes. The results showed that CuIIb inhibited the proliferation of concanavalin A (Con A-activated lymphocytes in a time- and dose-dependent manner. CuIIb treatment arrested their cell cycle in S and G2/M phases probably due to the disruption of the actin cytoskeleton and the modulation of p27(Kip1 and cyclin levels. Moreover, the surface expression of activation markers CD69 and CD25 on Con A-activated CD3(+ T lymphocytes was suppressed by CuIIb treatment. Both Con A- and phorbol ester plus ionomycin-induced expression of TNF-α, IFN-γ and IL-6 proteins was attenuated upon exposure to CuIIb. Mechanistically, CuIIb treatment suppressed the phosphorylation of JNK and Erk1/2 but not p38 in Con A-activated lymphocytes. Although CuIIb unexpectedly enhanced the phosphorylation of IκB and NF-κB (p65, it blocked the nuclear translocation of NF-κB (p65. In support of this, CuIIb significantly decreased the mRNA levels of IκBα and TNF-α, two target genes of NF-κB, in Con A-activated lymphocytes. In addition, CuIIb downregulated Con A-induced STAT3 phosphorylation and increased cell apoptosis. Collectively, these results suggest that CuIIb exhibits its anti-inflammatory activity through modulating multiple cellular behaviors and signaling pathways, leading to the suppression of the adaptive immune response.

Multi-cellular natural killer (NK) cell clusters enhance NK cell activation through localizing IL-2 within the cluster

Science.gov (United States)

Kim, Miju; Kim, Tae-Jin; Kim, Hye Mi; Doh, Junsang; Lee, Kyung-Mi

2017-01-01

Multi-cellular cluster formation of natural killer (NK) cells occurs during in vivo priming and potentiates their activation to IL-2. However, the precise mechanism underlying this synergy within NK cell clusters remains unclear. We employed lymphocyte-laden microwell technologies to modulate contact-mediated multi-cellular interactions among activating NK cells and to quantitatively assess the molecular events occurring in multi-cellular clusters of NK cells. NK cells in social microwells, which allow cell-to-cell contact, exhibited significantly higher levels of IL-2 receptor (IL-2R) signaling compared with those in lonesome microwells, which prevent intercellular contact. Further, CD25, an IL-2R α chain, and lytic granules of NK cells in social microwells were polarized toward MTOC. Live cell imaging of lytic granules revealed their dynamic and prolonged polarization toward neighboring NK cells without degranulation. These results suggest that IL-2 bound on CD25 of one NK cells triggered IL-2 signaling of neighboring NK cells. These results were further corroborated by findings that CD25-KO NK cells exhibited lower proliferation than WT NK cells, and when mixed with WT NK cells, underwent significantly higher level of proliferation. These data highlights the existence of IL-2 trans-presentation between NK cells in the local microenvironment where the availability of IL-2 is limited.

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

Science.gov (United States)

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.

Pomegranate Extracts and Cancer Prevention: Molecular and Cellular Activities

Science.gov (United States)

Syed, Deeba N.; Chamcheu, Jean-Christopher; Adhami, Vaqar M.; Mukhtar, Hasan

2014-01-01

There is increased appreciation by the scientific community that dietary phytochemicals can be potential weapons in the fight against cancer. Emerging data has provided new insights into the molecular and cellular framework needed to establish novel mechanism-based strategies for cancer prevention by selective bioactive food components. The unique chemical composition of the pomegranate fruit, rich in antioxidant tannins and flavonoids has drawn the attention of many investigators. Polyphenol rich fractions derived from the pomegranate fruit have been studied for their potential chemopreventive and/or cancer therapeutic effects in several animal models. Although data from in vitro and in vivo studies look convincing, well designed clinical trials in humans are needed to ascertain whether pomegranate can become part of our armamentarium against cancer. This review summarizes the available literature on the effects of pomegranate against various cancers. PMID:23094914

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.

Empirical study on entropy models of cellular manufacturing systems

Institute of Scientific and Technical Information of China (English)

Zhifeng Zhang; Renbin Xiao

2009-01-01

From the theoretical point of view,the states of manufacturing resources can be monitored and assessed through the amount of information needed to describe their technological structure and operational state.The amount of information needed to describe cellular manufacturing systems is investigated by two measures:the structural entropy and the operational entropy.Based on the Shannon entropy,the models of the structural entropy and the operational entropy of cellular manufacturing systems are developed,and the cognizance of the states of manufacturing resources is also illustrated.Scheduling is introduced to measure the entropy models of cellular manufacturing systems,and the feasible concepts of maximum schedule horizon and schedule adherence are advanced to quantitatively evaluate the effectiveness of schedules.Finally,an example is used to demonstrate the validity of the proposed methodology.

Bacterial RNA induces myocyte cellular dysfunction through the activation of PKR

Science.gov (United States)

Bleiblo, Farag; Michael, Paul; Brabant, Danielle; Ramana, Chilakamarti V.; Tai, TC; Saleh, Mazen; Parrillo, Joseph E.; Kumar, Anand

2012-01-01

Severe sepsis and the ensuing septic shock are serious life threatening conditions. These diseases are triggered by the host's over exuberant systemic response to the infecting pathogen. Several surveillance mechanisms have evolved to discriminate self from foreign RNA and accordingly trigger effective cellular responses to target the pathogenic threats. The RNA-dependent protein kinase (PKR) is a key component of the cytoplasmic RNA sensors involved in the recognition of viral double-stranded RNA (dsRNA). Here, we identify bacterial RNA as a distinct pathogenic pattern recognized by PKR. Our results indicate that natural RNA derived from bacteria directly binds to and activates PKR. We further show that bacterial RNA induces human cardiac myocyte apoptosis and identify the requirement for PKR in mediating this response. In addition to bacterial immunity, the results presented here may also have implications in cardiac pathophysiology. PMID:22833816

A synthetic ion transporter that disrupts autophagy and induces apoptosis by perturbing cellular chloride concentrations

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Busschaert, Nathalie; Park, Seong-Hyun; Baek, Kyung-Hwa; Choi, Yoon Pyo; Park, Jinhong; Howe, Ethan N. W.; Hiscock, Jennifer R.; Karagiannidis, Louise E.; Marques, Igor; Félix, Vítor; Namkung, Wan; Sessler, Jonathan L.; Gale, Philip A.; Shin, Injae

2017-07-01

Perturbations in cellular chloride concentrations can affect cellular pH and autophagy and lead to the onset of apoptosis. With this in mind, synthetic ion transporters have been used to disturb cellular ion homeostasis and thereby induce cell death; however, it is not clear whether synthetic ion transporters can also be used to disrupt autophagy. Here, we show that squaramide-based ion transporters enhance the transport of chloride anions in liposomal models and promote sodium chloride influx into the cytosol. Liposomal and cellular transport activity of the squaramides is shown to correlate with cell death activity, which is attributed to caspase-dependent apoptosis. One ion transporter was also shown to cause additional changes in lysosomal pH, which leads to impairment of lysosomal enzyme activity and disruption of autophagic processes. This disruption is independent of the initiation of apoptosis by the ion transporter. This study provides the first experimental evidence that synthetic ion transporters can disrupt both autophagy and induce apoptosis.

Domain-Specific Activation of Death-Associated Intracellular Signalling Cascades by the Cellular Prion Protein in Neuroblastoma Cells.

Science.gov (United States)

Vilches, Silvia; Vergara, Cristina; Nicolás, Oriol; Mata, Ágata; Del Río, José A; Gavín, Rosalina

2016-09-01

The biological functions of the cellular prion protein remain poorly understood. In fact, numerous studies have aimed to determine specific functions for the different protein domains. Studies of cellular prion protein (PrP(C)) domains through in vivo expression of molecules carrying internal deletions in a mouse Prnp null background have provided helpful data on the implication of the protein in signalling cascades in affected neurons. Nevertheless, understanding of the mechanisms underlying the neurotoxicity induced by these PrP(C) deleted forms is far from complete. To better define the neurotoxic or neuroprotective potential of PrP(C) N-terminal domains, and to overcome the heterogeneity of results due to the lack of a standardized model, we used neuroblastoma cells to analyse the effects of overexpressing PrP(C) deleted forms. Results indicate that PrP(C) N-terminal deleted forms were properly processed through the secretory pathway. However, PrPΔF35 and PrPΔCD mutants led to death by different mechanisms sharing loss of alpha-cleavage and activation of caspase-3. Our data suggest that both gain-of-function and loss-of-function pathogenic mechanisms may be associated with N-terminal domains and may therefore contribute to neurotoxicity in prion disease. Dissecting the molecular response induced by PrPΔF35 may be the key to unravelling the physiological and pathological functions of the prion protein.

Circulating cellular adhesion molecules and risk of diabetes: the Multi-Ethnic Study of Atherosclerosis (MESA).

Science.gov (United States)

Pankow, J S; Decker, P A; Berardi, C; Hanson, N Q; Sale, M; Tang, W; Kanaya, A M; Larson, N B; Tsai, M Y; Wassel, C L; Bielinski, S J

2016-07-01

To test the hypothesis that soluble cellular adhesion molecules would be positively and independently associated with risk of diabetes. Soluble levels of six cellular adhesion molecules (ICAM-1, E-selectin, VCAM-1, E-cadherin, L-selectin and P-selectin) were measured in participants in the Multi-Ethnic Study of Atherosclerosis, a prospective cohort study. Participants were then followed for up to 10 years to ascertain incident diabetes. Sample sizes ranged from 826 to 2185. After adjusting for age, sex, race/ethnicity, BMI and fasting glucose or HbA1c , four cellular adhesion molecules (ICAM-1, E-selectin, VCAM-1 and E-cadherin) were positively associated with incident diabetes and there was a statistically significant trend across quartiles. Comparing the incidence of diabetes in the highest and lowest quartiles of each cellular adhesion molecule, the magnitude of association was largest for E-selectin (hazard ratio 2.49; 95% CI 1.26-4.93) and ICAM-1 (hazard ratio 1.76; 95% CI 1.22-2.55) in fully adjusted models. Tests of effect modification by racial/ethnic group and sex were not statistically significant for any of the cellular adhesion molecules (P > 0.05). The finding of significant associations between multiple cellular adhesion molecules and incident diabetes may lend further support to the hypothesis that microvascular endothelial dysfunction contributes to risk of diabetes. © 2016 Diabetes UK.

CELLULAR DISTRIBUTION STUDIES OF THE NITRIC OXIDE-GENERATING ANTINEOPLASTIC PRODRUG JS-K, FORMULATED IN PLURONIC P123 MICELLES

Science.gov (United States)

Kaur, Imit; Terrazas, Moises; Kosak, Ken M.; Kern, Steven E.; Boucher, Kenneth M.; Shami, Paul J.

2014-01-01

Objective Nitric oxide (NO) possesses anti-tumor activity. It induces differentiation and apoptosis in acute myeloid leukemia (AML) cells. The NO prodrug O2-(2,4-dinitrophenyl)1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate, or JS-K, has potent antileukemic activity. JS-K is also active in vitro and in vivo against multiple myeloma, prostate cancer, non-small cell lung cancer, glioma and liver cancer. Using the Pluronic® P123 polymer, we have developed a micelle formulation for JS-K in order to increase its solubility and stability. The goal of the current study was to investigate the cellular distribution of JS-K in AML cells. Methods We investigated the intracellular distribution of JS-K (free drug) and JS-K formulated in P123 micelles (P123/JS-K) using HL-60 AML cells. We also studied the S-glutathionylating effects of JS-K on proteins in the cytoplasmic and nuclear cellular fractions. Key findings Both free JS-K and P123/JS-K accumulate primarily in the nucleus. Both free JS-K and P123/JS-K induced S-glutathionylation of nuclear proteins, although the effect produced was more pronounced with P123/JS-K. Minimal S-glutathionylation of cytoplasmic proteins was observed. Conclusions We conclude that a micelle formulation of JS-K increases its accumulation in the nucleus. Post-translational protein modification through S-glutathionylation may contribute to JS-K’s anti-leukemic properties. PMID:23927471

Special Issue: Redox Active Natural Products and Their Interaction with Cellular Signalling Pathways

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Claus Jacob

2014-11-01

Full Text Available During the last decade, research into natural products has experienced a certain renaissance. The urgent need for more and more effective antibiotics in medicine, the demand for ecologically friendly plant protectants in agriculture, “natural” cosmetics and the issue of a sustainable and healthy nutrition in an ageing society have fuelled research into Nature’s treasure chest of “green gold”. Here, redox active secondary metabolites from plants, fungi, bacteria and other (micro-organisms often have been at the forefront of the most interesting developments. These agents provide powerful means to interfere with many, probably most cellular signaling pathways in humans, animals and lower organisms, and therefore can be used to protect, i.e., in form of antioxidants, and to frighten off or even kill, i.e., in form of repellants, antibiotics, fungicides and selective, often catalytic “sensor/effector” anticancer agents. Interestingly, whilst natural product research dates back many decades, in some cases even centuries, and compounds such as allicin and various flavonoids have been investigated thoroughly in the past, it has only recently become possible to investigate their precise interactions and mode(s of action inside living cells. Here, fluorescent staining and labelling on the one side, and appropriate detection, either qualitatively under the microscope or quantitatively in flow cytometers and plate readers, on the other, enable researchers to obtain the various pieces of information necessary to construct a fairly complete puzzle of how such compounds act and interact in living cells. Complemented by the more traditional activity assays and Western Blots, and increasingly joined by techniques such as proteomics, chemogenetic screening and mRNA profiling, these cell based bioanalytical techniques form a powerful platform for “intracellular diagnostics”. In the case of redox active compounds, especially of Reactive Sulfur

Quantitative assessment of barriers to the clinical development and adoption of cellular therapies: A pilot study.

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Davies, Benjamin M; Rikabi, Sarah; French, Anna; Pinedo-Villanueva, Rafael; Morrey, Mark E; Wartolowska, Karolina; Judge, Andrew; MacLaren, Robert E; Mathur, Anthony; Williams, David J; Wall, Ivan; Birchall, Martin; Reeve, Brock; Atala, Anthony; Barker, Richard W; Cui, Zhanfeng; Furniss, Dominic; Bure, Kim; Snyder, Evan Y; Karp, Jeffrey M; Price, Andrew; Carr, Andrew; Brindley, David A

2014-01-01

There has been a large increase in basic science activity in cell therapy and a growing portfolio of cell therapy trials. However, the number of industry products available for widespread clinical use does not match this magnitude of activity. We hypothesize that the paucity of engagement with the clinical community is a key contributor to the lack of commercially successful cell therapy products. To investigate this, we launched a pilot study to survey clinicians from five specialities and to determine what they believe to be the most significant barriers to cellular therapy clinical development and adoption. Our study shows that the main concerns among this group are cost-effectiveness, efficacy, reimbursement, and regulation. Addressing these concerns can best be achieved by ensuring that future clinical trials are conducted to adequately answer the questions of both regulators and the broader clinical community.

Cellular Phone Text Communication in English Language Among ...

African Journals Online (AJOL)

Considering the place of English in Nigeria, pupils and students are enjoined to use it constantly in their activities including phone calls. In view of the significant roles that cellular phones play in the lives of youths, and sustainable development of the economy, this paper looks into Nigerian youths' cellular phone text ...

Relationship between plasma growth hormone concentration and cellular sodium transport in acromegaly

Energy Technology Data Exchange (ETDEWEB)

Herlitz, H.; Jonsson, O.; Bengtsson, B.-Aa. (Departments of Nephrology, Urology and Endocrinology, University of Goeteborg, Goeteborg (Sweden))

1992-01-01

We investigated the relationship between mean plasma growth hormone (GH) concentration and cellular sodium transport in untreated and treated acromegaly. Seventeen patients (age 55 [+-] 3 years) with active acromegaly were studied with respect to plasma GH (mean of 24 h GH profile) and erythrocyte electrolyte content as well as transmembrane sodium transport. The patients were reinvestigated two weeks after successful surgery (N = 14) and again after one year (N = 13). Erythrocyte electrolytes were analyzed by flame photometry and sodium influx and efflux rate constant determined by in vitro incubation using a modified Keyne's formula. In patients with active acromegaly there was a significant positive correlation between IGF-1 and cellular sodium transport, while GH tended to show a negative relatonship to the same parameter. After successful treatment, both IGF-1 and GH disclosed a positive relationship to cellular sodium transport. After one year, a significant increase in erythrocyte sodium content was seen in the patients compared to the preoperative situation. In conclusion, if this is a generalized phenomonen the results are compatible with a sodium-retaining effect of GH via stimulation of transmembrane sodium transport. In active acromegaly this may be counteracted by a sodium transport inhibitor giving the reverse relationship between GH and cellular sodium transport. (au).

17-AAG inhibits vemurafenib-associated MAP kinase activation and is synergistic with cellular immunotherapy in a murine melanoma model.

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Joshi, Sandeep S; Jiang, Shunlin; Unni, Emmanual; Goding, Stephen R; Fan, Tao; Antony, Paul A; Hornyak, Thomas J

2018-01-01

Heat shock protein 90 (HSP90) is a molecular chaperone which stabilizes client proteins with important roles in tumor growth. 17-allylamino-17-demethoxygeldanamycin (17-AAG), an inhibitor of HSP90 ATPase activity, occupies the ATP binding site of HSP90 causing a conformational change which destabilizes client proteins and directs them towards proteosomal degradation. Malignant melanomas have active RAF-MEK-ERK signaling which can occur either through an activating mutation in BRAF (BRAFV600E) or through activation of signal transduction upstream of BRAF. Prior work showed that 17-AAG inhibits cell growth in BRAFV600E and BRAF wildtype (BRAFWT) melanomas, although there were conflicting reports about the dependence of BRAFV600E and BRAFWT upon HSP90 activity for stability. Here, we demonstrate that BRAFWT and CRAF are bound by HSP90 in BRAFWT, NRAS mutant melanoma cells. HSP90 inhibition by 17-AAG inhibits ERK signaling and cell growth by destabilizing CRAF but not BRAFWT in the majority of NRAS mutant melanoma cells. The highly-selective BRAFV600E inhibitor, PLX4032 (vemurafenib), inhibits ERK signaling and cell growth in mutant BRAF melanoma cells, but paradoxically enhances signaling in cells with wild-type BRAF. In our study, we examined whether 17-AAG could inhibit PLX4032-enhanced ERK signaling in BRAFWT melanoma cells. As expected, PLX4032 alone enhanced ERK signaling in the BRAFWT melanoma cell lines Mel-Juso, SK-Mel-2, and SK-Mel-30, and inhibited signaling and cell growth in BRAFV600E A375 cells. However, HSP90 inhibition by 17-AAG inhibited PLX4032-enhanced ERK signaling and inhibited cell growth by destabilizing CRAF. Surprisingly, 17-AAG also stimulated melanin production in SK-Mel-30 cells and enhanced TYRP1 and DCT expression without stimulating TYR production in all three BRAFWT cell lines studied as well as in B16F10 mouse melanoma cells. In vivo, the combination of 17-AAG and cellular immunotherapy directed against Tyrp1 enhanced the inhibition of

17-AAG inhibits vemurafenib-associated MAP kinase activation and is synergistic with cellular immunotherapy in a murine melanoma model

Science.gov (United States)

Unni, Emmanual; Goding, Stephen R.; Fan, Tao; Antony, Paul A.; Hornyak, Thomas J.

2018-01-01

Heat shock protein 90 (HSP90) is a molecular chaperone which stabilizes client proteins with important roles in tumor growth. 17-allylamino-17-demethoxygeldanamycin (17-AAG), an inhibitor of HSP90 ATPase activity, occupies the ATP binding site of HSP90 causing a conformational change which destabilizes client proteins and directs them towards proteosomal degradation. Malignant melanomas have active RAF-MEK-ERK signaling which can occur either through an activating mutation in BRAF (BRAFV600E) or through activation of signal transduction upstream of BRAF. Prior work showed that 17-AAG inhibits cell growth in BRAFV600E and BRAF wildtype (BRAFWT) melanomas, although there were conflicting reports about the dependence of BRAFV600E and BRAFWT upon HSP90 activity for stability. Here, we demonstrate that BRAFWT and CRAF are bound by HSP90 in BRAFWT, NRAS mutant melanoma cells. HSP90 inhibition by 17-AAG inhibits ERK signaling and cell growth by destabilizing CRAF but not BRAFWT in the majority of NRAS mutant melanoma cells. The highly-selective BRAFV600E inhibitor, PLX4032 (vemurafenib), inhibits ERK signaling and cell growth in mutant BRAF melanoma cells, but paradoxically enhances signaling in cells with wild-type BRAF. In our study, we examined whether 17-AAG could inhibit PLX4032-enhanced ERK signaling in BRAFWT melanoma cells. As expected, PLX4032 alone enhanced ERK signaling in the BRAFWT melanoma cell lines Mel-Juso, SK-Mel-2, and SK-Mel-30, and inhibited signaling and cell growth in BRAFV600E A375 cells. However, HSP90 inhibition by 17-AAG inhibited PLX4032-enhanced ERK signaling and inhibited cell growth by destabilizing CRAF. Surprisingly, 17-AAG also stimulated melanin production in SK-Mel-30 cells and enhanced TYRP1 and DCT expression without stimulating TYR production in all three BRAFWT cell lines studied as well as in B16F10 mouse melanoma cells. In vivo, the combination of 17-AAG and cellular immunotherapy directed against Tyrp1 enhanced the inhibition of

Community structure, cellular rRNA content, and activity of sulfate-reducing bacteria in marine Arctic sediments

DEFF Research Database (Denmark)

Ravenschlag, K.; Sahm, K.; Knoblauch, C.

2000-01-01

The community structure of sulfate-reducing bacteria (SRB) of a marine Arctic sediment (Smeerenburg-fjorden, Svalbard) a-as characterized by both fluorescence in situ hybridization (FISH) and rRNA slot blot hybridization by using group- and genus-specific 16S rRNA-targeted oligonucleotide probes...... that FISH and rRNA slot blot hybridization gave comparable results. Furthermore, a combination of the two methods allowed us to calculate specific cellular rRNA contents with respect to localization in the sediment profile. The rRNA contents of Desulfosarcina-Desulfococcus cells were highest in the first 5...... mm of the sediment (0.9 and 1.4 fg, respectively) and decreased steeply with depth, indicating that maximal metabolic activity occurred close to the surface, Based on SRB cell numbers, cellular sulfate reduction rates were calculated. The rates were highest in the surface layer (0.14 fmol cell(-1...

The AAA+ ATPase p97, a cellular multitool.

Science.gov (United States)

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).

Cellular Activation of the Self-Quenched Fluorescent Reporter Probe in Tumor Microenvironment

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Alexei A. Bogdanov, Jr.

2002-01-01

Full Text Available The effect of intralysosomal proteolysis of near-infrared fluorescent (NIRF self-quenched macromolecular probe (PGC-Cy5.5 has been previously reported and used for tumor imaging. Here we demonstrate that proteolysis can be detected noninvasively in vivo at the cellular level. A codetection of GFP fluorescence (using two-photon excitation and NIRF was performed in tumor-bearing animals injected with PGC-Cy5.5. In vivo microscopy of tumor cells in subdermal tissue layers (up to 160 μm showed a strong Cy5.5 dequenching effect in GFP-negative cells. This observation was corroborated by flow cytometry, sorting, and reverse transcription polymerase chain reaction analysis of tumor-isolated cells. Both GFP-positive (81% total and GFP-negative (19% total populations contained Cy5.5-positive cells. The GFP-negative cells were confirmed to be host mouse cells by the absence of rat cathepsin mRNA signal. The subfraction of GFPnegative cells (2.5-3.0% had seven times higher NIRF intensity than the majority of GFP-positive or GFPnegative cells (372 and 55 AU, respectively. Highly NIRF-positive, FP-negative cells were CD45-and MAC3-positive. Our results indicate that: 1 intracellular proteolysis can be imaged in vivo at the cellular level using cathepsin-sensitive probes; 2 tumor-recruited cells of hematopoetic origin participate most actively in uptake and degradation of long-circulating macromolecular probes.

Evaluation of cellular influences caused by calcium carbonate nanoparticles.

Science.gov (United States)

Horie, Masanori; Nishio, Keiko; Kato, Haruhisa; Endoh, Shigehisa; Fujita, Katsuhide; Nakamura, Ayako; Kinugasa, Shinichi; Hagihara, Yoshihisa; Yoshida, Yasukazu; Iwahashi, Hitoshi

2014-03-05

The cellular effects of calcium carbonate (CaCO₃) nanoparticles were evaluated. Three kinds of CaCO₃ nanoparticles were employed in our examinations. One of the types of CaCO₃ nanoparticles was highly soluble. And solubility of another type of CaCO₃ nanoparticle was lower. A stable CaCO₃ nanoparticle medium dispersion was prepared and applied to human lung carcinoma A549 cells and human keratinocyte HaCaT cells. Then, mitochondrial activity, cell membrane damage, colony formation ability, DNA injury, induction of oxidative stress, and apoptosis were evaluated. Although the influences of CaCO₃ nanoparticles on mitochondrial activity and cell membrane damage were small, "soluble" CaCO₃ nanoparticles exerted some cellular influences. Soluble CaCO₃ nanoparticles also induced a cell morphological change. Colony formation was inhibited by CaCO₃ nanoparticle exposure. In particular, soluble CaCO₃ nanoparticles completely inhibited colony formation. The influence on intracellular the reactive oxygen species (ROS) level was small. Soluble CaCO₃ nanoparticles caused an increase in C/EBP-homologous protein (CHOP) expression and the activation of caspase-3. Moreover, CaCO₃ exposure increased intracellular the Ca²⁺ level and activated calpain. These results suggest that cellular the influences of CaCO₃ nanoparticles are mainly caused by intracellular calcium release and subsequently disrupt the effect of calcium signaling. In conclusion, there is possibility that soluble CaCO₃ nanoparticles induce cellular influences such as a cell morphological change. Cellular influence of CaCO₃ nanoparticles is caused by intracellular calcium release. If inhaled CaCO₃ nanoparticles have the potential to influence cellular events. However, the effect might be not severe because calcium is omnipresent element in cell. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Kinetic theory approach to modeling of cellular repair mechanisms under genome stress.

Directory of Open Access Journals (Sweden)

Jinpeng Qi

Full Text Available Under acute perturbations from outer environment, a normal cell can trigger cellular self-defense mechanism in response to genome stress. To investigate the kinetics of cellular self-repair process at single cell level further, a model of DNA damage generating and repair is proposed under acute Ion Radiation (IR by using mathematical framework of kinetic theory of active particles (KTAP. Firstly, we focus on illustrating the profile of Cellular Repair System (CRS instituted by two sub-populations, each of which is made up of the active particles with different discrete states. Then, we implement the mathematical framework of cellular self-repair mechanism, and illustrate the dynamic processes of Double Strand Breaks (DSBs and Repair Protein (RP generating, DSB-protein complexes (DSBCs synthesizing, and toxins accumulating. Finally, we roughly analyze the capability of cellular self-repair mechanism, cellular activity of transferring DNA damage, and genome stability, especially the different fates of a certain cell before and after the time thresholds of IR perturbations that a cell can tolerate maximally under different IR perturbation circumstances.

Kinetic theory approach to modeling of cellular repair mechanisms under genome stress.

Science.gov (United States)

Qi, Jinpeng; Ding, Yongsheng; Zhu, Ying; Wu, Yizhi

2011-01-01

Under acute perturbations from outer environment, a normal cell can trigger cellular self-defense mechanism in response to genome stress. To investigate the kinetics of cellular self-repair process at single cell level further, a model of DNA damage generating and repair is proposed under acute Ion Radiation (IR) by using mathematical framework of kinetic theory of active particles (KTAP). Firstly, we focus on illustrating the profile of Cellular Repair System (CRS) instituted by two sub-populations, each of which is made up of the active particles with different discrete states. Then, we implement the mathematical framework of cellular self-repair mechanism, and illustrate the dynamic processes of Double Strand Breaks (DSBs) and Repair Protein (RP) generating, DSB-protein complexes (DSBCs) synthesizing, and toxins accumulating. Finally, we roughly analyze the capability of cellular self-repair mechanism, cellular activity of transferring DNA damage, and genome stability, especially the different fates of a certain cell before and after the time thresholds of IR perturbations that a cell can tolerate maximally under different IR perturbation circumstances.

Integrin Beta 3 Regulates Cellular Senescence by Activating the TGF-β Pathway

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Valentina Rapisarda

2017-03-01

Full Text Available Cellular senescence is an important in vivo mechanism that prevents the propagation of damaged cells. However, the precise mechanisms regulating senescence are not well characterized. Here, we find that ITGB3 (integrin beta 3 or β3 is regulated by the Polycomb protein CBX7. β3 expression accelerates the onset of senescence in human primary fibroblasts by activating the transforming growth factor β (TGF-β pathway in a cell-autonomous and non-cell-autonomous manner. β3 levels are dynamically increased during oncogene-induced senescence (OIS through CBX7 Polycomb regulation, and downregulation of β3 levels overrides OIS and therapy-induced senescence (TIS, independently of its ligand-binding activity. Moreover, cilengitide, an αvβ3 antagonist, has the ability to block the senescence-associated secretory phenotype (SASP without affecting proliferation. Finally, we show an increase in β3 levels in a subset of tissues during aging. Altogether, our data show that integrin β3 subunit is a marker and regulator of senescence.

Sleep deprivation and activation of morning levels of cellular and genomic markers of inflammation.

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Irwin, Michael R; Wang, Minge; Campomayor, Capella O; Collado-Hidalgo, Alicia; Cole, Steve

2006-09-18

Inflammation is associated with increased risk of cardiovascular disorders, arthritis, diabetes mellitus, and mortality. The effects of sleep loss on the cellular and genomic mechanisms that contribute to inflammatory cytokine activity are not known. In 30 healthy adults, monocyte intracellular proinflammatory cytokine production was repeatedly assessed during the day across 3 baseline periods and after partial sleep deprivation (awake from 11 pm to 3 am). We analyzed the impact of sleep loss on transcription of proinflammatory cytokine genes and used DNA microarray analyses to characterize candidate transcription-control pathways that might mediate the effects of sleep loss on leukocyte gene expression. In the morning after a night of sleep loss, monocyte production of interleukin 6 and tumor necrosis factor alpha was significantly greater compared with morning levels following uninterrupted sleep. In addition, sleep loss induced a more than 3-fold increase in transcription of interleukin 6 messenger RNA and a 2-fold increase in tumor necrosis factor alpha messenger RNA. Bioinformatics analyses suggested that the inflammatory response was mediated by the nuclear factor kappaB inflammatory signaling system as well as through classic hormone and growth factor response pathways. Sleep loss induces a functional alteration of the monocyte proinflammatory cytokine response. A modest amount of sleep loss also alters molecular processes that drive cellular immune activation and induce inflammatory cytokines; mapping the dynamics of sleep loss on molecular signaling pathways has implications for understanding the role of sleep in altering immune cell physiologic characteristics. Interventions that target sleep might constitute new strategies to constrain inflammation with effects on inflammatory disease risk.

siRNA - Mediated LRP/LR knock-down reduces cellular viability of malignant melanoma cells through the activation of apoptotic caspases.

Science.gov (United States)

Rebelo, Thalia M; Vania, Leila; Ferreira, Eloise; Weiss, Stefan F T

2018-07-01

The 37 kDa/67 kDa laminin receptor (LRP/LR) is over-expressed in tumor cells and has been implicated in several tumourigenic processes such as metastasis and telomerase activation, however, more importantly the focus of the present study is on the maintenance of cellular viability and the evasion of apoptosis. The aim of the study was to investigate the role of LRP/LR on the cellular viability of early (A375) and late stage (A375SM) malignant melanoma cells. Flow cytometry and western blot analysis revealed that A375SM cells contain more cell-surface and total LRP/LR levels in comparison to the A375 cells, respectively. In order to determine the effect of LRP/LR on cell viability and apoptosis, LRP was down-regulated via siRNA technology. MTT assays revealed that LRP knock-down led to significant reductions in the viability of A375 and A375SM cells. Confocal microscopy indicated nuclear morphological changes suggestive of apoptotic induction in both cell lines and Annexin-V FITC/PI assays confirmed this observation. Additionally, caspase-3 activity assays revealed that apoptosis was induced in both cell lines after siRNA-mediated down-regulation of LRP. Caspase-8 and -9 activity assays suggested that post LRP knock-down; A375 cells undergo apoptosis solely via the extrinsic pathway, while A375SM cells undergo apoptosis via the intrinsic pathway. siRNAs mediated LRP knock-down might represent a powerful alternative therapeutic strategy for the treatment of malignant melanoma through the induction of apoptosis. Copyright © 2018. Published by Elsevier Inc.

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

Scavenging capacity of medicinal plants against free radical-induced cellular damage by radiation and photoactivation

Energy Technology Data Exchange (ETDEWEB)

Gadkar, Shalaka [Ruia College, Mumbai (India); Mohan, H [Chemistry Group, Bhabha Atomic Research Centre, Mumbai (India); Kamat, J P [Radiation Biology and Health Science Division, Bhabha Atomic Research Centre, Mumbai (India)

2004-01-01

The scavenging capacity of medicinal plants. Andrographis paniculata (Ap) and Swertia chirata (Sc) was examined against cellular damage, induced by radiation and photo-activation in sub-cellular membranes. The results demonstrated significant radical scavenging capacity of the extracts. The rate constants as evaluated by deoxyribose degradation studies and the pulse radiolysis studies carried in presence of ABTS radical well supported the antioxidant properties of the extracts. (author)

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…

Concurrent measurement of cellular turbidity and hemoglobin to evaluate the antioxidant activity of plants.

Science.gov (United States)

Bellik, Yuva; Iguer-Ouada, Mokrane

2016-01-01

In past decades, a multitude of analytical methods for measuring antioxidant activity of plant extracts has been developed. However, when using methods to determine hemoglobin released from human erythrocytes treated with ginger extracts, we found hemoglobin concentrations were significantly higher than in untreated control samples. This suggests in the presence of antioxidants that measuring hemoglobin alone is not sufficient to determine hemolysis. We show concurrent measurement of erythrocyte concentration and hemoglobin is essential in such assays, and describe a new protocol based on simultaneous measurement of cellular turbidity and hemoglobin. Copyright © 2015 Elsevier Ltd. All rights reserved.

Repaglinide at a cellular level

DEFF Research Database (Denmark)

Krogsgaard Thomsen, M; Bokvist, K; Høy, M

2002-01-01

To investigate the hormonal and cellular selectivity of the prandial glucose regulators, we have undertaken a series of experiments, in which we characterised the effects of repaglinide and nateglinide on ATP-sensitive potassium ion (KATP) channel activity, membrane potential and exocytosis in ra...

Studying Mechanosensitivity of Two-Pore Domain K+ Channels in Cellular and Reconstituted Proteoliposome Membranes.

Science.gov (United States)

Del Mármol, Josefina; Rietmeijer, Robert A; Brohawn, Stephen G

2018-01-01

Mechanical force sensation is fundamental to a wide breadth of biology from the classic senses of touch, pain, hearing, and balance to less conspicuous sensations of proprioception, blood pressure, and osmolarity and basic aspects of cell growth, differentiation, and development. These diverse and essential systems use force-gated (or mechanosensitive) ion channels that convert mechanical stimuli into cellular electrical signals. TRAAK, TREK1, and TREK2 are K + -selective ion channels of the two-pore domain K + (K2P) family that are mechanosensitive: they are gated open by increasing membrane tension. TRAAK and TREK channels are thought to play roles in somatosensory and other mechanosensory processes in neuronal and non-neuronal tissues. Here, we present protocols for three assays to study mechanical activation of these channels in cell membranes: (1) cell swelling, (2) cell poking, and (3) patched membrane stretching. Patched membrane stretching is also applicable to the study of mechanosensitive K2P channel activity in a cell-free system and a procedure for proteoliposome reconstitution and patching is also presented. These approaches are also readily applicable to the study of other mechanosensitive ion channels.

Design and cellular kinetics of dansyl-labeled CADA derivatives with anti-HIV and CD4 receptor down-modulating activity.

Science.gov (United States)

Vermeire, Kurt; Lisco, Andrea; Grivel, Jean-Charles; Scarbrough, Emily; Dey, Kaka; Duffy, Noah; Margolis, Leonid; Bell, Thomas W; Schols, Dominique

2007-08-15

A new class of anti-retrovirals, cyclotriazadisulfonamide (CADA) and its derivatives, specifically down-regulate CD4, the main receptor of HIV, and prevent HIV infection in vitro. In this work, several CADA derivatives, chemically labeled with a fluorescent dansyl group, were evaluated for their biological features and cellular uptake kinetics. We identified a derivative KKD-016 with antiviral and CD4 down-modulating capabilities similar to those of the parental compound CADA. By using flow cytometry, we demonstrated that the dose-dependent cellular uptake of this derivative correlated with CD4 down-modulation. The uptake and activity of the dansyl-labeled compounds were not dependent on the level of expression of CD4 at the cell surface. Removal of the CADA compounds from the cell culture medium resulted in their release from the cells followed by a complete restoration of CD4 expression. The inability of several fluorescent CADA derivatives to down-modulate CD4 was not associated with their lower cellular uptake and was not reversed by facilitating their cell penetration by a surfactant. These results prove the successful integration of the dansyl fluorophore into the chemical structure of a CD4 down-modulating anti-HIV compound, and show the feasibility of tracking a receptor and its down-modulator simultaneously. These fluorescent CADA analogs with reversible CD4 down-regulating potency can now be applied in further studies on receptor modulation, and in the exploration of their potentials as preventive and therapeutic anti-HIV drugs.

Cellular Transport Mechanisms of Cytotoxic Metallodrugs: An Overview beyond Cisplatin

Directory of Open Access Journals (Sweden)

Sarah Spreckelmeyer

2014-09-01

Full Text Available The field of medicinal inorganic chemistry has grown consistently during the past 50 years; however, metal-containing coordination compounds represent only a minor proportion of drugs currently on the market, indicating that research in this area has not yet been thoroughly realized. Although platinum-based drugs as cancer chemotherapeutic agents have been widely studied, exact knowledge of the mechanisms governing their accumulation in cells is still lacking. However, evidence suggests active uptake and efflux mechanisms are involved; this may be involved also in other experimental metal coordination and organometallic compounds with promising antitumor activities in vitro and in vivo, such as ruthenium and gold compounds. Such knowledge would be necessary to elucidate the balance between activity and toxicity profiles of metal compounds. In this review, we present an overview of the information available on the cellular accumulation of Pt compounds from in vitro, in vivo and clinical studies, as well as a summary of reports on the possible accumulation mechanisms for different families of experimental anticancer metal complexes (e.g., Ru Au and Ir. Finally, we discuss the need for rationalization of the investigational approaches available to study metallodrug cellular transport.

Quantitative assessment of barriers to the clinical development and adoption of cellular therapies: A pilot study

Directory of Open Access Journals (Sweden)

Benjamin M Davies

2014-09-01

Full Text Available There has been a large increase in basic science activity in cell therapy and a growing portfolio of cell therapy trials. However, the number of industry products available for widespread clinical use does not match this magnitude of activity. We hypothesize that the paucity of engagement with the clinical community is a key contributor to the lack of commercially successful cell therapy products. To investigate this, we launched a pilot study to survey clinicians from five specialities and to determine what they believe to be the most significant barriers to cellular therapy clinical development and adoption. Our study shows that the main concerns among this group are cost-effectiveness, efficacy, reimbursement, and regulation. Addressing these concerns can best be achieved by ensuring that future clinical trials are conducted to adequately answer the questions of both regulators and the broader clinical community.

Acetyl-CoA carboxylase in Reuber hepatoma cells: variation in enzyme activity, insulin regulation, and cellular lipid content.

Science.gov (United States)

Bianchi, A; Evans, J L; Nordlund, A C; Watts, T D; Witters, L A

1992-01-01

Reuber hepatoma cells are useful cultured lines for the study of insulin action, lipid and lipoprotein metabolism, and the regulation of acetyl-CoA carboxylase (ACC), the rate-limiting enzyme of fatty acid biosynthesis. During investigations in different clonal lines of these cells, we have uncovered marked intercellular variability in the activity, enzyme content, and insulin regulation of ACC paralleled by differences in cellular neutral lipid (triglyceride) content. Two contrasting clonal lines, Fao and H356A-1, have been studied in detail. Several features distinguish these two lines, including differences in ACC activity and enzyme kinetics, the content of the two major hepatic ACC isozymes (Mr 280,000 and 265,000 Da) and their heteroisozymic complex, the extent of ACC phosphorylation, and the ability of ACC to be activated on stimulation by insulin and insulinomimetic agonists. As studied by Nile Red staining and fluorescence-activated cell sorting, these two lines also display marked differences in neutral lipid content, which correlates with both basal levels of ACC activity and inhibition of ACC by the fatty acid analog, 5-(tetradecyloxy)-2-furoic acid (TOFA). These results emphasize the importance of characterization of any particular clonal line of Reuber cells for studies of enzyme regulation, substrate metabolism, and hormone action. With respect to ACC, studies in contrasting clonal lines of Reuber cells could provide valuable clues to understanding both the complex mechanisms of intracellular ACC regulation in the absence and presence of hormones and its regulatory role(s) in overall hepatic lipid metabolism.

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

Science.gov (United States)

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.

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.

Sleep deprivation and divergent toll-like receptor-4 activation of cellular inflammation in aging.

Science.gov (United States)

Carroll, Judith E; Carrillo, Carmen; Olmstead, Richard; Witarama, Tuff; Breen, Elizabeth C; Yokomizo, Megumi; Seeman, Teresa; Irwin, Michael R

2015-02-01

Sleep disturbance and aging are associated with increases in inflammation, as well as increased risk of infectious disease. However, there is limited understanding of the role of sleep loss on age-related differences in immune responses. This study examines the effects of sleep deprivation on toll-like receptor activation of monocytic inflammation in younger compared to older adults. Community-dwelling adults (n = 70) who were categorized as younger (25-39 y old, n = 21) and older (60-84 y old, n = 49) participants, underwent a sleep laboratory-based experimental partial sleep deprivation (PSD) protocol including adaptation, an uninterrupted night of sleep, sleep deprivation (sleep restricted to 03:00-07:00), and recovery. Blood samples were obtained each morning to measure toll-like receptor-4 activation of monocyte intracellular production of the inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Partial sleep deprivation induced a significant increase in the production of IL-6 and/or TNF-α that persisted after a night of recovery sleep (F(2,121.2) = 3.8, P sleep loss, such that younger adults had an increase in inflammatory cytokine production that was not present in older adults (F(2,121.2) = 4.0, P sleep loss. Whereas sleep loss increases cellular inflammation in younger adults and may contribute to inflammatory disorders, blunted toll-like receptor activation in older adults may increase the risk of infectious disease seen with aging. © 2015 Associated Professional Sleep Societies, LLC.

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.

Tetraspanin CD9 modulates human lymphoma cellular proliferation via histone deacetylase activity

Energy Technology Data Exchange (ETDEWEB)

Herr, Michael J. [Vascular Biology Center of Excellence, The University of Tennessee Health Science Center, Memphis, TN 38163 (United States); Department of Medicine, The University of Tennessee Health Science Center, Memphis, TN 38163 (United States); Department of Molecular Sciences, The University of Tennessee Health Science Center, Memphis, TN 38163 (United States); Department of Surgery, The University of Tennessee Health Science Center, Memphis, TN 38163 (United States); Longhurst, Celia M.; Baker, Benjamin [Vascular Biology Center of Excellence, The University of Tennessee Health Science Center, Memphis, TN 38163 (United States); Homayouni, Ramin [Department of Biology, Bioinformatics Program, University of Memphis, Memphis, TN 38152 (United States); Speich, Henry E.; Kotha, Jayaprakash [Vascular Biology Center of Excellence, The University of Tennessee Health Science Center, Memphis, TN 38163 (United States); Jennings, Lisa K., E-mail: ljennings@uthsc.edu [Vascular Biology Center of Excellence, The University of Tennessee Health Science Center, Memphis, TN 38163 (United States); Department of Medicine, The University of Tennessee Health Science Center, Memphis, TN 38163 (United States); Department of Molecular Sciences, The University of Tennessee Health Science Center, Memphis, TN 38163 (United States); Department of Surgery, The University of Tennessee Health Science Center, Memphis, TN 38163 (United States); Department of Biology, Bioinformatics Program, University of Memphis, Memphis, TN 38152 (United States)

2014-05-16

Highlights: • CD9 is differentially expressed in human Burkitt’s lymphoma cells. • We found that CD9 expression promotes these cells proliferation. • CD9 expression also increases HDAC activity. • HDAC inhibition decreased both cell proliferation and importantly CD9 expression. • CD9 may dictate HDAC efficacy and play a role in HDAC regulation. - Abstract: Non-Hodgkin Lymphoma (NHL) is a type of hematological malignancy that affects two percent of the overall population in the United States. Tetraspanin CD9 is a cell surface protein that has been thoroughly demonstrated to be a molecular facilitator of cellular phenotype. CD9 expression varies in two human lymphoma cell lines, Raji and BJAB. In this report, we investigated the functional relationship between CD9 and cell proliferation regulated by histone deacetylase (HDAC) activity in these two cell lines. Introduction of CD9 expression in Raji cells resulted in significantly increased cell proliferation and HDAC activity compared to Mock transfected Raji cells. The increase in CD9–Raji cell proliferation was significantly inhibited by HDAC inhibitor (HDACi) treatment. Pretreatment of BJAB cells with HDAC inhibitors resulted in a significant decrease in endogenous CD9 mRNA and cell surface expression. BJAB cells also displayed decreased cell proliferation after HDACi treatment. These results suggest a significant relationship between CD9 expression and cell proliferation in human lymphoma cells that may be modulated by HDAC activity.

Experimental study of adiabatic cellular premixed flames of methane (ethane, propane) + oxygen + carbon dioxide mixtures

NARCIS (Netherlands)

Konnov, A.A.; Dyakov, I.V.

2007-01-01

Experimental studies of adiabatic cellular flames of CH4 + O2 + CO2, C2H6 + O2 + CO2, and C3H8 + O2 + CO2 are presented. Visual and photographic observations of the flames were performed to quantify their cellular structure. Non-stretched flames of methane and propane were stabilized at atmospheric

Cellular therapies: Day by day, all the way.

Science.gov (United States)

Atilla, Erden; Kilic, Pelin; Gurman, Gunhan

2018-04-18

Tremendous effort and knowledge have elucidated a new era of 'cellular therapy,' also called "live" or "living" drugs. There are currently thousands of active clinical trials that are ongoing, seeking hope for incurable conditions thanks to the increased accessibility and reliability of gene editing and cellular reprogramming. Accomplishments in various adoptive T cell immunotherapies and chimeric antigen receptor (CART) T cell therapies oriented researchers to the field. Cellular therapies are believed to be the next generation of curative therapeutics in many ways, the classification and nomenclature for these applications have not yet reached a consensus. Trends in recent years are moving towards making tissues and cell processes only in centers with production permits. It is quite promising that competent authorities have increased licensing activities of tissue and cell establishments in their countries, under good practice (GxP) rules, and preclinical and clinical trials involving cell-based therapies have led to significant investments. Despite the initiatives undertaken and the large budgets that have been allocated, only limited success has been achieved in cellular therapy compared to conventional drug development. Cost, and cost effectiveness, are important issues for these novel therapies to meet unmet clinical needs, and there are still many scientific, translational, commercializational, and ethical questions that do not have answers. The main objectives of this review is to underline the current position of cellular therapies in research, highlight the timely topic of immunotherapy and chimeric antigen receptor (CAR) T-cell treatment, and compile information related to regulations and marketing of cellular therapeutic approaches worldwide. Copyright © 2018 Elsevier Ltd. All rights reserved.

IGF-I enhances cellular senescence via the reactive oxygen species-p53 pathway

Energy Technology Data Exchange (ETDEWEB)

Handayaningsih, Anastasia-Evi; Takahashi, Michiko; Fukuoka, Hidenori; Iguchi, Genzo; Nishizawa, Hitoshi; Yamamoto, Masaaki; Suda, Kentaro [Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe (Japan); Takahashi, Yutaka, E-mail: takahash@med.kobe-u.ac.jp [Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe (Japan)

2012-08-24

Highlights: Black-Right-Pointing-Pointer Cellular senescence plays an important role in tumorigenesis and aging process. Black-Right-Pointing-Pointer We demonstrated IGF-I enhanced cellular senescence in primary confluent cells. Black-Right-Pointing-Pointer IGF-I enhanced cellular senescence in the ROS and p53-dependent manner. Black-Right-Pointing-Pointer These results may explain the underlying mechanisms of IGF-I involvement in tumorigenesis and in regulation of aging. -- Abstract: Cellular senescence is characterized by growth arrest, enlarged and flattened cell morphology, the expression of senescence-associated {beta}-galactosidase (SA-{beta}-gal), and by activation of tumor suppressor networks. Insulin-like growth factor-I (IGF-I) plays a critical role in cellular growth, proliferation, tumorigenesis, and regulation of aging. In the present study, we show that IGF-I enhances cellular senescence in mouse, rat, and human primary cells in the confluent state. IGF-I induced expression of a DNA damage marker, {gamma}H2AX, the increased levels of p53 and p21 proteins, and activated SA-{beta}-gal. In the confluent state, an altered downstream signaling of IGF-I receptor was observed. Treatment with a reactive oxygen species (ROS) scavenger, N-acetylcystein (NAC) significantly suppressed induction of these markers, indicating that ROS are involved in the induction of cellular senescence by IGF-I. In p53-null mouse embryonic fibroblasts, the IGF-I-induced augmentation of SA-{beta}-gal and p21 was inhibited, demonstrating that p53 is required for cellular senescence induced by IGF-I. Thus, these data reveal a novel pathway whereby IGF-I enhances cellular senescence in the ROS and p53-dependent manner and may explain the underlying mechanisms of IGF-I involvement in tumorigenesis and in regulation of aging.

IGF-I enhances cellular senescence via the reactive oxygen species–p53 pathway

International Nuclear Information System (INIS)

Handayaningsih, Anastasia-Evi; Takahashi, Michiko; Fukuoka, Hidenori; Iguchi, Genzo; Nishizawa, Hitoshi; Yamamoto, Masaaki; Suda, Kentaro; Takahashi, Yutaka

2012-01-01

Highlights: ► Cellular senescence plays an important role in tumorigenesis and aging process. ► We demonstrated IGF-I enhanced cellular senescence in primary confluent cells. ► IGF-I enhanced cellular senescence in the ROS and p53-dependent manner. ► These results may explain the underlying mechanisms of IGF-I involvement in tumorigenesis and in regulation of aging. -- Abstract: Cellular senescence is characterized by growth arrest, enlarged and flattened cell morphology, the expression of senescence-associated β-galactosidase (SA-β-gal), and by activation of tumor suppressor networks. Insulin-like growth factor-I (IGF-I) plays a critical role in cellular growth, proliferation, tumorigenesis, and regulation of aging. In the present study, we show that IGF-I enhances cellular senescence in mouse, rat, and human primary cells in the confluent state. IGF-I induced expression of a DNA damage marker, γH2AX, the increased levels of p53 and p21 proteins, and activated SA-β-gal. In the confluent state, an altered downstream signaling of IGF-I receptor was observed. Treatment with a reactive oxygen species (ROS) scavenger, N-acetylcystein (NAC) significantly suppressed induction of these markers, indicating that ROS are involved in the induction of cellular senescence by IGF-I. In p53-null mouse embryonic fibroblasts, the IGF-I-induced augmentation of SA-β-gal and p21 was inhibited, demonstrating that p53 is required for cellular senescence induced by IGF-I. Thus, these data reveal a novel pathway whereby IGF-I enhances cellular senescence in the ROS and p53-dependent manner and may explain the underlying mechanisms of IGF-I involvement in tumorigenesis and in regulation of aging.

Mathematical analysis of complex cellular activity

CERN Document Server

Bertram, Richard; Teka, Wondimu; Vo, Theodore; Wechselberger, Martin; Kirk, Vivien; Sneyd, James

2015-01-01

This book contains two review articles on mathematical physiology that deal with closely related topics but were written and can be read independently. The first article reviews the basic theory of calcium oscillations (common to almost all cell types), including spatio-temporal behaviors such as waves. The second article uses, and expands on, much of this basic theory to show how the interaction of cytosolic calcium oscillators with membrane ion channels can result in highly complex patterns of electrical spiking. Through these examples one can see clearly how multiple oscillatory processes interact within a cell, and how mathematical methods can be used to understand such interactions better. The two reviews provide excellent examples of how mathematics and physiology can learn from each other, and work jointly towards a better understanding of complex cellular processes. Review 1: Richard Bertram, Joel Tabak, Wondimu Teka, Theodore Vo, Martin Wechselberger: Geometric Singular Perturbation Analysis of Burst...

Independent cellular effects of cold ischemia and reperfusion: experimental molecular study.

Science.gov (United States)

Lledó-García, E; Humanes-Sánchez, B; Mojena-Sánchez, M; Rodrígez, J C J; Hernández-Fernández, C; Tejedor-Jorge, A; Fernández, A L

2013-04-01

There is less information available on cell cultures on the exclusive effects of either duration of cold ischemia (CI) or rewarming-reperfusion in the kidney subjected to initial warm ischemia (WI). Therefore, the goals of our work were: (1) to evaluate the consequences on tubular cellular viability of different durations of CI on a kidney after an initial period of WI, and (2) to analyze the additional effect on tubular cell viability of rewarming of the same kidney. Sixteen mini-pig were used. All the animals were performed a right nephrectomy after 45-minute occlusion of the vascular pedicle. The kidneys were then divided into 2 groups (phase 1): cold storage in university of wisconsin (UW) solution for 3 hours (group A, n = 8) at 4°C, or cold storage in UW for 12 hours (group B, n = 8) at 4°C. Four organs of group A and four organs of group B were autotrasplanted (AT) and reperfused for 1 hour (phase 2). Nephrectomy was finally done. Biopsies were taken from all groups to perform cultures of proximal tubule epithelium cells. The biopsies were subjected to studies of cellular morphological viability (contrast phase microscopy [CPM]) and quantitative (confluence cell [CC]) parameters. Phase of pure CI effects (phase 1): Both CC rate and CPM parameters were significantly lower in group B compared with group A, where cell activity reached almost normal results. Phase of CI + AT (phase 2): At produced additional harmful effects in cell cultures compared with those obtained in phase 1, more evident in group B cells. The presence of cold storage followed by rewarming-reperfusion induces independent and cumulative detrimental effects in viability of renal proximal tubule cells. CI periods ≤ 3 hours may ameliorate the injuries secondary to reperfusion in comparison with longer CI periods. Copyright © 2013 Elsevier Inc. All rights reserved.

Cellular Imaging at 1.5 T: Detecting Cells in Neuroinflammation using Active Labeling with Superparamagnetic Iron Oxide

Directory of Open Access Journals (Sweden)

Ayman J. Oweida

2004-04-01

Full Text Available The ability to visualize cell infiltration in experimental autoimmune encephalomyelitis (EAE, a well-known animal model for multiple sclerosis in humans, was investigated using a clinical 1.5-T magnetic resonance imaging (MRI scanner, a custom-built, high-strength gradient coil insert, a 3-D fast imaging employing steady-state acquisition (FIESTA imaging sequence and a superparamagnetic iron oxide (SPIO contrast agent. An “active labeling” approach was used with SPIO administered intravenously during inflammation in EAE. Our results show that small, discrete regions of signal void corresponding to iron accumulation in EAE brain can be detected using FIESTA at 1.5 T. This work provides early evidence that cellular abnormalities that are the basis of diseases can be probed using cellular MRI and supports our earlier work which indicates that tracking of iron-labeled cells will be possible using clinical MR scanners.

HDACi: cellular effects, opportunities for restorative dentistry.

LENUS (Irish Health Repository)

Duncan, H F

2011-12-01

Acetylation of histone and non-histone proteins alters gene expression and induces a host of cellular effects. The acetylation process is homeostatically balanced by two groups of cellular enzymes, histone acetyltransferases (HATs) and histone deacetylases (HDACs). HAT activity relaxes the structure of the human chromatin, rendering it transcriptionally active, thereby increasing gene expression. In contrast, HDAC activity leads to gene silencing. The enzymatic balance can be \\'tipped\\' by histone deacetylase inhibitors (HDACi), leading to an accumulation of acetylated proteins, which subsequently modify cellular processes including stem cell differentiation, cell cycle, apoptosis, gene expression, and angiogenesis. There is a variety of natural and synthetic HDACi available, and their pleiotropic effects have contributed to diverse clinical applications, not only in cancer but also in non-cancer areas, such as chronic inflammatory disease, bone engineering, and neurodegenerative disease. Indeed, it appears that HDACi-modulated effects may differ between \\'normal\\' and transformed cells, particularly with regard to reactive oxygen species accumulation, apoptosis, proliferation, and cell cycle arrest. The potential beneficial effects of HDACi for health, resulting from their ability to regulate global gene expression by epigenetic modification of DNA-associated proteins, also offer potential for application within restorative dentistry, where they may promote dental tissue regeneration following pulpal damage.

Antiviral and Inflammatory Cellular Signaling Associated with Enterovirus 71 Infection

Directory of Open Access Journals (Sweden)

Yuefei Jin

2018-03-01

Full Text Available Enterovirus 71 (EV71 infection has become a major threat to global public health, especially in infants and young children. Epidemiological studies have indicated that EV71 infection is responsible for severe and even fatal cases of hand, foot, and mouth disease (HFMD. Accumulated evidence indicates that EV71 infection triggers a plethora of interactive signaling pathways, resulting in host immune evasion and inflammatory response. This review mainly covers the effects of EV71 infection on major antiviral and inflammatory cellular signal pathways. EV71 can activate cellular signaling networks including multiple cell surface and intracellular receptors, intracellular kinases, calcium flux, and transcription factors that regulate antiviral innate immunity and inflammatory response. Cellular signaling plays a critical role in the regulation of host innate immune and inflammatory pathogenesis. Elucidation of antiviral and inflammatory cellular signaling pathways initiated by EV71 will not only help uncover the potential mechanisms of EV71 infection-induced pathogenesis, but will also provide clues for the design of therapeutic strategies against EV71 infection.

Cellular and antitumor activity of a new diethylene glycol benzoporphyrin derivative (lemuteporfin).

Science.gov (United States)

Boch, Ron; Canaan, Alice J; Cho, Angela; Dolphin, David D; Hong, Lina; Jain, Ashok K; North, John R; Richter, Anna M; Smits, Claire; Sternberg, Ethan D

2006-01-01

A newly synthesized diethylene glycol functionalized chlorin-type photosensitizer, lemuteporfin, was characterized for use in photodynamic therapy (PDT) in a panel of in vitro and in vivo test systems. The photosensitizer was highly potent, killing cells at low nanomolar concentrations upon exposure to activating light. The cellular uptake of lemuteporfin was rapid, with maximum levels reached within 20 min. Mitogen-activated lymphoid cells accumulated more of the lemuteporfin than their quiescent equivalents, supporting selectivity. Photosensitizer fluorescence in the skin increased rapidly within the first few minutes following intravenous administration to mice, then decreased over the next 24 h. Skin photosensitivity reactions indicated rapid clearance of the photosensitizer. Intravenous doses as low as 1.4 micromol/kg combined with exposure to 50 J/cm2 red light suppressed tumor growth in a mouse model. In conclusion, this new benzoporphyrin was found to be an effective photosensitizer, showing rapid uptake and clearance both in vitro and in vivo. This rapid photosensitization of tumors could be useful in therapies requiring a potent, rapidly accumulating photosensitizer, while minimizing the potential for skin photosensitivity reactions to sunlight following treatment.

FTIR spectroscopic studies of bacterial cellular responses to environmental factors, plant-bacterial interactions and signalling

OpenAIRE

Kamnev, Alexander A.

2008-01-01

Modern spectroscopic techniques are highly useful in studying diverse processes in microbial cells related to or incited by environmental factors. Spectroscopic data for whole cells, supramolecular structures or isolated cellular constituents can reflect structural and/or compositional changes occurring in the course of cellular metabolic responses to the effects of pollutants, environmental conditions (stress factors); nutrients, signalling molecules (communication factors), etc. This inform...

Glider-based computing in reaction-diffusion hexagonal cellular automata

International Nuclear Information System (INIS)

Adamatzky, Andrew; Wuensche, Andrew; De Lacy Costello, Benjamin

2006-01-01

A three-state hexagonal cellular automaton, discovered in [Wuensche A. Glider dynamics in 3-value hexagonal cellular automata: the beehive rule. Int J Unconvention Comput, in press], presents a conceptual discrete model of a reaction-diffusion system with inhibitor and activator reagents. The automaton model of reaction-diffusion exhibits mobile localized patterns (gliders) in its space-time dynamics. We show how to implement the basic computational operations with these mobile localizations, and thus demonstrate collision-based logical universality of the hexagonal reaction-diffusion cellular automaton

Phenolic Acids Profiles and Cellular Antioxidant Activity in Tortillas Produced from Mexican Maize Landrace Processed by Nixtamalization and Lime Extrusion Cooking.

Science.gov (United States)

Gaxiola-Cuevas, Nallely; Mora-Rochín, Saraid; Cuevas-Rodriguez, Edith Oliva; León-López, Liliana; Reyes-Moreno, Cuauhtémoc; Montoya-Rodríguez, Alvaro; Milán-Carrillo, Jorge

2017-09-01

Phenolic acids profiles, chemical antioxidant activities (ABTS and ORAC), as well as cellular antioxidant activity (CAA) of tortilla of Mexican native maize landraces elaborated from nixtamalization and lime cooking extrusion processes were studied. Both cooking procedures decreased total phenolics, chemicals antioxidant activity when compared to raw grains. Extruded tortillas retained 79.6-83.5%, 74.1-77.6% and 79.8-80.5% of total phenolics, ABTS and ORAC values, respectively, compared to 47.8-49.8%, 41.3-42.3% and 43.7-44.4% assayed in traditional tortillas, respectively. Approximately 72.5-88.2% of ferulic acid in raw grains and their tortillas were in the bound form. Regarding of the CAA initially found in raw grains, the retained percentage for traditional and extruded tortillas ranged from 47.4 to 48.7% and 72.8 to 77.5%, respectively. These results suggest that Mexican maize landrace used in this study could be considered for the elaboration of nixtamalized and extruded food products with nutraceutical potential.

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.

Experimental study of auxetic behavior of cellular structure

Science.gov (United States)

Chentsov, A. V.; Lisovenko, D. S.

2018-04-01

The uniaxial tension of two-dimensional auxetic cellular constructions is studied experimentally. Samples were made of nonauxetic polyethylene terephthalate (PET-A amorphous) and subjected to monotonous uniaxial tension until the last moment when they still remained plane. As a result of the experimental data analysis, comparison of the mechanical properties is given for a faultless sample and constructions in which one horizontal or vertical element in the central area of the sample was removed. It is shown that the lack of one horizontal element of the construction has little influence on the auxetic properties of these constructions unlike the structures with one vertical element being absent.

Comparison of the free and bound phenolic profiles and cellular antioxidant activities of litchi pulp extracts from different solvents

Science.gov (United States)

2014-01-01

Background The phenolic contents and antioxidant activities of fruits could be underestimated if the bound phenolic compounds are not considered. In the present study, the extraction efficiencies of various solvents were investigated in terms of the total content of the free and bound phenolic compounds, as well as the phenolic profiles and antioxidant activities of the extracts. Methods Five different solvent mixtures were used to extract the free phenolic compounds from litchi pulp. Alkaline and acidic hydrolysis methods were compared for the hydrolysis of bound phenolic compounds from litchi pulp residue. The phenolic compositions of the free and bound fractions from the litchi pulp were identified using HPLC-DAD. The antioxidant activities of the litchi pulp extracts were determined by oxygen radical absorbance capacity (ORAC) and cellular antioxidant activity (CAA) assays. Results Of the solvents tested, aqueous acetone extracted the largest amount of total free phenolic compounds (210.7 mg GAE/100 g FW) from litchi pulp, followed sequentially by aqueous mixtures of methanol, ethanol and ethyl acetate, and water itself. The acid hydrolysis method released twice as many bound phenolic compounds as the alkaline hydrolysis method. Nine phenolic compounds were detected in the aqueous acetone extract. In contrast, not all of these compounds were found in the other four extracts. The classification and content of the bound phenolic compounds released by the acid hydrolysis method were higher than those achieved by the alkaline hydrolysis. The aqueous acetone extract showing the highest ORAC value (3406.9 μmol TE/100 g FW) for the free phenolic extracts. For the CAA method, however, the aqueous acetone and methanol extracts (56.7 and 55.1 μmol QE/100 g FW) showed the highest levels of activity of the five extracts tested. The ORAC and CAA values of the bound phenolic compounds obtained by acid hydrolysis were 2.6- and 1.9-fold higher than those obtained using the

Seasonal variations of cellular stress response of the gilthead sea bream (Sparus aurata).

Science.gov (United States)

Feidantsis, Konstantinos; Antonopoulou, Efthimia; Lazou, Antigone; Pörtner, Hans O; Michaelidis, Basile

2013-07-01

The present study aimed to investigate the seasonal cellular stress response in vital organs, like the heart, the liver, the whole blood and the skeletal (red and white) muscles of the Mediterranean fish Sparus aurata during a 1-year acclimatization period in the field, in two examined depths (0-2 m and 10-12 m). Processes studied included heat shock protein expression and protein kinase activation. Molecular responses were addressed through the expression of Hsp70 and Hsp90, the phosphorylation of stress-activated protein kinases and particularly p38 mitogen-activated protein kinase (p38 MAPK), the extracellular signal-regulated kinases (ERK-1/2) and c-Jun N-terminal kinases (JNK1/2/3). The induction of Hsp70 and Hsp90 and the phosphorylation of p38 MAPK, JNKs and ERKs in the examined five tissues of the gilthead sea bream indicated a cellular stress response under the prism of a seasonal pattern which was characterized by distinct tissue specificity. Specifically, Hsp induction and MAPK activation occurred before peak summer water temperatures, with no further increases in their levels despite increases in water temperatures. Moreover, although water temperature did not vary significantly with depth of immersion, significant effects of depth on cellular stress response were observed, probably caused by different light regime. The expression and the activation of these certain proteins can be used as tools to define the extreme thermal limits of the gilthead sea bream.

A high-throughput cellular assay to quantify the p53-degradation activity of E6 from different human papillomavirus types.

Science.gov (United States)

Gagnon, David; Archambault, Jacques

2015-01-01

A subset of human papillomaviruses (HPVs), known as the high-risk types, are the causative agents of cervical cancer and other malignancies of the anogenital region and oral mucosa. The capacity of these viruses to induce cancer and to immortalize cells in culture relies in part on a critical function of their E6 oncoprotein, that of promoting the poly-ubiquitination of the cellular tumor suppressor protein p53 and its subsequent degradation by the proteasome. Here, we describe a cellular assay to measure the p53-degradation activity of E6 from different HPV types. This assay is based on a translational fusion of p53 to Renilla luciferase (Rluc-p53) that remains sensitive to degradation by high-risk E6 and whose steady-state levels can be accurately measured in standard luciferase assays. The p53-degradation activity of any E6 protein can be tested and quantified in transiently transfected cells by determining the amount of E6-expression vector required to reduce by half the levels of RLuc-p53 luciferase activity (50 % effective concentration [EC50]). The high-throughput and quantitative nature of this assay makes it particularly useful to compare the p53-degradation activities of E6 from several HPV types in parallel.

TWO-DIMENSIONAL CELLULAR AUTOMATON MODEL FOR THE EVOLUTION OF ACTIVE REGION CORONAL PLASMAS

Energy Technology Data Exchange (ETDEWEB)

López Fuentes, Marcelo [Instituto de Astronomía y Física del Espacio, CONICET-UBA, CC. 67, Suc. 28, 1428 Buenos Aires (Argentina); Klimchuk, James A., E-mail: lopezf@iafe.uba.ar [NASA Goddard Space Flight Center, Code 671, Greenbelt, MD 20771 (United States)

2015-02-01

We study a two-dimensional cellular automaton (CA) model for the evolution of coronal loop plasmas. The model is based on the idea that coronal loops are made of elementary magnetic strands that are tangled and stressed by the displacement of their footpoints by photospheric motions. The magnetic stress accumulated between neighbor strands is released in sudden reconnection events or nanoflares that heat the plasma. We combine the CA model with the Enthalpy Based Thermal Evolution of Loops model to compute the response of the plasma to the heating events. Using the known response of the X-Ray Telescope on board Hinode, we also obtain synthetic data. The model obeys easy-to-understand scaling laws relating the output (nanoflare energy, temperature, density, intensity) to the input parameters (field strength, strand length, critical misalignment angle). The nanoflares have a power-law distribution with a universal slope of –2.5, independent of the input parameters. The repetition frequency of nanoflares, expressed in terms of the plasma cooling time, increases with strand length. We discuss the implications of our results for the problem of heating and evolution of active region coronal plasmas.

The inhibitory effect of apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3G (APOBEC3G) and its family members on the activity of cellular microRNAs.

Science.gov (United States)

Zhang, Hui

2010-01-01

The apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3G (APOBEC3G or APOBEC3G) and its fellow cytidine deaminase family members are potent restrictive factors for human immunodeficiency virus type 1 (HIV-1) and many other retroviruses. However, the cellular function of APOBEC3G remains to be further clarified. It has been reported that APOBEC3s can restrict the mobility of endogenous retroviruses and LTR-retrotransposons, suggesting that they can maintain stability in host genomes. However, APOBEC3G is normally cytoplasmic. Further studies have demonstrated that it is associated with an RNase-sensitive high molecular mass (HMM) and located in processing bodies (P-bodies) of replicating T-cells, indicating that the major cellular function of APOBEC3G seems to be related to P-body-related RNA processing and metabolism. As the function of P-body is closely related to miRNA activity, APOBEC3G could affect the miRNA function. Recent studies have demonstrated that APOBEC3G and its family members counteract miRNA-mediated repression of protein translation. Further, APOBEC3G enhances the association of miRNA-targeted mRNA with polysomes, and facilitates the dissociation of miRNA-targeted mRNA from P-bodies. As such, APOBEC3G regulate the activity of cellular miRNAs. Whether this function is related to its potent antiviral activity remains to be further determined.

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.

Evidence for increased cellular uptake of glutamate and aspartate in the rat hippocampus during kainic acid seizures. A microdialysis study using the "indicator diffusion' method

DEFF Research Database (Denmark)

Bruhn, T; Christensen, Thomas; Diemer, Nils Henrik

1997-01-01

Using a newly developed technique, based on microdialysis, which allows cellular uptake of glutamate and aspartate to be studied in awake animals, we investigated uptake of glutamate and aspartate in the hippocampal formation of rats during limbic seizures induced by systemical administration of ....... The results indicate that during KA-induced seizures, uptake of glutamate and aspartate is increased, possibly aimed at maintaining the extracellular homeostasis of these two excitatory amino acids.......Using a newly developed technique, based on microdialysis, which allows cellular uptake of glutamate and aspartate to be studied in awake animals, we investigated uptake of glutamate and aspartate in the hippocampal formation of rats during limbic seizures induced by systemical administration...... of kainic acid (KA). With [14C]mannitol as an extracellular reference substance, the cellular extraction of the test substance [3H]D-aspartate was measured at different stages of seizure-activity. The results were compared to those obtained in a sham operated control group. During severe generalized clonic...

Cellular senescence and organismal aging.

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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.

Exogenous coenzyme Q10 modulates MMP-2 activity in MCF-7 cell line as a breast cancer cellular model

Directory of Open Access Journals (Sweden)

Mirmiranpour Hossein

2010-11-01

Full Text Available Abstract Background/Aims Matrix Metalloproteinases 2 is a key molecule in cellular invasion and metastasis. Mitochondrial ROS has been established as a mediator of MMP activity. Coenzyme Q10 contributes to intracellular ROS regulation. Coenzyme Q10 beneficial effects on cancer are still in controversy but there are indications of Coenzyme Q10 complementing effect on tamoxifen receiving breast cancer patients. Methods In this study we aimed to investigate the correlation of the effects of co-incubation of coenzyme Q10 and N-acetyl-L-cysteine (NAC on intracellular H2O2 content and Matrix Metalloproteinase 2 (MMP-2 activity in MCF-7 cell line. Results and Discussion Our experiment was designed to assess the effect in a time and dose related manner. Gelatin zymography and Flowcytometric measurement of H2O2 by 2'7',-dichlorofluorescin-diacetate probe were employed. The results showed that both coenzyme Q10 and N-acetyl-L-cysteine reduce MMP-2 activity along with the pro-oxidant capacity of the MCF-7 cell in a dose proportionate manner. Conclusions Collectively, the present study highlights the significance of Coenzyme Q10 effect on the cell invasion/metastasis effecter molecules.

Imaging the lipidome: omega-alkynyl fatty acids for detection and cellular visualization of lipid-modified proteins.

Science.gov (United States)

Hannoush, Rami N; Arenas-Ramirez, Natalia

2009-07-17

Fatty acylation or lipid modification of proteins controls their cellular activation and diverse roles in physiology. It mediates protein-protein and protein-membrane interactions and plays an important role in regulating cellular signaling pathways. Currently, there is need for visualizing lipid modifications of proteins in cells. Herein we report novel chemical probes based on omega-alkynyl fatty acids for biochemical detection and cellular imaging of lipid-modified proteins. Our study shows that omega-alkynyl fatty acids of varying chain length are metabolically incorporated onto cellular proteins. Using fluorescence imaging, we describe the subcellular distribution of lipid-modified proteins across a panel of different mammalian cell lines and during cell division. Our results demonstrate that this methodology is a useful diagnostic tool for analyzing the lipid content of cellular proteins and for studying the dynamic behavior of lipid-modified proteins in various disease or physiological states.

Activity against Mycobacterium tuberculosis with concomitant induction of cellular immune responses by a tetraaza-macrocycle with acetate pendant arms.

Science.gov (United States)

David, S; Ordway, D; Arroz, M J; Costa, J; Delgado, R

2001-01-01

The novel tetraaza-macrocyclic compound 3,7,11-tris(carboxymethyl)-3,7,11,17-tetraaza-bicyclo[11.3.1]heptadeca-1(17),13,15-triene, abbreviated as ac3py14, was investigated for its activity against Mycobacterium tuberculosis and for induction of protective cellular immune responses. Perspective results show that ac3py14 and its Fe3+ 1:1 complex, [Fe(ac3py14)], inhibited radiometric growth of several strains of M. tuberculosis. Inhibition with 25 microg/mL varied from 99% for H37Rv to 80% and above for multiple drug-resistant clinical isolates. The capacity of ac3py14 to elicit a beneficial immune response without cellular apoptosis was assessed and compared to the effects of virulent M. tuberculosis. The present study produces evidence that after stimulation with ac3py14 there was significant production of interferon gamma (IFN-gamma), whereas the production of interleukin-5 (IL-5) remained low, and there was development of a memory population (CD45RO). The level of binding of Annexin V, a marker of apoptosis, was not sufficient to result in toxic effects toward alphabeta and gammadelta T cells and CD14+ macrophages. This preliminary study is the first report of a compound that simultaneously exerts an inhibitory effect against M. tuberculosis and induces factors associated with protective immune responses.

A comparative analysis of electronic and molecular quantum dot cellular automata

International Nuclear Information System (INIS)

Umamahesvari, H.; Ajitha, D.

2015-01-01

This paper presents a comparative analysis of electronic quantum-dot cellular automata (EQCA) and Magnetic quantum dot Cellular Automata (MQCA). QCA is a computing paradigm that encodes and processes information by the position of individual electrons. To enhance the high dense and ultra-low power devices, various researches have been actively carried out to find an alternative way to continue and follow Moore’s law, so called “beyond CMOS technology”. There have been several proposals for physically implementing QCA, EQCA and MQCA are the two important QCAs reported so far. This paper provides a comparative study on these two QCAs

Cellular glutathione prevents cytolethality of monomethylarsonic acid

International Nuclear Information System (INIS)

Sakurai, Teruaki; Kojima, Chikara; Ochiai, Masayuki; Ohta, Takami; Sakurai, Masumi H.; Waalkes, Michael P.; Fujiwara, Kitao

2004-01-01

Inorganic arsenicals are clearly toxicants and carcinogens in humans. In mammals, including humans, inorganic arsenic often undergoes methylation, forming compounds such as monomethylarsonic acid (MMAs V ) and dimethylarsinic acid (DMAs V ). However, much less information is available on the in vitro toxic potential or mechanisms of these methylated arsenicals, especially MMAs V . We studied the molecular mechanisms of in vitro cytolethality of MMAs V using a rat liver epithelial cell line (TRL 1215). MMAs V was not cytotoxic in TRL 1215 cells even at concentrations exceeding 10 mM, but it became weakly cytotoxic and induced both necrotic and apoptotic cell death when cellular reduced glutathione (GSH) was depleted with the glutathione synthase inhibitor, L-buthionine-[S,R]-sulfoximine (BSO), or the glutathione reductase inhibitor, carmustine. Similar results were observed in the other mammalian cells, such as human skin TIG-112 cells, chimpanzee skin CRT-1609 cells, and mouse metallothionein (MT) positive and MT negative embryonic cells. Ethacrynic acid (EA), an inhibitor of glutathione S-transferase (GST) that catalyses GSH-substrate conjugation, also enhanced the cytolethality of MMAs V , but aminooxyacetic acid (AOAA), an inhibitor of β-lyase that catalyses the final breakdown of GSH-substrate conjugates, had no effect. Both the cellular GSH levels and the cellular GST activity were increased by the exposure to MMAs V in TRL 1215 cells. On the other hand, the addition of exogenous extracellular GSH enhanced the cytolethality of MMAs V , although cellular GSH levels actually prevented the cytolethality of combined MMAs V and exogenous GSH. These findings indicate that human arsenic metabolite MMAs V is not a highly toxic compound in mammalian cells, and the level of cellular GSH is critical to its eventual toxic effects

Integrin specificity and enhanced cellular activities associated with surfaces presenting a recombinant fibronectin fragment compared to RGD supports.

Science.gov (United States)

Petrie, Timothy A; Capadona, Jeffrey R; Reyes, Catherine D; García, Andrés J

2006-11-01

Biomimetic strategies focusing on presenting short bioadhesive oligopeptides, including the arginine-glycine-aspartic acid (RGD) motif present in numerous adhesive proteins, on a non-fouling support have emerged as promising approaches to improve cellular activities and healing responses. Nevertheless, these bio-inspired strategies are limited by low activity of the oligopeptides compared to the native ligand due to the absence of complementary or modulatory domains. In the present analysis, we generated well-defined biointerfaces presenting RGD-based ligands of increasing complexity to directly compare their biological activities in terms of cell adhesion strength, integrin binding and signaling. Mixed self-assembled monolayers of alkanethiols on gold were optimized to engineer robust supports that present anchoring groups for ligand tethering within a non-fouling, protein adsorption-resistant background. Controlled bioadhesive interfaces were generated by tethering adhesive ligands via standard peptide chemistry. On a molar basis, biointerfaces functionalized with the FNIII7-10 recombinant fragment presenting the RGD and PHSRN adhesive motifs in the correct structural context exhibited significantly higher adhesion strength, FAK activation, and cell proliferation rate than supports presenting RGD ligand or RGD-PHSRN, an oligopeptide presenting these two sites separated by a polyglycine linker. Moreover, FNIII7-10-functionalized surfaces displayed specificity for alpha5beta1 integrin, while cell adhesion to supports presenting RGD or RGD-PHSRN was primarily mediated by alphavbeta3 integrin. These results are significant to the rational engineering of bioactive materials that convey integrin binding specificity for directed cellular and tissue responses in biomedical and biotechnological applications.

Stimulation of toll-like receptor 2 with bleomycin results in cellular activation and secretion of pro-inflammatory cytokines and chemokines

International Nuclear Information System (INIS)

Razonable, Raymund R.; Henault, Martin; Paya, Carlos V.

2006-01-01

The clinical use of bleomycin results in systemic and pulmonary inflammatory syndromes that are mediated by the production of cytokines and chemokines. In this study, we demonstrate that cell activation is initiated upon the recognition of bleomycin as a pathogen-associated molecular pattern by toll-like receptor (TLR) 2. The THP1 human monocytic cell line, which constitutively expresses high levels of TLR2, secretes interleukin (IL)-1β, IL-8, and tumor necrosis factor (TNF)-α during bleomycin exposure. The TLR2-dependent nature of cell activation and cytokine secretion is supported by (1) the inability of TLR2-deficient human embryonic kidney (HEK) 293 cells to exhibit nuclear factor-kappa B (NF-κB) activation and secrete IL-8 in response to bleomycin; (2) the acquired ability of HEK293 to exhibit NF-κB activation and secrete IL-8 upon experimental expression of TLR2; and (3) the inhibition of cell activation in TLR2-expressing HEK293 and THP1 by anti-TLR2 monoclonal antibody. Collectively, these observations identify TLR2 activation as a critical event that triggers NF-κB activation and secretion of cytokines and chemokines during bleomycin exposure. Our in vitro findings could serve as a molecular mechanism underlying the pro-inflammatory toxicity associated with bleomycin. Whether bleomycin engages with other cellular receptors that results in activation of alternate signaling pathways and whether the TLR2-agonist activity of bleomycin contribute to its anti-neoplastic property deserve further study

Biosensor Architectures for High-Fidelity Reporting of Cellular Signaling

Science.gov (United States)

Dushek, Omer; Lellouch, Annemarie C.; Vaux, David J.; Shahrezaei, Vahid

2014-01-01

Understanding mechanisms of information processing in cellular signaling networks requires quantitative measurements of protein activities in living cells. Biosensors are molecular probes that have been developed to directly track the activity of specific signaling proteins and their use is revolutionizing our understanding of signal transduction. The use of biosensors relies on the assumption that their activity is linearly proportional to the activity of the signaling protein they have been engineered to track. We use mechanistic mathematical models of common biosensor architectures (single-chain FRET-based biosensors), which include both intramolecular and intermolecular reactions, to study the validity of the linearity assumption. As a result of the classic mechanism of zero-order ultrasensitivity, we find that biosensor activity can be highly nonlinear so that small changes in signaling protein activity can give rise to large changes in biosensor activity and vice versa. This nonlinearity is abolished in architectures that favor the formation of biosensor oligomers, but oligomeric biosensors produce complicated FRET states. Based on this finding, we show that high-fidelity reporting is possible when a single-chain intermolecular biosensor is used that cannot undergo intramolecular reactions and is restricted to forming dimers. We provide phase diagrams that compare various trade-offs, including observer effects, which further highlight the utility of biosensor architectures that favor intermolecular over intramolecular binding. We discuss challenges in calibrating and constructing biosensors and highlight the utility of mathematical models in designing novel probes for cellular signaling. PMID:25099816

SM22α-induced activation of p16INK4a/retinoblastoma pathway promotes cellular senescence caused by a subclinical dose of γ-radiation and doxorubicin in HepG2 cells

International Nuclear Information System (INIS)

Kim, Tae Rim; Lee, Hee Min; Lee, So Yong; Kim, Eun Jin; Kim, Kug Chan; Paik, Sang Gi; Cho, Eun Wie; Kim, In Gyu

2010-01-01

Research highlights: → SM22α overexpression in HepG2 cells leads cells to a growth arrest state, and the treatment of a subclinical dose of γ-radiation or doxorubicin promotes cellular senescence. → SM22α overexpression elevates p16 INK4a followed by pRB activation, but there are no effects on p53/p21 WAF1/Cip1 pathway. → SM22α-induced MT-1G activates p16 INK4a /pRB pathway, which promotes cellular senescence by damaging agents. -- Abstract: Smooth muscle protein 22-alpha (SM22α) is known as a transformation- and shape change-sensitive actin cross-linking protein found in smooth muscle tissue and fibroblasts; however, its functional role remains uncertain. We reported previously that SM22α overexpression confers resistance against anti-cancer drugs or radiation via induction of metallothionein (MT) isozymes in HepG2 cells. In this study, we demonstrate that SM22α overexpression leads cells to a growth arrest state and promotes cellular senescence caused by treatment with a subclinical dose of γ-radiation (0.05 and 0.1 Gy) or doxorubicin (0.01 and 0.05 μg/ml), compared to control cells. Senescence growth arrest is known to be controlled by p53 phosphorylation/p21 WAF1/Cip1 induction or p16 INK4a /retinoblastoma protein (pRB) activation. SM22α overexpression in HepG2 cells elevated p16 INK4a followed by pRB activation, but did not activate the p53/p21 WAF1/Cip1 pathway. Moreover, MT-1G, which is induced by SM22α overexpression, was involved in the activation of the p16 INK4a /pRB pathway, which led to a growth arrest state and promoted cellular senescence caused by damaging agents. Our findings provide the first demonstration that SM22α modulates cellular senescence caused by damaging agents via regulation of the p16 INK4a /pRB pathway in HepG2 cells and that these effects of SM22α are partially mediated by MT-1G.

Frequent cellular phone use modifies hypothalamic-pituitary-adrenal axis response to a cellular phone call after mental stress in healthy children and adolescents: A pilot study.

Science.gov (United States)

Geronikolou, Styliani A; Chamakou, Aikaterini; Mantzou, Aimilia; Chrousos, George; KanakaGantenbein, Christina

2015-12-01

The hypothalamic-pituitary-adrenal (HPA) axis is the main "gate-keeper" of the organism's response to every somatic or mental stress. This prospective study aims to investigate the HPA-axis response to a cellular phone call exposure after mental stress in healthy children and adolescents and to assess the possible predictive role of baseline endocrine markers to this response. Two groups of healthy school-age children aged 11-14 (12.5±1.5) years were included in the study, the one comprising those who are occasional users of a cellular phone (Group A) while the second those who do regularly use one (Group B). Blood samples were obtained from all participants at 8.00 am after a 12-hour overnight fasting for thyroid hormone, glucose, insulin, and cortisol levels determination. The participants performed the Trier Social Stress Test for Children (TSST-C) (5 minoral task followed by 5 min arithmetic task). Salivary cortisol samples were obtained at baseline, 10' and 20' min after the TSST-C and 10' and 20' after a 5 minute cellular phone call. Significant changes in the salivary cortisol levels were noted between 10' and 20' mins after the cellular phone call with different responses between the two groups. Baseline thyroid hormone levels seem to predict the cortisol response to mental stress mainly in group A, while HOMA had no impact on salivary cortisol response at any phase of the test, in either group. HPA axis response to cellular phone after mental stress in children and adolescents follow a different pattern in frequent users than in occasional users that seems to be influenced by the baseline thyroid hormone levels. Copyright © 2015 Elsevier B.V. All rights reserved.

The Study Of Properties Of The Word Of Mouth Marketing Using Cellular Automata

Directory of Open Access Journals (Sweden)

Kowalska-Styczeń Agnieszka

2014-02-01

Full Text Available This article presents the possibility of using cellular automata, to study the properties of word of mouth (w-o-m marketing. Cellular automata allow to analyze the dynamics of changes in views and attitudes in social groups based on local interactions between people in small groups of friends, family members etc. The proposed paper shows the possibility of modelling the dynamics of word of mouth mechanism, if the basic assumptions of this process are: different size groups where this phenomenon occurs, and varied access to information. On the competing firms market, the dependence of the w-o-m mechanism dynamics on the model parameters is shown

Hyperglycemia- and hyperinsulinemia-induced insulin resistance causes alterations in cellular bioenergetics and activation of inflammatory signaling in lymphatic muscle.

Science.gov (United States)

Lee, Yang; Fluckey, James D; Chakraborty, Sanjukta; Muthuchamy, Mariappan

2017-07-01

Insulin resistance is a well-known risk factor for obesity, metabolic syndrome (MetSyn) and associated cardiovascular diseases, but its mechanisms are undefined in the lymphatics. Mesenteric lymphatic vessels from MetSyn or LPS-injected rats exhibited impaired intrinsic contractile activity and associated inflammatory changes. Hence, we hypothesized that insulin resistance in lymphatic muscle cells (LMCs) affects cell bioenergetics and signaling pathways that consequently alter contractility. LMCs were treated with different concentrations of insulin or glucose or both at various time points to determine insulin resistance. Onset of insulin resistance significantly impaired glucose uptake, mitochondrial function, oxygen consumption rates, glycolysis, lactic acid, and ATP production in LMCs. Hyperglycemia and hyperinsulinemia also impaired the PI3K/Akt while enhancing the ERK/p38MAPK/JNK pathways in LMCs. Increased NF-κB nuclear translocation and macrophage chemoattractant protein-1 and VCAM-1 levels in insulin-resistant LMCs indicated activation of inflammatory mechanisms. In addition, increased phosphorylation of myosin light chain-20, a key regulator of lymphatic muscle contraction, was observed in insulin-resistant LMCs. Therefore, our data elucidate the mechanisms of insulin resistance in LMCs and provide the first evidence that hyperglycemia and hyperinsulinemia promote insulin resistance and impair lymphatic contractile status by reducing glucose uptake, altering cellular metabolic pathways, and activating inflammatory signaling cascades.-Lee, Y., Fluckey, J. D., Chakraborty, S., Muthuchamy, M. Hyperglycemia- and hyperinsulinemia-induced insulin resistance causes alterations in cellular bioenergetics and activation of inflammatory signaling in lymphatic muscle. © FASEB.

Progress of research on activation function of NK cell exposed to low dose radiation in adoptive cellular immunotherapy

International Nuclear Information System (INIS)

Pan Xiaosong; Shi Yujia; Yao Yimin; Xu Hong; Liu Fenju

2009-01-01

Natural killer cells is an important immunological factor in killing malignant cells. Low dose radiation can enhance proliferation and biological activity of NK cell. The involvement of P38MAPK signal pathway and endogenous glutathione induced by LDR may be the probable mechanism. Natural killer cell, especially adherent natural killer cell, is the preferential choice for adoptive cellular immunotherapy, which has a remarkable foreground in malignancy therapy.(authors)

The Effects Radiation on Cellular Components of the Immune

International Nuclear Information System (INIS)

Zubaidah-Alatas

2001-01-01

The immune system describes the body's ability to defend itself against various foreign intruders named as antigens by calling on an immune mechanism. Antigens penetration into body activate the body's immune system that may be humoral response, cellular response, or both. The immune response is primarily mediated by two cell types, lymphocyte and macrophage. This paper will discuss the cellular component of immune system and the radiation effects on various cells involved in system. Moreover, the effects of radiation on humoral and cellular responses and the relation among immunity, cancer and radiotherapy are also described. (author)

Insecticidal activity of the metalloprotease AprA occurs through suppression of host cellular and humoral immunity.

Science.gov (United States)

Lee, Seung Ah; Jang, Seong Han; Kim, Byung Hyun; Shibata, Toshio; Yoo, Jinwook; Jung, Yunjin; Kawabata, Shun-Ichiro; Lee, Bok Luel

2018-04-01

The biochemical characterization of virulence factors from entomopathogenic bacteria is important to understand entomopathogen-insect molecular interactions. Pseudomonas entomophila is a typical entomopathogenic bacterium that harbors virulence factors against several insects. However, the molecular actions of these factors against host innate immune responses are not clearly elucidated. In this study, we observed that bean bugs (Riptortus pedestris) that were injected with P. entomophila were highly susceptible to this bacterium. To determine how P. entomophila counteracts the host innate immunity to survive within the insect, we purified a highly enriched protein with potential host insect-killing activity from the culture supernatant of P. entomophila. Then, a 45-kDa protein was purified to homogeneity and identified as AprA which is an alkaline zinc metalloprotease of the genus Pseudomonas by liquid chromatography mass spectrometry (LC-MS). Purified AprA showed a pronounced killing effect against host insects and suppressed both host cellular and humoral innate immunity. Furthermore, to show that AprA is an important insecticidal protein of P. entomophila, we used an aprA-deficient P. entomophila mutant strain (ΔaprA). When ΔaprA mutant cells were injected to host insects, this mutant exhibited extremely attenuated virulence. In addition, the cytotoxicity against host hemocytes and the antimicrobial peptide-degrading ability of the ΔaprA mutant were greatly decreased. These findings suggest that AprA functions as an important insecticidal protein of P. entomophila via suppression of host cellular and humoral innate immune responses. Copyright © 2017 Elsevier Ltd. All rights reserved.

Programmed cellular response to ionizing radiation damage

International Nuclear Information System (INIS)

Crompton, N.E.A.

1998-01-01

Three forms of radiation response were investigated to evaluate the hypothesis that cellular radiation response is the result of active molecular signaling and not simply a passive physicochemical process. The decision whether or not a cell should respond to radiation-induced damage either by induction of rescue systems, e.g. mobilization of repair proteins, or induction of suicide mechanisms, e.g. programmed cell death, appears to be the expression of intricate cellular biochemistry. A cell must recognize damage in its genetic material and then activate the appropriate responses. Cell type is important; the response of a fibroblast to radiation damage is both quantitatively and qualitatively different form that of a lymphocyte. The programmed component of radiation response is significant in radiation oncology and predicted to create unique opportunities for enhanced treatment success. (orig.)

Adsorption of cellular peptides of Microcystis aeruginosa and two herbicides onto activated carbon. Effect of surface charge and interactions

Czech Academy of Sciences Publication Activity Database

Hnaťuková, Petra; Kopecká, Ivana; Pivokonský, Martin

2011-01-01

Roč. 45, č. 11 (2011), s. 3359-3368 ISSN 0043-1354 R&D Projects: GA AV ČR IAA200600902; GA ČR GPP105/10/P515 Institutional research plan: CEZ:AV0Z20600510 Keywords : cellular organic matter * granular activated carbon * molecular weight distribution * surface charge * cyanobacterial peptides Subject RIV: BK - Fluid Dynamics Impact factor: 4.865, year: 2011

Study of rare-gas dimer ions by the variational cellular method

International Nuclear Information System (INIS)

Wentzcovitch, R.M.M.

1982-01-01

The Variational Cellular Method to study ionized molecules in their ground and excited states with the scope of testing the validity of such method in these cases have been used. The ions studied are Ne +2 , Ar +2 , where the latter is the system with the largest number of electrons tested by VCM so far. The electronic transitions in these systems are important mechanisms of efficiency decay for the noble gas halide lasers ('excimer lasers'). (Author) [pt

Chemical constituents of Hericium erinaceum associated with the inhibitory activity against cellular senescence in human umbilical vascular endothelial cells.

Science.gov (United States)

Noh, Hyung Jun; Yang, Hyo Hyun; Kim, Geum Soog; Lee, Seung Eun; Lee, Dae Young; Choi, Je Hun; Kim, Seung Yu; Lee, Eun Suk; Ji, Seung Heon; Kang, Ki Sung; Park, Hye-Jin; Kim, Jae-Ryong; Kim, Ki Hyun

2015-12-01

Hericium erinaceum is an edible and medicinal mushroom widely used in Korea, Japan, and China. On the search for biologically active compounds supporting the medicinal usage, the MeOH extract of the fruiting bodies of H. erinaceum was investigated for its chemical constituents. Six compounds were isolated and identified as hericenone D (1), (22E,24R)-5α,8α-epidioxyergosta-6,22-dien-3β-ol (2), erinacerin B (3), hericenone E (4), hericenone F (5) and isohericerin (6) by comparing their spectroscopic data with previously reported values. The inhibitory effects on adriamycin-induced cellular senescence in human dermal fibroblasts (HDFs) and human umbilical vein endothelial cells (HUVECs) of the isolates (1-6) were studied. Among the isolated compounds, ergosterol peroxide (2) reduced senescence associated β-galactosidase (SA-β-gal) activity increased in HUVECs treated with adriamycin. According to experimental data obtained, the active compound may inspire the development of a new pharmacologically useful substance to be used in the treatment and prevention of age-related diseases.

Rearrangement of Upstream Sequences of the hTERT Gene During Cellular Immortalization

Science.gov (United States)

Zhao, Yuanjun; Wang, Shuwen; Popova, Evgenya Y.; Grigoryev, Sergei A.; Zhu, Jiyue

2010-01-01

Telomerase expression, resulting from transcriptional activation of the hTERT gene, allows cells to acquire indefinite proliferative potential during cellular immortalization and tumorigenesis. However, mechanisms of hTERT gene activation in many immortal cell lines and cancer cells are poorly understood. Here, we report our studies on hTERT activation using genetically related pairs of telomerase-negative (Tel−) and -positive (Tel+) fibroblast lines. First, whereas transiently transfected plasmid reporters did not recapitulate the endogenous hTERT promoter, the promoter in chromosomally integrated bacterial artificial chromosome (BAC) reporters was activated in a subset of Tel+ cells, indicating that activation of the hTERT promoter required native chromatin context and/or distal regulatory elements. Second, the hTERT gene, located near the telomere of chromosome 5p, was translocated in all three Tel+ cell lines but not in their parental pre-crisis cells and Tel− immortal siblings. The breakage points were mapped to regions upstream of the hTERT promoter, indicating that the hTERT gene was the target of these chromosomal rearrangements. In two Tel+ cell lines, translocation of the endogenous hTERT gene appeared to be the major mechanism of its activation as the activity of hTERT promoter in many chromosomally integrated BAC reporters, with intact upstream and downstream neighboring loci, remained relatively low. Therefore, our results suggest that rearrangement of upstream sequences is an important new mechanism of hTERT promoter activation during cellular immortalization. The chromosomal rearrangements likely occurred during cellular crisis and facilitated by telomere dysfunction. Such translocations allowed the hTERT promoter to escape from the native condensed chromatin environment. PMID:19672873

Cellular Promyelocytic Leukemia Protein Is an Important Dengue Virus Restriction Factor

OpenAIRE

Giovannoni, Federico; Damonte, Elsa B.; Garc?a, Cybele C.

2015-01-01

The intrinsic antiviral defense is based on cellular restriction factors that are constitutively expressed and, thus, active even before a pathogen enters the cell. The promyelocytic leukemia (PML) nuclear bodies (NBs) are discrete nuclear foci that contain several cellular proteins involved in intrinsic antiviral responses against a number of viruses. Accumulating reports have shown the importance of PML as a DNA virus restriction factor and how these pathogens evade this antiviral activity....

A study of the biological effects of rare earth elements at cellular level using nuclear techniques

International Nuclear Information System (INIS)

Feng Zhihui; Wang Xi; Zhang Sunxi; An Lizhi; Zhang Jingxia; Yao Huiying

2001-01-01

Objective: To investigate the biological effects and the effecting mechanisms of rare earth elements La, Gd and Ce on cultured rat cells. Methods: The biological effects of La 3+ on cultured rat cells and the subcellular distribution of La and Gd and Ce, and the inflow of 45 Ca 2+ into the cells and total cellular calcium were measured by isotopic tracing, Proton Induced X Ray Emission Analysis (PIXE) and the techniques of biochemistry and cellular biology. Results: La 3+ at the concentration of 10- 10( or 10 -9 ) - 10 -6 mol/L significantly increased quantity of incorporation of 3 H-TdR into DNA, total cellular protein and the activity of succinic dehydrogenase of mitochondria. The cell cycle analysis showed that the proportions of cells in S phase were accordingly increased acted by La 3+ at above range of concentration. But these values were significantly decreased when concentration of La 3+ raised to 10 -4 - 10 -3 mol/L. It was further discovered that La, Gd and Ce distributed mostly in the nuclei, and then in membranes. Gd and Ce also promoted the inflow of 45 Ca 2+ into the cells and increased the total calcium content in cells. Conclusions: 1) La 3+ at a wide concentration range of 10 -10 ( or 10 -9 ) - 10 -6 mol/L promotes proliferation of cultured rat cells, but at even higher concentration (10 -4 - 10 -3 mol/L) shows cellular toxicity, and there is a striking dose-effect relationship. 2) La, Gd and Ce can enter the cells and mainly distribute in the nuclei. 3) Gd and Ce can promote the inflow of extracellular Ca 2+ into the cells and increase total cellular calcium

High-speed atomic force microscopy combined with inverted optical microscopy for studying cellular events.

Science.gov (United States)

Suzuki, Yuki; Sakai, Nobuaki; Yoshida, Aiko; Uekusa, Yoshitsugu; Yagi, Akira; Imaoka, Yuka; Ito, Shuichi; Karaki, Koichi; Takeyasu, Kunio

2013-01-01

A hybrid atomic force microscopy (AFM)-optical fluorescence microscopy is a powerful tool for investigating cellular morphologies and events. However, the slow data acquisition rates of the conventional AFM unit of the hybrid system limit the visualization of structural changes during cellular events. Therefore, high-speed AFM units equipped with an optical/fluorescence detection device have been a long-standing wish. Here we describe the implementation of high-speed AFM coupled with an optical fluorescence microscope. This was accomplished by developing a tip-scanning system, instead of a sample-scanning system, which operates on an inverted optical microscope. This novel device enabled the acquisition of high-speed AFM images of morphological changes in individual cells. Using this instrument, we conducted structural studies of living HeLa and 3T3 fibroblast cell surfaces. The improved time resolution allowed us to image dynamic cellular events.

Study on cellular survival adaptive response induced by low dose irradiation of 153Sm

International Nuclear Information System (INIS)

Zhu Shoupeng; Xiao Dong

1999-01-01

The present study engages in determining whether low dose irradiation of 153 Sm could cut down the responsiveness of cellular survival to subsequent high dose exposure of 153 Sm so as to make an inquiry into approach the protective action of adaptive response by second irradiation of 153 Sm. Experimental results indicate that for inductive low dose of radionuclide 153 Sm 3.7 kBq/ml irradiated beforehand to cells has obvious resistant effect in succession after high dose irradiation of 153 Sm 3.7 x 10 2 kBq/ml was observed. Cells exposed to low dose irradiation of 153 Sm become adapted and therefore the subsequent cellular survival rate induced by high dose of 153 Sm is sufficiently higher than high dose of 153 Sm merely. It is evident that cellular survival adaptive response could be induced by pure low dose irradiation of 153 Sm only

Cellular targets of inhalational anaesthetic- and opioid receptor ...

African Journals Online (AJOL)

Secondly, the cardioprotective effects occur independently of the ... cardioprotection take place and highlights the cellular ... Activation of sarcolemmal KATP channels hyperpolarizes cells, ..... respiration and its supramolecular organization.

Cellular Phone Use in Class: Implications for Teaching and Learning a Pilot Study

Science.gov (United States)

Burns, Shari M.; Lohenry, Kevin

2010-01-01

Students equipped with the cell phones enter college classrooms daily. Realizing the impact of technology on fellow learners and faculty represents an area of concern. A pilot study was conducted to determine student and faculty perception regarding cellular phone use in the classroom. A quantitative descriptive study examined the perception of…

Cellular size as a means of tracking mTOR activity and cell fate of CD4+ T cells upon antigen recognition.

Directory of Open Access Journals (Sweden)

Kristen N Pollizzi

Full Text Available mTOR is a central integrator of metabolic and immunological stimuli, dictating immune cell activation, proliferation and differentiation. In this study, we demonstrate that within a clonal population of activated T cells, there exist both mTORhi and mTORlo cells exhibiting highly divergent metabolic and immunologic functions. By taking advantage of the role of mTOR activation in controlling cellular size, we demonstrate that upon antigen recognition, mTORhi CD4+ T cells are destined to become highly glycolytic effector cells. Conversely, mTORlo T cells preferentially develop into long-lived cells that express high levels of Bcl-2, CD25, and CD62L. Furthermore, mTORlo T cells have a greater propensity to differentiate into suppressive Foxp3+ T regulatory cells, and this paradigm was also observed in human CD4+ T cells. Overall, these studies provide the opportunity to track the development of effector and memory T cells from naïve precursors, as well as facilitate the interrogation of immunologic and metabolic programs that inform these fates.

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...

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

Science.gov (United States)

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

SM22{alpha}-induced activation of p16{sup INK4a}/retinoblastoma pathway promotes cellular senescence caused by a subclinical dose of {gamma}-radiation and doxorubicin in HepG2 cells

Energy Technology Data Exchange (ETDEWEB)

Kim, Tae Rim; Lee, Hee Min; Lee, So Yong; Kim, Eun Jin; Kim, Kug Chan [Department of Radiation Biology, Environmental Radiation Research Group, Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of); Paik, Sang Gi [Department of Biology, School of Biosciences and Biotechnology, Chungnam National University, Daejeon (Korea, Republic of); Cho, Eun Wie, E-mail: ewcho@kribb.re.kr [Daejeon-KRIBB-FHCRC Cooperation Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon (Korea, Republic of); Kim, In Gyu, E-mail: igkim@kaeri.re.kr [Department of Radiation Biology, Environmental Radiation Research Group, Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

2010-09-10

Research highlights: {yields} SM22{alpha} overexpression in HepG2 cells leads cells to a growth arrest state, and the treatment of a subclinical dose of {gamma}-radiation or doxorubicin promotes cellular senescence. {yields} SM22{alpha} overexpression elevates p16{sup INK4a} followed by pRB activation, but there are no effects on p53/p21{sup WAF1/Cip1} pathway. {yields} SM22{alpha}-induced MT-1G activates p16{sup INK4a}/pRB pathway, which promotes cellular senescence by damaging agents. -- Abstract: Smooth muscle protein 22-alpha (SM22{alpha}) is known as a transformation- and shape change-sensitive actin cross-linking protein found in smooth muscle tissue and fibroblasts; however, its functional role remains uncertain. We reported previously that SM22{alpha} overexpression confers resistance against anti-cancer drugs or radiation via induction of metallothionein (MT) isozymes in HepG2 cells. In this study, we demonstrate that SM22{alpha} overexpression leads cells to a growth arrest state and promotes cellular senescence caused by treatment with a subclinical dose of {gamma}-radiation (0.05 and 0.1 Gy) or doxorubicin (0.01 and 0.05 {mu}g/ml), compared to control cells. Senescence growth arrest is known to be controlled by p53 phosphorylation/p21{sup WAF1/Cip1} induction or p16{sup INK4a}/retinoblastoma protein (pRB) activation. SM22{alpha} overexpression in HepG2 cells elevated p16{sup INK4a} followed by pRB activation, but did not activate the p53/p21{sup WAF1/Cip1} pathway. Moreover, MT-1G, which is induced by SM22{alpha} overexpression, was involved in the activation of the p16{sup INK4a}/pRB pathway, which led to a growth arrest state and promoted cellular senescence caused by damaging agents. Our findings provide the first demonstration that SM22{alpha} modulates cellular senescence caused by damaging agents via regulation of the p16{sup INK4a}/pRB pathway in HepG2 cells and that these effects of SM22{alpha} are partially mediated by MT-1G.

Arylamine N-acetyltransferase activity in bronchial epithelial cells and its inhibition by cellular oxidants

International Nuclear Information System (INIS)

Dairou, Julien; Petit, Emile; Ragunathan, Nilusha; Baeza-Squiban, Armelle; Marano, Francelyne; Dupret, Jean-Marie; Rodrigues-Lima, Fernando

2009-01-01

Bronchial epithelial cells express xenobiotic-metabolizing enzymes (XMEs) that are involved in the biotransformation of inhaled toxic compounds. The activities of these XMEs in the lung may modulate respiratory toxicity and have been linked to several diseases of the airways. Arylamine N-acetyltransferases (NAT) are conjugating XMEs that play a key role in the biotransformation of aromatic amine pollutants such as the tobacco-smoke carcinogens 4-aminobiphenyl (4-ABP) and β-naphthylamine (β-NA). We show here that functional human NAT1 or its murine counterpart Nat2 are present in different lung epithelial cells i.e. Clara cells, type II alveolar cells and bronchial epithelial cells, thus indicating that inhaled aromatic amines may undergo NAT-dependent biotransformation in lung epithelium. Exposure of these cells to pathophysiologically relevant amounts of oxidants known to contribute to lung dysfunction, such as H 2 O 2 or peroxynitrite, was found to impair the NAT1/Nat2-dependent cellular biotransformation of aromatic amines. Genetic and non genetic impairment of intracellular NAT enzyme activities has been suggested to compromise the important detoxification pathway of aromatic amine N-acetylation and subsequently to contribute to an exacerbation of untoward effects of these pollutants on health. Our study suggests that oxidative/nitroxidative stress in lung epithelial cells, due to air pollution and/or inflammation, could contribute to local and/or systemic dysfunctions through the alteration of the functions of pulmonary NAT enzymes.

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...

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

Science.gov (United States)

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.

Poloxamer-Based Thermoreversible Gel for Topical Delivery of Emodin: Influence of P407 and P188 on Solubility of Emodin and Its Application in Cellular Activity Screening

Directory of Open Access Journals (Sweden)

Eunmi Ban

2017-02-01

Full Text Available Emodin is a component in a Chinese herb, Rheum officinale Baill, traditionally used for diabetes and anticancer. Its poor solubility is one of the major challenges to pharmaceutical scientists. We previously reported on thermoreversible gel formulations based on poloxamer for the topical delivery of emodin. The present study was to understand the effect of poloxamer type on emodin solubility and its application in cellular activity screening. Various gel formulations composed of poloxamer 407 (P407, poloxamer 188 (P188 and PEG400 were prepared and evaluated. Major evaluation parameters were the gelation temperature (Tgel and solubility of emodin. The emodin solubility increased with increasing poloxamer concentration and the Tgel was modulated by the proper combination of P407. In particular, this study showed that the amount of P407 in thermoreversible poloxamer gel (PG was the dominant factor in enhancing solubility and P188 was effective at fixing gelation temperature in the desired range. A thermoreversible emodin PG was selected as the proper composition with the liquid state at room temperature and gel state at body temperature. The gel showed the solubility enhancement of emodin at least 100-fold compared to 10% ethanol or water. The thermoreversible formulation was applied for in vitro cellular activity screening in the human dermal fibroblast cell line and DLD-1 colon cancer cell line after dilution with cell culture media. The thermoreversible gel formulation remained as a clear solution in the microplate, which allowed reliable cellular activity screening. In contrast, emodin solution in ethanol or DMSO showed precipitation at the corresponding emodin concentration, complicating data interpretation. In conclusion, the gel formulation is proposed as a useful prototype topical formulation for testing emodin in vivo as well as in vitro.

Pathway towards Programmable Wave Anisotropy in Cellular Metamaterials

Science.gov (United States)

Celli, Paolo; Zhang, Weiting; Gonella, Stefano

2018-01-01

In this work, we provide a proof-of-concept experimental demonstration of the wave-control capabilities of cellular metamaterials endowed with populations of tunable electromechanical resonators. Each independently tunable resonator comprises a piezoelectric patch and a resistor-inductor shunt, and its resonant frequency can be seamlessly reprogrammed without interfering with the cellular structure's default properties. We show that, by strategically placing the resonators in the lattice domain and by deliberately activating only selected subsets of them, chosen to conform to the directional features of the beamed wave response, it is possible to override the inherent wave anisotropy of the cellular medium. The outcome is the establishment of tunable spatial patterns of energy distillation resulting in a nonsymmetric correction of the wave fields.

Study of spatially extended dynamical systems using probabilistic cellular automata

International Nuclear Information System (INIS)

Vanag, Vladimir K

1999-01-01

Spatially extended dynamical systems are ubiquitous and include such things as insect and animal populations; complex chemical, technological, and geochemical processes; humanity itself, and much more. It is clearly desirable to have a certain universal tool with which the highly complex behaviour of nonlinear dynamical systems can be analyzed and modelled. For this purpose, cellular automata seem to be good candidates. In the present review, emphasis is placed on the possibilities that various types of probabilistic cellular automata (PCA), such as DSMC (direct simulation Monte Carlo) and LGCA (lattice-gas cellular automata), offer. The methods are primarily designed for modelling spatially extended dynamical systems with inner fluctuations accounted for. For the Willamowskii-Roessler and Oregonator models, PCA applications to the following problems are illustrated: the effect of fluctuations on the dynamics of nonlinear systems; Turing structure formation; the effect of hydrodynamic modes on the behaviour of nonlinear chemical systems (stirring effects); bifurcation changes in the dynamical regimes of complex systems with restricted geometry or low spatial dimension; and the description of chemical systems in microemulsions. (reviews of topical problems)

Oxidative Damage and Cellular Defense Mechanisms in Sea Urchin Models of Aging

Science.gov (United States)

Du, Colin; Anderson, Arielle; Lortie, Mae; Parsons, Rachel; Bodnar, Andrea

2013-01-01

The free radical or oxidative stress theory of aging proposes that the accumulation of oxidative cellular damage is a major contributor to the aging process and a key determinant of species longevity. This study investigates the oxidative stress theory in a novel model for aging research, the sea urchin. Sea urchins present a unique model for the study of aging due to the existence of species with tremendously different natural life spans including some species with extraordinary longevity and negligible senescence. Cellular oxidative damage, antioxidant capacity and proteasome enzyme activities were measured in the tissues of three sea urchin species: short-lived Lytechinus variegatus, long-lived Strongylocentrotus franciscanus and Strongylocentrotus purpuratus which has an intermediate lifespan. Levels of protein carbonyls and 4-hydroxynonenal (HNE) measured in tissues (muscle, nerve, esophagus, gonad, coelomocytes, ampullae) and 8-hydroxy-2’-deoxyguanosine (8-OHdG) measured in cell-free coelomic fluid showed no general increase with age. The fluorescent age-pigment lipofuscin measured in muscle, nerve and esophagus, increased with age however it appeared to be predominantly extracellular. Antioxidant mechanisms (total antioxidant capacity, superoxide dismutase) and proteasome enzyme activities were maintained with age. In some instances, levels of oxidative damage were lower and antioxidant activity higher in cells or tissues of the long-lived species compared to the short-lived species, however further studies are required to determine the relationship between oxidative damage and longevity in these animals. Consistent with the predictions of the oxidative stress theory of aging, the results suggest that negligible senescence is accompanied by a lack of accumulation of cellular oxidative damage with age and maintenance of antioxidant capacity and proteasome enzyme activities may be important mechanisms to mitigate damage. PMID:23707327

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 ...

In vitro studies of cellular response to DNA damage induced by boron neutron capture therapy

International Nuclear Information System (INIS)

Perona, M.; Pontiggia, O.; Carpano, M.; Thomasz, L.; Thorp, S.; Pozzi, E.; Simian, M.; Kahl, S.; Juvenal, G.; Pisarev, M.; Dagrosa, A.

2011-01-01

The aim of these studies was to evaluate the mechanisms of cellular response to DNA damage induced by BNCT. Thyroid carcinoma cells were incubated with 10 BPA or 10 BOPP and irradiated with thermal neutrons. The surviving fraction, the cell cycle distribution and the expression of p53 and Ku70 were analyzed. Different cellular responses were observed for each irradiated group. The decrease of Ku70 in the neutrons +BOPP group could play a role in the increase of sensitization to radiation.

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

Genomic stability during cellular reprogramming: Mission impossible?

Energy Technology Data Exchange (ETDEWEB)

Joest, Mathieu von; Búa Aguín, Sabela; Li, Han, E-mail: han.li@pasteur.fr

2016-06-15

The generation of induced pluripotent stem cells (iPSCs) from adult somatic cells is one of the most exciting discoveries in recent biomedical research. It holds tremendous potential in drug discovery and regenerative medicine. However, a series of reports highlighting genomic instability in iPSCs raises concerns about their clinical application. Although the mechanisms cause genomic instability during cellular reprogramming are largely unknown, several potential sources have been suggested. This review summarizes current knowledge on this active research field and discusses the latest efforts to alleviate the genomic insults during cellular reprogramming to generate iPSCs with enhanced quality and safety.

Subjective Positive and Negative Sleep Variables Differentially Affect Cellular Immune Activity in a Breast Cancer Survivor: A Time-series Analysis Approach

Directory of Open Access Journals (Sweden)

Magdalena Singer

2018-01-01

Full Text Available This study on a breast cancer survivor suffering from cancer-related fatigue (CaRF and depression investigated the bidirectional relationship between cellular immune activity and subjective sleep. The 49-year-old patient (breast cancer diagnosis 5 years before the study, currently in remission collected her full urine output for 28 days in 12-h intervals (8:00 p.m. to 8:00 a.m. and 8:00 a.m. to 8:00 p.m.. These urine samples were used to determine urinary neopterin (cellular immune activation marker and creatinine concentrations via high-pressure liquid chromatography (HPLC. Each morning, the patient answered questions on five sleep variables: sleep quality (SQ, sleep recreational value (SRV, total sleep time (TST, total wake time (TWT, and awakenings during sleep period (ADS. For the purpose of this study, the time series of the nighttime urinary neopterin levels and the five sleep variables were determined. Using centered moving average (CMA smoothing and cross-correlational analysis, this study showed that increases in the positive sleep variables SQ and SRV were followed by urinary neopterin concentration decreases after 96–120 h (SQ, lag 4: r = −0.411; p = 0.044; SRV: lag 4: r = −0.472; p = 0.021 and 120–144 h (SRV, lag 5: r = −0.464; p = 0.026. Increases in the negative sleep variable TWT, by contrast, were followed by increases in urinary neopterin concentrations 72–96 h later (lag 3: r = 0.522; p = 0.009. No systematic effects in the other direction, i.e., from urinary neopterin levels to sleep, were observed in this study. Although preliminary, the findings of this study highlight the benefit of carefully investigating temporal delays and directions of effects when studying the dynamic relationship between sleep and immune variables in the natural context of everyday life.

Measurement of whole body cellular and collagen nitrogen, potassium, and other elements by neutron activation and whole body counting

International Nuclear Information System (INIS)

James, H.M.; Fabricius, P.J.; Dykes, P.W.

1987-01-01

Whole body nitrogen can be measured by neutron activation analysis with an acceptable radiation dose; it is an index of body protein which, in normal subjects, is 65% cellular protein and 35% extracellular connective collagen. Whole body potassium can be measured by whole body counting without irradiating the subject; it is an index of body cell mass. We measured whole body nitrogen, potassium, extracellular water, intracellular water, and fat-folds. The differences between 37 malnourished patients and five normal subjects suggested that the patients had 9 kg less cell mass than normal, but no difference in extracellular mass. Measurements were made on eight patients before and after 14 days of total parenteral nutrition; balance of nitrogen intake and excretion also was measured. The changes were consistent with mean increases of 3 kg of cellular mass and 3 kg of fat with no change of extracellular mass. The accuracy and sensitivity of the whole body measurements need further confirmation for use in patients with changing body composition. Where tissue wasting is largely from the cellular compartment, potassium could be a more sensitive index of wasting than nitrogen. Multielement analysis of nitrogen, potassium, chlorine, and carbon will probably be valuable in elucidating body composition in malnutrition

Health and Cellular Impacts of Air Pollutants: From Cytoprotection to Cytotoxicity

Directory of Open Access Journals (Sweden)

Karine Andreau

2012-01-01

Full Text Available Air pollution as one of the ravages of our modern societies is primarily linked to urban centers, industrial activities, or road traffic. These atmospheric pollutants have been incriminated in deleterious health effects by numerous epidemiological and in vitro studies. Environmental air pollutants are a heterogeneous mixture of particles suspended into a liquid and gaseous phase which trigger the disruption of redox homeostasis—known under the term of cellular oxidative stress—in relation with the establishment of inflammation and cell death via necrosis, apoptosis, or autophagy. Activation or repression of the apoptotic process as an adaptative response to xenobiotics might lead to either acute or chronic toxicity. The purpose of this paper is to highlight the central role of oxidative stress induced by air pollutants and to focus on the subsequent cellular impacts ranging from cytoprotection to cytotoxicity by decreasing or stimulating apoptosis, respectively.

Cellular and Molecular Pathways Leading to External Root Resorption

Science.gov (United States)

Iglesias-Linares, A.; Hartsfield, J.K.

2016-01-01

External apical root resorption during orthodontic treatment implicates specific molecular pathways that orchestrate nonphysiologic cellular activation. To date, a substantial number of in vitro and in vivo molecular, genomic, and proteomic studies have supplied data that provide new insights into root resorption. Recent mechanisms and developments reviewed here include the role of the cellular component—specifically, the balance of CD68+, iNOS+ M1- and CD68+, CD163+ M2-like macrophages associated with root resorption and root surface repair processes linked to the expression of the M1-associated proinflammatory cytokine tumor necrosis factor, inducible nitric oxide synthase, the M1 activator interferon γ, the M2 activator interleukin 4, and M2-associated anti-inflammatory interleukin 10 and arginase I. Insights into the role of mesenchymal dental pulp cells in attenuating dentin resorption in homeostasis are also reviewed. Data on recently deciphered molecular pathways are reviewed at the level of (1) clastic cell adhesion in the external apical root resorption process and the specific role of α/β integrins, osteopontin, and related extracellular matrix proteins; (2) clastic cell fusion and activation by the RANKL/RANK/OPG and ATP-P2RX7-IL1 pathways; and (3) regulatory mechanisms of root resorption repair by cementum at the proteomic and transcriptomic levels. PMID:27811065

Ionizing Radiation Induces Cellular Senescence of Articular Chondrocytes via Negative Regulation of SIRT1 by p38 Kinase

Energy Technology Data Exchange (ETDEWEB)

Hong, Eun Hee; Hwang, Sang Gu [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

2009-05-15

Senescent cells exhibit irreversible growth arrest, large flat morphology, and up-regulated senescence-associated {beta}-galactosidase activity at pH 6.0. Several conditions, including oncogenic stress, oxidative stress, and DNA damage are associated with cellular senescence. Massive acute DNA double-strand breaks occurring as a result of mechanical and chemical stress can be repaired, but some DNA damage persists, eventually triggering premature senescence. Since ionizing radiation directly induces DBS, it is possible that cellular senescence is activated under these conditions. The biological events in chondrocytes following irradiation are poorly understood, and limited information is available on the molecular signal transduction mechanisms of cellular senescence at present. In this study, we identify SIRT1 as a target molecule of p38 kinase and demonstrate that the interactions between p38 kinase and SIRT1 protein play an important role in the regulation of cellular senescence in response to IR.

Assessment of radiofrequency exposure from cellular telephone daily use in an epidemiological study: German Validation study of the international case-control study of cancers of the brain--INTERPHONE-Study.

Science.gov (United States)

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

2005-05-01

The objective of the study is to validate self-reported cellular phone use information by comparing it with the cumulative emitted power and duration of calls measured by software-modified cellular phones (SMP). The information was obtained using a questionnaire developed for the international case-control study on the risk of the use of mobile phones in tumours of the brain or salivary gland (INTERPHONE-study). The study was conducted in Bielefeld, Germany. Volunteers were asked to use SMPs instead of their own cellular phones for a period of 1 month. The SMP recorded the power emitted by the mobile phone handset during each base station contact. Information on cellular phone use for the same time period from traffic records of the network providers and from face-to-face interviews with the participants 3 months after the SMP use was assessed. Pearson's correlation coefficients and linear regression models were used to analyse the association between information from the interview and from the SMP. In total, 1757 personal mobile phone calls were recorded for 45 persons by SMP and traffic records. The correlation between the self-reported information about the number and the duration of calls with the cumulative power of calls was 0.50 (P<0.01) and 0.48 (P<0.01), respectively. Almost 23% of the variance of the cumulative power was explained by either the number or the cumulative duration of calls. After inclusion of possible confounding factors in the regression model, the variance increased to 26%. Minor confounding factors were "network provider", "contract form", and "cellular phone model". The number of calls alone is a sufficient parameter to estimate the cumulative power emitted by the handset of a cellular telephone. The cumulative power emitted by these phones is only associated with number of calls but not with possible confounding factors. Using the mobile phone while driving, mainly in cities, or mainly in rural areas is not associated with the recorded

Repair and mutagenesis in procaryotes as cellular responses to ambiental agents

International Nuclear Information System (INIS)

Gomes, R.A.

1982-01-01

The correct and incorrect mechanisms of DNA repair are discussed, as well as the cellular responses induced by the DNA lesions; the reductone mollecular effects; the cellular interactions among irradiated populations of microorganisms and the utilization of microbial assays for the detection of oncogenic activities of chemicals. (M.A.) [pt

Cytokine modulation by glucocorticoids: mechanisms and actions in cellular studies.

Science.gov (United States)

Brattsand, R; Linden, M

1996-01-01

cascades, this means that steroid treatment can block expression of the subsequent cytokines. The blocked cytokine activity does not depend on a reduced cytokine receptor expression; in fact available in vitro investigations show that while the cytokine expression is blunted, its receptor is upregulated. The cellular studies presented here may represent the maximum potential of steroids to modulate cytokine expression in human mononuclear cells. It remains to be determined by clinical-experimental studies how effective cytokine modulation can be achieved in situ in inflamed bowel by systemic or by topical steroid therapy. Such studies may also answer whether a blocked cytokine production/action is the key or just a secondary mechanism behind the unique efficacy of steroids in active inflammatory bowel disease.

A cellular model to study drug-induced liver injury in nonalcoholic fatty liver disease: Application to acetaminophen

Energy Technology Data Exchange (ETDEWEB)

Michaut, Anaïs; Le Guillou, Dounia [INSERM, U991, Université de Rennes 1, Rennes (France); Moreau, Caroline [INSERM, U991, Université de Rennes 1, Rennes (France); Service de Biochimie et Toxicologie, CHU Pontchaillou, Rennes (France); Bucher, Simon [INSERM, U991, Université de Rennes 1, Rennes (France); McGill, Mitchell R. [Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States); Martinais, Sophie [INSERM, U991, Université de Rennes 1, Rennes (France); Gicquel, Thomas; Morel, Isabelle [INSERM, U991, Université de Rennes 1, Rennes (France); Service de Biochimie et Toxicologie, CHU Pontchaillou, Rennes (France); Robin, Marie-Anne [INSERM, U991, Université de Rennes 1, Rennes (France); Jaeschke, Hartmut [Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States); Fromenty, Bernard, E-mail: bernard.fromenty@inserm.fr [INSERM, U991, Université de Rennes 1, Rennes (France)

2016-02-01

Obesity and nonalcoholic fatty liver disease (NAFLD) can increase susceptibility to hepatotoxicity induced by some xenobiotics including drugs, but the involved mechanisms are poorly understood. For acetaminophen (APAP), a role of hepatic cytochrome P450 2E1 (CYP2E1) is suspected since the activity of this enzyme is consistently enhanced during NAFLD. The first aim of our study was to set up a cellular model of NAFLD characterized not only by triglyceride accumulation but also by higher CYP2E1 activity. To this end, human HepaRG cells were incubated for one week with stearic acid or oleic acid, in the presence of different concentrations of insulin. Although cellular triglycerides and the expression of lipid-responsive genes were similar with both fatty acids, CYP2E1 activity was significantly increased only by stearic acid. CYP2E1 activity was reduced by insulin and this effect was reproduced in cultured primary human hepatocytes. Next, APAP cytotoxicity was assessed in HepaRG cells with or without lipid accretion and CYP2E1 induction. Experiments with a large range of APAP concentrations showed that the loss of ATP and glutathione was almost always greater in the presence of stearic acid. In cells pretreated with the CYP2E1 inhibitor chlormethiazole, recovery of ATP was significantly higher in the presence of stearate with low (2.5 mM) or high (20 mM) concentrations of APAP. Levels of APAP-glucuronide were significantly enhanced by insulin. Hence, HepaRG cells can be used as a valuable model of NAFLD to unveil important metabolic and hormonal factors which can increase susceptibility to drug-induced hepatotoxicity. - Highlights: • Nonalcoholic fatty liver disease (NAFLD) is frequent in obese individuals. • NAFLD can favor hepatotoxicity induced by some drugs including acetaminophen (APAP). • A model of NAFLD was set up by using HepaRG cells incubated with stearate or oleate. • Stearate-loaded HepaRG cells presented higher cytochrome P450 2E1 (CYP2E1

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

The Effect of a p38 Mitogen-Activated Protein Kinase Inhibitor on Cellular Senescence of Cultivated Human Corneal Endothelial Cells.

Science.gov (United States)

Hongo, Akane; Okumura, Naoki; Nakahara, Makiko; Kay, EunDuck P; Koizumi, Noriko

2017-07-01

We have begun a clinical trial of a cell-based therapy for corneal endothelial dysfunction in Japan. The purpose of this study was to investigate the usefulness of a p38 MAPK inhibitor for prevention cellular senescence in cultivated human corneal endothelial cells (HCECs). HCECs of 10 donor corneas were divided and cultured with or without SB203580 (a p38 MAPK inhibitor). Cell density and morphology were evaluated by phase-contrast microscopy. Expression of function-related proteins was examined by immunofluorescent staining. Cellular senescence was evaluated by SA-β-gal staining and Western blotting for p16 and p21. Senescence-associated factors were evaluated by membrane blotting array, quantitative PCR, and ELISA. Phase-contrast microscopy showed a significantly higher cell density for HCECs cultured with SB203580 than without SB203580 (2623 ± 657 cells/mm2 and 1752 ± 628 cells/mm2, respectively). The HCECs cultured with SB203580 maintained a hexagonal morphology and expressed ZO-1, N-cadherin, and Na+/K+-ATPase in the plasma membrane, whereas the control HCECs showed an altered staining pattern for these marker proteins. HCECs cultured without SB203580 showed high positive SA-β-gal staining, a low nuclear/cytoplasm ratio, and expression of p16 and p21. IL-6, IL-8, CCL2, and CXCL1 were observed at high levels in low cell density HCECs cultured without SB203580. Activation of p38 MAPK signaling due to culture stress might be a causative factor that induces cellular senescence; therefore, the use of p38 MAPK inhibitor to counteract senescence may achieve sufficient numbers of HCECs for tissue engineering therapy for corneal endothelial dysfunction.

Digital and traditional slides for teaching cellular morphology: a comparative analysis of learning outcomes.

Science.gov (United States)

Solberg, Brooke L

2012-01-01

Recent advances in technology have brought forth an intriguing new tool for teaching hematopoietic cellular identification skills: the digital slide. Although digitized slides offer a number of appealing options for educators, little research has been done to examine how their utilization would impact learning outcomes. To fill that void, this study was designed to examine student performance, skill retention and transferability, and self-efficacy beliefs amongst undergraduate MLS students learning cellular morphology with digital versus traditional slides. Results showed that students learning with digital slides performed better on assessments containing only traditional slide specimens than students learning with traditional slides, both immediately following the learning activity and after a considerable duration of time. Students learning with digital slides also reported slightly higher levels of self-efficacy related to cellular identification. The findings of this study suggest that students learning cellular identification skills with digital slides are able to transfer that skill directly to traditional slides, and that their ability to identify cells is not negatively affected in present or future settings.

The MAP kinase-activated protein kinase Rck2p regulates cellular responses to cell wall stresses, filamentation and virulence in the human fungal pathogen Candida albicans.

Science.gov (United States)

Li, Xichuan; Du, Wei; Zhao, Jingwen; Zhang, Lilin; Zhu, Zhiyan; Jiang, Linghuo

2010-06-01

Rck2p is the Hog1p-MAP kinase-activated protein kinase required for the attenuation of protein synthesis in response to an osmotic challenge in Saccharomyces cerevisiae. Rck2p also regulates rapamycin sensitivity in both S. cerevisiae and Candida albicans. In this study, we demonstrate that the deletion of CaRCK2 renders C. albicans cells sensitive to, and CaRck2p translocates from the cytosol to the nucleus in response to, cell wall stresses caused by Congo red, Calcoflor White, elevated heat and zymolyase. However, the kinase activity of CaRck2p is not required for the cellular response to these cell wall stresses. Furthermore, transcripts of cell wall protein-encoding genes CaBGL2, CaHWP1 and CaXOG1 are reduced in C. albicans cells lacking CaRCK2. The deletion of CaRCK2 also reduces the in vitro filamentation of C. albicans and its virulence in a mouse model of systemic candidasis. The kinase activity of CaRck2p is required for the virulence, but not for the in vitro filamentation, in C. albicans. Therefore, Rck2p regulates cellular responses to cell wall stresses, filamentation and virulence in the human fungal pathogen C. albicans.

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.

Silymarin Suppresses Cellular Inflammation By Inducing Reparative Stress Signaling

Energy Technology Data Exchange (ETDEWEB)

Lovelace, Erica S.; Wagoner, Jessica; MacDonald, James; Bammler, Theo; Bruckner, Jacob; Brownell, Jessica; Beyer, Richard; Zink, Erika M.; Kim, Young-Mo; Kyle, Jennifer E.; Webb-Robertson, Bobbie-Jo M.; Waters, Katrina M.; Metz, Thomas O.; Farin, Federico; Oberlies, Nicholas H.; Polyak, Steve

2015-08-28

Silymarin (SM), a natural product, is touted as a liver protectant and preventer of both chronic inflammation and diseases. To define how SM elicits these effects at a systems level, we performed transcriptional profiling, metabolomics, and signaling studies in human liver and T cell lines. Multiple pathways associated with cellular stress and metabolism were modulated by SM treatment within 0.5 to four hours: activation of Activating Transcription Factor 4 (ATF-4) and adenosine monophosphate protein kinase (AMPK) and inhibition of mammalian target of rapamycin (mTOR) signaling, the latter being associated with induction of DNA-damage-inducible transcript 4 (DDIT4). Metabolomics analyses revealed suppression of glycolytic, TCA cycle, and amino acid metabolism by SM treatment. Antiinflammatory effects arose with prolonged (i.e. 24 hours) SM exposure, with suppression of multiple proinflammatory mRNAs and nuclear factor kappa B (NF-κB) and forkhead box O (FOXO) signaling. Studies with murine knock out cells revealed that SM inhibition of both mTOR and NF-κB was partially AMPK dependent, while SM inhibition of the mTOR pathway in part required DDIT4. Thus, SM activates stress and repair responses that culminate in an anti-inflammatory phenotype. Other natural products induced similar stress responses, which correlated with their ability to suppress inflammation. Therefore, natural products like SM may be useful as tools to define how metabolic, stress, and repair pathways regulate cellular inflammation.

Cellular uptake of 99mTcN-NOET in human leukaemic HL-60 cells is related to calcium channel activation and cell proliferation

International Nuclear Information System (INIS)

Guillermet, Stephanie; Vuillez, Jean-Philippe; Caravel, Jean-Pierre; Marti-Batlle, Daniele; Fagret, Daniel; Fontaine, Eric; Pasqualini, Roberto

2006-01-01

A major goal of nuclear oncology is the development of new radiolabelled tracers as proliferation markers. Intracellular calcium waves play a fundamental role in the course of the cell cycle. These waves occur in non-excitable tumour cells via store-operated calcium channels (SOCCs). Bis(N-ethoxy, N-ethyldithiocarbamato) nitrido technetium (V)-99m ( 99m TcN-NOET) has been shown to interact with L-type voltage-operated calcium channels (VOCCs) in cultured cardiomyocytes. Considering the analogy between VOCCs and SOCCs, we sought to determine whether 99m TcN-NOET also binds to activated SOCCs in tumour cells in order to clarify the potential value of this tracer as a proliferation marker. Uptake kinetics of 99m TcN-NOET were measured in human leukaemic HL-60 cells over 60 min and the effect of several calcium channel modulators on 1-min tracer uptake was studied. The uptake kinetics of 99m TcN-NOET were compared both with the variations of cytosolic free calcium concentration measured by indo-1/AM and with the variations in the SG 2 M cellular proliferation index. All calcium channel inhibitors significantly decreased the cellular uptake of 99m TcN-NOET whereas the activator thapsigargin induced a significant 10% increase. In parallel, SOCC activation by thapsigargin, as measured using the indo-1/AM probe, was inhibited by nicardipine. These results indicate that the uptake of 99m TcN-NOET is related to the activation of SOCCs. Finally, a correlation was observed between the tracer uptake and variations in the proliferation index SG 2 M. The uptake of 99m TcN-NOET seems to be related to SOCC activation and to cell proliferation in HL-60 cells. These results indicate that 99m TcN-NOET might be a marker of cell proliferation. (orig.)

Cellular phones, cordless phones, and the risks of glioma and meningioma (Interphone Study Group, Germany)

DEFF Research Database (Denmark)

Schüz, Joachim; Böhler, Eva; Berg, Gabriele

2006-01-01

The widespread use of cellular telephones has generated concern about possible adverse health effects, particularly brain tumors. In this population-based case-control study carried out in three regions of Germany, all incident cases of glioma and meningioma among patients aged 30-69 years were...... ascertained during 2000-2003. Controls matched on age, gender, and region were randomly drawn from population registries. In total, 366 glioma cases, 381 meningioma cases, and 1,494 controls were interviewed. Overall use of a cellular phone was not associated with brain tumor risk; the respective odds ratios...

Phyto-mediated nanostructured carriers based on dual vegetable actives involved in the prevention of cellular damage.

Science.gov (United States)

Istrati, D; Lacatusu, I; Bordei, N; Badea, G; Oprea, O; Stefan, L M; Stan, R; Badea, N; Meghea, A

2016-07-01

The growing scientific interest in exploitation of vegetable bioactives has raised a number of questions regarding their imminent presence in pharmaceutical formulations. This study intends to demonstrate that a dual combination between vegetable oil (e.g. thistle oil, safflower oil, sea buckthorn oil) and a carrot extract represents an optimal approach to formulate safe carrier systems that manifest cell regeneration effect and promising antioxidant and anti-inflammatory activity. Inclusion of both natural actives into lipid carriers imparted a strong negative charge on the nanocarrier surface (up to -45mV) and displayed average sizes of 70nm to 140nm. The entrapment efficiency of carrot extract into nanostructured carriers ranged between 78.3 and 88.3%. The in vitro release study has demonstrated that the entrapment of the extract represents a viable way for an equilibrated release of carotenoids. Besides the excellent antioxidant properties (e.g. scavenging up to 98% of the free oxygen radicals), the results of cellular integrity (e.g. cell viability of 133%) recommend these nanocarriers based on dual carrot extract-bioactive oil as a promising trend for the treatment of certain disorders in which oxidative stress plays a prominent role. In addition, the lipid nanocarriers based on safflower oil and sea buckthorn oil demonstrated an anti-inflammatory effect on LPS induced THP-1 macrophages, by inhibiting the secretion of two pro-inflammatory cytokines, IL-6 and TNF-α. Copyright © 2016 Elsevier B.V. All rights reserved.

A Review on Hemeoxygenase-2: Focus on Cellular Protection and Oxygen Response

Directory of Open Access Journals (Sweden)

Jorge Muñoz-Sánchez

2014-01-01

Full Text Available Hemeoxygenase (HO system is responsible for cellular heme degradation to biliverdin, iron, and carbon monoxide. Two isoforms have been reported to date. Homologous HO-1 and HO-2 are microsomal proteins with more than 45% residue identity, share a similar fold and catalyze the same reaction. However, important differences between isoforms also exist. HO-1 isoform has been extensively studied mainly by its ability to respond to cellular stresses such as hemin, nitric oxide donors, oxidative damage, hypoxia, hyperthermia, and heavy metals, between others. On the contrary, due to its apparently constitutive nature, HO-2 has been less studied. Nevertheless, its abundance in tissues such as testis, endothelial cells, and particularly in brain, has pointed the relevance of HO-2 function. HO-2 presents particular characteristics that made it a unique protein in the HO system. Since attractive results on HO-2 have been arisen in later years, we focused this review in the second isoform. We summarize information on gene description, protein structure, and catalytic activity of HO-2 and particular facts such as its cellular impact and activity regulation. Finally, we call attention on the role of HO-2 in oxygen sensing, discussing proposed hypothesis on heme binding motifs and redox/thiol switches that participate in oxygen sensing as well as evidences of HO-2 response to hypoxia.

The cellular mastermind(?) – Mechanotransduction and the nucleus

Science.gov (United States)

Kaminski, Ashley; Fedorchak, Gregory R.; Lammerding, Jan

2015-01-01

Cells respond to mechanical stimulation by activation of specific signaling pathways and genes that allow the cell to adapt to its dynamic physical environment. How cells sense the various mechanical inputs and translate them into biochemical signals remains an area of active investigation. Recent reports suggest that the cell nucleus may be directly implicated in this cellular mechanotransduction process. In this chapter, we discuss how forces applied to the cell surface and cytoplasm induce changes in nuclear structure and organization, which could directly affect gene expression, while also highlighting the complex interplay between nuclear structural proteins and transcriptional regulators that may further modulate mechanotransduction signaling. Taken together, these findings paint a picture of the nucleus as a central hub in cellular mechanotransduction—both structurally and biochemically—with important implications in physiology and disease. PMID:25081618

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.

Expression of human papilloma virus type 16 E5 protein in amelanotic melanoma cells regulates endo-cellular pH and restores tyrosinase activity

Directory of Open Access Journals (Sweden)

Coccia Raffaella

2009-01-01

Full Text Available Abstract Background Melanin synthesis, the elective trait of melanocytes, is regulated by tyrosinase activity. In tyrosinase-positive amelanotic melanomas this rate limiting enzyme is inactive because of acidic endo-melanosomal pH. The E5 oncogene of the Human Papillomavirus Type 16 is a small transmembrane protein with a weak transforming activity and a role during the early steps of viral infections. E5 has been shown to interact with 16 kDa subunit C of the trans-membrane Vacuolar ATPase proton pump ultimately resulting in its functional suppressions. However, the cellular effects of such an interaction are still under debate. With this work we intended to explore whether the HPV16 E5 oncoprotein does indeed interact with the vacuolar ATPase proton pump once expressed in intact human cells and whether this interaction has functional consequences on cell metabolism and phenotype. Methods The expression of the HPV16-E5 oncoproteins was induced in two Tyrosinase-positive amelanotic melanomas (the cell lines FRM and M14 by a retroviral expression construct. Modulation of the intracellular pH was measured with Acridine orange and fluorescence microscopy. Expression of tyrosinase and its activity was followed by RT-PCR, Western Blot and enzyme assay. The anchorage-independence growth and the metabolic activity of E5 expressing cells were also monitored. Results We provide evidence that in the E5 expressing cells interaction between E5 and V-ATPase determines an increase of endo-cellular pH. The cellular alkalinisation in turn leads to the post-translational activation of tyrosinase, melanin synthesis and phenotype modulation. These effects are associated with an increased activation of tyrosine analogue anti-blastic drugs. Conclusion Once expressed within intact human cells the HPV16-E5 oncoprotein does actually interact with the vacuolar V-ATPase proton pump and this interaction induces a number of functional effects. In amelanotic melanomas these

Human papillomavirus 16E6 and NFX1-123 potentiate notch signaling and differentiation without activating cellular arrest

Energy Technology Data Exchange (ETDEWEB)

Vliet-Gregg, Portia A.; Hamilton, Jennifer R. [Center for Global Infectious Disease Research, Seattle Children' s Research Institute, 1900 Ninth Ave., Seattle, WA 98101 (United States); Katzenellenbogen, Rachel A., E-mail: rkatzen@uw.edu [Center for Global Infectious Disease Research, Seattle Children' s Research Institute, 1900 Ninth Ave., Seattle, WA 98101 (United States); Department of Pediatrics, Division of Adolescent Medicine, University of Washington, Seattle WA (United States)

2015-04-15

High-risk human papillomavirus (HR HPV) oncoproteins bind host cell proteins to dysregulate and uncouple apoptosis, senescence, differentiation, and growth. These pathways are important for both the viral life cycle and cancer development. HR HPV16 E6 (16E6) interacts with the cellular protein NFX1-123, and they collaboratively increase the growth and differentiation master regulator, Notch1. In 16E6 expressing keratinocytes (16E6 HFKs), the Notch canonical pathway genes Hes1 and Hes5 were increased with overexpression of NFX1-123, and their expression was directly linked to the activation or blockade of the Notch1 receptor. Keratinocyte differentiation genes Keratin 1 and Keratin 10 were also increased, but in contrast their upregulation was only indirectly associated with Notch1 receptor stimulation and was fully unlinked to growth arrest, increased p21{sup Waf1/CIP1}, or decreased proliferative factor Ki67. This leads to a model of 16E6, NFX1-123, and Notch1 differently regulating canonical and differentiation pathways and entirely uncoupling cellular arrest from increased differentiation. - Highlights: • 16E6 and NFX1-123 increased the Notch canonical pathway through Notch1. • 16E6 and NFX1-123 increased the differentiation pathway indirectly through Notch1. • 16E6 and NFX1-123 increased differentiation gene expression without growth arrest. • Increased NFX1-123 with 16E6 may create an ideal cellular phenotype for HPV.

Antioxidant Activity of Lawsonia inermis Extracts Inhibits Chromium(VI-Induced Cellular and DNA Toxicity

Directory of Open Access Journals (Sweden)

Gunjan Guha

2011-01-01

Full Text Available Hexavalent chromium Cr(VI is a very strong oxidant which consequently causes high cytotoxicity through oxidative stress. Prevention of Cr(VI-induced cellular damage has been sought in this study in aqueous and methanolic extracts of Lawsonia inermis Linn. (Lythraceae, commonly known as Henna. The extracts showed significant (P < .05 potential in scavenging free radicals (DPPH• and ABTS•+ and Fe3+, and in inhibiting lipid peroxidation. DNA damage caused by exposure of pBR322 to Cr(VI-UV is markedly inhibited by both extracts in varying degrees. A distinct decline in Cr(VI-induced cytotoxicity was noticed in MDA-MB-435S (human breast carcinoma cells with an increase in dosage of both extracts individually. Furthermore, both extracts proved to contain a high content of phenolic compounds which were found to have a strong and significant (P < .05 positive correlation to the radical scavenging potential, lipid peroxidation inhibition capacity and cyto-protective efficiency against Cr(VI-induced oxidative cellular damage. HPLC analysis identified some of the major phenolic compounds in both extracts, which might be responsible for the antioxidant potential and the properties of DNA and cyto-protection. This study contributes to the search for natural resources that might yield potent therapeutic drugs against Cr(VI-induced oxidative cell damage.

Cellular biomarker responses of bagrid catfish, Chrysichthys ...

African Journals Online (AJOL)

An assessment of the pollution status of Agboyi creek, a water body associated with various anthropogenic activities was carried out in order to determine responses induced in Catfishes, Chrysichthys nigrodigitatus inhabiting it. Cellular biomarkers of stress including the antioxidative stress enzyme, catalase (CAT), lipid ...

Toxicology and cellular effect of manufactured nanomaterials

Science.gov (United States)

Chen, Fanqing

2014-07-22

The increasing use of nanotechnology in consumer products and medical applications underlies the importance of understanding its potential toxic effects to people and the environment. Herein are described methods and assays to predict and evaluate the cellular effects of nanomaterial exposure. Exposing cells to nanomaterials at cytotoxic doses induces cell cycle arrest and increases apoptosis/necrosis, activates genes involved in cellular transport, metabolism, cell cycle regulation, and stress response. Certain nanomaterials induce genes indicative of a strong immune and inflammatory response within skin fibroblasts. Furthermore, the described multiwall carbon nanoonions (MWCNOs) can be used as a therapeutic in the treatment of cancer due to its cytotoxicity.

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.

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)

Frequency-dependent micromechanics of cellularized biopolymer networks

Science.gov (United States)

Jones, Chris; Kim, Jihan; McIntyre, David; Sun, Bo

Mechanical interactions between cells and the extracellular matrix (ECM) influence many cellular behaviors such as growth, differentiation, and migration. These are dynamic processes in which the cells actively remodel the ECM. Reconstituted collagen gel is a common model ECM for studying cell-ECM interactions in vitro because collagen is the most abundant component of mammalian ECM and gives the ECM its material stiffness. We embed micron-sized particles in collagen and use holographic optical tweezers to apply forces to the particles in multiple directions and over a range of frequencies up to 10 Hz. We calculate the local compliance and show that it is dependent on both the direction and frequency of the applied force. Performing the same measurement on many particles allows us to characterize the spatial inhomogeneity of the mechanical properties and shows that the compliance decreases at higher frequencies. Performing these measurements on cell-populated collagen gels shows that cellular remodeling of the ECM changes the mechanical properties of the collagen and we investigate whether this change is dependent on the local strain and distance from nearby cells.

High Cellular Monocyte Activation in People Living With Human Immunodeficiency Virus on Combination Antiretroviral Therapy and Lifestyle-Matched Controls Is Associated With Greater Inflammation in Cerebrospinal Fluid

NARCIS (Netherlands)

Booiman, Thijs; Wit, Ferdinand W.; Maurer, Irma; de Francesco, Davide; Sabin, Caroline A.; Harskamp, Agnes M.; Prins, Maria; Garagnani, Paolo; Pirazzini, Chiara; Franceschi, Claudio; Fuchs, Dietmar; Gisslén, Magnus; Winston, Alan; Reiss, Peter; Kootstra, Neeltje A.; Schouten, J.; Kooij, K. W.; van Zoest, R. A.; Elsenga, B. C.; Janssen, F. R.; Heidenrijk, M.; Zikkenheiner, W.; van der Valk, M.; Booiman, T.; Harskamp-Holwerda, A. M.; Boeser-Nunnink, B.; Maurer, I.; Mangas Ruiz, M. M.; Girigorie, A. F.; Villaudy, J.; Frankin, E.; Pasternak, A.; Berkhout, B.; van der Kuyl, T.; Portegies, P.; Schmand, B. A.; Geurtsen, G. J.; ter Stege, J. A.; Klein Twennaar, M.; Majoie, C. B. L. M.; Caan, M. W. A.; Su, T.; Weijer, K.; Bisschop, P. H. L. T.; Kalsbeek, A.; Wezel, M.; Visser, I.; Ruhé, H. G.; Franceschi, C.; Garagnani, P.

2017-01-01

Increased monocyte activation and intestinal damage have been shown to be predictive for the increased morbidity and mortality observed in treated people living with human immunodeficiency virus (PLHIV). A cross-sectional analysis of cellular and soluble markers of monocyte activation, coagulation,

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.

The rational design of a novel potent analogue of the 5’-AMP-activated protein kinase inhibitor compound C with improved selectivity and cellular activity

Science.gov (United States)

Machrouhi, Fouzia; Ouhamou, Nouara; Laderoute, Keith; Calaoagan, Joy; Bukhtiyarova, Marina; Ehrlich, Paula J.; Klon, Anthony E.

2010-01-01

We have designed and synthesized analogues of compound C, a non-specific inhibitor of 5’-AMP-activated protein kinase (AMPK), using a computational fragment-based drug design (FBDD) approach. Synthesizing only twenty-seven analogues yielded a compound that was equipotent to compound C in the inhibition of the human AMPK (hAMPK) α2 subunit in the heterotrimeric complex in vitro, exhibited significantly improved selectivity against a subset of relevant kinases, and demonstrated enhanced cellular inhibition of AMPK. PMID:20932747

Antifungal Activity of Oleuropein against Candida albicans—The In Vitro Study

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Nataša Zorić

2016-11-01

Full Text Available In the present study we investigated activity of oleuropein, a complex phenol present in large quantities in olive tree products, against opportunistic fungal pathogen Candida albicans. Oleuropein was found to have in vitro antifungal activity with a minimal inhibitory concentration (MIC value of 12.5 mg·mL−1. Morphological changes in the nuclei after staining with fluorescent DNA-binding dyes revealed that apoptosis was a primary mode of cell death in the analyzed samples treated with subinhibitory concentrations of oleuropein. Our results suggest that this antifungal agent targets virulence factors essential for establishment of the fungal infection. We noticed that oleuropein modulates morphogenetic conversion and inhibits filamentation of C. albicans. The hydrophobicity assay showed that oleuropein in sub-MIC values has significantly decreased, in both aerobic and anaerobic conditions, the cellular surface hydrophobicity (CSH of C. albicans, a factor associated with adhesion to epithelial cells. It was also demonstrated that the tested compound inhibits the activity of SAPs, cellular enzymes secreted by C. albicans, which are reported to be related to the pathogenicity of the fungi. Additionally, we detected that oleuropein causes a reduction in total sterol content in the membrane of C. albicans cells, which might be involved in the mechanism of its antifungal activity.

Evaluation of cellular phenotypes implicated in immunopathogenesis and monitoring immune reconstitution inflammatory syndrome in HIV/leprosy cases.

Science.gov (United States)

Giacoia-Gripp, Carmem Beatriz Wagner; Sales, Anna Maria; Nery, José Augusto da Costa; Santos-Oliveira, Joanna Reis; de Oliveira, Ariane Leite; Sarno, Euzenir Nunes; Morgado, Mariza Gonçalves

2011-01-01

It is now evident that HAART-associated immunological improvement often leads to a variety of new clinical manifestations, collectively termed immune reconstitution inflammatory syndrome, or IRIS. This phenomenon has already been described in cases of HIV coinfection with Mycobacterium leprae, most of them belonging to the tuberculoid spectrum of leprosy disease, as observed in leprosy reversal reaction (RR). However, the events related to the pathogenesis of this association need to be clarified. This study investigated the immunological profile of HIV/leprosy patients, with special attention to the cellular activation status, to better understand the mechanisms related to IRIS/RR immunopathogenesis, identifying any potential biomarkers for IRIS/RR intercurrence. Eighty-five individuals were assessed in this study: HIV/leprosy and HIV-monoinfected patients, grouped according to HIV-viral load levels, leprosy patients without HIV coinfection, and healthy controls. Phenotypes were evaluated by flow cytometry for T cell subsets and immune differentiation/activation markers. As expected, absolute counts of the CD4+ and CD8+ T cells from the HIV-infected individuals changed in relation to those of the leprosy patients and controls. However, there were no significant differences among the groups, whether in the expression of cellular differentiation phenotypes or cellular activation, as reflected by the expression of CD38 and HLA-DR. Six HIV/leprosy patients identified as IRIS/RR were analyzed during IRIS/RR episodes and after prednisone treatment. These patients presented high cellular activation levels regarding the expression of CD38 in CD8+ cells T during IRIS/RR (median: 77,15%), dropping significantly (p<0,05) during post-IRIS/RR moments (median: 29,7%). Furthermore, an increase of cellular activation seems to occur prior to IRIS/RR. These data suggest CD38 expression in CD8+ T cells interesting tool identifying HIV/leprosy individuals at risk for IRIS/RR. So, a

Evaluation of cellular phenotypes implicated in immunopathogenesis and monitoring immune reconstitution inflammatory syndrome in HIV/leprosy cases.

Directory of Open Access Journals (Sweden)

Carmem Beatriz Wagner Giacoia-Gripp

Full Text Available BACKGROUND: It is now evident that HAART-associated immunological improvement often leads to a variety of new clinical manifestations, collectively termed immune reconstitution inflammatory syndrome, or IRIS. This phenomenon has already been described in cases of HIV coinfection with Mycobacterium leprae, most of them belonging to the tuberculoid spectrum of leprosy disease, as observed in leprosy reversal reaction (RR. However, the events related to the pathogenesis of this association need to be clarified. This study investigated the immunological profile of HIV/leprosy patients, with special attention to the cellular activation status, to better understand the mechanisms related to IRIS/RR immunopathogenesis, identifying any potential biomarkers for IRIS/RR intercurrence. METHODS/PRINCIPAL FINDINGS: Eighty-five individuals were assessed in this study: HIV/leprosy and HIV-monoinfected patients, grouped according to HIV-viral load levels, leprosy patients without HIV coinfection, and healthy controls. Phenotypes were evaluated by flow cytometry for T cell subsets and immune differentiation/activation markers. As expected, absolute counts of the CD4+ and CD8+ T cells from the HIV-infected individuals changed in relation to those of the leprosy patients and controls. However, there were no significant differences among the groups, whether in the expression of cellular differentiation phenotypes or cellular activation, as reflected by the expression of CD38 and HLA-DR. Six HIV/leprosy patients identified as IRIS/RR were analyzed during IRIS/RR episodes and after prednisone treatment. These patients presented high cellular activation levels regarding the expression of CD38 in CD8+ cells T during IRIS/RR (median: 77,15%, dropping significantly (p<0,05 during post-IRIS/RR moments (median: 29,7%. Furthermore, an increase of cellular activation seems to occur prior to IRIS/RR. CONCLUSION/SIGNIFICANCE: These data suggest CD38 expression in CD8+ T cells

Cell patch seeding and functional analysis of cellularized scaffolds for tissue engineering

Energy Technology Data Exchange (ETDEWEB)

Kumar, P R Anil [Division of Implant Biology, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, Kerala 695012 (India); Varma, H K [Bioceramics Laboratory, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, Kerala 695012 (India); Kumary, T V [Division of Implant Biology, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, Kerala 695012 (India)

2007-03-01

Cell seeding has a direct impact on the final structure and function of tissue constructs, especially for applications like tissue engineering and regeneration. In this study seeding cell patches retrieved from the thermoresponsive poly(N-isopropylacrylamide) surface were used to generate in vitro tissue constructs. Porous and dense bone substitute materials were cellularized using osteoblast cells by a patch transfer and a trypsin method. The function and proliferation of cells was analyzed after 7 days of culture. The relative cell growth rate was found to be higher in cellularized porous hydroxyapatite (PHA) than in dense hydroxyapatite. Live-dead staining confirmed viable cells inside the pores of PHA. Increased alkaline phosphatase activity of cells transferred by the cell patch over the trypsin method revealed the significance of cell patch seeding. This novel method of generating tissue constructs by cell patch seeding was successful in cellularizing scaffolds with intact cell function.

Cell patch seeding and functional analysis of cellularized scaffolds for tissue engineering

International Nuclear Information System (INIS)

Kumar, P R Anil; Varma, H K; Kumary, T V

2007-01-01

Cell seeding has a direct impact on the final structure and function of tissue constructs, especially for applications like tissue engineering and regeneration. In this study seeding cell patches retrieved from the thermoresponsive poly(N-isopropylacrylamide) surface were used to generate in vitro tissue constructs. Porous and dense bone substitute materials were cellularized using osteoblast cells by a patch transfer and a trypsin method. The function and proliferation of cells was analyzed after 7 days of culture. The relative cell growth rate was found to be higher in cellularized porous hydroxyapatite (PHA) than in dense hydroxyapatite. Live-dead staining confirmed viable cells inside the pores of PHA. Increased alkaline phosphatase activity of cells transferred by the cell patch over the trypsin method revealed the significance of cell patch seeding. This novel method of generating tissue constructs by cell patch seeding was successful in cellularizing scaffolds with intact cell function

Nitric Oxide and ERK mediates regulation of cellular processes by Ecdysterone

Energy Technology Data Exchange (ETDEWEB)

Omanakuttan, Athira; Bose, Chinchu; Pandurangan, Nanjan; Kumar, Geetha B.; Banerji, Asoke; Nair, Bipin G., E-mail: bipin@amrita.edu

2016-08-15

The complex process of wound healing is a major problem associated with diabetes, venous or arterial disease, old age and infection. A wide range of pharmacological effects including anabolic, anti-diabetic and hepato-protective activities have been attributed to Ecdysterone. In earlier studies, Ecdysterone has been shown to modulate eNOS and iNOS expression in diabetic animals and activate osteogenic differentiation through the Extracellular-signal-Regulated Kinase (ERK) pathway in periodontal ligament stem cells. However, in the wound healing process, Ecdysterone has only been shown to enhance granulation tissue formation in rabbits. There have been no studies to date, which elucidate the molecular mechanism underlying the complex cellular process involved in wound healing. The present study, demonstrates a novel interaction between the phytosteroid Ecdysterone and Nitric Oxide Synthase (NOS), in an Epidermal Growth Factor Receptor (EGFR)-dependent manner, thereby promoting cell proliferation, cell spreading and cell migration. These observations were further supported by the 4-amino-5-methylamino- 2′ ,7′ -difluorofluorescein diacetate (DAF FM) fluorescence assay which indicated that Ecdysterone activates NOS resulting in increased Nitric Oxide (NO) production. Additionally, studies with inhibitors of both the EGFR and ERK, demonstrated that Ecdysterone activates NOS through modulation of EGFR and ERK. These results clearly demonstrate, for the first time, that Ecdysterone enhances Nitric Oxide production and modulates complex cellular processes by activating ERK1/2 through the EGF pathway. - Highlights: • Ecdysterone significantly enhances cell migration in a dose dependent manner. • Ecdysterone augments cell spreading during the initial phase of cell migration through actin cytoskeletal rearrangement. • Ecdysterone enhances cell proliferation in a nitric oxide dependent manner. • Ecdysterone enhances nitric oxide production via activation of EGFR

Nitric Oxide and ERK mediates regulation of cellular processes by Ecdysterone

International Nuclear Information System (INIS)

Omanakuttan, Athira; Bose, Chinchu; Pandurangan, Nanjan; Kumar, Geetha B.; Banerji, Asoke; Nair, Bipin G.

2016-01-01

The complex process of wound healing is a major problem associated with diabetes, venous or arterial disease, old age and infection. A wide range of pharmacological effects including anabolic, anti-diabetic and hepato-protective activities have been attributed to Ecdysterone. In earlier studies, Ecdysterone has been shown to modulate eNOS and iNOS expression in diabetic animals and activate osteogenic differentiation through the Extracellular-signal-Regulated Kinase (ERK) pathway in periodontal ligament stem cells. However, in the wound healing process, Ecdysterone has only been shown to enhance granulation tissue formation in rabbits. There have been no studies to date, which elucidate the molecular mechanism underlying the complex cellular process involved in wound healing. The present study, demonstrates a novel interaction between the phytosteroid Ecdysterone and Nitric Oxide Synthase (NOS), in an Epidermal Growth Factor Receptor (EGFR)-dependent manner, thereby promoting cell proliferation, cell spreading and cell migration. These observations were further supported by the 4-amino-5-methylamino- 2′ ,7′ -difluorofluorescein diacetate (DAF FM) fluorescence assay which indicated that Ecdysterone activates NOS resulting in increased Nitric Oxide (NO) production. Additionally, studies with inhibitors of both the EGFR and ERK, demonstrated that Ecdysterone activates NOS through modulation of EGFR and ERK. These results clearly demonstrate, for the first time, that Ecdysterone enhances Nitric Oxide production and modulates complex cellular processes by activating ERK1/2 through the EGF pathway. - Highlights: • Ecdysterone significantly enhances cell migration in a dose dependent manner. • Ecdysterone augments cell spreading during the initial phase of cell migration through actin cytoskeletal rearrangement. • Ecdysterone enhances cell proliferation in a nitric oxide dependent manner. • Ecdysterone enhances nitric oxide production via activation of EGFR

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...

Effect of inhomogeneous activity distributions and airway geometry on cellular doses in radon lung dosimetry

International Nuclear Information System (INIS)

Szoke, Istvan; Balashazy, Imre; Farkas, Arpad; Hofmann, Werner

2007-01-01

The human tracheobronchial system has a very complex structure including cylindrical airway ducts connected by airway bifurcation units. The deposition of the inhaled aerosols within the airways exhibits a very inhomogeneous pattern. The formation of deposition hot spots near the carinal ridge has been confirmed by experimental and computational fluid and particle dynamics (CFPD) methods. In spite of these observations, current radon lung dosimetry models apply infinitely long cylinders as models of the airway system and assume uniform deposition of the inhaled radon progenies along the airway walls. The aim of this study is to investigate the effect of airway geometry and non-uniform activity distributions within bronchial bifurcations on cellular dose distributions. In order to answer these questions, the nuclear doses of the bronchial epithelium were calculated in three different irradiation situations. (1) First, CFPD methods were applied to calculate the distribution of the deposited alpha-emitting nuclides in a numerically constructed idealized airway bifurcation. (2) Second, the deposited radionuclides were randomly distributed along the surface of the above-mentioned geometry. (3) Finally, calculations were made in cylindrical geometries corresponding to the parent and daughter branches of the bifurcation geometry assuming random nuclide activity distribution. In all three models, the same 218 Po and 214 Po surface activities per tissue volumes were assumed. Two conclusions can be drawn from this analysis: (i) average nuclear doses are very similar in all three cases (minor differences can be attributed to differences in the linear energy transfer (LET) spectra) and (ii) dose distributions are significantly different in all three cases, with the highest doses at the carinal ridge in case 3. (authors)

Disruption of Pyridine Nucleotide Redox Status During Oxidative Challenge at Normal and Low-Glucose States: Implications for Cellular Adenosine Triphosphate, Mitochondrial Respiratory Activity, and Reducing Capacity in Colon Epithelial Cells

Science.gov (United States)

Circu, Magdalena L.; Maloney, Ronald E.

2011-01-01

Abstract We recently demonstrated that menadione (MQ), a redox cycling quinone, mediated the loss of mitochondrial glutathione/glutathione disulfide redox balance. In this study, we showed that MQ significantly disrupted cellular pyridine nucleotide (NAD+/NADH, NADP+/NADPH) redox balance that compromised cellular ATP, mitochondrial respiratory activity, and NADPH-dependent reducing capacity in colonic epithelial cells, a scenario that was exaggerated by low glucose. In the cytosol, MQ induced NAD+ loss concurrent with increased NADP+ and NAD kinase activity, but decreased NADPH. In the mitochondria, NADH loss occurred in conjunction with increased nicotinamide nucleotide transhydrogenase activity and NADP+, and decreased NADPH. These results are consistent with cytosolic NAD+-to-NADP+ and mitochondrial NADH-to-NADPH shifts, but compromised NADPH availability. Thus, despite the sacrifice of NAD+/NADH in favor of NADPH generation, steady-state NADPH levels were not maintained during MQ challenge. Impairments of cellular bioenergetics were evidenced by ATP losses and increased mitochondrial O2 dependence of pyridine nucleotide oxidation–reduction; half-maximal oxidation (P50) was 10-fold higher in low glucose, which was lowered by glutamate or succinate supplementation. This exaggerated O2 dependence is consistent with increased O2 diversion to nonmitochondrial O2 consumption by MQ-semiquinone redox cycling secondary to decreased NADPH-dependent MQ detoxication at low glucose, a situation that was corrected by glucose-sparing mitochondrial substrates. Antioxid. Redox Signal. 14, 2151–2162. PMID:21083422

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

Cellular variability of RpoS expression underlies subpopulation activation of an integrative and conjugative element.

Directory of Open Access Journals (Sweden)

Ryo Miyazaki

Full Text Available Conjugative transfer of the integrative and conjugative element ICEclc in the bacterium Pseudomonas knackmussii is the consequence of a bistable decision taken in some 3% of cells in a population during stationary phase. Here we study the possible control exerted by the stationary phase sigma factor RpoS on the bistability decision. The gene for RpoS in P. knackmussii B13 was characterized, and a loss-of-function mutant was produced and complemented. We found that, in absence of RpoS, ICEclc transfer rates and activation of two key ICEclc promoters (P(int and P(inR decrease significantly in cells during stationary phase. Microarray and gene reporter analysis indicated that the most direct effect of RpoS is on P(inR, whereas one of the gene products from the P(inR-controlled operon (InrR transmits activation to P(int and other ICEclc core genes. Addition of a second rpoS copy under control of its native promoter resulted in an increase of the proportion of cells expressing the P(int and P(inR promoters to 18%. Strains in which rpoS was replaced by an rpoS-mcherry fusion showed high mCherry fluorescence of individual cells that had activated P(int and P(inR, whereas a double-copy rpoS-mcherry-containing strain displayed twice as much mCherry fluorescence. This suggested that high RpoS levels are a prerequisite for an individual cell to activate P(inR and thus ICEclc transfer. Double promoter-reporter fusions confirmed that expression of P(inR is dominated by extrinsic noise, such as being the result of cellular variability in RpoS. In contrast, expression from P(int is dominated by intrinsic noise, indicating it is specific to the ICEclc transmission cascade. Our results demonstrate how stochastic noise levels of global transcription factors can be transduced to a precise signaling cascade in a subpopulation of cells leading to ICE activation.

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.

Single-cell-based system to monitor carrier driven cellular auxin homeostasis

Science.gov (United States)

2013-01-01

Background Abundance and distribution of the plant hormone auxin play important roles in plant development. Besides other metabolic processes, various auxin carriers control the cellular level of active auxin and, hence, are major regulators of cellular auxin homeostasis. Despite the developmental importance of auxin transporters, a simple medium-to-high throughput approach to assess carrier activities is still missing. Here we show that carrier driven depletion of cellular auxin correlates with reduced nuclear auxin signaling in tobacco Bright Yellow-2 (BY-2) cell cultures. Results We developed an easy to use transient single-cell-based system to detect carrier activity. We use the relative changes in signaling output of the auxin responsive promoter element DR5 to indirectly visualize auxin carrier activity. The feasibility of the transient approach was demonstrated by pharmacological and genetic interference with auxin signaling and transport. As a proof of concept, we provide visual evidence that the prominent auxin transport proteins PIN-FORMED (PIN)2 and PIN5 regulate cellular auxin homeostasis at the plasma membrane and endoplasmic reticulum (ER), respectively. Our data suggest that PIN2 and PIN5 have different sensitivities to the auxin transport inhibitor 1-naphthylphthalamic acid (NPA). Also the putative PIN-LIKES (PILS) auxin carrier activity at the ER is insensitive to NPA in our system, indicating that NPA blocks intercellular, but not intracellular auxin transport. Conclusions This single-cell-based system is a useful tool by which the activity of putative auxin carriers, such as PINs, PILS and WALLS ARE THIN1 (WAT1), can be indirectly visualized in a medium-to-high throughput manner. Moreover, our single cell system might be useful to investigate also other hormonal signaling pathways, such as cytokinin. PMID:23379388

Reporters to monitor cellular MMP12 activity

Science.gov (United States)

Cobos-Correa, Amanda; Mall, Marcus A.; Schultz, Carsten

2010-02-01

Macrophage elastase, also called MMP12, belongs to a family of proteolytic enzymes whose best known physiological function is the remodeling of the extracellular matrix. Under certain pathological conditions, including inflammation, chronic overexpression of MMP12 has been observed and its elevated proteolytic activity has been suggested to be the cause of pulmonary emphysema. However, it was until recently impossible to monitor the activity of MMP12 under disease conditions, mainly due to a lack of detection methods. Recent development of new reporters for monitoring MMP12 activity in living cells, such as LaRee1, provided novel insights into the pathobiology of MMP12 in pulmonary inflammation.1 In the future, these reporters might contribute to improved diagnosis and in finding better treatments for chronic inflammatory lung diseases and emphysema. Our approach for visualizing MMP12 activity is based on peptidic, membrane-targeted FRET (Foerster Resonance Energy Transfer) reporters. Here we describe a set of new reporters containing different fluorophore pairs as well as modifications in the membrane-targeting lipid moiety. We studied the influence of these modifications on reporter performance and the reporter mobility on live cell membranes by FRAP (fluorescence recovery after photobleaching). Finally, we generated several new fluorescently labeled MMP inhibitors based on the peptidic reporter structures as prototypes for future tools to inhibit and monitor MMP activity at the same time.

BICD2, dynactin, and LIS1 cooperate in regulating dynein recruitment to cellular structures

NARCIS (Netherlands)

D. Splinter (Daniël); D.S. Razafsky (David); M.A. Schlager (Max); A. Serra-Marques (Andrea); I. Grigoriev (Ilya); J.A.A. Demmers (Jeroen); N. Keijzer (Nanda); K. Jiang (Kai); S. Poser; A. Hyman (Anthony); C.C. Hoogenraad (Casper); S.J. King (Stephen); A.S. Akhmanova (Anna)

2012-01-01

textabstractCytoplasmic dynein is the major microtubule minus-end-directed cellular motor. Most dynein activities require dynactin, but the mechanisms regulating cargo-dependent dynein-dynactin interaction are poorly understood. In this study, we focus on dynein-dynactin recruitment to cargo by the

Exposure of Daphnia magna to trichloroethylene (TCE) and vinyl chloride (VC): evaluation of gene transcription, cellular activity, and life-history parameters.

Science.gov (United States)

Houde, Magali; Douville, Mélanie; Gagnon, Pierre; Sproull, Jim; Cloutier, François

2015-06-01

Trichloroethylene (TCE) is a ubiquitous contaminant classified as a human carcinogen. Vinyl chloride (VC) is primarily used to manufacture polyvinyl chloride and can also be a degradation product of TCE. Very few data exist on the toxicity of TCE and VC in aquatic organisms particularly at environmentally relevant concentrations. The aim of this study was to evaluate the sub-lethal effects (10 day exposure; 0.1; 1; 10 µg/L) of TCE and VC in Daphnia magna at the gene, cellular, and life-history levels. Results indicated impacts of VC on the regulation of genes related to glutathione-S-transferase (GST), juvenile hormone esterase (JHE), and the vitelline outer layer membrane protein (VMO1). On the cellular level, exposure to 0.1, 1, and 10 µg/L of VC significantly increased the activity of JHE in D. magna and TCE increased the activity of chitinase (at 1 and 10 µg/L). Results for life-history parameters indicated a possible tendency of TCE to affect the number of molts at the individual level in D. magna (p=0.051). Measurement of VG-like proteins using the alkali-labile phosphates (ALP) assay did not show differences between TCE treated organisms and controls. However, semi-quantitative measurement using gradient gel electrophoresis (213-218 kDa) indicated significant decrease in VG-like protein levels following exposure to TCE at all three concentrations. Overall, results indicate effects of TCE and VC on genes and proteins related to metabolism, reproduction, and growth in D. magna. Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.

Development of second generation peptides modulating cellular adiponectin receptor responses

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Laszlo eOtvos

2014-10-01

Full Text Available The adipose tissue participates in the regulation of energy homeostasis as an important endocrine organ that secretes a number of biologically active adipokines, including adiponectin. Recently we developed and characterized a first-in-class peptide-based adiponectin receptor agonist by using in vitro and in vivo models of glioblastoma and breast cancer (BC. In the current study, we further explored the effects of peptide ADP355 in additional cellular models and found that ADP355 inhibited chronic myeloid leukemia (CML cell proliferation and renal myofibroblast differentiation with mid-nanomolar IC50 values. According to molecular modeling calculations, ADP355 was remarkably flexible in the global minimum with a turn present in the middle of the peptide. Considering these structural features of ADP355 and the fact that adiponectin normally circulates as multimeric complexes, we developed and tested the activity of a linear branched dimer (ADP399. The dimer exhibited approximately 20-fold improved cellular activity inhibiting K562 CML and MCF-7 cell growth with high pM - low nM relative IC50 values. Biodistribution studies suggested superior tissue dissemination of both peptides after subcutaneous administration relative to intraperitoneal inoculation. After screening of a 397-member adiponectin active site library, a novel octapeptide (ADP400 was designed that counteracted 10-1000 nM ADP355- and ADP399-mediated effects on CML and BC cell growth at nanomolar concentrations. ADP400 induced mitogenic effects in MCF-7 BC cells perhaps due to antagonizing endogenous adiponectin actions or acting as an inverse agonist. While the linear dimer agonist ADP399 meets pharmacological criteria of a contemporary peptide drug lead, the peptide showing antagonist activity (ADP400 at similar concentrations will be an important target validation tool to study adiponectin functions.

Development of second generation peptides modulating cellular adiponectin receptor responses

Science.gov (United States)

Otvos, Laszlo; Knappe, Daniel; Hoffmann, Ralf; Kovalszky, Ilona; Olah, Julia; Hewitson, Tim; Stawikowska, Roma; Stawikowski, Maciej; Cudic, Predrag; Lin, Feng; Wade, John; Surmacz, Eva; Lovas, Sandor

2014-10-01

The adipose tissue participates in the regulation of energy homeostasis as an important endocrine organ that secretes a number of biologically active adipokines, including adiponectin. Recently we developed and characterized a first-in-class peptide-based adiponectin receptor agonist by using in vitro and in vivo models of glioblastoma and breast cancer (BC). In the current study, we further explored the effects of peptide ADP355 in additional cellular models and found that ADP355 inhibited chronic myeloid leukemia (CML) cell proliferation and renal myofibroblast differentiation with mid-nanomolar IC50 values. According to molecular modeling calculations, ADP355 was remarkably flexible in the global minimum with a turn present in the middle of the peptide. Considering these structural features of ADP355 and the fact that adiponectin normally circulates as multimeric complexes, we developed and tested the activity of a linear branched dimer (ADP399). The dimer exhibited approximately 20-fold improved cellular activity inhibiting K562 CML and MCF-7 cell growth with high pM - low nM relative IC50 values. Biodistribution studies suggested superior tissue dissemination of both peptides after subcutaneous administration relative to intraperitoneal inoculation. After screening of a 397-member adiponectin active site library, a novel octapeptide (ADP400) was designed that counteracted 10-1000 nM ADP355- and ADP399-mediated effects on CML and BC cell growth at nanomolar concentrations. ADP400 induced mitogenic effects in MCF-7 BC cells perhaps due to antagonizing endogenous adiponectin actions or acting as an inverse agonist. While the linear dimer agonist ADP399 meets pharmacological criteria of a contemporary peptide drug lead, the peptide showing antagonist activity (ADP400) at similar concentrations will be an important target validation tool to study adiponectin functions.

Multivalent adhesion molecule 7 clusters act as signaling platform for host cellular GTPase activation and facilitate epithelial barrier dysfunction.

Directory of Open Access Journals (Sweden)

Jenson Lim

2014-09-01

Full Text Available Vibrio parahaemolyticus is an emerging bacterial pathogen which colonizes the gastrointestinal tract and can cause severe enteritis and bacteraemia. During infection, V. parahaemolyticus primarily attaches to the small intestine, where it causes extensive tissue damage and compromises epithelial barrier integrity. We have previously described that Multivalent Adhesion Molecule (MAM 7 contributes to initial attachment of V. parahaemolyticus to epithelial cells. Here we show that the bacterial adhesin, through multivalent interactions between surface-induced adhesin clusters and phosphatidic acid lipids in the host cell membrane, induces activation of the small GTPase RhoA and actin rearrangements in host cells. In infection studies with V. parahaemolyticus we further demonstrate that adhesin-triggered activation of the ROCK/LIMK signaling axis is sufficient to redistribute tight junction proteins, leading to a loss of epithelial barrier function. Taken together, these findings show an unprecedented mechanism by which an adhesin acts as assembly platform for a host cellular signaling pathway, which ultimately facilitates breaching of the epithelial barrier by a bacterial pathogen.

A nucleator arms race: cellular control of actin assembly.

Science.gov (United States)

Campellone, Kenneth G; Welch, Matthew D

2010-04-01

For over a decade, the actin-related protein 2/3 (ARP2/3) complex, a handful of nucleation-promoting factors and formins were the only molecules known to directly nucleate actin filament formation de novo. However, the past several years have seen a surge in the discovery of mammalian proteins with roles in actin nucleation and dynamics. Newly recognized nucleation-promoting factors, such as WASP and SCAR homologue (WASH), WASP homologue associated with actin, membranes and microtubules (WHAMM), and junction-mediating regulatory protein (JMY), stimulate ARP2/3 activity at distinct cellular locations. Formin nucleators with additional biochemical and cellular activities have also been uncovered. Finally, the Spire, cordon-bleu and leiomodin nucleators have revealed new ways of overcoming the kinetic barriers to actin polymerization.

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...

The Relationship between Cellular Phone Use, Performance, and Reaction Time among College Students: Implications for Cellular Phone Use while Driving

Science.gov (United States)

Szyfman, Adam; Wanner, Gregory; Spencer, Leslie

2003-01-01

Two studies were performed to determine the relationship between cellular phone use and either reaction time or performance among college students. In the first study 60 undergraduates completed a computerized reaction time test. Mean reaction times were significantly higher when participants were talking on a cellular phone, either handheld or on…

Magnolol Affects Cellular Proliferation, Polyamine Biosynthesis and Catabolism-Linked Protein Expression and Associated Cellular Signaling Pathways in Human Prostate Cancer Cells in vitro

Directory of Open Access Journals (Sweden)

Brendan T. McKeown

2015-01-01

Full Text Available Background: Prostate cancer is the most commonly diagnosed form of cancer in men in Canada and the United States. Both genetic and environmental factors contribute to the development and progression of many cancers, including prostate cancer. Context and purpose of this study: This study investigated the effects of magnolol, a compound found in the roots and bark of the magnolia tree Magnolia officinalis, on cellular proliferation and proliferation-linked activities of PC3 human prostate cancer cells in vitro. Results: PC3 cells exposed to magnolol at a concentration of 80 μM for 6 hours exhibited decreased protein expression of ornithine decarboxylase, a key regulator in polyamine biosynthesis, as well as affecting the expression of other proteins involved in polyamine biosynthesis and catabolism. Furthermore, protein expression of the R2 subunit of ribonucleotide reductase, a key regulatory protein associated with DNA synthesis, was significantly decreased. Finally, the MAPK (mitogen-activated protein kinase, PI3K (phosphatidylinositol 3-kinase, NFκB (nuclear factor of kappa-light-chain-enhancer of activated B cells and AP-1 (activator protein 1 cellular signaling pathways were assayed to determine which, if any, of these pathways magnolol exposure would alter. Protein expressions of p-JNK-1 and c-jun were significantly increased while p-p38, JNK-1/2, PI3Kp85, p-PI3Kp85, p-Akt, NFκBp65, p-IκBα and IκBα protein expressions were significantly decreased. Conclusions: These alterations further support the anti-proliferative effects of magnolol on PC3 human prostate cancer cells in vitro and suggest that magnolol may have potential as a novel anti-prostate cancer agent.

Phyto-mediated nanostructured carriers based on dual vegetable actives involved in the prevention of cellular damage

Energy Technology Data Exchange (ETDEWEB)

Istrati, D.; Lacatusu, I.; Bordei, N.; Badea, G.; Oprea, O. [University Politehnica of Bucharest, Faculty of Applied Chemistry and Materials Science, Polizu Street No. 1, 011061 Bucharest (Romania); Stefan, L.M. [National Institute of Research and Development for Biological Sciences, Splaiul Independentei Street No. 296, 060031 Bucharest (Romania); Stan, R. [University Politehnica of Bucharest, Faculty of Applied Chemistry and Materials Science, Polizu Street No. 1, 011061 Bucharest (Romania); Badea, N., E-mail: nicoleta.badea@gmail.com [University Politehnica of Bucharest, Faculty of Applied Chemistry and Materials Science, Polizu Street No. 1, 011061 Bucharest (Romania); Meghea, A. [University Politehnica of Bucharest, Faculty of Applied Chemistry and Materials Science, Polizu Street No. 1, 011061 Bucharest (Romania)

2016-07-01

The growing scientific interest in exploitation of vegetable bioactives has raised a number of questions regarding their imminent presence in pharmaceutical formulations. This study intends to demonstrate that a dual combination between vegetable oil (e.g. thistle oil, safflower oil, sea buckthorn oil) and a carrot extract represents an optimal approach to formulate safe carrier systems that manifest cell regeneration effect and promising antioxidant and anti-inflammatory activity. Inclusion of both natural actives into lipid carriers imparted a strong negative charge on the nanocarrier surface (up to − 45 mV) and displayed average sizes of 70 nm to 140 nm. The entrapment efficiency of carrot extract into nanostructured carriers ranged between 78.3 and 88.3%. The in vitro release study has demonstrated that the entrapment of the extract represents a viable way for an equilibrated release of carotenoids. Besides the excellent antioxidant properties (e.g. scavenging up to 98% of the free oxygen radicals), the results of cellular integrity (e.g. cell viability of 133%) recommend these nanocarriers based on dual carrot extract–bioactive oil as a promising trend for the treatment of certain disorders in which oxidative stress plays a prominent role. In addition, the lipid nanocarriers based on safflower oil and sea buckthorn oil demonstrated an anti-inflammatory effect on LPS induced THP-1 macrophages, by inhibiting the secretion of two pro-inflammatory cytokines, IL-6 and TNF-α. - Highlights: • Safety phyto-mediated nanostructured carriers (NLC) based on two kinds of bioactives • Carrot extract incorporation into nanostructured carriers ranged from 78 to 88.3%. • High antioxidant activity of NLC by scavenging up to 98% free oxygen radicals • Extract entrapment represents a viable way for an equilibrated release of carotenoids. • Remarkable regenerative effect of L929 cell, with a proliferation of 133.4%.

Phyto-mediated nanostructured carriers based on dual vegetable actives involved in the prevention of cellular damage

International Nuclear Information System (INIS)

Istrati, D.; Lacatusu, I.; Bordei, N.; Badea, G.; Oprea, O.; Stefan, L.M.; Stan, R.; Badea, N.; Meghea, A.

2016-01-01

The growing scientific interest in exploitation of vegetable bioactives has raised a number of questions regarding their imminent presence in pharmaceutical formulations. This study intends to demonstrate that a dual combination between vegetable oil (e.g. thistle oil, safflower oil, sea buckthorn oil) and a carrot extract represents an optimal approach to formulate safe carrier systems that manifest cell regeneration effect and promising antioxidant and anti-inflammatory activity. Inclusion of both natural actives into lipid carriers imparted a strong negative charge on the nanocarrier surface (up to − 45 mV) and displayed average sizes of 70 nm to 140 nm. The entrapment efficiency of carrot extract into nanostructured carriers ranged between 78.3 and 88.3%. The in vitro release study has demonstrated that the entrapment of the extract represents a viable way for an equilibrated release of carotenoids. Besides the excellent antioxidant properties (e.g. scavenging up to 98% of the free oxygen radicals), the results of cellular integrity (e.g. cell viability of 133%) recommend these nanocarriers based on dual carrot extract–bioactive oil as a promising trend for the treatment of certain disorders in which oxidative stress plays a prominent role. In addition, the lipid nanocarriers based on safflower oil and sea buckthorn oil demonstrated an anti-inflammatory effect on LPS induced THP-1 macrophages, by inhibiting the secretion of two pro-inflammatory cytokines, IL-6 and TNF-α. - Highlights: • Safety phyto-mediated nanostructured carriers (NLC) based on two kinds of bioactives • Carrot extract incorporation into nanostructured carriers ranged from 78 to 88.3%. • High antioxidant activity of NLC by scavenging up to 98% free oxygen radicals • Extract entrapment represents a viable way for an equilibrated release of carotenoids. • Remarkable regenerative effect of L929 cell, with a proliferation of 133.4%

Saccharomyces cerevisiae Ngl3p is an active 3′–5′ exonuclease with a specificity towards poly-A RNA reminiscent of cellular deadenylases

DEFF Research Database (Denmark)

Feddersen, Ane; Dedic, Emil; Poulsen, Esben Guldahl

2012-01-01

RNAs that yeast Ngl3p is a functional 3′–5′ exonuclease most active at slightly acidic conditions. We further show that the enzyme depends on divalent metal ions for activity and possesses specificity towards poly-A RNA similar to what has been observed for cellular deadenylases. The results suggest that Ngl3p...

Giardia-specific cellular immune responses in post-giardiasis chronic fatigue syndrome.

Science.gov (United States)

Hanevik, Kurt; Kristoffersen, Einar; Mørch, Kristine; Rye, Kristin Paulsen; Sørnes, Steinar; Svärd, Staffan; Bruserud, Øystein; Langeland, Nina

2017-01-28

The role of pathogen specific cellular immune responses against the eliciting pathogen in development of post-infectious chronic fatigue syndrome (PI-CFS) is not known and such studies are difficult to perform. The aim of this study was to evaluate specific anti-Giardia cellular immunity in cases that developed CFS after Giardia infection compared to cases that recovered well. Patients reporting chronic fatigue in a questionnaire study three years after a Giardia outbreak were clinically evaluated five years after the outbreak and grouped according to Fukuda criteria for CFS and idiopathic chronic fatigue. Giardia specific immune responses were evaluated in 39 of these patients by proliferation assay, T cell activation and cytokine release analysis. 20 Giardia exposed non-fatigued individuals and 10 healthy unexposed individuals were recruited as controls. Patients were clinically classified into CFS (n = 15), idiopathic chronic fatigue (n = 5), fatigue from other causes (n = 9) and recovered from fatigue (n = 10). There were statistically significant antigen specific differences between these Giardia exposed groups and unexposed controls. However, we did not find differences between the Giardia exposed fatigue classification groups with regard to CD4 T cell activation, proliferation or cytokine levels in 6 days cultured PBMCs. Interestingly, sCD40L was increased in patients with PI-CFS and other persons with fatigue after Giardia infection compared to the non-fatigued group, and correlated well with fatigue levels at the time of sampling. Our data show antigen specific cellular immune responses in the groups previously exposed to Giardia and increased sCD40L in fatigued patients.

A study of the mechanism of action of pyridoxal isonicotinoyl hydrazone at the cellular level using reticulocytes loaded with non-heme 59Fe

International Nuclear Information System (INIS)

Huang, A.R.; Ponka, P.; McGill Univ., Montreal, Quebec; Jewish General Hospital, Montreal, Quebec

1983-01-01

Pyridoxal isonicotinoyl hydrazone (PIH) has recently been identified as a new iron chelating agent with a high degree of iron mobilizing activity in vitro and in vivo which makes this compound a candidate drug in the treatment of iron overload. This study was undertaken to elucidate the mechanism of action of the iron mobilizing activity of PIH at the cellular level. An in vitro system of rabbit reticulocytes with a high level of non-heme 59 Fe was used as a model of iron overload. The effects of various biochemical and physiological manoeuvers on the mobilization of 59 Fe by PIH from the cells were studied. The fate of [ 14 C]-PIH in the in vitro system was also studied. Studies were also carried out using a crude mitochondrial fraction. (orig./AJ)

Glis family proteins are differentially implicated in the cellular reprogramming of human somatic cells.

Science.gov (United States)

Lee, Seo-Young; Noh, Hye Bin; Kim, Hyeong-Taek; Lee, Kang-In; Hwang, Dong-Youn

2017-09-29

The ground-breaking discovery of the reprogramming of somatic cells into pluripotent cells, termed induced pluripotent stem cells (iPSCs), was accomplished by delivering 4 transcription factors, Oct4, Sox2, Klf4, and c-Myc, into fibroblasts. Since then, several efforts have attempted to unveil other factors that are directly implicated in or might enhance reprogramming. Importantly, a number of transcription factors are reported to retain reprogramming activity. A previous study suggested Gli-similar 1 (Glis1) as a factor that enhances the reprogramming of fibroblasts during iPSC generation. However, the implication of other Glis members, including Glis2 and Glis3 (variants 1 and 2), in cellular reprogramming remains unknown. In this study, we investigated the potential involvement of human Glis family proteins, including hGlis1-3, in cellular reprogramming. Our results demonstrate that hGlis1, which is reported to reprogram human fibroblasts, promotes the reprogramming of human adipose-derived stromal cells (hADSCs), indicating that the reprogramming activity of Glis1 is not cell type-specific. Strikingly, hGlis3 promoted the reprogramming of hADSCs as efficiently as hGlis1. On the contrary, hGlis2 showed a strong negative effect on reprogramming. Together, our results reveal clear differences in the cellular reprogramming activity among Glis family members and provide valuable insight into the development of a new reprogramming strategy using Glis family proteins.

[In vitro study over statins effects on cellular growth curves and its reversibility with mevalonate].

Science.gov (United States)

Millan Núñez-Cortés, Jesús; Alvarez Rodriguez, Ysmael; Alvarez Novés, Granada; Recarte Garcia-Andrade, Carlos; Alvarez-Sala Walther, Luis

2014-01-01

HMG-CoA-Reductase inhibitors, also known as statins, are currently the most powerful cholesterol-lowering drugs available on the market. Clinical trials and experimental evidence suggest that statins have heavy anti-atherosclerotic effects. These are in part consequence of lipid lowering but also result from pleiotropic actions of the drugs. These so-called pleiotropic properties affect various aspects of cell function, inflammation, coagulation, and vasomotor activity. These effects are mediated either indirectly through LDL-c reduction or via a direct effect on cellular functions. Although many of the pleiotropic properties of statins may be a class effect, some may be unique to certain agents and account for differences in their pharmacological activity. So, although statins typically have similar effects on LDL-c levels, differences in chemical structure and pharmacokinetic profile can lead to variations in pleiotropic effects. In this paper we analize the in vitro effects of different statins over different cell lines from cells implicated in atherosclerotic process: endothelial cells, fibroblasts, and vascular muscular cells. In relation with our results we can proof that the effects of different dosis of different statins provides singular effects over growth curves of different cellular lines, a despite of a class-dependent effects. So, pleiotropic effects and its reversibility with mevalonate are different according with the molecule and the dosis. Copyright © 2013 Elsevier España, S.L. y SEA. All rights reserved.

Algorithm for cellular reprogramming.

Science.gov (United States)

Ronquist, Scott; Patterson, Geoff; Muir, Lindsey A; Lindsly, Stephen; Chen, Haiming; Brown, Markus; Wicha, Max S; Bloch, Anthony; Brockett, Roger; Rajapakse, Indika

2017-11-07

The day we understand the time evolution of subcellular events at a level of detail comparable to physical systems governed by Newton's laws of motion seems far away. Even so, quantitative approaches to cellular dynamics add to our understanding of cell biology. With data-guided frameworks we can develop better predictions about, and methods for, control over specific biological processes and system-wide cell behavior. Here we describe an approach for optimizing the use of transcription factors (TFs) in cellular reprogramming, based on a device commonly used in optimal control. We construct an approximate model for the natural evolution of a cell-cycle-synchronized population of human fibroblasts, based on data obtained by sampling the expression of 22,083 genes at several time points during the cell cycle. To arrive at a model of moderate complexity, we cluster gene expression based on division of the genome into topologically associating domains (TADs) and then model the dynamics of TAD expression levels. Based on this dynamical model and additional data, such as known TF binding sites and activity, we develop a methodology for identifying the top TF candidates for a specific cellular reprogramming task. Our data-guided methodology identifies a number of TFs previously validated for reprogramming and/or natural differentiation and predicts some potentially useful combinations of TFs. Our findings highlight the immense potential of dynamical models, mathematics, and data-guided methodologies for improving strategies for control over biological processes. Copyright © 2017 the Author(s). Published by PNAS.

Cellular microparticle and thrombogram phenotypes in the Prospective Observational Multicenter Major Trauma Transfusion (PROMMTT) Study: correlation with coagulopathy

Science.gov (United States)

Matijevic, Nena; Wang, Yao-Wei W.; Wade, Charles E.; Holcomb, John B.; Cotton, Bryan A.; Schreiber, Martin A.; Muskat, Peter; Fox, Erin E.; del Junco, Deborah J.; Cardenas, Jessica C.; Rahbar, Mohammad H.; Cohen, Mitchell Jay

2014-01-01

Background Trauma-induced coagulopathy following severe injury is associated with increased bleeding and mortality. Injury may result in alteration of cellular phenotypes and release of cell-derived microparticles (MP). Circulating MPs are procoagulant and support thrombin generation (TG) and clotting. We evaluated MP and TG phenotypes in severely injured patients at admission, in relation to coagulopathy and bleeding. Methods As part of the Prospective Observational Multicenter Major Trauma Transfusion (PROMMTT) study, research blood samples were obtained from 180 trauma patients requiring transfusions at 5 participating centers. Twenty five healthy controls and 40 minimally injured patients were analyzed for comparisons. Laboratory criteria for coagulopathy was activated partial thromboplastin time (APTT) ≥35 sec. Samples were analyzed by Calibrated Automated Thrombogram to assess TG, and by flow cytometry for MP phenotypes [platelet (PMP), erythrocyte (RMP), leukocyte (LMP), endothelial (EMP), tissue factor (TFMP), and Annexin V positive (AVMP)]. Results 21.7% of patients were coagulopathic with the median (IQR) APTT of 44 sec (37, 53), and an Injury Severity Score of 26 (17, 35). Compared to controls, patients had elevated EMP, RMP, LMP, and TFMP (all p<0.001), and enhanced TG (p<0.0001). However, coagulopathic PROMMTT patients had significantly lower PMP, TFMP, and TG, higher substantial bleeding, and higher mortality compared to non-coagulopathic patients (all p<0.001). Conclusions Cellular activation and enhanced TG are predominant after trauma and independent of injury severity. Coagulopathy was associated with lower thrombin peak and rate compared to non-coagulopathic patients, while lower levels of TF-bearing PMPs were associated with substantial bleeding. PMID:25086657

The relationships between body mass index and television viewing, internet use and cellular phone use: the moderating effects of socio-demographic characteristics and exercise.

Science.gov (United States)

Yen, Cheng-Fang; Hsiao, Ray C; Ko, Chih-Hung; Yen, Ju-Yu; Huang, Chi-Fen; Liu, Shu-Chun; Wang, Shing-Yaw

2010-09-01

This study aimed to examine the relationships between body mass index (BMI) and television viewing, Internet use and cellular phone use and the moderators for these relationships in adolescents. The relationship between BMI and the time spent on three kinds of sedentary activities and the moderators for these relationships were analyzed among 9,278 Taiwanese adolescents. The different relationships between BMI and various Internet and cellular phone-related activities were analyzed. High television viewing and high Internet use were associated with increased BMI in adolescents. Exercising had a moderating effect on the relationship between BMI and television viewing. Several Internet and cellular phone-related activities were associated with increased BMI. The results support the relationships between adolescent BMI and television viewing and Internet use. The moderating effect of exercise and various Internet and cellular phone-related activities should be considered when developing intervention strategies for overweight adolescents. © 2009 by Wiley Periodicals, Inc.

An agent-based model of cellular dynamics and circadian variability in human endotoxemia.

Directory of Open Access Journals (Sweden)

Tung T Nguyen

Full Text Available As cellular variability and circadian rhythmicity play critical roles in immune and inflammatory responses, we present in this study an agent-based model of human endotoxemia to examine the interplay between circadian controls, cellular variability and stochastic dynamics of inflammatory cytokines. The model is qualitatively validated by its ability to reproduce circadian dynamics of inflammatory mediators and critical inflammatory responses after endotoxin administration in vivo. Novel computational concepts are proposed to characterize the cellular variability and synchronization of inflammatory cytokines in a population of heterogeneous leukocytes. Our results suggest that there is a decrease in cell-to-cell variability of inflammatory cytokines while their synchronization is increased after endotoxin challenge. Model parameters that are responsible for IκB production stimulated by NFκB activation and for the production of anti-inflammatory cytokines have large impacts on system behaviors. Additionally, examining time-dependent systemic responses revealed that the system is least vulnerable to endotoxin in the early morning and most vulnerable around midnight. Although much remains to be explored, proposed computational concepts and the model we have pioneered will provide important insights for future investigations and extensions, especially for single-cell studies to discover how cellular variability contributes to clinical implications.

BRD4 regulates cellular senescence in gastric cancer cells via E2F/miR-106b/p21 axis.

Science.gov (United States)

Dong, Xingchen; Hu, Xiangming; Chen, Jinjing; Hu, Dan; Chen, Lin-Feng

2018-02-12

Small molecules targeting bromodomains of BET proteins possess strong anti-tumor activities and have emerged as potential therapeutics for cancer. However, the underlying mechanisms for the anti-proliferative activity of these inhibitors are still not fully characterized. In this study, we demonstrated that BET inhibitor JQ1 suppressed the proliferation and invasiveness of gastric cancer cells by inducing cellular senescence. Depletion of BRD4, which was overexpressed in gastric cancer tissues, but not other BET proteins recapitulated JQ1-induced cellular senescence with increased cellular SA-β-Gal activity and elevated p21 levels. In addition, we showed that the levels of p21 were regulated at the post-transcriptional level by BRD4-dependent expression of miR-106b-5p, which targets the 3'-UTR of p21 mRNA. Overexpression of miR-106b-5p prevented JQ1-induced p21 expression and BRD4 inhibition-associated cellular senescence, whereas miR-106b-5p inhibitor up-regulated p21 and induced cellular senescence. Finally, we demonstrated that inhibition of E2F suppressed the binding of BRD4 to the promoter of miR-106b-5p and inhibited its transcription, leading to the increased p21 levels and cellular senescence in gastric cancer cells. Our results reveal a novel mechanism by which BRD4 regulates cancer cell proliferation by modulating the cellular senescence through E2F/miR-106b-5p/p21 axis and provide new insights into using BET inhibitors as potential anticancer drugs.

Targeting Mitochondria to Counteract Age-Related Cellular Dysfunction

Directory of Open Access Journals (Sweden)

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.

Tat-dependent repression of human immunodeficiency virus type 1 long terminal repeat promoter activity by fusion of cellular transcription factors

International Nuclear Information System (INIS)

Zhao Cunyou; Chen Yali; Park, Jiyoung; Kim, Jae Bum; Tang Hong

2004-01-01

Transcription initiation from HIV-1 long terminal repeat (LTR) promoter requires the virally encoded transactivator, Tat, and several cellular co-factors to accomplish the Tat-dependent processive transcription elongation. Individual cellular transcription activators, LBP-1b and Oct-1, on the other hand, have been shown to inhibit LTR promoter activities probably via competitive binding against TFIID to the TATA-box in LTR promoter. To explore the genetic interference strategies against the viral replication, we took advantage of the existence of the bipartite DNA binding domains and the repression domains of LBP-1b and Oct-1 factors to generate a chimeric transcription repressor. Our results indicated that the fusion protein of LBP-1b and Oct-1 exhibited higher DNA binding affinity to the viral promoter than the individual factors, and little interference with the host cell gene expression due to its anticipated rare cognate DNA sites in the host cell genome. Moreover, the chimera exerted increased Tat-dependent repression of transcription initiation at the LTR promoter both in vitro and in vivo compared to LBP-1b, Oct-1 or combination of LBP-1b and Oct-1. These results might provide the lead in generating a therapeutic reagent useful to suppress HIV-1 replication

Cellular telephone use among primary school children in Germany

International Nuclear Information System (INIS)

Boehler, Eva; Schuez, Joachim

2004-01-01

Background: There is some concern about potential health risks of cellular telephone use to children. We assessed data on how many children own a cellular telephone and on how often they use it in a population-based sample. Methods: We carried out a cross-sectional study among children in their fourth elementary school year, with a median-age of 10 years. The study was carried out in Mainz (Germany), a city with about 200,000 inhabitants. The study base comprised all 37 primary schools in Mainz and near surroundings. Altogether, 1933 children from 34 primary schools took part in the survey (participation rate of 87.8%). Results: Roughly a third of all children (n = 671, 34.7%) reported to own a cellular telephone. Overall, 119 (6.2%) children used a cellular telephone for making calls at least once a day, 123 (6.4%) used it several times a week and 876 (45.3%) children used it only once in a while. The remaining 805 (41.6%) children had never used a cellular telephone. The probability of owning a cellular telephone among children was associated with older age, being male, having no siblings, giving full particulars to height and weight, more time spent watching TV and playing computer games, being picked up by their parents from school by car (instead of walking or cycling) and going to bed late. The proportion of cellular telephone owners was somewhat higher in classes with more children from socially disadvantaged families. Conclusions: Our study shows that both ownership of a cellular telephone as well as the regular use of it are already quite frequent among children in the fourth grade of primary school. With regard to potential long-term effects, we recommend follow-up studies with children

Activation of human natural killer cells by the soluble form of cellular prion protein

International Nuclear Information System (INIS)

Seong, Yeon-Jae; Sung, Pil Soo; Jang, Young-Soon; Choi, Young Joon; Park, Bum-Chan; Park, Su-Hyung; Park, Young Woo; Shin, Eui-Cheol

2015-01-01

Cellular prion protein (PrP C ) is widely expressed in various cell types, including cells of the immune system. However, the specific roles of PrP C in the immune system have not been clearly elucidated. In the present study, we investigated the effects of a soluble form of recombinant PrP C protein on human natural killer (NK) cells. Recombinant soluble PrP C protein was generated by fusion of human PrP C with the Fc portion of human IgG 1 (PrP C -Fc). PrP C -Fc binds to the surface of human NK cells, particularly to CD56 dim NK cells. PrP C -Fc induced the production of cytokines and chemokines and the degranulation of granzyme B from NK cells. In addition, PrP C -Fc facilitated the IL-15-induced proliferation of NK cells. PrP C -Fc induced phosphorylation of ERK-1/2 and JNK in NK cells, and inhibitors of the ERK or the JNK pathways abrogated PrP C -Fc-induced cytokine production in NK cells. In conclusion, the soluble form of recombinant PrP C -Fc protein activates human NK cells via the ERK and JNK signaling pathways. - Highlights: • Recombinant soluble PrP C (PrP C -Fc) was generated by fusion of human PrP C with IgG1 Fc portion. • PrP C -Fc protein induces the production of cytokines and degranulation from human NK cells. • PrP C -Fc protein enhances the IL-15-induced proliferation of human NK cells. • PrP C -Fc protein activates human NK cells via the ERK and JNK signaling pathways

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.

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.

Reduced labor and condensed schedules with cellular concrete solutions

Energy Technology Data Exchange (ETDEWEB)

Lavis, D. [CEMATRIX Inc., Calgary, AB (Canada)

2008-07-01

This paper discussed the use of cellular concrete materials in oil sands tank base foundation systems, shallow buried utility insulation systems, roadways, slabs, and buried modules. The concrete is formed from Portland cement, water, specialized pre-formed foaming agents, and air mixed in controlled proportions. Fly ash and polypropylene or glass fibers can also be used as additions. Cellular concrete can often be used to speed up construction and minimize labour requirements. Cellular concrete can be cast-in-place, and has soil-stabilizing and self-compacting features. The concrete can be produced and placed on-site at rates exceeding 120 cubic meters per hour. Cellular concrete can be pumped into place over long distances through flexible hoses. A case study comparing the cellular concrete to traditional plastic foam insulation was used to demonstrate the equivalency and adequacy of insulation, structural properties and installation costs. The study showed that although the cellular concrete had a high installation cost, greater compressive strength was gained. The concrete was self-levelling and did not require compaction or vibration. The use of the cellular concrete resulted in an accelerated construction schedule. 6 refs., 2 tabs., 6 figs.

Discovery of imidazopyridine derivatives as novel c-Met kinase inhibitors: Synthesis, SAR study, and biological activity.

Science.gov (United States)

Yang, Yifei; Zhang, Yuan; Yang, LingYun; Zhao, Leilei; Si, Lianghui; Zhang, Huibin; Liu, Qingsong; Zhou, Jinpei

2017-02-01

Receptor tyrosine kinase c-Met acts as an alternative angiogenic pathway in the process and contents of cancers. A series of imidazopyridine derivatives were designed and synthesized according to the established docking studies as possible c-Met inhibitors. Most of these imidazopyridine derivatives displayed nanomolar potency against c-Met in both biochemical enzymatic screens and cellular pharmacology studies. Especially, compound 7g exhibited the most inhibitory activity against c-Met with IC 50 of 53.4nM and 253nM in enzymatic and cellular level, respectively. Following that, the compound 7g was docked into the protein of c-Met and the structure-activity relationship was analyzed in detail. These findings indicated that the novel imidazopyridine derivative compound 7g was a potential c-Met inhibitor deserving further investigation for cancer treatment. Copyright © 2016. Published by Elsevier Inc.

Facilitating arrhythmia simulation: the method of quantitative cellular automata modeling and parallel running

Directory of Open Access Journals (Sweden)

Mondry Adrian

2004-08-01

Full Text Available Abstract Background Many arrhythmias are triggered by abnormal electrical activity at the ionic channel and cell level, and then evolve spatio-temporally within the heart. To understand arrhythmias better and to diagnose them more precisely by their ECG waveforms, a whole-heart model is required to explore the association between the massively parallel activities at the channel/cell level and the integrative electrophysiological phenomena at organ level. Methods We have developed a method to build large-scale electrophysiological models by using extended cellular automata, and to run such models on a cluster of shared memory machines. We describe here the method, including the extension of a language-based cellular automaton to implement quantitative computing, the building of a whole-heart model with Visible Human Project data, the parallelization of the model on a cluster of shared memory computers with OpenMP and MPI hybrid programming, and a simulation algorithm that links cellular activity with the ECG. Results We demonstrate that electrical activities at channel, cell, and organ levels can be traced and captured conveniently in our extended cellular automaton system. Examples of some ECG waveforms simulated with a 2-D slice are given to support the ECG simulation algorithm. A performance evaluation of the 3-D model on a four-node cluster is also given. Conclusions Quantitative multicellular modeling with extended cellular automata is a highly efficient and widely applicable method to weave experimental data at different levels into computational models. This process can be used to investigate complex and collective biological activities that can be described neither by their governing differentiation equations nor by discrete parallel computation. Transparent cluster computing is a convenient and effective method to make time-consuming simulation feasible. Arrhythmias, as a typical case, can be effectively simulated with the methods

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.

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

Science.gov (United States)

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.

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

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.

Driver hand-held cellular phone use: a four-year analysis.

Science.gov (United States)

Eby, David W; Vivoda, Jonathon M; St Louis, Renée M

2006-01-01

The use of hand-held cellular (mobile) phones while driving has stirred more debate, passion, and research than perhaps any other traffic safety issue in the past several years. There is ample research showing that the use of either hand-held or hands-free cellular phones can lead to unsafe driving patterns. Whether or not these performance deficits increase the risk of crash is difficult to establish, but recent studies are beginning to suggest that cellular phone use elevates crash risk. The purpose of this study was to assess changes in the rate of hand-held cellular phone use by motor-vehicle drivers on a statewide level in Michigan. This study presents the results of 13 statewide surveys of cellular phone use over a 4-year period. Hand-held cellular phone use data were collected through direct observation while vehicles were stopped at intersections and freeway exit ramps. Data were weighted to be representative of all drivers traveling during daylight hours in Michigan. The study found that driver hand-held cellular phone use has more than doubled between 2001 and 2005, from 2.7% to 5.8%. This change represents an average increase of 0.78 percentage points per year. The 5.8% use rate observed in 2005 means that at any given daylight hour, around 36,550 drivers were conversing on cellular phones while driving on Michigan roadways. The trend line fitted to these data predicts that by the year 2010, driver hand-held cellular phone use will be around 8.6%, or 55,000 drivers at any given daylight hour. These results make it clear that cellular phone use while driving will continue to be an important traffic safety issue, and highlight the importance of continued attempts to generate new ways of alleviating this potential hazard.

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

Human T lymphotropic virus type-1 p30II alters cellular gene expression to selectively enhance signaling pathways that activate T lymphocytes

Directory of Open Access Journals (Sweden)

Feuer Gerold

2004-11-01

Full Text Available Abstract Background Human T-lymphotropic virus type-1 (HTLV-1 is a deltaretrovirus that causes adult T-cell leukemia/lymphoma and is implicated in a variety of lymphocyte-mediated disorders. HTLV-1 contains both regulatory and accessory genes in four pX open reading frames. pX ORF-II encodes two proteins, p13II and p30II, which are incompletely defined in the virus life cycle or HTLV-1 pathogenesis. Proviral clones of the virus with pX ORF-II mutations diminish the ability of the virus to maintain viral loads in vivo. Exogenous expression of p30II differentially modulates CREB and Tax-responsive element-mediated transcription through its interaction with CREB-binding protein/p300 and represses tax/rex RNA nuclear export. Results Herein, we further characterized the role of p30II in regulation of cellular gene expression, using stable p30II expression system employing lentiviral vectors to test cellular gene expression with Affymetrix U133A arrays, representing ~33,000 human genes. Reporter assays in Jurkat T cells and RT-PCR in Jurkat and primary CD4+ T-lymphocytes were used to confirm selected gene expression patterns. Our data reveals alterations of interrelated pathways of cell proliferation, T-cell signaling, apoptosis and cell cycle in p30II expressing Jurkat T cells. In all categories, p30II appeared to be an overall repressor of cellular gene expression, while selectively increasing the expression of certain key regulatory genes. Conclusions We are the first to demonstrate that p30II, while repressing the expression of many genes, selectively activates key gene pathways involved in T-cell signaling/activation. Collectively, our data suggests that this complex retrovirus, associated with lymphoproliferative diseases, relies upon accessory gene products to modify cellular environment to promote clonal expansion of the virus genome and thus maintain proviral loads in vivo.

Identification of human genes involved in cellular responses to ionizing radiation: molecular and cellular studies of gene encoding the p68 helicase in mammalian cells

International Nuclear Information System (INIS)

Menaa, F.

2003-12-01

Cells submitted to genotoxic factors -like IR- activate several and important mechanisms such as repair, cell cycle arrest or 'apoptosis' to maintain genetic integrity. So, the damaged cells will induce many and different genes. The human transcriptome analysis by 'SSH' method in a human breast carcinoma cell line MCF7 γ-irradiated versus not irradiated, allowed to identify about one hundred genes. Among of these genes, we have focused our study on a radio-induced gene encoding the p68 helicase. In the conditions of irradiation used, our results show that the kinetic and the regulation of this gene expression differs between the nature of radiations used. Indeed, in γ-irradiated mammalian cells, ATM, a protein kinase activated by DSB and IR, is required to induce quickly P68 gene via the important transcription factor p53 stabilized by IR. In the case of UVC-irradiated cells, the P68 gene induction is late and the intracellular signalling pathway that lead to this induction is independent from the p53 protein. Finally, we show that the p68 protein under-expression is responsible for an increased radiosensitivity of MCF7 cells. Consequently, we can postulate that the p68 protein is involved in cellular responses to radiations to reduce the increased radiosensitivity of cells exposed to γ-rays. (author)

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.

Activation Mechanism of LRRK2 and Its Cellular Functions in Parkinson's Disease

NARCIS (Netherlands)

Rosenbusch, Katharina E.; Kortholt, Arjan

2016-01-01

Human LRRK2 (Leucine-Rich Repeat Kinase 2) has been associated with both familial and idiopathic Parkinson's disease (PD). Although several LRRK2 mediated pathways and interaction partners have been identified, the cellular functions of LRRK2 and LRRK2 mediated progression of PD are still only

Cellular response to alkylating agent MNNG is impaired in STAT1-deficients cells.

Science.gov (United States)

Ah-Koon, Laurent; Lesage, Denis; Lemadre, Elodie; Souissi, Inès; Fagard, Remi; Varin-Blank, Nadine; Fabre, Emmanuelle E; Schischmanoff, Olivier

2016-10-01

The SN 1 alkylating agents activate the mismatch repair system leading to delayed G2 /M cell cycle arrest and DNA repair with subsequent survival or cell death. STAT1, an anti-proliferative and pro-apoptotic transcription factor is known to potentiate p53 and to affect DNA-damage cellular response. We studied whether STAT1 may modulate cell fate following activation of the mismatch repair system upon exposure to the alkylating agent N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Using STAT1-proficient or -deficient cell lines, we found that STAT1 is required for: (i) reduction in the extent of DNA lesions, (ii) rapid phosphorylation of T68-CHK2 and of S15-p53, (iii) progression through the G2 /M checkpoint and (iv) long-term survival following treatment with MNNG. Presence of STAT1 is critical for the formation of a p53-DNA complex comprising: STAT1, c-Abl and MLH1 following exposure to MNNG. Importantly, presence of STAT1 allows recruitment of c-Abl to p53-DNA complex and links c-Abl tyrosine kinase activity to MNNG-toxicity. Thus, our data highlight the important modulatory role of STAT1 in the signalling pathway activated by the mismatch repair system. This ability of STAT1 to favour resistance to MNNG indicates the targeting of STAT1 pathway as a therapeutic option for enhancing the efficacy of SN1 alkylating agent-based chemotherapy. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Cellular uptake and cytotoxic potential of respirable bentonite particles with different quartz contents and chemical modifications in human lung fibroblasts

Energy Technology Data Exchange (ETDEWEB)

Geh, Stefan; Rettenmeier, Albert W.; Dopp, Elke [University Hospital, Institute of Hygiene and Occupational Medicine, Essen (Germany); Yuecel, Raif [University Hospital, Institute of Cell Biology (Cancer Research), Essen (Germany); Duffin, Rodger [Institute of Environmental Health Research (IUF), Duesseldorf (Germany); University of Edinburgh, ELEGI COLT Lab, Scotland (United Kingdom); Albrecht, Catrin; Borm, Paul J.A. [Institute of Environmental Health Research (IUF), Duesseldorf (Germany); Armbruster, Lorenz [Verein fuer Technische Sicherheit und Umweltschutz e.V., Gotha (Germany); Raulf-Heimsoth, Monika; Bruening, Thomas [Research Institute for Occupational Medicine of the Institutions for Statutory Accident Insurance and Prevention (BGFA), Bochum (Germany); Hoffmann, Eik [University of Rostock, Institute of Biology, Department of Cell Biology and Biosystems Technology, Rostock (Germany)

2006-02-01

Considering the biological reactivity of pure quartz in lung cells, there is a strong interest to clarify the cellular effects of respirable siliceous dusts, like bentonites. In the present study, we investigated the cellular uptake and the cytotoxic potential of bentonite particles (Oe< 10 {mu}m) with an {alpha}-quartz content of up to 6% and different chemical modifications (activation: alkaline, acidic, organic) in human lung fibroblasts (IMR90). Additionally, the ability of the particles to induce apoptosis in IMR90-cells and the hemolytic activity was tested. All bentonite samples were tested for endotoxins with the in vitro-Pyrogen test and were found to be negative. Cellular uptake of particles by IMR90-cells was studied by transmission electron microscopy (TEM). Cytotoxicity was analyzed in IMR90-cells by determination of viable cells using flow cytometry and by measuring of the cell respiratory activity. Induced apoptotic cells were detected by AnnexinV/Propidiumiodide-staining and gel electrophoresis. Our results demonstrate that activated bentonite particles are better taken up by IMR90-cells than untreated (native) bentonite particles. Also, activated bentonite particles with a quartz content of 5-6% were more cytotoxic than untreated bentonites or bentonites with a quartz content lower than 4%. The bentonite samples induced necrotic as well as apoptotic cell death. In general, bentonites showed a high membrane-damaging potential shown as hemolytic activity in human erythrocytes. We conclude that cellular effects of bentonite particles in human lung cells are enhanced after chemical treatment of the particles. The cytotoxic potential of the different bentonites is primarily characterized by a strong lysis of the cell membrane. (orig.)

A generalized cellular automata approach to modeling first order ...

Indian Academy of Sciences (India)

... inhibitors deforming the allosteric site or inhibitors changing the structure of active ... Cell-based models with discrete state variables, such as Cellular Automata ... capture the essential features of a discrete real system, consisting of space, ...

Cellular communication through light.

Directory of Open Access Journals (Sweden)

Daniel Fels

Full Text Available Information transfer is a fundamental of life. A few studies have reported that cells use photons (from an endogenous source as information carriers. This study finds that cells can have an influence on other cells even when separated with a glass barrier, thereby disabling molecule diffusion through the cell-containing medium. As there is still very little known about the potential of photons for intercellular communication this study is designed to test for non-molecule-based triggering of two fundamental properties of life: cell division and energy uptake. The study was performed with a cellular organism, the ciliate Paramecium caudatum. Mutual exposure of cell populations occurred under conditions of darkness and separation with cuvettes (vials allowing photon but not molecule transfer. The cell populations were separated either with glass allowing photon transmission from 340 nm to longer waves, or quartz being transmittable from 150 nm, i.e. from UV-light to longer waves. Even through glass, the cells affected cell division and energy uptake in neighboring cell populations. Depending on the cuvette material and the number of cells involved, these effects were positive or negative. Also, while paired populations with lower growth rates grew uncorrelated, growth of the better growing populations was correlated. As there were significant differences when separating the populations with glass or quartz, it is suggested that the cell populations use two (or more frequencies for cellular information transfer, which influences at least energy uptake, cell division rate and growth correlation. Altogether the study strongly supports a cellular communication system, which is different from a molecule-receptor-based system and hints that photon-triggering is a fine tuning principle in cell chemistry.

SPATIAL DEFORESTATION MODELILNG USING CELLULAR AUTOMATA (CASE STUDY: CENTRAL ZAGROS FORESTS

Directory of Open Access Journals (Sweden)

M. Naghdizadegan

2013-09-01

Full Text Available Forests have been highly exploited in recent decades in Iran and deforestation is going to be the major environmental concern due to its role in destruction of natural ecosystem and soil cover. Therefore, finding the effective parameters in deforestation and simulation of this process can help the management and preservation of forests. It helps predicting areas of deforestation in near future which is a useful tool for making socioeconomic disciplines in order to prevent deforestation in the area. Recently, GIS technologies are widely employed to support public policies in order to preserve ecosystems from undesirable human activities. The aim of this study is modelling the distribution of forest destruction in part of Central Zagros Mountains and predicting its process in future. In this paper we developed a Cellular Automata (CA model for deforestation process due to its high performance in spatial modelling, land cover change prediction and its compatibility with GIS. This model is going to determine areas with deforestation risk in the future. Land cover maps were explored using high spatial resolution satellite imageries and the forest land cover was extracted. In order to investigate the deforestation modelling, major elements of forest destruction relating to human activity and also physiographic parameters was explored and the suitability map was produced. Then the suitability map in combination with neighbourhood parameter was used to develop the CA model. Moreover, neighbourhood, suitability and stochastic disturbance term were calibrated in order to improve the simulation results. Regarding this, several neighbourhood configurations and different temporal intervals were tested. The accuracy of model was evaluated using satellite image. The results showed that the developed CA model in this research has proper performance in simulation of deforestation process. This model also predicted the areas with high potential for future

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

Science.gov (United States)

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.

Cellular Phone Users- Willingness to Shop Online

OpenAIRE

Norazah Mohd Suki; Norbayah Mohd Suki

2009-01-01

This study aims to identify cellular phone users- shopping motivating factors towards online shopping. 100 university students located in Klang Valley, Malaysia were involved as the respondents. They were required to complete a set of questionnaire and had to own a cellular phone in order to be selected as sample in this study. Three from five proposed hypotheses were supported: purchasing information, shopping utilities and service quality. As a result, marketers and retailers should concent...

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...

Pathogenesis of pulmonary emphysema – cellular and molecular events

Directory of Open Access Journals (Sweden)

Antonio Di Petta

2010-06-01

Full Text Available Pulmonary emphysema is a chronic obstructive disease, resulting fromimportant alterations in the whole distal structure of terminal bronchioles, either by enlargement of air spaces or by destruction of the alveolar wall, leading to loss of respiratory surface, decreased elastic recoil and lung hyperinflation. For many years, the hypothesis of protease-antiprotease unbalance prevailed as the central theme in the pathogenesis of pulmonary emphysema. According to this hypothesis, the release of active proteolytic enzymes, produced mainly by neutrophils and macrophages, degrades the extracellular matrix, affecting the integrity of its components, especially collagen and elastic fibers. However, new concepts involving cellular and molecular events were proposed, including oxidative stress, cell apoptosis, cellular senescence and failed lung tissue repair. The aim of this review paper was to evaluate the cellular and molecular mechanisms seen in the pathogenesis of pulmonary emphysema.

Mitochondrial dysfunction induced by frataxin deficiency is associated with cellular senescence and abnormal calcium metabolism

Directory of Open Access Journals (Sweden)

Arantxa eBolinches-Amorós

2014-05-01

Full Text Available Friedreich ataxia is considered a neurodegenerative disorder involving both the peripheral and central nervous systems. Dorsal root ganglia (DRG are the major target tissue structures. This neuropathy is caused by mutations in the FXN gene that encodes frataxin. Here, we investigated the mitochondrial and cell consequences of frataxin depletion in a cellular model based on frataxin silencing in SH-SY5Y human neuroblastoma cells, a cell line that has been used widely as in vitro models for studies on neurological diseases. We showed that the reduction of frataxin induced mitochondrial dysfunction due to a bioenergetic deficit and abnormal Ca2+ homeostasis in the mitochondria that were associated with oxidative and endoplasmic reticulum stresses. The depletion of frataxin did not cause cell death but increased autophagy, which may have a cytoprotective effect against cellular insults such as oxidative stress. Frataxin silencing provoked slow cell growth associated with cellular senescence, as demonstrated by increased SA-βgal activity and cell cycle arrest at the G1 phase. We postulate that cellular senescence might be related to a hypoplastic defect in the DRG during neurodevelopment, as suggested by necropsy studies.

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

Science.gov (United States)

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.

Evaluation of Cellular Phenotypes Implicated in Immunopathogenesis and Monitoring Immune Reconstitution Inflammatory Syndrome in HIV/Leprosy Cases

Science.gov (United States)

Giacoia-Gripp, Carmem Beatriz Wagner; Sales, Anna Maria; Nery, José Augusto da Costa; Santos-Oliveira, Joanna Reis; de Oliveira, Ariane Leite; Sarno, Euzenir Nunes; Morgado, Mariza Gonçalves

2011-01-01

Background It is now evident that HAART-associated immunological improvement often leads to a variety of new clinical manifestations, collectively termed immune reconstitution inflammatory syndrome, or IRIS. This phenomenon has already been described in cases of HIV coinfection with Mycobacterium leprae, most of them belonging to the tuberculoid spectrum of leprosy disease, as observed in leprosy reversal reaction (RR). However, the events related to the pathogenesis of this association need to be clarified. This study investigated the immunological profile of HIV/leprosy patients, with special attention to the cellular activation status, to better understand the mechanisms related to IRIS/RR immunopathogenesis, identifying any potential biomarkers for IRIS/RR intercurrence. Methods/Principal Findings Eighty-five individuals were assessed in this study: HIV/leprosy and HIV-monoinfected patients, grouped according to HIV-viral load levels, leprosy patients without HIV coinfection, and healthy controls. Phenotypes were evaluated by flow cytometry for T cell subsets and immune differentiation/activation markers. As expected, absolute counts of the CD4+ and CD8+ T cells from the HIV-infected individuals changed in relation to those of the leprosy patients and controls. However, there were no significant differences among the groups, whether in the expression of cellular differentiation phenotypes or cellular activation, as reflected by the expression of CD38 and HLA-DR. Six HIV/leprosy patients identified as IRIS/RR were analyzed during IRIS/RR episodes and after prednisone treatment. These patients presented high cellular activation levels regarding the expression of CD38 in CD8+ cells T during IRIS/RR (median: 77,15%), dropping significantly (pleprosy individuals at risk for IRIS/RR. So, a comparative investigation to leprosy patients at RR should be conducted. PMID:22205964

Decreased Fc receptor expression on innate immune cells is associated with impaired antibody-mediated cellular phagocytic activity in chronically HIV-1 infected individuals.

Science.gov (United States)

Dugast, Anne-Sophie; Tonelli, Andrew; Berger, Christoph T; Ackerman, Margaret E; Sciaranghella, Gaia; Liu, Qingquan; Sips, Magdalena; Toth, Ildiko; Piechocka-Trocha, Alicja; Ghebremichael, Musie; Alter, Galit

2011-07-05

In addition to neutralization, antibodies mediate other antiviral activities including antibody-dependent cellular phagocytosis (ADCP), antibody-dependent cellular cytotoxicity (ADCC), as well as complement deposition. While it is established that progressive HIV infection is associated with reduced ADCC and ADCP, the underlying mechanism for this loss of function is unknown. Here we report considerable changes in FcR expression over the course of HIV infection on both mDCs and monocytes, including elevated FcγRI expression in acute HIV infection and reduced expression of FcγRII and FcγRIIIa in chronic HIV infection. Furthermore, selective blockade of FcγRII alone was associated with a loss in ADCP activity, suggesting that FcγRII plays a central role in modulating ADCP. Overall, HIV infection is associated with a number of changes in FcR expression on phagocytic cells that are associated with changes in their ability to respond to antibody-opsonized targets, potentially contributing to a failure in viral clearance in progressive HIV-1 infection. Copyright © 2011 Elsevier Inc. All rights reserved.

Decreased Fc-Receptor expression on innate immune cells is associated with impaired antibody mediated cellular phagocytic activity in chronically HIV-1 infected individuals

Science.gov (United States)

Dugast, Anne-Sophie; Tonelli, Andrew; Berger, Christoph T.; Ackerman, Margaret E.; Sciaranghella, Gaia; Liu, Qingquan; Sips, Magdalena; Toth, Ildiko; Piechocka-Trocha, Alicja; Ghebremichael, Musie; Alter, Galit

2011-01-01

In addition to neutralization, antibodies mediate other antiviral activities including antibody-dependent cellular-phagocytosis (ADCP), antibody dependent cellular-cytotoxicity (ADCC), as well as complement deposition. While it is established that progressive HIV infection is associated with reduced ADCC and ADCP, the underlying mechanism for this loss of function is unknown. Here we report considerable changes in FcR expression over the course of HIV infection on both mDCs and monocytes, including elevated FcγRI expression in acute HIV infection and reduced expression of FcγRII and FcγRIIIa in chronic HIV infection. Furthermore, selective blockade of FcγRII alone was associated with a loss in ADCP activity, suggesting that FcγRII plays a central role in modulating ADCP. Overall, HIV infection is associated with a number of changes in FcR expression on phagocytic cells that are associated with changes in their ability to respond to antibody-opsonized targets, potentially contributing to a failure in viral clearance in progressive HIV-1 infection. PMID:21565376

The study of selective accumulation of radionuclides cesium 137, strontium 90 and cerium 144 in the cellular compartments of charophyta algae

International Nuclear Information System (INIS)

Marchyulenene, D.P.; Moteyunene, E.B.; Gudavichene, N.A.; Polikarpov, G.G.

1976-01-01

The study of the accumulation of 137 Cs, 90 Sr and 144 Ce in separate compartments of Chara algae (cellular wall, protoplasm, vacuoles), testifies to the fact that the entrance and accumulation level of the radionuclides depend upon the selective permeability of the cellular wall and plasmalemma, which is regulated both by the ratio of the chemical analogues of the radionuclides in the medium, and by the level of cellular metabolism [fr

Dual inhibition of γ-oryzanol on cellular melanogenesis: inhibition of tyrosinase activity and reduction of melanogenic gene expression by a protein kinase A-dependent mechanism.

Science.gov (United States)

Jun, Hee-jin; Lee, Ji Hae; Cho, Bo-Ram; Seo, Woo-Duck; Kang, Hang-Won; Kim, Dong-Woo; Cho, Kang-Jin; Lee, Sung-Joon

2012-10-26

The in vitro effects on melanogenesis of γ-oryzanol (1), a rice bran-derived phytosterol, were investigated. The melanin content in B16F1 cells was significantly and dose-dependently reduced (-13% and -28% at 3 and 30 μM, respectively). Tyrosinase enzyme activity was inhibited by 1 both in a cell-free assay and when analyzed based on the measurement of cellular tyrosinase activity. Transcriptome analysis was performed to investigate the biological pathways altered by 1, and it was found that gene expression involving protein kinase A (PKA) signaling was markedly altered. Subsequent analyses revealed that 1 stimulation in B16 cells reduced cytosolic cAMP concentrations, PKA activity (-13% for cAMP levels and -40% for PKA activity), and phosphorylation of the cAMP-response element binding protein (-57%), which, in turn, downregulated the expression of microphthalmia-associated transcription factor (MITF; -59% for mRNA and -64% for protein), a key melanogenic gene transcription factor. Accordingly, tyrosinase-related protein 1 (TRP-1; -69% for mRNA and -82% for protein) and dopachrome tautomerase (-51% for mRNA and -92% for protein) in 1-stimulated B16F1 cells were also downregulated. These results suggest that 1 has dual inhibitory activities for cellular melanogenesis by inhibiting tyrosinase enzyme activity and reducing MITF and target genes in the PKA-dependent pathway.

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

Protective effect of gallic acid and Syzygium cumini extract against oxidative stress-induced cellular injury in human lymphocytes.

Science.gov (United States)

De Bona, Karine Santos; Bonfanti, Gabriela; Bitencourt, Paula Eliete Rodrigues; da Silva, Thainan Paz; Borges, Raphaela Maleski; Boligon, Aline; Pigatto, Aline; Athayde, Margareth Lynde; Moretto, Maria Beatriz

2016-01-01

Syzygium cumini (Myrtaceae) presents antioxidant, anti-inflammatory, hypoglycemic and antibacterial effects; however, the cellular and molecular mechanisms of action in the immune system are not yet completely elucidated. This study evaluates the in vitro effect of gallic acid and aqueous S. cumini leaf extract (ASc) on adenosine deaminase (ADA) and dipeptidyl peptidase IV (DPP-IV) activities, cell viability and oxidative stress parameters in lymphocytes exposed to 2, 2'-azobis-2-amidinopropane dihydrochloride (AAPH). Lymphocytes were incubated with ASc (100 and 500 µg/ml) and gallic acid (50 and 200 µM) at 37 °C for 30 min followed by incubation with AAPH (1 mM) at 37 °C for 2 h. After the incubation time, the lymphocytes were used for determinations of ADA, DPP-IV and lactate dehydrogenase (LDH) activities, lipid peroxidation, protein thiol (P-SH) group levels and cellular viability by colorimetric methods. (i) HPLC fingerprinting of ASc revealed the presence of catechin, epicatechin, rutin, quercitrin, isoquercitrin, quercetin, kaempferol and chlorogenic, caffeic, gallic and ellagic acids; (ii) for the first time, ASc reduced the AAPH-induced increase in ADA activity, but no effect was observed on DPP-IV activity; (iii) ASc increased P-SH groups and cellular viability and decreased LDH activity, but was not able to reduce the AAPH-induced lipid peroxidation; (iv) gallic acid showed less protective effects than ASc. ASc affects the purinergic system and may modulate adenosine levels, indicating that the extract of this plant exhibits immunomodulatory properties. ASc also may potentially prevent the cellular injury induced by oxidative stress, highlighting its cytoprotective effects.

Evidence of parasexual activity in "asexual amoebae" Cochliopodium spp. (Amoebozoa): extensive cellular and nuclear fusion.

Science.gov (United States)

Tekle, Yonas I; Anderson, O Roger; Lecky, Ariel F

2014-09-01

The majority of microbial eukaryotes have long been considered asexual, though new evidence indicates sex, or sexual-like (parasexual) behaviors that deviate from the usual union of two gametes, among other variant aspects. Over a dozen amoebozoans are implicated to have sexual stages. However, the exact mechanism by which sex occurs in these lineages remains elusive. This is mainly due to the diverse quality and cryptic nature of their life cycle. In this study we present evidence of some previously unreported aspects of the life cycle of an amoeba, Cochliopodium, that undergoes unusual intraspecific interactions using light microscopy and immunocytochemistry. Similar to other amoebozoans, Cochliopodium, is considered asexual with no published reports of sex or parasexuality. We also investigated environmental conditions that govern the observed intraspecific interactions. Both light microscopic and immunocytochemistry evidence demonstrates Cochliopodium undergoes cellular fusion (plasmogamy) and nuclear fusion (karyogamy). Large plasmodia eventually undergo karyogamy and contain large fused, polyploid, nuclei. These are observed to fragment, subsequently, by karyotomy (nuclear fission) and cytoplasmic fission to yield uninucleated amoebae. This process could lead to a non-meiotic, parasexual exchange of chromosomes in Cochliopodium. These findings strongly suggest that Cochliopodium is involved in parasexual activity and should no longer be considered strictly asexual. Copyright © 2014 Elsevier GmbH. All rights reserved.

Activation of human natural killer cells by the soluble form of cellular prion protein

Energy Technology Data Exchange (ETDEWEB)

Seong, Yeon-Jae [Laboratory of Immunology and Infectious Diseases, Graduate School of Medical Science and Engineering, KAIST, Daejeon (Korea, Republic of); Hafis Clinic, Seoul (Korea, Republic of); Sung, Pil Soo; Jang, Young-Soon; Choi, Young Joon [Laboratory of Immunology and Infectious Diseases, Graduate School of Medical Science and Engineering, KAIST, Daejeon (Korea, Republic of); Park, Bum-Chan [Aging Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon (Korea, Republic of); Park, Su-Hyung [Laboratory of Translational Immunology and Vaccinology, Graduate School of Medical Science and Engineering, KAIST, Daejeon (Korea, Republic of); Park, Young Woo [Aging Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon (Korea, Republic of); Shin, Eui-Cheol, E-mail: ecshin@kaist.ac.kr [Laboratory of Immunology and Infectious Diseases, Graduate School of Medical Science and Engineering, KAIST, Daejeon (Korea, Republic of)

2015-08-21

Cellular prion protein (PrP{sup C}) is widely expressed in various cell types, including cells of the immune system. However, the specific roles of PrP{sup C} in the immune system have not been clearly elucidated. In the present study, we investigated the effects of a soluble form of recombinant PrP{sup C} protein on human natural killer (NK) cells. Recombinant soluble PrP{sup C} protein was generated by fusion of human PrP{sup C} with the Fc portion of human IgG{sub 1} (PrP{sup C}-Fc). PrP{sup C}-Fc binds to the surface of human NK cells, particularly to CD56{sup dim} NK cells. PrP{sup C}-Fc induced the production of cytokines and chemokines and the degranulation of granzyme B from NK cells. In addition, PrP{sup C}-Fc facilitated the IL-15-induced proliferation of NK cells. PrP{sup C}-Fc induced phosphorylation of ERK-1/2 and JNK in NK cells, and inhibitors of the ERK or the JNK pathways abrogated PrP{sup C}-Fc-induced cytokine production in NK cells. In conclusion, the soluble form of recombinant PrP{sup C}-Fc protein activates human NK cells via the ERK and JNK signaling pathways. - Highlights: • Recombinant soluble PrP{sup C} (PrP{sup C}-Fc) was generated by fusion of human PrP{sup C} with IgG1 Fc portion. • PrP{sup C}-Fc protein induces the production of cytokines and degranulation from human NK cells. • PrP{sup C}-Fc protein enhances the IL-15-induced proliferation of human NK cells. • PrP{sup C}-Fc protein activates human NK cells via the ERK and JNK signaling pathways.

Cellular and molecular screening of connective tissue dysplasia in adolescent athletes (pilot study

Directory of Open Access Journals (Sweden)

M. V. Dvornichenko

2017-01-01

Full Text Available The purpose of the study is to evaluate the cellular and molecular parameters of bone remodeling in the blood as potential markers of undifferentiated forms of connective tissue dysplasiaMaterials and methods. The structural and functional status of cellular elements of in vitro culturing of mononuclear leukocytes of peripheral blood in adolescent athletes connected with phenotypic manifestations of undifferentiated connective tissue dysplasia (UCTD were investigated. 25 pupils of sport schools from 10–14 years old (main disciplines: figure skating, gymnastics, athletics were examined with the help of express analysis. The average age of the examined adolescents was (12,0 ± 1,7 years. Clinical examination of adolescents allowed ranking the UCTD signs on a scale of 4–11,5 points.Results. A comparison of questionnaire survey results and an evaluation of bone remodeling distant markers allowed the revelation of 2 groups in the distribution of adolescent athletes: those with minimal signs of UCTD (scores lesser than 7 points – 10 pupils, and those with expressed UCTD phenotype (scores are equal or more than 7 points –15 pupils. Significant statistical decrease in the content of collagen type I degradation products (CrossLaps (by 80% and ionized calcium (by 5% has been determined in the peripheral blood of adolescent athletes with expressed UCTD phenotype. In conditions of short-term 72-h cultivation of mononuclear leukocytes in the presence of a 3D matrix imitating the properties of the mineral substance of the regenerating bone tissue, morphofunctional features of cellular reaction in adolescent athletes with clinical manifestations of UCTD, as well the heterogeneity of the cell population associated with the appearance of cells with an osteoblast-like phenotype in the blood have been revealed. The results of investigation propose the use of distant cellular and molecular parameters of bone remodeling to screen the mechanisms and dynamics

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.

Semen modulated secretory activity of oviductal epithelial cells is linked to cellular proteostasis network remodeling: Proteomic insights into the early phase of interaction in the oviduct in vivo.

Science.gov (United States)

Steinberger, Birgit; Yu, Hans; Brodmann, Theodor; Milovanovic, Daniela; Reichart, Ursula; Besenfelder, Urban; Artemenko, Konstantin; Razzazi-Fazeli, Ebrahim; Brem, Gottfried; Mayrhofer, Corina

2017-06-23

The oviductal epithelium is crucial for the integrity of the female organ. Previously we got evidence that the surface proteome of oviductal epithelial cells (Oecs) is promptly altered in response to insemination and thus suggested that this early phase plays a notable regulatory role in maintaining cellular function. This study further aimed to assess the effect of semen on the cellular and molecular mechanisms in rabbit Oecs. A quantitative gel-based proteomic approach was applied to analyze changes at three time points (0h, 1h, 2h) after intrauterine insemination (IUI) compared to time matched controls. Within two hours the abundance of 22 protein species was evidently altered in the intracellular fraction. Functional analysis revealed that the proteins were primarily involved in proteostasis as well as metabolic processes. The analysis of phosphoproteins specified a role of mitogen-activated protein kinase (MAPK) signaling molecules. Concurrently, semen increased oviduct-specific glycoprotein (OVGP1) secretion. A correlation between OVGP1 abundance and microtubule-associated proteins 1A/1B-light chain 3 lipidation was observed. The localization and changes in abundance of selected proteins were corroborated by antibody-based methods. These results clearly show that the early phase of interaction acts as a trigger for cellular adaptation to meet an altered demand in the female organ. The oviductal epithelium and its secreted proteins exert a pivotal role in reproductive processes, including the final maturation of male gametes. Thereby, the regulation and subsequently the functionality of the oviductal epithelial cell layer are important factors for the establishment of the appropriate milieu in the female reproductive tract. Notably, male gametes themselves have been shown to be an extrinsic modulatory factor of the oviductal epithelium. Accordingly a comprehensive knowledge about the underlying cellular and molecular mechanisms in the epithelial cells is of

Hierarchical Targeting Strategy for Enhanced Tumor Tissue Accumulation/Retention and Cellular Internalization.

Science.gov (United States)

Wang, Sheng; Huang, Peng; Chen, Xiaoyuan

2016-09-01

Targeted delivery of therapeutic agents is an important way to improve the therapeutic index and reduce side effects. To design nanoparticles for targeted delivery, both enhanced tumor tissue accumulation/retention and enhanced cellular internalization should be considered simultaneously. So far, there have been very few nanoparticles with immutable structures that can achieve this goal efficiently. Hierarchical targeting, a novel targeting strategy based on stimuli responsiveness, shows good potential to enhance both tumor tissue accumulation/retention and cellular internalization. Here, the recent design and development of hierarchical targeting nanoplatforms, based on changeable particle sizes, switchable surface charges and activatable surface ligands, will be introduced. In general, the targeting moieties in these nanoplatforms are not activated during blood circulation for efficient tumor tissue accumulation, but re-activated by certain internal or external stimuli in the tumor microenvironment for enhanced cellular internalization. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Cellular phones were found to pose no health risks

International Nuclear Information System (INIS)

Puranen, L.

1997-01-01

A cellular phone emits radiation very close to a person's head. Any harmful effects that might arise from the use of cellular phones are being studied carefully, but so far no health risks have been determined. However, the phones may interfere with the operation of electrical devices located close-by, such as a cardiac pacemaker. The biological effects of the microwaves emitted by cellular phones might be based on the resultant higher temperatures in the tissues of the head. Since, even in the worst cases, a cellular phone cannot raise the temperature of tissues by more than some tenths of a degree, no health risks based on thermal effects can be attributed to the use of a cellular phone. No reliable theory has been presented for the non-thermal effects of microwaves. Such effects may exist, however. The studies conducted so far have been unable to show that these effects might be harmful to human health. (orig.)

Cellularized Bilayer Pullulan-Gelatin Hydrogel for Skin Regeneration.

Science.gov (United States)

Nicholas, Mathew N; Jeschke, Marc G; Amini-Nik, Saeid

2016-05-01

Skin substitutes significantly reduce the morbidity and mortality of patients with burn injuries and chronic wounds. However, current skin substitutes have disadvantages related to high costs and inadequate skin regeneration due to highly inflammatory wounds. Thus, new skin substitutes are needed. By combining two polymers, pullulan, an inexpensive polysaccharide with antioxidant properties, and gelatin, a derivative of collagen with high water absorbency, we created a novel inexpensive hydrogel-named PG-1 for "pullulan-gelatin first generation hydrogel"-suitable for skin substitutes. After incorporating human fibroblasts and keratinocytes onto PG-1 using centrifugation over 5 days, we created a cellularized bilayer skin substitute. Cellularized PG-1 was compared to acellular PG-1 and no hydrogel (control) in vivo in a mouse excisional skin biopsy model using newly developed dome inserts to house the skin substitutes and prevent mouse skin contraction during wound healing. PG-1 had an average pore size of 61.69 μm with an ideal elastic modulus, swelling behavior, and biodegradability for use as a hydrogel for skin substitutes. Excellent skin cell viability, proliferation, differentiation, and morphology were visualized through live/dead assays, 5-bromo-2'-deoxyuridine proliferation assays, and confocal microscopy. Trichrome and immunohistochemical staining of excisional wounds treated with the cellularized skin substitute revealed thicker newly formed skin with a higher proportion of actively proliferating cells and incorporation of human cells compared to acellular PG-1 or control. Excisional wounds treated with acellular or cellularized hydrogels showed significantly less macrophage infiltration and increased angiogenesis 14 days post skin biopsy compared to control. These results show that PG-1 has ideal mechanical characteristics and allows ideal cellular characteristics. In vivo evidence suggests that cellularized PG-1 promotes skin regeneration and may

Bacterial RNA induces myocyte cellular dysfunction through the activation of PKR

OpenAIRE

Bleiblo, Farag; Michael, Paul; Brabant, Danielle; Ramana, Chilakamarti V.; Tai, TC; Saleh, Mazen; Parrillo, Joseph E.; Kumar, Anand; Kumar, Aseem

2012-01-01

Severe sepsis and the ensuing septic shock are serious life threatening conditions. These diseases are triggered by the host's over exuberant systemic response to the infecting pathogen. Several surveillance mechanisms have evolved to discriminate self from foreign RNA and accordingly trigger effective cellular responses to target the pathogenic threats. The RNA-dependent protein kinase (PKR) is a key component of the cytoplasmic RNA sensors involved in the recognition of viral double-strande...

Adjuvant activity of peanut, cottonseed and rice oils on cellular and humoral response

Directory of Open Access Journals (Sweden)

Erika Freitas

2013-04-01

Full Text Available The potentiality of the usage of vegetable oils such as soybean, corn, olive, sesame, murici seed, rapeseed, linseed, rice and cashew nuts as adjuvant of the humoral and cellular immune response has been recently shown. In the present work, besides of evaluating the adjuvant action of peanut, cottonseed and rice oils on humoral and cellular immune responses against ovalbumin (OVA we also evaluated the protective immune response induced by Leishmania antigens. The peanut oil significantly increased the synthesis of anti-ovalbumin antibodies in the primary response, but it did not favor cellular response. Concerning mice immunized with L. amazonensis antigens emulsified with peanut oil exacerbated skin lesions and lymph node parasite load what suggests stimulation of the Th2 immune response and down regulation of Th1 response. The cottonseed oil was shown to have adjuvant effect to the humoral response, stimulating a secondary response and also favored the delayed-type hypersensitivity (DTH response to OVA. The rice oil stimulated a strong DTH reaction to OVA and enhanced the synthesis of antibodies after the third dose. Mice immunized with L. amazonensis antigens emulsified with rice oil or cotton seed oil were protected from developing skin lesions and lymph node parasite load. These results emphasize the interest and importance of the vegetable oils as tools in different procedures of immunization and their differential role in relation to the other adjuvant under usage.

Regulation of HTLV-1 Tax Stability, Cellular Trafficking and NF-κB Activation by the Ubiquitin-Proteasome Pathway

Science.gov (United States)

Lavorgna, Alfonso; Harhaj, Edward William

2014-01-01

Human T-cell leukemia virus type 1 (HTLV-1) is a complex retrovirus that infects CD4+ T cells and causes adult T-cell leukemia/lymphoma (ATLL) in 3%–5% of infected individuals after a long latent period. HTLV-1 Tax is a trans-activating protein that regulates viral gene expression and also modulates cellular signaling pathways to enhance T-cell proliferation and cell survival. The Tax oncoprotein promotes T-cell transformation, in part via constitutive activation of the NF-κB transcription factor; however, the underlying mechanisms remain unknown. Ubiquitination is a type of post-translational modification that occurs in a three-step enzymatic cascade mediated by E1, E2 and E3 enzymes and regulates protein stability as well as signal transduction, protein trafficking and the DNA damage response. Emerging studies indicate that Tax hijacks the ubiquitin machinery to activate ubiquitin-dependent kinases and downstream NF-κB signaling. Tax interacts with the E2 conjugating enzyme Ubc13 and is conjugated on C-terminal lysine residues with lysine 63-linked polyubiquitin chains. Tax K63-linked polyubiquitination may serve as a platform for signaling complexes since this modification is critical for interactions with NEMO and IKK. In addition to NF-κB signaling, mono- and polyubiquitination of Tax also regulate its subcellular trafficking and stability. Here, we review recent advances in the diverse roles of ubiquitin in Tax function and how Tax usurps the ubiquitin-proteasome pathway to promote oncogenesis. PMID:25341660

The surfactant protein C mutation A116D alters cellular processing, stress tolerance, surfactant lipid composition, and immune cell activation

Directory of Open Access Journals (Sweden)

Zarbock Ralf

2012-03-01

Full Text Available Abstract Background Surfactant protein C (SP-C is important for the function of pulmonary surfactant. Heterozygous mutations in SFTPC, the gene encoding SP-C, cause sporadic and familial interstitial lung disease (ILD in children and adults. Mutations mapping to the BRICHOS domain located within the SP-C proprotein result in perinuclear aggregation of the proprotein. In this study, we investigated the effects of the mutation A116D in the BRICHOS domain of SP-C on cellular homeostasis. We also evaluated the ability of drugs currently used in ILD therapy to counteract these effects. Methods SP-CA116D was expressed in MLE-12 alveolar epithelial cells. We assessed in vitro the consequences for cellular homeostasis, immune response and effects of azathioprine, hydroxychloroquine, methylprednisolone and cyclophosphamide. Results Stable expression of SP-CA116D in MLE-12 alveolar epithelial cells resulted in increased intracellular accumulation of proSP-C processing intermediates. SP-CA116D expression further led to reduced cell viability and increased levels of the chaperones Hsp90, Hsp70, calreticulin and calnexin. Lipid analysis revealed decreased intracellular levels of phosphatidylcholine (PC and increased lyso-PC levels. Treatment with methylprednisolone or hydroxychloroquine partially restored these lipid alterations. Furthermore, SP-CA116D cells secreted soluble factors into the medium that modulated surface expression of CCR2 or CXCR1 receptors on CD4+ lymphocytes and neutrophils, suggesting a direct paracrine effect of SP-CA116D on neighboring cells in the alveolar space. Conclusions We show that the A116D mutation leads to impaired processing of proSP-C in alveolar epithelial cells, alters cell viability and lipid composition, and also activates cells of the immune system. In addition, we show that some of the effects of the mutation on cellular homeostasis can be antagonized by application of pharmaceuticals commonly applied in ILD therapy

Continuous cellularization of calcium phosphate hybrid scaffolds induced by plasma polymer activation

Energy Technology Data Exchange (ETDEWEB)

Bergemann, Claudia [University Medical Center Rostock, Cell Biology, Schillingallee 69, D-18057 Rostock (Germany); Cornelsen, Matthias [University of Rostock, Fluid Technology and Microfluidics, Justus-von-Liebig Weg 6, D-18059 Rostock (Germany); Quade, Antje [Leibniz-Institute for Plasma Science and Technology (INP), Felix-Hausdorff-Str. 2, D-17489 Greifswald (Germany); Laube, Thorsten; Schnabelrauch, Matthias [INNOVENT e.V., Biomaterials Department, Pruessingstrasse 27B, D-07745 Jena (Germany); Rebl, Henrike [University Medical Center Rostock, Cell Biology, Schillingallee 69, D-18057 Rostock (Germany); Weißmann, Volker [Institute for Polymer Technologies (IPT) e.V., Alter Holzhafen 19, D-23966 Wismar (Germany); Seitz, Hermann [University of Rostock, Fluid Technology and Microfluidics, Justus-von-Liebig Weg 6, D-18059 Rostock (Germany); Nebe, Barbara, E-mail: barbara.nebe@med.uni-rostock.de [University Medical Center Rostock, Cell Biology, Schillingallee 69, D-18057 Rostock (Germany)

2016-02-01

The generation of hybrid materials based on β-tricalcium phosphate (TCP) and various biodegradable polymers like poly(L-lactide-co-D,L-lactide) (PLA) represents a common approach to overcoming the disadvantages of pure TCP devices. These disadvantages lie in TCP's mechanical properties, such as brittleness. The positive characteristic of PLA — improvement of compressive strength of calcium phosphate scaffolds – is diametrically opposed to its cell attractiveness. Therefore, the objective of this work was to optimize osteoblast migration and cellularization inside a three-dimensionally (3D) printed, PLA polymer stabilized TCP hybrid scaffold by a plasma polymer process depositing amino groups via allylamine. MG-63 osteoblastic cells inside the 10 mm hybrid scaffold were dynamically cultivated for 14 days in a 3D model system integrated in a perfusion reactor. The whole TCP/PLA hybrid scaffold was continuously colonized due to plasma polymerized allylamine activation inducing the migration potential of osteoblasts. - Highlights: • Mechanical stabilization of β-tricalcium phosphate scaffolds by PLA infiltration • Hybrid scaffolds with higher cell attraction due to plasma polymerized allylamine • 3D perfusion in vitro model for observation of cell migration inside scaffolds • Enhanced cell migration within plasma polymer coated TCP hybrid scaffolds.

Continuous cellularization of calcium phosphate hybrid scaffolds induced by plasma polymer activation

International Nuclear Information System (INIS)

Bergemann, Claudia; Cornelsen, Matthias; Quade, Antje; Laube, Thorsten; Schnabelrauch, Matthias; Rebl, Henrike; Weißmann, Volker; Seitz, Hermann; Nebe, Barbara

2016-01-01

The generation of hybrid materials based on β-tricalcium phosphate (TCP) and various biodegradable polymers like poly(L-lactide-co-D,L-lactide) (PLA) represents a common approach to overcoming the disadvantages of pure TCP devices. These disadvantages lie in TCP's mechanical properties, such as brittleness. The positive characteristic of PLA — improvement of compressive strength of calcium phosphate scaffolds – is diametrically opposed to its cell attractiveness. Therefore, the objective of this work was to optimize osteoblast migration and cellularization inside a three-dimensionally (3D) printed, PLA polymer stabilized TCP hybrid scaffold by a plasma polymer process depositing amino groups via allylamine. MG-63 osteoblastic cells inside the 10 mm hybrid scaffold were dynamically cultivated for 14 days in a 3D model system integrated in a perfusion reactor. The whole TCP/PLA hybrid scaffold was continuously colonized due to plasma polymerized allylamine activation inducing the migration potential of osteoblasts. - Highlights: • Mechanical stabilization of β-tricalcium phosphate scaffolds by PLA infiltration • Hybrid scaffolds with higher cell attraction due to plasma polymerized allylamine • 3D perfusion in vitro model for observation of cell migration inside scaffolds • Enhanced cell migration within plasma polymer coated TCP hybrid scaffolds

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

Activation of cellular apoptosis in the caecal epithelium is associated with increased oxidative reactions in lactating goats after feeding a high-concentrate diet.

Science.gov (United States)

Tao, Shiyu; Tian, Jing; Cong, Rihua; Sun, Lili; Duanmu, Yongqian; Dong, Haibo; Ni, Yingdong; Zhao, Ruqian

2015-03-01

What is the central question of this study? What are the ultrastructural changes of the caecal mucosa and the status of epithelial cellular apoptosis and oxidative reactions in lactating goats after prolonged feeding with a high-concentrate diet? What is the main finding and its importance? High-concentrate diet results in ultrastructural damage to the caprine caecal epithelium. Increased oxidative and decreased antioxidative reactions are involved in the process of activating epithelial apoptosis in the caecal epithelium of goats fed a high-concentrate diet. Our results provide new insight into the relationship between abnormal fermentation in the hindgut and damage to the intestinal mucosal barrier. The effect of feeding a high-concentrate diet (HC) to lactating ruminants on their hindgut epithelial structure remains unknown. In this study, 12 lactating goats were randomly assigned to either HC (65% of dry matter as concentrate; n = 6) or a low-concentrate diet (LC; 35% of dry matter as concentrate; n = 6). After 10 weeks, the epithelial ultrastructure and cell apoptotic status in the caecal mucosa were determined by transmission electron microscopy and TUNEL, respectively. The results showed that the level of free lipopolysaccharide (P epithelium, as evidenced by more TUNEL-positive apoptotic cells. Western blot analysis showed that there was no significant difference in activated caspase-3, Bax protein expression in caecal epithelial mucosa between HC- and LC-fed goats (P > 0.05). However, the level of malondialdehyde content in the caecal epithelium from HC-fed goats was markedly higher than that in LC-fed goats (P < 0.05), whereas the level of glutathione peroxidase and the superoxide dismutase activity were significantly decreased. Gene expressions of cytokines, including interleukin-1β, interleukin-6, interleukin-10, tumour necrosis factor-α and interferon-γ, as well as myeloperoxidase activity in the caecal mucosa did not show any significant

Coordination of Cellular Dynamics Contributes to Tooth Epithelium Deformations

Science.gov (United States)

Morita, Ritsuko; Kihira, Miho; Nakatsu, Yousuke; Nomoto, Yohei; Ogawa, Miho; Ohashi, Kazumasa; Mizuno, Kensaku; Tachikawa, Tetsuhiko; Ishimoto, Yukitaka; Morishita, Yoshihiro; Tsuji, Takashi

2016-01-01

The morphologies of ectodermal organs are shaped by appropriate combinations of several deformation modes, such as invagination and anisotropic tissue elongation. However, how multicellular dynamics are coordinated during deformation processes remains to be elucidated. Here, we developed a four-dimensional (4D) analysis system for tracking cell movement and division at a single-cell resolution in developing tooth epithelium. The expression patterns of a Fucci probe clarified the region- and stage-specific cell cycle patterns within the tooth germ, which were in good agreement with the pattern of the volume growth rate estimated from tissue-level deformation analysis. Cellular motility was higher in the regions with higher growth rates, while the mitotic orientation was significantly biased along the direction of tissue elongation in the epithelium. Further, these spatio-temporal patterns of cellular dynamics and tissue-level deformation were highly correlated with that of the activity of cofilin, which is an actin depolymerization factor, suggesting that the coordination of cellular dynamics via actin remodeling plays an important role in tooth epithelial morphogenesis. Our system enhances the understanding of how cellular behaviors are coordinated during ectodermal organogenesis, which cannot be observed from histological analyses. PMID:27588418

Extraction protocol and liquid chromatography/tandem mass spectrometry method for determining micelle-entrapped paclitaxel at the cellular and subcellular levels: Application to a cellular uptake and distribution study.

Science.gov (United States)

Zheng, Nan; Lian, Bin; Du, Wenwen; Xu, Guobing; Ji, Jiafu

2018-01-01

Paclitaxel-loaded polymeric micelles (PTX-PM) are commonly used as tumor-targeted nanocarriers and display outstanding antitumor features in clinic, but its accumulation and distribution in vitro are lack of investigation. It is probably due to the complex micellar system and its low concentration at the cellular or subcellular levels. In this study, we developed an improved extraction method, which was a combination of mechanical disruption and liquid-liquid extraction (LLE), to extract the total PTX from micelles in the cell lysate and subcellular compartments. An ultra-performance liquid chromatography tandem mass spectroscopy (UPLC-MS/MS) method was optimized to detect the low concentration of PTX at cellular and subcellular levels simultaneously, using docetaxel as internal standard (IS). The method was proved to release PTX totally from micelles (≥95.93%) with a consistent and reproducible extraction recovery (≥75.04%). Good linearity was obtained at concentrations ranging from 0.2 to 20ng/mL. The relative error (RE%) for accuracy varied from 0.68 to 7.56%, and the intra- and inter-precision (relative standard deviation, RSD%) was less than 8.64% and 13.14%, respectively. This method was fully validated and successfully applied to the cellular uptake and distribution study of PTX-loaded PLGA-PEG micelles in human breast cancer cells (MCF-7). Copyright © 2017 Elsevier B.V. All rights reserved.

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...

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.

Improved cellular activity of antisense peptide nucleic acids by conjugation to a cationic peptide-lipid (CatLip) domain

DEFF Research Database (Denmark)

Koppelhus, Uffe; Shiraishi, Takehiko; Zachar, Vladimir

2008-01-01

Conjugation to cationic cell penetrating peptides (such as Tat, Penetratin, or oligo arginines) efficiently improves the cellular uptake of large hydrophilic molecules such as oligonucleotides and peptide nucleic acids, but the cellular uptake is predominantly via an unproductive endosomal pathway...... for future in vivo applications. We find that simply conjugating a lipid domain (fatty acid) to the cationic peptide (a CatLip conjugate) increases the biological effect of the corresponding PNA (CatLip) conjugates in a luciferase cellular antisense assay up to 2 orders of magnitude. The effect increases...... with increasing length of the fatty acid (C8-C16) but in parallel also results in increased cellular toxicity, with decanoic acid being optimal. Furthermore, the relative enhancement is significantly higher for Tat peptide compared to oligoarginine. Confocal microscopy and chloroquine enhancement indicates...

A comprehensive review of metal-induced cellular transformation studies.

Science.gov (United States)

Chen, Qiao Yi; Costa, Max

2017-09-15

In vitro transformation assays not only serve practical purposes in screening for potential carcinogenic substances in food, drug, and cosmetic industries, but more importantly, they provide a means of understanding the critical biological processes behind in vivo cancer development. In resemblance to cancer cells in vivo, successfully transformed cells display loss of contact inhibition, gain of anchorage independent growth, resistant to proper cell cycle regulation such as apoptosis, faster proliferation rate, potential for cellular invasion, and ability to form tumors in experimental animals. Cells purposely transformed using metal exposures enable researchers to examine molecular changes, dissect various stages of tumor formation, and ultimately elucidate metal induced cancer mode of action. For practical purposes, this review specifically focuses on studies incorporating As-, Cd-, Cr-, and Ni-induced cell transformation. Through investigating and comparing an extensive list of studies using various methods of metal-induced transformation, this review serves to bridge an information gap and provide a guide for avoiding procedural discrepancies as well as maximizing experimental efficiency. Copyright © 2017 Elsevier Inc. All rights reserved.

Cellular uptake of {sup 99m}TcN-NOET in human leukaemic HL-60 cells is related to calcium channel activation and cell proliferation

Energy Technology Data Exchange (ETDEWEB)

Guillermet, Stephanie; Vuillez, Jean-Philippe; Caravel, Jean-Pierre; Marti-Batlle, Daniele; Fagret, Daniel [Universite de Grenoble, Radiopharmaceutiques Biocliniques, La Tronche (France); Fontaine, Eric [Universite de Grenoble, Laboratoire de Bioenergetique Fondamentale et Appliquee, Grenoble (France); Pasqualini, Roberto [Cis Bio International Schering SA, Gif-sur-Yvette (France)

2006-01-01

A major goal of nuclear oncology is the development of new radiolabelled tracers as proliferation markers. Intracellular calcium waves play a fundamental role in the course of the cell cycle. These waves occur in non-excitable tumour cells via store-operated calcium channels (SOCCs). Bis(N-ethoxy, N-ethyldithiocarbamato) nitrido technetium (V)-99m ({sup 99m}TcN-NOET) has been shown to interact with L-type voltage-operated calcium channels (VOCCs) in cultured cardiomyocytes. Considering the analogy between VOCCs and SOCCs, we sought to determine whether {sup 99m}TcN-NOET also binds to activated SOCCs in tumour cells in order to clarify the potential value of this tracer as a proliferation marker. Uptake kinetics of {sup 99m}TcN-NOET were measured in human leukaemic HL-60 cells over 60 min and the effect of several calcium channel modulators on 1-min tracer uptake was studied. The uptake kinetics of {sup 99m}TcN-NOET were compared both with the variations of cytosolic free calcium concentration measured by indo-1/AM and with the variations in the SG{sub 2}M cellular proliferation index. All calcium channel inhibitors significantly decreased the cellular uptake of {sup 99m}TcN-NOET whereas the activator thapsigargin induced a significant 10% increase. In parallel, SOCC activation by thapsigargin, as measured using the indo-1/AM probe, was inhibited by nicardipine. These results indicate that the uptake of {sup 99m}TcN-NOET is related to the activation of SOCCs. Finally, a correlation was observed between the tracer uptake and variations in the proliferation index SG{sub 2}M. The uptake of {sup 99m}TcN-NOET seems to be related to SOCC activation and to cell proliferation in HL-60 cells. These results indicate that {sup 99m}TcN-NOET might be a marker of cell proliferation. (orig.)

Cellular and molecular mechanisms of metformin: an overview

Science.gov (United States)

Viollet, Benoit; Guigas, Bruno; Sanz Garcia, Nieves; Leclerc, Jocelyne; Foretz, Marc; Andreelli, Fabrizio

2012-01-01

Considerable efforts have been made since the 1950s to better understand the cellular and molecular mechanisms of action of metformin, a potent antihyperglycemic agent now recommended as the first line oral therapy for type 2 diabetes (T2D). The main effect of this drug from the biguanide family is to acutely decrease hepatic glucose production, mostly through a mild and transient inhibition of the mitochondrial respiratory-chain complex 1. In addition, the resulting decrease in hepatic energy status activates the AMP-activated protein kinase (AMPK), a cellular metabolic sensor, providing a generally accepted mechanism for metformin action on hepatic gluconeogenic program. The demonstration that the respiratory-chain complex 1, but not AMPK, is the primary target of metformin was recently strengthened by showing that the metabolic effect of the drug is preserved in liver-specific AMPK-deficient mice. Beyond its effect on glucose metabolism, metformin was reported to restore ovarian function in polycystic ovary syndrome, reduce fatty liver and to lower microvascular and macrovascular complications associated with T2D. Its use was also recently suggested as an adjuvant treatment for cancer or gestational diabetes, and for the prevention in pre-diabetic populations. These emerging new therapeutic areas for metformin will be reviewed together with recent data from pharmacogenetic studies linking genetic variations to drug response, a promising new step towards personalized medicine in the treatment of T2D. PMID:22117616

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

Immunotherapy in allergy and cellular tests

Science.gov (United States)

Chirumbolo, Salvatore

2014-01-01

The basophil activation test (BAT) is an in vitro assay where the activation of basophils upon exposure to various IgE-challenging molecules is measured by flow cytometry. It is a cellular test able to investigate basophil behavior during allergy and allergy immunotherapy. A panoply of critical issues and suggestive advances have rendered this assay a promising yet puzzling tool to endeavor a full comprehension of innate immunity of allergy desensitization and manage allergen or monoclonal anti-IgE therapy. In this review a brief state of art of BAT in immunotherapy is described focusing onto the analytical issue pertaining BAT performance in allergy specific therapy. PMID:24717453

Role of the blood service in cellular therapy.

Science.gov (United States)

Rebulla, Paolo; Giordano, Rosaria

2012-05-01

Cellular therapy is a novel form of medical or surgical treatment using cells in place of or in addition to traditional chemical drugs. The preparation of cellular products - called advanced therapy medicinal products - ATMP in Europe, requires compliance with good manufacturing practices (GMP). Based on long-term experience in blood component manufacturing, product traceability and hemovigilance, selected blood services may represent ideal settings for the development and experimental use of ATMP. International harmonization of the protocols and procedures for the preparation of ATMP is of paramount importance to facilitate the development of multicenter clinical trials with adequate sample size, which are urgently needed to determine the clinical efficacy of ATMP. This article describes European regulations on cellular therapy and summarizes the activities of the 'Franco Calori' Cell Factory, a GMP unit belonging to the department of regenerative medicine of a large public university hospital, which acquired a certification for the GMP production of ATMP in 2007 and developed nine experimental clinical protocols during 2003-2011. Copyright © 2011 The International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.

Lunar Dust and Lunar Simulant Activation, Monitoring, Solution and Cellular Toxicity Properties

Science.gov (United States)

Wallace, William; Jeevarajan, A. S.

2009-01-01

During the Apollo missions, many undesirable situations were encountered that must be mitigated prior to returning humans to the moon. Lunar dust (that part of the lunar regolith less than 20 microns in diameter) was found to produce several problems with mechanical equipment and could have conceivably produced harmful physiological effects for the astronauts. For instance, the abrasive nature of the dust was found to cause malfunctions of various joints and seals of the spacecraft and suits. Additionally, though efforts were made to exclude lunar dust from the cabin of the lunar module, a significant amount of material nonetheless found its way inside. With the loss of gravity correlated with ascent from the lunar surface, much of the finer fraction of this dust began to float and was inhaled by the astronauts. The short visits tothe Moon during Apollo lessened exposure to the dust, but the plan for future lunar stays of up to six months demands that methods be developed to minimize the risk of dust inhalation. The guidelines for what constitutes "safe" exposure will guide the development of engineering controls aimed at preventing the presence of dust in the lunar habitat. This work has shown the effects of grinding on the activation level of lunar dust, the changes in dissolution properties of lunar simulant, and the production of cytokines by cellular systems. Grinding of lunar dust leads to the production of radicals in solution and increased dissolution of lunar simulant in buffers of different pH. Additionally, ground lunar simulant has been shown to promote the production of IL-6 and IL-8, pro-inflammatory cytokines, by alveolar epithelial cells. These results provide evidence of the need for further studies on these materials prior to returning to the lunar surface.

Conceptions of Marketing Management and Strategic Planning at the Market of Cellular Communication Services

Directory of Open Access Journals (Sweden)

Marina Vladimirovna Perevoznikova

2015-12-01

Full Text Available The article is devoted to the study and analysis of marketing management and strategic planning of the companies working in the field of cellular communication services. The article represented the concept of marketing management and strategic planning, and their importance in the business development. Objectives and tasks of marketing management in the telecommunications are considered. Тhe conceptions of marketing management and the advisability of their use in the market of cellular communication are described. Relationship of marketing management and strategic planning at activities of the organization are determined. The stages of strategic planning and types of global and corporate development strategies of companies in the telecommunication market are analyzed. The application features of the marketing management concepts and development strategies in the telecommunications sector are considered. The evaluation criteria and mobile operators performance indicators (data are formed. The conclusions about the role of the effective marketing management and strategic planning in the activities of mobile operators are formulated, that allows keeping marginality and high level of business profitability, creating competitive advantages in the conditions of highly competitive market, forming effective purchasing, sales activities and promotional activities, determining the correct tactics of behavior at the market.

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.

Numerical Studies of Homogenization under a Fast Cellular Flow

KAUST Repository

Iyer, Gautam

2012-09-13

We consider a two dimensional particle diffusing in the presence of a fast cellular flow confined to a finite domain. If the flow amplitude A is held fixed and the number of cells L 2 →∞, then the problem homogenizes; this has been well studied. Also well studied is the limit when L is fixed and A→∞. In this case the solution averages along stream lines. The double limit as both the flow amplitude A→∞and the number of cells L 2 →∞was recently studied [G. Iyer et al., preprint, arXiv:1108.0074]; one observes a sharp transition between the homogenization and averaging regimes occurring at A = L 2. This paper numerically studies a few theoretically unresolved aspects of this problem when both A and L are large that were left open in [G. Iyer et al., preprint, arXiv:1108.0074] using the numerical method devised in [G. A. Pavliotis, A. M. Stewart, and K. C. Zygalakis, J. Comput. Phys., 228 (2009), pp. 1030-1055]. Our treatment of the numerical method uses recent developments in the theory of modified equations for numerical integrators of stochastic differential equations [K. C. Zygalakis, SIAM J. Sci. Comput., 33 (2001), pp. 102-130]. © 2012 Society for Industrial and Applied Mathematics.

Numerical Studies of Homogenization under a Fast Cellular Flow

KAUST Repository

Iyer, Gautam; Zygalakis, Konstantinos C.

2012-01-01

We consider a two dimensional particle diffusing in the presence of a fast cellular flow confined to a finite domain. If the flow amplitude A is held fixed and the number of cells L 2 →∞, then the problem homogenizes; this has been well studied. Also well studied is the limit when L is fixed and A→∞. In this case the solution averages along stream lines. The double limit as both the flow amplitude A→∞and the number of cells L 2 →∞was recently studied [G. Iyer et al., preprint, arXiv:1108.0074]; one observes a sharp transition between the homogenization and averaging regimes occurring at A = L 2. This paper numerically studies a few theoretically unresolved aspects of this problem when both A and L are large that were left open in [G. Iyer et al., preprint, arXiv:1108.0074] using the numerical method devised in [G. A. Pavliotis, A. M. Stewart, and K. C. Zygalakis, J. Comput. Phys., 228 (2009), pp. 1030-1055]. Our treatment of the numerical method uses recent developments in the theory of modified equations for numerical integrators of stochastic differential equations [K. C. Zygalakis, SIAM J. Sci. Comput., 33 (2001), pp. 102-130]. © 2012 Society for Industrial and Applied Mathematics.

UPF1 silenced cellular model systems for screening of read-through agents active on β039 thalassemia point mutation.

Science.gov (United States)

Salvatori, Francesca; Pappadà, Mariangela; Breveglieri, Giulia; D'Aversa, Elisabetta; Finotti, Alessia; Lampronti, Ilaria; Gambari, Roberto; Borgatti, Monica

2018-05-15

Nonsense mutations promote premature translational termination, introducing stop codons within the coding region of mRNAs and causing inherited diseases, including thalassemia. For instance, in β 0 39 thalassemia the CAG (glutamine) codon is mutated to the UAG stop codon, leading to premature translation termination and to mRNA destabilization through the well described NMD (nonsense-mediated mRNA decay). In order to develop an approach facilitating translation and, therefore, protection from NMD, ribosomal read-through molecules, such as aminoglycoside antibiotics, have been tested on mRNAs carrying premature stop codons. These findings have introduced new hopes for the development of a pharmacological approach to the β 0 39 thalassemia therapy. While several strategies, designed to enhance translational read-through, have been reported to inhibit NMD efficiency concomitantly, experimental tools for systematic analysis of mammalian NMD inhibition by translational read-through are lacking. We developed a human cellular model of the β 0 39 thalassemia mutation with UPF-1 suppressed and showing a partial NMD suppression. This novel cellular model could be used for the screening of molecules exhibiting preferential read-through activity allowing a great rescue of the mutated transcripts.

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

Self-assembled diphenylalanine nanowires for cellular studies and sensor applications

DEFF Research Database (Denmark)

Sasso, Luigi; Vedarethinam, Indumathi; Emnéus, Jenny

2012-01-01

In this paper we present a series of experiments showing that vertical self-assembled diphenylalanine peptide nanowires (PNWs) are a suitable candidate material for cellular biosensing. We grew HeLa and PC12 cells onto PNW modified gold surfaces and observed no hindrance of cell growth caused by ...

Effects of type I collagen coating on titanium osseointegration: histomorphometric, cellular and molecular analyses

International Nuclear Information System (INIS)

Sverzut, Alexander Tadeu; Crippa, Grasiele Edilaine; Tambasco de Oliveira, Paulo; Beloti, Marcio Mateus; Rosa, Adalberto Luiz; Morra, Marco

2012-01-01

The investigation of titanium (Ti) surface modifications aiming to increase implant osseointegration is one of the most active research areas in dental implantology. This study was carried out to evaluate the benefits of coating Ti with type I collagen on the osseointegration of dental implants. Acid etched Ti implants (AETi), either untreated or coated with type I collagen (ColTi), were placed in dog mandibles for three and eight weeks for histomorphometric, cellular and molecular evaluations of bone tissue response. While the histological aspects were essentially the same with both implants being surrounded by lamellar bone trabeculae, histomorphometric analysis showed more abundant bone formation in ColTi, mainly at three weeks. Cellular evaluation showed that cells harvested from bone fragments in close contact with ColTi display lower proliferative capacity and higher alkaline phosphatase activity, phenotypic features associated with more differentiated osteoblasts. Confirming these findings, molecular analyses showed that ColTi implants up-regulates the expression of a panel of genes well known as osteoblast markers. Our results present a set of evidences that coating AETi with collagen fastens the osseointegration by stimulating bone formation at the cellular and molecular levels, making this combination of morphological and biochemical modification a promising approach to treat Ti surfaces. (paper)

In vitro study on porous silver scaffolds prepared by electroplating method using cellular carbon skeleton as the substrate

International Nuclear Information System (INIS)

Guo, M.; Wang, X.; Zhou, H.M.; Li, L.; Nie, F.L.; Cheng, Y.; Zheng, Y.F.

2012-01-01

Porous silver scaffolds, with the porosity ranging from 68% to 81% and the apparent density ranging from 0.4 to 1 g⋅cm −3 were prepared by electroplating method using cellular carbon skeleton as the substrate. The microstructure, mechanical property, cytotoxicity and antibacterial activity of the prepared porous silver scaffold were studied. The present porous silver scaffolds had a highly three-dimensional trabecular porous structure with the porosity and the apparent density close to that of the cancellous bone. Furthermore, the mechanical property such as elastic modulus and yield strength of the porous silver scaffolds were lower than that of commercial available porous Ti and porous Ti alloys but much closer to that of the cancellous bone and porous Ta. In addition, study of in vitro behavior showed that the porous silver scaffold possessed significant antibacterial capability of inhibition of bacterial proliferation and adherence against Staphylococcus aureus and Staphylococcus epidermidis, and little cytotoxicity to Mg-63 cell line and NIH-3T3 cell line. Consequently, the porous silver scaffolds prepared by electrodeposition possess a promising application for bone implants. - Highlights: ► Porous Ag scaffolds were produced by electroplating Ag on cellular carbon skeleton. ► Porous Ag scaffolds have the porosity 68–81% and the apparent density 0.4–1 g⋅cm −3 . ► The mechanical property of porous Ag is close to cancellous bone and porous Ta. ► Porous Ag inhibits the proliferation and adherence of S. aureus and S. epidermidis.

Seasonal variations of cellular stress response in the heart and gastrocnemius muscle of the water frog (Pelophylax ridibundus).

Science.gov (United States)

Feidantsis, Konstantinos; Anestis, Andreas; Vasara, Eleni; Kyriakopoulou-Sklavounou, Pasqualina; Michaelidis, Basile

2012-08-01

The present study aimed to investigate the seasonal cellular stress response in the heart and the gastrocnemius muscle of the amphibian Pelophylax ridibundus (former name Rana ridibunda) during an 8 month acclimatization period in the field. Processes studied included heat shock protein expression and protein kinase activation. The cellular stress response was addressed through the expression of Hsp70 and Hsp90 and the phosphorylation of stress-activated protein kinases and particularly p38 mitogen-activated protein kinase (p38 MAPK), the extracellular signal-regulated kinases (ERK-1/2) and c-Jun N-terminal kinases (JNK1/2/3). Due to a general metabolic depression during winter hibernation, the induction of Hsp70 and Hsp90 and the phosphorylation of p38 MAPK, JNKs and ERKs are retained at low levels of expression in the examined tissues of P. ridibundus. Recovery from hibernation induces increased levels of the specific proteins, probably providing stamina to the animals during their arousal. Copyright © 2012 Elsevier Inc. All rights reserved.

Microstructural effects in drug release by solid and cellular polymeric dosage forms: A comparative study.

Science.gov (United States)

Blaesi, Aron H; Saka, Nannaji

2017-11-01

In recent studies, we have introduced melt-processed polymeric cellular dosage forms to achieve both immediate drug release and predictable manufacture. Dosage forms ranging from minimally-porous solids to highly porous, open-cell and thin-walled structures were prepared, and the drug release characteristics investigated as the volume fraction of cells and the excipient molecular weight were varied. In the present study, both minimally-porous solid and cellular dosage forms consisting of various weight fractions of Acetaminophen drug and polyethylene glycol (PEG) excipient are prepared and analyzed. Microstructures of the solid forms and the cell walls range from single-phase solid solutions of the excipient and a small amount of drug molecules to two-phase composites of the excipient and tightly packed drug particles. Results of dissolution experiments show that the minimally-porous solid forms disintegrate and release drug by slow surface erosion. The erosion rate decreases as the drug weight fraction is increased. By contrast, the open-cell structures disintegrate rapidly by viscous exfoliation, and the disintegration time is independent of drug weight fraction. Drug release models suggest that the solid forms erode by convective mass transfer of the faster-eroding excipient if the drug volume fraction is small. At larger drug volume fractions, however, the slower-eroding drug particles hinder access of the free-flowing fluid to the excipient, thus slowing down erosion of the composite. Conversely, the disintegration rate of the cellular forms is limited by diffusion of the dissolution fluid into the excipient phase of the thin cell walls. Because the wall thickness is of the order of the drug particle size, and the particles are enveloped by the excipient during melt-processing, the drug particles cannot hinder diffusion through the excipient across the walls. Thus the disintegration time of the cellular forms is mostly unaffected by the volume fraction of drug

A study on the cellular stromal reaction and immunologic response of regional lymph nodes in gastric cancer

International Nuclear Information System (INIS)

Jyokoh, Hiroshi

1986-01-01

In an attempt to find a correlation between background factors and prognosis, cellular stromal reaction and PHA blastformation in the regional lymph nodes in gastric cancer were investigated in a total of 234 cases with advanced gastric cancer consisting of 104 patients who had undergone preoperative radiaiton therapy and 130 non-irradiated patients. The following results were obtained: 1) Interstitial matrix and fibrotic components around the gastric cancer cells proliferate. In addition, cellular components consisting mainly of lymphocytes appear in varied degrees. 2) In both non-irradiated and irradiated groups, there was no remarkable difference in the cellular stromal reaction among any major cancer sites. 3) In non-irradiated patients, no correlation existed between tumor diameters and cellular stromal reaction, while, in the irradiated cases, there were increases in the cellular stromal reaction where the tumor size is 5 cm or less. 4) In both non-irradiated and irradiated groups, cellular stromal reaction was more remarkable in highly differentiated carcinoma. 5) There were decreases in the cellular stromal reaction in ps(+) cases, of both non-irradiated and irradiated groups. 6) The cellular stromal reaction was remarkable in non-irradiated and irradiated patients who were found to be histologically negative in lymph node metastasis. 7) With the advance in staging, the cellular stromal reaction decreased in both irradiated and non-irradiated patients. 8) In both non-irradiated and irradiated groups, the cellular stromal reaction decreased in the patients who had shown vascular invasion. 9) PHA blastformation of the lymphocytes in lymph nodes of non-metastatic cases was more remarkable than that of metastatic cases, retaining high degrees of immunity. 10) In the non-metastatic patients in the lymph nodes outside the irradiated area, the lymphocytes in the lymph nodes demonstrated high degrees of PHA blastformation. (J.P.N.)

Regulation of Ras exchange factors and cellular localization of Ras activation by lipid messengers in T cells

Directory of Open Access Journals (Sweden)

Jesse E. Jun

2013-09-01

Full Text Available The Ras-MAPK signaling pathway is highly conserved throughout evolution and is activated downstream of a wide range of receptor stimuli. Ras guanine nucleotide exchange factors (RasGEFs catalyze GTP loading of Ras and play a pivotal role in regulating receptor-ligand induced Ras activity. In T cells, three families of functionally important RasGEFs are expressed: RasGRF, RasGRP, and SOS-family GEFs.Early on it was recognized that Ras activation is critical for T cell development and that the RasGEFs play an important role herein. More recent work has revealed that nuances in Ras activation appear to significantly impact T cell development and selection. These nuances include distinct biochemical patterns of analog versus digital Ras activation, differences in cellular localization of Ras activation, and intricate interplays between the RasGEFs during distinct T cell developmental stages as revealed by various new mouse models. In many instances, the exact nature of these nuances in Ras activation or how these may result from fine-tuning of the RasGEFs is not understood.One large group of biomolecules critically involved in the control of Ras-GEFs´functions are lipid second messengers. Multiple, yet distinct lipid products are generated following T cell receptor (TCR stimulation and bind to different domains in the RasGRP and SOS RasGEFs to facilitate the activation of the membrane-anchored Ras GTPases. In this review we highlight how different lipid-based elements are generated by various enzymes downstream of the TCR and other receptors and how these dynamic and interrelated lipid products may fine-tune Ras activation by RasGEFs in developing T cells.

Suitability of the cellular viability technique as a control tool of the chlorine dosage on the activated sludge of a biological process affected by bulking

International Nuclear Information System (INIS)

Montaya Martinez, T.; Zornoza Zornoza, A.; Granell Munoz, P.; Fayos, G.; Fajarddo, V.; Zorrilla, F.; Alonso Molina, J. L.; Morenilla Martinez, J. J.; Bernacer Bonora, I.; Martinez Francisco, F. J.

2009-01-01

This work demonstrates the suitability of the cellular viability technique as a control tool of the chlorine dosage on the activated sludge of a biological process affected by the overabundance of the filamentous bacteria (Thiothrix-021N). This technique was used to establish the chlorine dosage according to the observed damages on cellular membranes of both, floc-forming bacteria as well as filamentous bacteria. To identify the filamentous bacteria responsible for the macro-structural alteration of the flocs, several criteria were, met, including morphologic characteristics as well as conventional microbiological stains: Gram, Neisser and polyhydroxy alkanoates. FISH was used to confirm the obtained results, providing a definitive identification of the filamentous bacteria responsible for the alteration. (Author) 11 refs

Molecular and cellular mechanisms of cadmium carcinogenesis

International Nuclear Information System (INIS)

Waisberg, Michael; Joseph, Pius; Hale, Beverley; Beyersmann, Detmar

2003-01-01

Cadmium is a heavy metal, which is widely used in industry, affecting human health through occupational and environmental exposure. In mammals, it exerts multiple toxic effects and has been classified as a human carcinogen by the International Agency for Research on Cancer. Cadmium affects cell proliferation, differentiation, apoptosis and other cellular activities. Cd 2+ does not catalyze Fenton-type reactions because it does not accept or donate electrons under physiological conditions, and it is only weakly genotoxic. Hence, indirect mechanisms are implicated in the carcinogenicity of cadmium. In this review multiple mechanisms are discussed, such as modulation of gene expression and signal transduction, interference with enzymes of the cellular antioxidant system and generation of reactive oxygen species (ROS), inhibition of DNA repair and DNA methylation, role in apoptosis and disruption of E-cadherin-mediated cell-cell adhesion. Cadmium affects both gene transcription and translation. The major mechanisms of gene induction by cadmium known so far are modulation of cellular signal transduction pathways by enhancement of protein phosphorylation and activation of transcription and translation factors. Cadmium interferes with antioxidant defense mechanisms and stimulates the production of reactive oxygen species, which may act as signaling molecules in the induction of gene expression and apoptosis. The inhibition of DNA repair processes by cadmium represents a mechanism by which cadmium enhances the genotoxicity of other agents and may contribute to the tumor initiation by this metal. The disruption of E-cadherin-mediated cell-cell adhesion by cadmium probably further stimulates the development of tumors. It becomes clear that there exist multiple mechanisms which contribute to the carcinogenicity of cadmium, although the relative weights of these contributions are difficult to estimate

Development of a novel LC/MS method to quantitate cellular stearoyl-CoA desaturase activity

International Nuclear Information System (INIS)

Dillon, Roslyn; Greig, Michael J.; Bhat, B. Ganesh

2008-01-01

Stearoyl-CoA desaturase 1 (SCD1) is an enzyme that catalyzes the rate-limiting step in de novo synthesis of monounsaturated fatty acids-mainly oleate and palmitoleate from stearoyl-CoA and palmitoyl-Co A, respectively. These products are the most abundant monounsaturated fatty acids in membrane phospholipids, triglycerides, cholesterol esters. Reports on mice with a targeted disruption of SCD1 gene (SCD1-/-) exhibit improved glucose tolerance and insulin sensitivity compared to wild-type suggesting SCD1 could be a therapeutic target for diabetes and related metabolic diseases. Measurement of SCD1 activity is technically challenging and traditional cell-based SCD1 assay procedure is labor intensive with low throughput. We describe here a novel medium-throughput LC/MS cell-based assay for determining cellular SCD1 activity, facilitating screening of potential SCD1 inhibitor compounds. Confluent HepG2 cells were grown in 24-well plates and incubated with vehicle or an inhibitor followed by incubation with deuterium labeled saturated fatty acid substrates. Total cell lipids were extracted and the conversion of stearate to oleate was measured by liquid chromatography-mass spectrometry. Sterculate, a known inhibitor of SCD1, inhibited the enzyme activity in a dose dependent manner in this assay with a calculated EC 50 of 247 nM. The medium-throughput method described here is an important step towards identifying an inhibitor of SCD1 to treat diabetes and related metabolic diseases

Cellular radiobiology of heavy-ion beams

International Nuclear Information System (INIS)

Tobias, C.A.; Blakely, E.A.; Ngo, F.Q.H.; Roots, R.J.; Yang, T.C.

1981-01-01

Progress is reported in the following areas of this research program: relative biological effectiveness and oxygen enhancement ratio of silicon ion beams; heavy ion effects on the cell cycle; the potentiation effect (2 doses of high LET heavy-ion radiations separated by 2 to 3 hours); potentially lethal damage in actively growing cells and plateau growth cells; radiation induced macromolecular lesions and cellular radiation chemistry; lethal effects of dual radiation; and the development of a biophysical repair/misrepair model

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...

Cellular structure of lean hydrogen flames in microgravity

Science.gov (United States)

Patnaik, G.; Kailasanath, K.

1990-01-01

Detailed, time-dependent, two-dimensional numerical simulations of premixed laminar flames have been used to study the initiation and subsequent development of cellular structures in lean hydrogen-air flames. The model includes detailed hydrogen-oxygen combustion with 24 elementary reactions of eight reactive species and a nitrogen diluent, molecular diffusion of all species, thermal conduction, viscosity, and convection. This model has been used to study the nonlinear evolution of cellular flame structure and shows that cell splitting, as observed in experiments, can be predicted numerically for sufficiently reactive mixtures. The structures that evolved also resembled the cellular structures observed in experiments. The present study shows that the 'cell-split limit' postulated from experimental observations is an intrinsic property of the mixture and that external factors such as heat losses are not necessary to cause this limit.

Numerical Study on the Projectile Impact Resistance of Multi-Layer Sandwich Panels with Cellular Cores

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Liming Chen

Full Text Available Abstract The projectile impact resistance of sandwich panels with cellular cores with different layer numbers has been numerically investigated by perpendicular impact of rigid blunt projectile in ABAQUS/Explicit. These panels with corrugation, hexagonal honeycomb and pyramidal truss cores are impacted at velocities between 50 m/s and 202 m/s while the relative density ranges from 0.001 to 0.15 The effects of core configuration and layer number on projectile impact resistance of sandwich panels with cellular cores are studied. At low impact velocity, sandwich panels with cellular cores outperform the corresponding solid ones and non-montonicity between relative density and projectile resistance of sandwich panels is found and analyzed. Multiplying layer can reduce the maximum central deflection of back face sheet of the above three sandwich panels except pyramidal truss ones in high relative density. Hexagonal honeycomb sandwich panel is beneficial to increasing layer numbers in lowering the contact force and prolonging the interaction time. At high impact velocity, though corrugation and honeycomb sandwich panels are inferior to the equal-weighted solid panels, pyramidal truss ones with high relative density outperform the corresponding solid panels. Multiplying layer is not the desirable way to improve high-velocity projectile resistance.

Primary cellular meningeal defects cause neocortical dysplasia and dyslamination

Science.gov (United States)

Hecht, Jonathan H.; Siegenthaler, Julie A.; Patterson, Katelin P.; Pleasure, Samuel J.

2010-01-01

Objective Cortical malformations are important causes of neurological morbidity, but in many cases their etiology is poorly understood. Mice with Foxc1 mutations have cellular defects in meningeal development. We use hypomorphic and null alleles of Foxc1 to study the effect of meningeal defects on neocortical organization. Methods Embryos with loss of Foxc1 activity were generated using the hypomorphic Foxc1hith allele and the null Foxc1lacZ allele. Immunohistologic analysis was used to assess cerebral basement membrane integrity, marginal zone heterotopia formation, neuronal overmigration, meningeal defects, and changes in basement membrane composition. Dysplasia severity was quantified using two measures. Results Cortical dysplasia resembling cobblestone cortex, with basement membrane breakdown and lamination defects, is seen in Foxc1 mutants. As Foxc1 activity was reduced, abnormalities in basement membrane integrity, heterotopia formation, neuronal overmigration, and meningeal development appeared earlier in gestation and were more severe. Surprisingly, the basement membrane appeared intact at early stages of development in the face of severe deficits in meningeal development. Prominent defects in basement membrane integrity appeared as development proceeded. Molecular analysis of basement membrane laminin subunits demonstrated that loss of the meninges led to changes in basement membrane composition. Interpretation Cortical dysplasia can be caused by cellular defects in the meninges. The meninges are not required for basement membrane establishment but are needed for remodeling as the brain expands. Specific changes in basement membrane composition may contribute to subsequent breakdown. Our study raises the possibility that primary meningeal defects may cortical dysplasia in some cases. PMID:20976766

High Cellular Monocyte Activation in People Living With Human Immunodeficiency Virus on Combination Antiretroviral Therapy and Lifestyle-Matched Controls Is Associated With Greater Inflammation in Cerebrospinal Fluid

NARCIS (Netherlands)

Booiman, Thijs; Wit, Ferdinand W N M; Maurer, Irma; De Francesco, Davide; Sabin, Caroline A; Harskamp, Agnes M; Prins, Maria; Garagnani, Paolo; Pirazzini, Chiara; Franceschi, Claudio; Fuchs, Dietmar; Gisslén, Magnus; Winston, Alan; Reiss, Peter; Kootstra, Neeltje A; Kalsbeek, A.

2017-01-01

BACKGROUND: Increased monocyte activation and intestinal damage have been shown to be predictive for the increased morbidity and mortality observed in treated people living with human immunodeficiency virus (PLHIV). METHODS: A cross-sectional analysis of cellular and soluble markers of monocyte

Antiglycopeptide Mouse Monoclonal Antibody LpMab-21 Exerts Antitumor Activity Against Human Podoplanin Through Antibody-Dependent Cellular Cytotoxicity and Complement-Dependent Cytotoxicity.

Science.gov (United States)

Kato, Yukinari; Kunita, Akiko; Fukayama, Masashi; Abe, Shinji; Nishioka, Yasuhiko; Uchida, Hiroaki; Tahara, Hideaki; Yamada, Shinji; Yanaka, Miyuki; Nakamura, Takuro; Saidoh, Noriko; Yoshida, Kanae; Fujii, Yuki; Honma, Ryusuke; Takagi, Michiaki; Ogasawara, Satoshi; Murata, Takeshi; Kaneko, Mika K

2017-02-01

The interaction between podoplanin (PDPN) and C-type lectin-like receptor 2 (CLEC-2) is involved in tumor malignancy. We have established many monoclonal antibodies (mAbs) against human podoplanin using the cancer-specific mAb (CasMab) technology. LpMab-21, one of the mouse antipodoplanin mAbs, is of the IgG 2a subclass, and its minimum epitope was determined to be Thr76-Arg79 of the human podoplanin. Importantly, sialic acid is linked to Thr76; therefore, LpMab-21 is an antiglycopeptide mAb (GpMab). In this study, we investigated whether LpMab-21 shows antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) against human podoplanin-expressing cancer cell lines in vitro and also studied its antitumor activities using a xenograft model. LpMab-21 showed high ADCC and CDC activities against not only podoplanin-expressing Chinese hamster ovary cells but also LN319 glioblastoma cells and PC-10 lung cancer cells, both of which endogenously express podoplanin. Furthermore, LpMab-21 decreased tumor growth in vivo, indicating that LpMab-21 could be useful for antibody therapy against human podoplanin-expressing cancers.

Antibody dependent cellular phagocytosis by macrophages is a novel mechanism of action of elotuzumab.

Science.gov (United States)

Kurdi, Ahmed T; Glavey, Siobhan V; Bezman, Natalie A; Jhatakia, Amy; Guerriero, Jennifer L; Manier, Salomon; Moschetta, Michele; Mishima, Yuji; Roccaro, Aldo; Detappe, Alexandre; Liu, Chia-Jen; Sacco, Antonio; Huynh, Daisy; Tai, Yu-Tzu; Robbins, Michael D; Azzi, Jamil; Ghobrial, Irene M

2018-04-13

Elotuzumab, a recently approved antibody for the treatment of multiple myeloma (MM), has been shown to stimulate Fcγ receptor (FcγR)-mediated antibody-dependent cellular cytotoxicity (ADCC) by natural killer (NK) cells towards myeloma cells. The modulatory effects of elotuzumab on other effector cells in the tumor microenvironment, however, has not been fully explored. Antibody dependent cellular phagocytosis (ADCP) is a mechanism by which macrophages contribute to anti-tumor potency of monoclonal antibodies. Herein, we studied the NK cell independent effect of elotuzumab on tumor associated macrophages (TAMs) using a xenograft tumor model deficient in NK and adaptive immune cells. We demonstrate significant anti-tumor efficacy of single agent elotuzumab in immunocompromised xenograft models of multiple myeloma, which is in part mediated by Fc-FcγR interaction of elotuzumab with macrophages. Elotuzumab is shown in this study to induce phenotypic activation of macrophages in-vivo and mediates ADCP of myeloma cells though a FcγR dependent manner in-vitro. Together, these findings propose a novel immune mediated mechanism by which elotuzumab exerts anti-myeloma activity and helps to provide rationale for combination therapies that can enhance macrophage activity. Copyright ©2018, American Association for Cancer Research.

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

Wood Cellular Dendroclimatology: A Pilot Study on Bristlecone Pine in the Southwest US

Science.gov (United States)

Ziaco, E.; Biondi, F.; Heinrich, I.

2015-12-01

Tree-rings provide paleoclimatic records at annual to seasonal resolution for regions or periods with no instrumental climatic data. Relationships between climatic variability and wood cellular features allow for a more complete understanding of the physiological mechanisms that control the climatic response of trees. Given the increasing importance of wood anatomy as a source of dendroecological information, such studies are now starting in the US. We analyzed 10 cores of bristlecone pine (Pinus longaeva D.K. Bailey) from a high-elevation site included in the Nevada Climate-ecohydrological Assessment Network (NevCAN). Century-long chronologies (1870-2013) of wood anatomical parameters (lumen area, cell diameter, cell wall thickness) can be developed by capturing strongly contrasted microscopic images using a Confocal Laser Scanning Microscope, and then measuring cellular parameters with task-specific software. Measures of empirical signal strength were used to test the strength of the environmental information embedded in wood anatomy. Correlation functions between ring-width, cellular features, and PRISM climatic variables were produced for the period 1926-2013. Time series of anatomical features present lower autocorrelation compared to ring widths, highlighting the role of environmental conditions occurring at the time of cell formation. Mean chronologies of radial lumen length and cell diameter carry a stronger climatic signal compared to cell wall thickness, and are significantly correlated with climatic variables (maximum temperature and total precipitation) in spring (Mar-Apr) and during the growing season (Jun-Sep), whereas ring widths show weaker or no correlation. Wood anatomy holds great potential to refine dendroclimatic reconstructions at higher temporal resolution, providing better estimates of hydroclimatic variability and plant physiological adaptations in the southwest US.

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,...

Cellular mechanics and motility

Science.gov (United States)

Hénon, Sylvie; Sykes, Cécile

2015-10-01

cross-linked or branched networks. It is a highly dynamical system in which filaments are able to elongate or slide one on the other with the contribution of very active cellular proteins like molecular motors. The versatile properties of this cytoskeleton ensure the diversity of mechanical behaviors to explain cell rigidity as well as cell motility.

Implications of TGFβ on transcriptome and cellular biofunctions of palatal mesenchyme

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Xiujuan eZhu

2012-04-01

Full Text Available Development of the palate comprises sequential stages of growth, elevation and fusion of the palatal shelves. The mesenchymal component of palates plays a major role in early phases of palatogenesis, such as growth and elevation. Failure in these steps may result in cleft palate, the second most common birth defect in the world. These early stages of palatogenesis require precise and chronological orchestration of key physiological processes, such as growth, proliferation, differentiation, migration, and apoptosis. There is compelling evidence for the vital role of TGFβ-mediated regulation of palate development. We hypothesized that the isoforms of TGFβ regulate different cellular biofunctions of the palatal mesenchyme to various extents. Human embryonic palatal mesenchyme (HEPM cells were treated with TGFβ1, β2, and β3 for microarray-based gene expression studies in order to identify the roles of TGFβ in the transcriptome of the palatal mesenchyme. Following normalization and modeling of 28,869 human genes, 566 transcripts were detected as differentially expressed in TGFβ-treated HEPM cells. Out of these altered transcripts, 234 of them were clustered in cellular biofunctions, including growth and proliferation, development, morphology, movement, cell cycle, and apoptosis. Biological interpretation and network analysis of the genes active in cellular biofunctions were performed using IPA. Among the differentially expressed genes, 11 of them were previously identified as being crucial for palatogenesis (EDN1, INHBA, LHX8, PDGFC, PIGA, RUNX1, SNAI1, SMAD3, TGFβ1, TGFβ2, and TGFβR1. These genes were used for a merged interaction network with cellular behaviors. Overall, we have determined that more than 2% of human transcripts were differentially expressed in response to TGFβ treatment in HEPM cells. Our results suggest that both TGFβ1 and TGFβ2 orchestrate major cellular biofunctions within the palatal mesenchyme in vitro by

POSSIBILITIES OF CURRENT CELLULAR TECHNOLOGIES FOR ARTICULAR CARTILAGE REPAIR (ANALYTICAL REVIEW

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M. S. Bozhokin

2016-01-01

Full Text Available Despite a wide variety of surgical procedures utilized in clinical practice for treatment of articular cartilage lesions, the search for other options of articular reconstruction remains a relevant and open issue at the current stage of medicine and biotechnologies development. The recent years demonstrated a strong belief in cellular methods of hyaline cartilage repair such as implantation of autologous chondrocytes (ACI or cultures of mesenchymal stem cells (MSC including techniques for genetic modification of cells.The purpose of presented review is to summarize the published scientific data on up to date results of perspective cellular technologies for articular cartilage repair that are being developed. Autologous chondrocyte transplantation originally performed by Swedish researchers in 1987 is considered the first clinically applied technique for restoration of hyaline cartilage using cellular technologies. However, the transplanted cell culture featured low proliferative capacity and inability to form a regenerate resistant to high physical activity. Another generation of methods originated at the turn of the century utilized mesenchymal stem cells instead of autologous chondrocytes. Preparation of MSCs is a less invasive procedure compared to chondrocytes harvesting and the culture is featured by a higher proliferative ability. Researchers use various biodegradable carriers (matrices to secure cell fixation. Despite good clinical mid-term outcomes the transplanted tissue-engineering structures deteriorate with time due to cellular de-differentiation. Next generation of techniques being currently under pre-clinical studies is featured by the preliminary chondrogenic modification of transplanted cell culture. Usage of various growth factors, modified cell product and gene-activated matrices allow to gain a stable regulatory and key proteins synthesis and achieve a focused influence on regenerate's chondrogenic proliferation and in result

Fabrication of curcumin-loaded bovine serum albumin (BSA)-dextran nanoparticles and the cellular antioxidant activity.

Science.gov (United States)

Fan, Yuting; Yi, Jiang; Zhang, Yuzhu; Yokoyama, Wallace

2018-01-15

Bovine serum albumin (BSA)-dextran conjugate was prepared with glycation. Self-assembly nanoparticles were synthesized with a green, and facile approach. The effects of dry-heating time on the fabrication and characteristics of BSA-dextran conjugate nanoparticles were examined. Stable nanoparticles (dextran was grafted onto the BSA to provide significant steric hindrance. Particle size decreased with the increase of dry-heating time and the lowest particle size (51.2nm) was obtained after 24h dry-heating. The nanoparticles were stable in a wide pH range (pH 2.0-7.0). The particle size of nanoparticles increased to 115nm after curcumin incorporation and was stable even after one-month storage. TEM results demonstrated that curcumin-loaded nanoparticles displayed a spherical structure and were homogeneously dispersed. Curcumin in BSA-dextran nanoparticle showed better stability, compared to free curcumin. In addition, BSA-dextran nanoparticles can improve the cellular antioxidant activity of curcumin in Caco-2 cells. Copyright © 2017 Elsevier Ltd. All rights reserved.

Synthesis, activity, and structure--activity relationship studies of novel cationic lipids for DNA transfer.

Science.gov (United States)

Byk, G; Dubertret, C; Escriou, V; Frederic, M; Jaslin, G; Rangara, R; Pitard, B; Crouzet, J; Wils, P; Schwartz, B; Scherman, D

1998-01-15

We have designed and synthesized original cationic lipids for gene delivery. A synthetic method on solid support allowed easy access to unsymmetrically monofunctionalized polyamine building blocks of variable geometries. These polyamine building blocks were introduced into cationic lipids. To optimize the transfection efficiency in the novel series, we have carried out structure-activity relationship studies by introduction of variable-length lipids, of variable-length linkers between lipid and cationic moiety, and of substituted linkers. We introduce the concept of using the linkers within cationic lipids molecules as carriers of side groups harboring various functionalities (side chain entity), as assessed by the introduction of a library composed of cationic entities, additional lipid chains, targeting groups, and finally the molecular probes rhodamine and biotin for cellular traffic studies. The transfection activity of the products was assayed in vitro on Hela carcinoma, on NIH3T3, and on CV1 fibroblasts and in vivo on the Lewis Lung carcinoma model. Products from the series displayed high transfection activities. Results indicated that the introduction of a targeting side chain moiety into the cationic lipid is permitted. A primary physicochemical characterization of the DNA/lipid complexes was demonstrated with this leading compound. Selected products from the series are currently being developed for preclinical studies, and the labeled lipopolyamines can be used to study the intracellular traffic of DNA/cationic lipid complexes.

Structure of modified [epsilon]-polylysine micelles and their application in improving cellular antioxidant activity of curcuminoids

Energy Technology Data Exchange (ETDEWEB)

Yu, Hailong; Li, Ji; Shi, Ke; Huang, Qingrong (Rutgers)

2015-10-15

The micelle structure of octenyl succinic anhydride modified {var_epsilon}-polylysine (M-EPL), an anti-microbial surfactant prepared from natural peptide {var_epsilon}-polylysine in aqueous solution has been studied using synchrotron small-angle X-ray scattering (SAXS). Our results revealed that M-EPLs formed spherical micelles with individual size of 24-26 {angstrom} in aqueous solution which could further aggregate to form a larger dimension with averaged radius of 268-308 {angstrom}. Furthermore, M-EPL micelle was able to encapsulate curcuminoids, a group of poorly-soluble bioactive compounds from turmeric with poor oral bioavailability, and improve their water solubility. Three loading methods, including solvent evaporation, dialysis, and high-speed homogenization were compared. The results indicated that the dialysis method generated the highest loading capacity and curcuminoids water solubility. The micelle encapsulation was confirmed as there were no free curcuminoid crystals detected in the differential scanning calorimetry analysis. It was also demonstrated that M-EPL encapsulation stabilized curcuminoids against hydrolysis at pH 7.4 and the encapsulated curcuminoids showed elevated cellular antioxidant activity compared with free curcuminoids. This work suggested that M-EPL could be used as new biopolymer micelles for delivering poorly soluble drugs/phytochemicals and improving their bioactivities.

Optimization of the diabetic nephropathy treatment with attention to the special features of cellular inflammation mechanisms

Directory of Open Access Journals (Sweden)

Тетяна Дмитрівна Щербань

2016-02-01

Full Text Available Aim. Optimization of the diabetic nephropathy (DN treatment in association with hypertonic disease (HD based on the study of neutrophil chain of pathogenic cellular mechanisms of these diseases development and the special features of its clinical course.Materials and methods. There were complexly examined 86 patients with HD associated with DN and 30 patients with isolated HD. The control group was formed by 30 practically healthy persons. The activity of NO-synthases in neutrophils was detected by Green colorimetric methods using Griess reagent. The expression of ІСАМ-1 (CD54, CD11b-integrin and inducible NO-synthase on neutrophils was detected by the indirect immunocytochemical method. Oxygen-depending activity of neutrophils was assessed in NBT-test.Results. Expression of adhesive molecules of CD54and CD11b-integrin on neutrophils of peripheral blood essentially increases (р <0,001 in patients with DN in association with HD comparing with isolated HD and the control group.At associated pathology on the background of high oxygen-depending activity of neutrophils its functional reserve decreases that results in intensification of inflammatory processes in kidneys (р<0,001.In comorbid patients chronization of pathological process results in imbalance of NO-synthases system in neutrophils: on the background of decrease of activity of constituent NO-synthases the expression and activity of inducible NO-synthase increase (р<0,001 .The use of L-arginine hydrochloride in the complex therapy of patients with DN associated with HD intensifies organoprotective effect of basal therapy, results in facilitation of the clinical course, decreases albuminuria, corrects the functional indices of neutrophils and diminishes imbalance in NO-synthases system.Conclusions. In patients with DN in association with HD the neutrophil chain of cellular inflammation mechanisms are activated: expression of adhesive molecules grows, oxygen-depending metabolism is

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

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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.

Lempel-Ziv complexity analysis of one dimensional cellular automata.

Science.gov (United States)

Estevez-Rams, E; Lora-Serrano, R; Nunes, C A J; Aragón-Fernández, B

2015-12-01

Lempel-Ziv complexity measure has been used to estimate the entropy density of a string. It is defined as the number of factors in a production factorization of a string. In this contribution, we show that its use can be extended, by using the normalized information distance, to study the spatiotemporal evolution of random initial configurations under cellular automata rules. In particular, the transfer information from time consecutive configurations is studied, as well as the sensitivity to perturbed initial conditions. The behavior of the cellular automata rules can be grouped in different classes, but no single grouping captures the whole nature of the involved rules. The analysis carried out is particularly appropriate for studying the computational processing capabilities of cellular automata rules.

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

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.

Cellular energy allocation in zebra mussels exposed along a pollution gradient: linking cellular effects to higher levels of biological organization.

Science.gov (United States)

Smolders, R; Bervoets, L; De Coen, W; 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.

Building synthetic cellular organization

OpenAIRE

Polka, Jessica K.; Silver, Pamela A.

2013-01-01

The elaborate spatial organization of cells enhances, restricts, and regulates protein–protein interactions. However, the biological significance of this organization has been difficult to study without ways of directly perturbing it. We highlight synthetic biology tools for engineering novel cellular organization, describing how they have been, and can be, used to advance cell biology.

Taming the sphinx: Mechanisms of cellular sphingolipid homeostasis.

Science.gov (United States)

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.

Immunohistochemical evaluation of fibrovascular and cellular pre-iridal membranes in dogs.

Science.gov (United States)

Bauer, Bianca S; Sandmeyer, Lynne S; Hall, Riley B; Grahn, Bruce H

2012-03-01

Histologically, two morphologically distinct types of pre-iridal membranes appear to occur in diseased canine globes: fibrovascular and cellular. Cellular pre-iridal membranes of corneal endothelial origin exist in iridocorneal endothelial (ICE) syndrome in humans and arise through metaplastic transformation of corneal endothelial cells into epithelial-like cells.(1) The purpose of this study was to (i) evaluate immunohistochemical staining of these two types of membranes in diseased canine globes, (ii) determine whether endothelial cell metaplasia or iridal vascular budding plays a role in cellular membrane formation and (iii) compare the primary histopathologic diagnosis between the two groups. Hematoxylin and eosin (H&E)-stained slides of 28 enucleated canine specimens with pre-iridal membranes were randomly selected and examined with light microscopy. The globes were divided into two groups based on the appearance of the membrane: fibrovascular or cellular, and the histopathologic diagnoses were recorded. Immunohistochemical staining for vimentin, cytokeratin AE1/AE3, and Von Willebrand's factor (Factor VIII) was completed on the slides of each globe. The histopathologic diagnoses were compared between the two groups. The fibrovascular and cellular membranes stained positive for vimentin and negative for cytokeratin AE1/AE3. All fibrovascular membranes stained positive for Factor VIII compared with the cellular membranes which stained negative. In the cellular membrane group, primary glaucoma was a common histologic diagnosis. Immunohistochemical evaluation in this study does not support the hypothesis of metaplastic transformation of endothelial cells into epithelial-like cells in the canine globes with cellular membranes. The cellular membranes in this study do not represent a canine version of ICE syndrome and are not of vascular endothelial origin. © 2012 American College of Veterinary Ophthalmologists.

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.

Building mathematics cellular phone learning communities

Directory of Open Access Journals (Sweden)

Wajeeh M. Daher

2011-04-01

Full Text Available Researchers emphasize the importance of maintaining learning communities and environments. This article describes the building and nourishment of a learning community, one comprised of middle school students who learned mathematics out-of-class using the cellular phone. The building of the learning community was led by three third year pre-service teachers majoring in mathematics and computers. The pre-service teachers selected thirty 8th grade students to learn mathematics with the cellular phone and be part of a learning community experimenting with this learning. To analyze the building and development stages of the cellular phone learning community, two models of community building stages were used; first the team development model developed by Tuckman (1965, second the life cycle model of a virtual learning community developed by Garber (2004. The research findings indicate that a learning community which is centered on a new technology has five 'life' phases of development: Pre-birth, birth, formation, performing, and maturity. Further, the research finding indicate that the norms that were encouraged by the preservice teachers who initiated the cellular phone learning community resulted in a community which developed, nourished and matured to be similar to a community of experienced applied mathematicians who use mathematical formulae to study everyday phenomena.

Chatty Mitochondria: Keeping Balance in Cellular Protein Homeostasis.

Science.gov (United States)

Topf, Ulrike; Wrobel, Lidia; Chacinska, Agnieszka

2016-08-01

Mitochondria are multifunctional cellular organelles that host many biochemical pathways including oxidative phosphorylation (OXPHOS). Defective mitochondria pose a threat to cellular homeostasis and compensatory responses exist to curtail the source of stress and/or its consequences. The mitochondrial proteome comprises proteins encoded by the nuclear and mitochondrial genomes. Disturbances in protein homeostasis may originate from mistargeting of nuclear encoded mitochondrial proteins. Defective protein import and accumulation of mistargeted proteins leads to stress that triggers translation alterations and proteasomal activation. These cytosolic pathways are complementary to the mitochondrial unfolded protein response (UPRmt) that aims to increase the capacity of protein quality control mechanisms inside mitochondria. They constitute putative targets for interventions aimed at increasing the fitness, stress resistance, and longevity of cells and organisms. Copyright © 2016 Elsevier Ltd. All rights reserved.

Histone H2AX is a critical factor for cellular protection against DNA alkylating agents.

Science.gov (United States)

Meador, J A; Zhao, M; Su, Y; Narayan, G; Geard, C R; Balajee, A S

2008-09-25

Histone H2A variant H2AX is a dose-dependent suppressor of oncogenic chromosome translocations. H2AX participates in DNA double-strand break repair, but its role in other DNA repair pathways is not known. In this study, role of H2AX in cellular response to alkylation DNA damage was investigated. Cellular sensitivity to two monofunctional alkylating agents (methyl methane sulfonate and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)) was dependent on H2AX dosage, and H2AX null cells were more sensitive than heterozygous cells. In contrast to wild-type cells, H2AX-deficient cells displayed extensive apoptotic death due to a lack of cell-cycle arrest at G(2)/M phase. Lack of G(2)/M checkpoint in H2AX null cells correlated well with increased mitotic irregularities involving anaphase bridges and gross chromosomal instability. Observation of elevated poly(ADP) ribose polymerase 1 (PARP-1) cleavage suggests that MNNG-induced apoptosis occurs by PARP-1-dependent manner in H2AX-deficient cells. Consistent with this, increased activities of PARP and poly(ADP) ribose (PAR) polymer synthesis were detected in both H2AX heterozygous and null cells. Further, we demonstrate that the increased PAR synthesis and apoptotic death induced by MNNG in H2AX-deficient cells are due to impaired activation of mitogen-activated protein kinase pathway. Collectively, our novel study demonstrates that H2AX, similar to PARP-1, confers cellular protection against alkylation-induced DNA damage. Therefore, targeting either PARP-1 or histone H2AX may provide an effective way of maximizing the chemotherapeutic value of alkylating agents for cancer treatment.

The threshold of coexistence and critical behaviour of a predator-prey cellular automaton

International Nuclear Information System (INIS)

Arashiro, Everaldo; Tome, Tania

2007-01-01

We study a probabilistic cellular automaton to describe two population biology problems: the threshold of species coexistence in a predator-prey system and the spreading of an epidemic in a population. By carrying out mean-field approximations and numerical simulations we obtain the phase boundaries (thresholds) related to the transition between an active state, where prey and predators present a stable coexistence, and a prey absorbing state. The numerical estimates for the critical exponents show that the transition belongs to the directed percolation universality class. In the limit where the cellular automaton maps into a model for the spreading of an epidemic with immunization we observe a crossover from directed percolation class to the dynamic percolation class. Patterns of growing clusters related to species coexistence and spreading of epidemic are shown and discussed