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Sample records for cellular interaction relevant

  1. CELLULAR INTERACTIONS MEDIATED BY GLYCONECTIDS

    OpenAIRE

    Popescu, O.; Sumanovski, L. T.; I. Checiu; Elisabeta Popescu; G. N. Misevic

    1999-01-01

    Cellular interactions involve many types of cell surface molecules and operate via homophilic and/or heterophilic protein-protein and protein-carbohydrate binding. Our investigations in different model-systems (marine invertebrates and mammals) have provided direct evidence that a novel class of primordial proteoglycans, named by us gliconectins, can mediate cell adhesion via a new alternative molecular mechanism of polyvalent carbohydrate-carbohydrate binding. Biochemical characterization of...

  2. Microglia in the mouse retina alter the structure and function of retinal pigmented epithelial cells: a potential cellular interaction relevant to AMD.

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    Wenxin Ma

    Full Text Available BACKGROUND: Age-related macular degeneration (AMD is a leading cause of legal blindness in the elderly in the industrialized word. While the immune system in the retina is likely to be important in AMD pathogenesis, the cell biology underlying the disease is incompletely understood. Clinical and basic science studies have implicated alterations in the retinal pigment epithelium (RPE layer as a locus of early change. Also, retinal microglia, the resident immune cells of the retina, have been observed to translocate from their normal position in the inner retina to accumulate in the subretinal space close to the RPE layer in AMD eyes and in animal models of AMD. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we examined the effects of retinal microglia on RPE cells using 1 an in vitro model where activated retinal microglia are co-cultured with primary RPE cells, and 2 an in vivo mouse model where retinal microglia are transplanted into the subretinal space. We found that retinal microglia induced in RPE cells 1 changes in RPE structure and distribution, 2 increased expression and secretion of pro-inflammatory, chemotactic, and pro-angiogenic molecules, and 3 increased extent of in vivo choroidal neovascularization in the subretinal space. CONCLUSIONS/SIGNIFICANCE: These findings share similarities with important pathological features found in AMD and suggest the relevance of microglia-RPE interactions in AMD pathogenesis. We speculate that the migration of retinal microglia into the subretinal space in early stages of the disease induces significant changes in RPE cells that perpetuate further microglial accumulation, increase inflammation in the outer retina, and fosters an environment conducive for the formation of neovascular changes responsible for much of vision loss in advanced AMD.

  3. CELLULAR INTERACTIONS MEDIATED BY GLYCONECTIDS

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    O.Popescu

    1999-01-01

    Full Text Available Cellular interactions involve many types of cell surface molecules and operate via homophilic and/or heterophilic protein-protein and protein-carbohydrate binding. Our investigations in different model-systems (marine invertebrates and mammals have provided direct evidence that a novel class of primordial proteoglycans, named by us gliconectins, can mediate cell adhesion via a new alternative molecular mechanism of polyvalent carbohydrate-carbohydrate binding. Biochemical characterization of isolated and purified glyconectins revealed the presence of specific carbohydrate structures, acidic glycans, different from classical glycosaminoglycans. Such acidic glycans of high molecular weight containing fucose, glucuronic or galacturonic acids, and sulfate groups, originally found in sponges and sea urchin embryos, may represent a new class of carbohydrate carcino-embryonal antigens in mice and humans. Such interactions between biological macromolecules are usually investigated by kinetic binding studies, calorimetric methods, X-ray diffraction, nuclear magnetic resonance, and other spectroscopic analyses. However, these methods do not supply a direct estimation of the intermolecular binding forces that are fundamental for the function of the ligand-receptor association. Recently, we have introduced atomic force microscopy to quantify the binding strength between cell adhesion proteoglycans. Measurement of binding forces intrinsic to cell adhesion proteoglycans is necessary to assess their contribution to the maintenance of the anatomical integrity of multicellular organisms. As a model, we selected the glyconectin 1, a cell adhesion proteoglycan isolated from the marine sponge Microciona prolifera. This glyconectin mediates in vivo cell recognition and aggregation via homophilic, species-specific, polyvalent, and calcium ion-dependent carbohydrate-carbohydrate interactions. Under physiological conditions, an adhesive force of up to 400 piconewtons

  4. Cellular encoding for interactive evolutionary robotics

    NARCIS (Netherlands)

    Gruau, F.C.; Quatramaran, K.

    1996-01-01

    This work reports experiments in interactive evolutionary robotics. The goal is to evolve an Artificial Neural Network (ANN) to control the locomotion of an 8-legged robot. The ANNs are encoded using a cellular developmental process called cellular encoding. In a previous work similar experiments ha

  5. Valerian: No Evidence for Clinically Relevant Interactions

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    Olaf Kelber

    2014-01-01

    Full Text Available In recent popular publications as well as in widely used information websites directed to cancer patients, valerian is claimed to have a potential of adverse interactions with anticancer drugs. This questions its use as a safe replacement for, for example, benzodiazepines. A review on the interaction potential of preparations from valerian root (Valeriana officinalis L. root was therefore conducted. A data base search and search in a clinical drug interaction data base were conducted. Thereafter, a systematic assessment of publications was performed. Seven in vitro studies on six CYP 450 isoenzymes, on p-glycoprotein, and on two UGT isoenzymes were identified. However, the methodological assessment of these studies did not support their suitability for the prediction of clinically relevant interactions. In addition, clinical studies on various valerian preparations did not reveal any relevant interaction potential concerning CYP 1A2, 2D6, 2E1, and 3A4. Available animal and human pharmacodynamic studies did not verify any interaction potential. The interaction potential of valerian preparations therefore seems to be low and thereby without clinical relevance. We conclude that there is no specific evidence questioning their safety, also in cancer patients.

  6. PREDICTING RELEVANT EMPTY SPOTS IN SOCIAL INTERACTION

    Institute of Scientific and Technical Information of China (English)

    Yoshiharu MAENO; Yukio OHSAWA

    2008-01-01

    An empty spot refers to an empty hard-to-fill space which can be found in the records of the social interaction, and is the clue to the persons in the underlying social network who do not appear in the records. This contribution addresses a problem to predict relevant empty spots in social interaction. Homogeneous and inhomogeneous networks are studied as a model underlying the social interaction. A heuristic predictor function method is presented as a new method to address the problem. Simulation experiment is demonstrated over a homogeneous network. A test data set in the form of market baskets is generated from the simulated communication. Precision to predict the empty spots is calculated to demonstrate the performance of the presented method.

  7. Cellular interactions with tissue-engineered microenvironments and nanoparticles

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    Pan, Zhi

    Tissue-engineered hydrogels composed of intermolecularlly crosslinked hyaluronan (HA-DTPH) and fibronectin functional domains (FNfds) were applied as a physiological relevant ECM mimic with controlled mechanical and biochemical properties. Cellular interactions with this tissue-engineered environment, especially physical interactions (cellular traction forces), were quantitatively measured by using the digital image speckle correlation (DISC) technique and finite element method (FEM). By correlating with other cell functions such as cell morphology and migration, a comprehensive structure-function relationship between cells and their environments was identified. Furthermore, spatiotemporal redistribution of cellular traction stresses was time-lapse measured during cell migration to better understand the dynamics of cell mobility. The results suggest that the reinforcement of the traction stresses around the nucleus, as well as the relaxation of nuclear deformation, are critical steps during cell migration, serving as a speed regulator, which must be considered in any dynamic molecular reconstruction model of tissue cell migration. Besides single cell migration, en masse cell migration was studied by using agarose droplet migration assay. Cell density was demonstrated to be another important parameter to influence cell behaviors besides substrate properties. Findings from these studies will provide fundamental design criteria to develop novel and effective tissue-engineered constructs. Cellular interactions with rutile and anatase TiO2 nanoparticles were also studied. These particles can penetrate easily through the cell membrane and impair cell function, with the latter being more damaging. The exposure to nanoparticles was found to decrease cell area, cell proliferation, motility, and contractility. To prevent this, a dense grafted polymer brush coating was applied onto the nanoparticle surface. These modified nanoparticles failed to adhere to and penetrate

  8. Interactions of Pellet with Reactor Relevant Plasma

    Institute of Scientific and Technical Information of China (English)

    PENGLilin; DENGBaiquan; YANJiancheng

    2003-01-01

    Extended algorithm has been developed for ablation rate calculations of Li, Be, B impurity pellets and five combinations of solid isotopic hydrogenic H2, HD, D2, DT, T2 pellets. Numerical calculations have been performed for reactor relevant plasma.

  9. Relevance of cellular to clinical electrophysiology in interpreting antiarrhythmic drug action.

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    Vaughan Williams, E M

    1989-12-01

    The usefulness of cellular electrophysiologic techniques in elucidating the fundamental actions of antiarrhythmic drugs is contrasted with their apparent lack of relevance to the selection of drugs for the treatment of particular arrhythmias. Clinical electrophysiologists employ different techniques, but their results may be explained in terms of cellular drug actions. The varying clinical effects of class IA, IB and IC agents are due to differences in the speed of their attachment to, and detachment from, sodium channels. The role of sympathetic activity in arrhythmogenesis is complex, but again readily explicable in terms of the electrophysiologic cellular actions of stimulation of the individual types of adrenoceptors (alpha 1, alpha 2, beta 1 and beta 2) and the distribution of these receptors, and of the longterm effects of sympathetic deprivation, either by antisympathetic drugs (class II) or by sympathetic denervation. Delayed repolarization (e.g., by class III drugs or prolonged beta blockade) is antiarrhythmic because it is homogeneous, despite the incidental prolongation of QT. If, however, QT is prolonged by heterogeneity of conduction or repolarization, or by partial sympathetic denervation (long QT syndrome or post myocardial infarction), this indicates increased risk of arrhythmia. Finally, the efficacy of calcium antagonists (class IV) in supraventricular arrhythmias is attributable to the cellular electrophysiologic characteristics of sinoatrial and atrioventricular nodal and transitional elements.

  10. Integrated approaches for assessment of cellular performance in industrially relevant filamantous fungi

    DEFF Research Database (Denmark)

    Workman, Mhairi; Andersen, Mikael Rørdam; Thykær, Jette

    2013-01-01

    The performance of filamentous fungi in submerged cultivation determines their suitability for large-scale industrial biotechnology processes and is the result of complex interplay between the physical and chemical parameters of the process and the cellular biology of the fungi. Filamentous fungi...... of these organisms. Increased future focus on multicellular physiology and relevant assays will lead to fungal cells and processes that are customizable to a greater degree, finally allowing the full potential of these complex organisms and their product diversity to unfold....

  11. Identification of a novel Rev-interacting cellular protein

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    Werner Thomas

    2005-04-01

    Full Text Available Abstract Background Human cell types respond differently to infection by human immunodeficiency virus (HIV. Defining specific interactions between host cells and viral proteins is essential in understanding how viruses exploit cellular functions and the innate strategies underlying cellular control of HIV replication. The HIV Rev protein is a post-transcriptional inducer of HIV gene expression and an important target for interaction with cellular proteins. Identification of Rev-modulating cellular factors may eventually contribute to the design of novel antiviral therapies. Results Yeast-two hybrid screening of a T-cell cDNA library with Rev as bait led to isolation of a novel human cDNA product (16.4.1. 16.4.1-containing fusion proteins showed predominant cytoplasmic localization, which was dependent on CRM1-mediated export from the nucleus. Nuclear export activity of 16.4.1 was mapped to a 60 amino acid region and a novel transport signal identified. Interaction of 16.4.1 with Rev in human cells was shown in a mammalian two-hybrid assay and by colocalization of Rev and 16.4.1 in nucleoli, indicating that Rev can recruit 16.4.1 to the nucleus/nucleoli. Rev-dependent reporter expression was inhibited by overexpressing 16.4.1 and stimulated by siRNAs targeted to 16.4.1 sequences, demonstrating that 16.4.1 expression influences the transactivation function of Rev. Conclusion These results suggest that 16.4.1 may act as a modulator of Rev activity. The experimental strategies outlined in this study are applicable to the identification and biological characterization of further novel Rev-interacting cellular factors.

  12. 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, electromagnetic fields has grown significantly. Health professionals and government administrators and regulators, scientists and engineers, and, importantly, an increasing number of individuals in the general public are interested in this health issue. The goal of research at the cellular 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

  13. Ketoconazole inhibits the cellular uptake of anandamide via inhibition of FAAH at pharmacologically relevant concentrations.

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    Emmelie Björklund

    Full Text Available BACKGROUND: The antifungal compound ketoconazole has, in addition to its ability to interfere with fungal ergosterol synthesis, effects upon other enzymes including human CYP3A4, CYP17, lipoxygenase and thromboxane synthetase. In the present study, we have investigated whether ketoconazole affects the cellular uptake and hydrolysis of the endogenous cannabinoid receptor ligand anandamide (AEA. METHODOLOGY/PRINCIPAL FINDINGS: The effects of ketoconazole upon endocannabinoid uptake were investigated using HepG2, CaCo2, PC-3 and C6 cell lines. Fatty acid amide hydrolase (FAAH activity was measured in HepG2 cell lysates and in intact C6 cells. Ketoconazole inhibited the uptake of AEA by HepG2 cells and CaCo2 cells with IC50 values of 17 and 18 µM, respectively. In contrast, it had modest effects upon AEA uptake in PC-3 cells, which have a low expression of FAAH. In cell-free HepG2 lysates, ketoconazole inhibited FAAH activity with an IC50 value (for the inhibitable component of 34 µM. CONCLUSIONS/SIGNIFICANCE: The present study indicates that ketoconazole can inhibit the cellular uptake of AEA at pharmacologically relevant concentrations, primarily due to its effects upon FAAH. Ketoconazole may be useful as a template for the design of dual-action FAAH/CYP17 inhibitors as a novel strategy for the treatment of prostate cancer.

  14. The influence of osmotic pressure on the lifespan of cellularly inspired energy-relevant materials

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    Kapania, Esha; Guillen, Katherine; Freeman, Eric; Philen, Michael

    2014-04-01

    Bimolecular unit cells have recently become a focus for biologically-inspired smart materials. This is largely due their ability to exhibit many of the same properties as the natural cell membrane. In this study, two lipid monolayers formed at a water/oil interface are brought together, creating a lipid bilayer at their interface with each droplet containing a different concentration of ions. This ionic concentration gradient leads to the development of a membrane potential across the bilayer as ions begin to passively diffuse across the membrane at varying rates, providing the proof of concept for energy storage through cellular mechanics. The focus of the study is to determine the influence of osmotic pressure on the lifespan of the lipid bilayer. We hypothesize that the greater osmotic pressure that develops from a greater ionic concentration gradient will prove to have a negative impact on the lifespan of the bilayer membrane, causing it to rupture sooner. This is due to the substantial amount of osmotic swelling that will occur to compensate for the ionic concentration gradient. This study will demonstrate how osmotic pressure will continue to be a limiting factor in the effectiveness and stability of cellularly-inspired energy relevant materials.

  15. Nematic order by elastic interactions and cellular rigidity sensing

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    Friedrich, B. M.; Safran, S. A.

    2011-01-01

    We predict spontaneous nematic order in an ensemble of active force generators with elastic interactions as a minimal model for early nematic alignment of short stress fibers in non-motile, adhered cells. Mean-field theory is formally equivalent to Maier-Saupe theory for a nematic liquid. However, the elastic interactions are long-ranged (and thus depend on cell shape and matrix elasticity) and originate in cell activity. Depending on the density of force generators, we find two regimes of cellular rigidity sensing for which orientational, nematic order of stress fibers depends on matrix rigidity either in a step-like manner or with a maximum at an optimal rigidity.

  16. Clinically relevant drug interactions with anti-Alzheimer's drugs.

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    Caraci, Filippo; Sultana, Janet; Drago, Filippo; Spina, Edoardo

    2017-03-03

    The aging world population had led to an increase in the prevalence of Alzheimer's disease (AD). The drugs used to slow down the onset of AD, galantamine, donepezil, rivastigmine and memantine, are generally well-tolerated. However, drug interactions between these drugs and other drugs are an important aspect of patient safety that should be borne in mind, particularly given the high burden of polypharmacy in the elderly. The aim of this review is to provide an updated review of clinically significant drug-drug interactions concerning drugs approved for AD. PubMed was searched for relevant keywords. No time limit was imposed but only articles in English published in peer-reviewed journals were selected. Relevant literature was also identified from the references of identified articles. Further information was obtained from drug summary of product characteristics. The major pharmacokinetic interactions identified concerned fluoxetine, paroxetine and ketoconazole when used with galantamine or donepezil. On the other hand, the major potential pharmacodynamic interactions concerned anti-dementia drugs and general anesthesia agents, anti-cholinergic drugs, conventional antipsychotics and bradycardia-inducing drugs. In clinical practice memantine shows a lower potential for pharmacodynamic drug-drug interactions (DDIs) compared to other drug classes. In conclusion, the concomitant use of anti-dementia drugs with other drugs can have variable clinical effects, making appropriate prescribing of these drugs very challenging. A simple and coherent way of presenting evidence on complex drug interaction information from heterogenous sources to clinicians is needed in order for the voluminous data available to have an impact on clinical practice.

  17. Laser-plasma interactions relevant to Inertial Confinement Fusion

    Energy Technology Data Exchange (ETDEWEB)

    Wharton, K.B.

    1998-11-02

    Research into laser-driven inertial confinement fusion is now entering a critical juncture with the construction of the National Ignition Facility (NIF) at Lawrence Livermore National Laboratory (LLNL). Many of the remaining unanswered questions concerning NIF involve interactions between lasers and plasmas. With the eventual goal of fusion power in mind, laser-plasma interactions relevant to laser fusion schemes is an important topic in need of further research. This work experimentally addresses some potential shortcuts and pitfalls on the road to laser-driven fusion power. Current plans on NIF have 192 laser beams directed into a small cylindrical cavity which will contain the fusion fuel; to accomplish this the beams must cross in the entrance holes, and this intersection will be in the presence of outward-flowing plasma. To investigate the physics involved, interactions of crossing laser beams in flowing plasmas are investigated with experiments on the Nova laser facility at LLNL. It was found that in a flowing plasma, energy is transferred between two crossing laser beams, and this may have deleterious consequences for energy balance and ignition in NIF. Possible solutions to this problem are presented. A recently-proposed alternative to standard laser-driven fusion, the ''fast ignitor'' concept, is also experimentally addressed in this dissertation. Many of the laser-plasma interactions necessary for the success of the fast ignitor have not previously been explored at the relevant laser intensities. Specifically, the transfer of high-intensity laser energy to electrons at solid-target interfaces is addressed. 20-30% conversion efficiencies into forward-propagated electrons were measured, along with an average electron energy that varied with the type of target material. The directionality of the electrons was also measured, revealing an apparent beaming of the highest energy electrons. This work was extended to various intensities and

  18. Integrated cellular network of transcription regulations and protein-protein interactions

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    Chen Bor-Sen

    2010-03-01

    Full Text Available Abstract Background With the accumulation of increasing omics data, a key goal of systems biology is to construct networks at different cellular levels to investigate cellular machinery of the cell. However, there is currently no satisfactory method to construct an integrated cellular network that combines the gene regulatory network and the signaling regulatory pathway. Results In this study, we integrated different kinds of omics data and developed a systematic method to construct the integrated cellular network based on coupling dynamic models and statistical assessments. The proposed method was applied to S. cerevisiae stress responses, elucidating the stress response mechanism of the yeast. From the resulting integrated cellular network under hyperosmotic stress, the highly connected hubs which are functionally relevant to the stress response were identified. Beyond hyperosmotic stress, the integrated network under heat shock and oxidative stress were also constructed and the crosstalks of these networks were analyzed, specifying the significance of some transcription factors to serve as the decision-making devices at the center of the bow-tie structure and the crucial role for rapid adaptation scheme to respond to stress. In addition, the predictive power of the proposed method was also demonstrated. Conclusions We successfully construct the integrated cellular network which is validated by literature evidences. The integration of transcription regulations and protein-protein interactions gives more insight into the actual biological network and is more predictive than those without integration. The method is shown to be powerful and flexible and can be used under different conditions and for different species. The coupling dynamic models of the whole integrated cellular network are very useful for theoretical analyses and for further experiments in the fields of network biology and synthetic biology.

  19. Cellular interactions in the pathogenesis of interstitial lung diseases

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    Gianluca Bagnato

    2015-03-01

    Full Text Available Interstitial lung disease (ILD encompasses a large and diverse group of pathological conditions that share similar clinical, radiological and pathological manifestations, despite potentially having quite different aetiologies and comorbidities. Idiopathic pulmonary fibrosis (IPF represents probably the most aggressive form of ILD and systemic sclerosis is a multiorgan fibrotic disease frequently associated with ILD. Although the aetiology of these disorders remains unknown, in this review we analyse the pathogenic mechanisms by cell of interest (fibroblast, fibrocyte, myofibroblast, endothelial and alveolar epithelial cells and immune competent cells. New insights into the complex cellular contributions and interactions will be provided, comparing the role of cell subsets in the pathogenesis of IPF and systemic sclerosis.

  20. Biophysical responses upon the interaction of nanomaterials with cellular interfaces.

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    Wu, Yun-Long; Putcha, Nirupama; Ng, Kee Woei; Leong, David Tai; Lim, Chwee Teck; Loo, Say Chye Joachim; Chen, Xiaodong

    2013-03-19

    The explosion of study of nanomaterials in biological applications (the nano-bio interface) can be ascribed to nanomaterials' growing importance in diagnostics, therapeutics, theranostics (therapeutic diagnostics), and targeted modulation of cellular processes. However, a growing number of critics have raised concerns over the potential risks of nanomaterials to human health and safety. It is essential to understand nanomaterials' potential toxicity before they are tested in humans. These risks are complicated to unravel, however, because of the complexity of cells and their nanoscale macromolecular components, which enable cells to sense and respond to environmental cues, including nanomaterials. In this Account, we explore these risks from the perspective of the biophysical interactions between nanomaterials and cells. Biophysical responses to the uptake of nanomaterials can include conformational changes in biomolecules like DNA and proteins, and changes to the cellular membrane and the cytoskeleton. Changes to the latter two, in particular, can induce changes in cell elasticity, morphology, motility, adhesion, and invasion. This Account reviews what is known about cells' biophysical responses to the uptake of the most widely studied and used nanoparticles, such as carbon-based, metal, metal-oxide, and semiconductor nanomaterials. We postulate that the biophysical structure impairment induced by nanomaterials is one of the key causes of nanotoxicity. The disruption of cellular structures is affected by the size, shape, and chemical composition of nanomaterials, which are also determining factors of nanotoxicity. Currently, popular nanotoxicity characterizations, such as the MTT and lactate dehydrogenase (LDH) assays, only provide end-point results through chemical reactions. Focusing on biophysical structural changes induced by nanomaterials, possibly in real-time, could deepen our understanding of the normal and altered states of subcellular structures and

  1. Predict drug-protein interaction in cellular networking.

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    Xiao, Xuan; Min, Jian-Liang; Wang, Pu; Chou, Kuo-Chen

    2013-01-01

    Involved with many diseases such as cancer, diabetes, neurodegenerative, inflammatory and respiratory disorders, GPCRs (G-protein-coupled receptors) are the most frequent targets for drug development: over 50% of all prescription drugs currently on the market are actually acting by targeting GPCRs directly or indirectly. Found in every living thing and nearly all cells, ion channels play crucial roles for many vital functions in life, such as heartbeat, sensory transduction, and central nervous system response. Their dysfunction may have significant impact to human health, and hence ion channels are deemed as "the next GPCRs". To develop GPCR-targeting or ion-channel-targeting drugs, the first important step is to identify the interactions between potential drug compounds with the two kinds of protein receptors in the cellular networking. In this minireview, we are to introduce two predictors. One is called iGPCR-Drug accessible at http://www.jci-bioinfo.cn/iGPCR-Drug/; the other called iCDI-PseFpt at http://www.jci-bioinfo.cn/iCDI-PseFpt. The former is for identifying the interactions of drug compounds with GPCRs; while the latter for that with ion channels. In both predictors, the drug compound was formulated by the two-dimensional molecular fingerprint, and the protein receptor by the pseudo amino acid composition generated with the grey model theory, while the operation engine was the fuzzy K-nearest neighbor algorithm. For the convenience of most experimental pharmaceutical and medical scientists, a step-bystep guide is provided on how to use each of the two web-servers to get the desired results without the need to follow the complicated mathematics involved originally for their establishment.

  2. Thymocyte migration: an affair of multiple cellular interactions?

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    Savino W.

    2003-01-01

    Full Text Available Cell migration is a crucial event in the general process of thymocyte differentiation. The cellular interactions involved in the control of this migration are beginning to be defined. At least chemokines and extracellular matrix proteins appear to be part of the game. Cells of the thymic microenvironment produce these two groups of molecules, whereas developing thymocytes express the corresponding receptors. Moreover, although chemokines and extracellular matrix can drive thymocyte migration per se, a combined role for these molecules appears to contribute to the resulting migration patterns of thymocytes in their various stages of differentiation. The dynamics of chemokine and extracellular matrix production and degradation is not yet well understood. However, matrix metalloproteinases are likely to play a role in the breakdown of intrathymic extracellular matrix contents. Thus, the physiological migration of thymocytes should be envisioned as a resulting vector of multiple, simultaneous and/or sequential stimuli involving chemokines, adhesive and de-adhesive extracellular matrix proteins, as well as matrix metalloproteinases. Accordingly, it is conceivable that any pathological change in any of these loops may result in the alteration of normal thymocyte migration. This seems to be the case in murine infection by the protozoan parasite Trypanosoma cruzi, the causative agent of Chagas' disease. A better knowledge of the physiological mechanisms governing thymocyte migration will provide new clues for designing therapeutic strategies targeting developing T cells.

  3. Cellular behavior in micropatterned hydrogels by bioprinting system depended on the cell types and cellular interaction.

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    Hong, Soyoung; Song, Seung-Joon; Lee, Jae Yeon; Jang, Hwanseok; Choi, Jaesoon; Sun, Kyung; Park, Yongdoo

    2013-08-01

    The fabrication of patterned microstructures within three-dimensional (3D) matrices is a challenging subject in tissue engineering and regenerative medicine. A 3D, free-moving bioprinting system was developed and hydrogels were patterned by varying the process parameters of z-axis moving velocity and ejection velocity. The patterning of hydrogel based microfibers in a 3D matrigel was achieved with dimensions of 4.5 mm length and widths from 79 to 200 μm. Hyaluronan-based hydrogels mixed with fibroblasts (L929), mouse endothelial cells (MS1), or human mesenchymal stem cells (hMSCs) were patterned using a 3D moving axis bioprinter and cell behavior was monitored in culture for up to 16 days. L929 and MS1 cells and hMSCs in patterned hydrogel revealed cell-cell interactions and a morphological dependency on cell types. HMSCs formed spheres through cell aggregation, while L929 cells increased in cellular mass without cell aggregation and MS1 dispersed into the matrix instead of aggregating. The aggregation of hMSCs was attenuated by treatment with Rho kinase (ROCK) inhibitor and cadherin antibody. This reflected the close relationship between cell aggregation and migration with RhoA and cell-cell adhesion molecules. Angiogenic-specific gene expression profiles showed that expression of CD105 decreased to 22% in the ROCK inhibitor group compared to control group. These results showed that cell-based patterns in a 3D matrix are highly dependent on both cell aggregation and migration over time.

  4. Mycosphaerella podagrariae-a necrotrophic phytopathogen forming a special cellular interaction with its host Aegopodium podagraria

    NARCIS (Netherlands)

    Simon, U.K.; Groenewald, J.Z.; Stierhof, Y.D.; Crous, P.W.; Bauer, R.

    2010-01-01

    We present a new kind of cellular interaction found between Mycosphaerella podagrariae and Aegopodium podagraria, which is remarkably different to the interaction type of the obligate biotrophic fungus Cymadothea trifolii, another member of the Mycosphaerellaceae (Capnodiales, Dothideomycetes, Ascom

  5. Mycosphaerella podagrariae - a necrotrophic phytopathogen forming a special cellular interaction with its host Aegopodium podagraria

    NARCIS (Netherlands)

    Simon, U.K.; Groenewald, J.Z.; Stierhof, Y.D.; Crous, P.W.; Bauer, R.

    2010-01-01

    We present a new kind of cellular interaction found between Mycosphaerella podagrariae and Aegopodium podagraria, which is remarkably different to the interaction type of the obligate biotrophic fungus Cymadothea trifolii, another member of the Mycosphaerellaceae (Capnodiales, Dothideomycetes, Ascom

  6. Cellular interactions of lauric acid and dextran-coated magnetite nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Pradhan, Pallab [School of Biosciences and Bioengineering, Indian Institute of Technology, Mumbai 400076 (India); Giri, Jyotsnendu [Department of Metallurgical Engineering and Materials Science, Indian Institute of Technology, Mumbai 400076 (India); Banerjee, Rinti [School of Biosciences and Bioengineering, Indian Institute of Technology, Mumbai 400076 (India); Bellare, Jayesh [School of Biosciences and Bioengineering, Indian Institute of Technology, Mumbai 400076 (India); Bahadur, Dhirendra [Department of Metallurgical Engineering and Materials Science, Indian Institute of Technology, Mumbai 400076 (India)]. E-mail: dhirenb@iitb.ac.in

    2007-04-15

    In vitro cytocompatibility and cellular interactions of lauric acid and dextran-coated magnetite nanoparticles were evaluated with two different cell lines (mouse fibroblast and human cervical carcinoma). Lauric acid-coated magnetite nanoparticles were less cytocompatible than dextran-coated magnetite nanoparticles and cellular uptake of lauric acid-coated magnetic nanoparticles was more than that of dextran-coated magnetite nanoparticles. Lesser cytocompatibility and higher uptake of lauric acid-coated magnetite nanoparticles as compared to dextran-coated magnetic nanoparticles may be due to different cellular interactions by coating material. Thus, coating plays an important role in modulation of biocompatibility and cellular interaction of magnetic nanoparticles.

  7. Cellular interactions of lauric acid and dextran-coated magnetite nanoparticles

    Science.gov (United States)

    Pradhan, Pallab; Giri, Jyotsnendu; Banerjee, Rinti; Bellare, Jayesh; Bahadur, Dhirendra

    2007-04-01

    In vitro cytocompatibility and cellular interactions of lauric acid and dextran-coated magnetite nanoparticles were evaluated with two different cell lines (mouse fibroblast and human cervical carcinoma). Lauric acid-coated magnetite nanoparticles were less cytocompatible than dextran-coated magnetite nanoparticles and cellular uptake of lauric acid-coated magnetic nanoparticles was more than that of dextran-coated magnetite nanoparticles. Lesser cytocompatibility and higher uptake of lauric acid-coated magnetite nanoparticles as compared to dextran-coated magnetic nanoparticles may be due to different cellular interactions by coating material. Thus, coating plays an important role in modulation of biocompatibility and cellular interaction of magnetic nanoparticles.

  8. Cytosolic iron-sulfur cluster assembly (CIA) system: factors, mechanism, and relevance to cellular iron regulation.

    Science.gov (United States)

    Sharma, Anil K; Pallesen, Leif J; Spang, Robert J; Walden, William E

    2010-08-27

    FeS cluster biogenesis is an essential process in virtually all forms of life. Complex protein machineries that are conserved from bacteria through higher eukaryotes facilitate assembly of the FeS cofactor in proteins. In the last several years, significant strides have been made in our understanding of FeS cluster assembly and the functional overlap of this process with cellular iron homeostasis. This minireview summarizes the present understanding of the cytosolic iron-sulfur cluster assembly (CIA) system in eukaryotes, with a focus on information gained from studies in budding yeast and mammalian systems.

  9. The Relevance of Apoptosis for Cellular Homeostasis and Tumorogenesis in the Intestine

    Directory of Open Access Journals (Sweden)

    Andrew G Renehan

    2001-01-01

    Full Text Available Intestinal epithelium is a rapidly renewing tissue in which cell homeostasis is regulated by a balance among proliferation, growth arrest, differentiation and apoptosis (programmed cell death. Until recently, studies on oncogenesis have focused on the regulation of cell proliferation. The recognition that apoptosis must be understood to comprehend how appropriate cell numbers are maintained and how alterations in any part of the equation can contribute to malignancy has led to an explosion of research in this field. The first half of this review gives an overview of morphology and mechanisms of apoptosis, emphasizing key areas of genetic control such as the bcl-2 family and p53. The second half of the review focuses on the role of apoptosis in normal cellular homeostasis and tumorigenesis in the gastrointestinal epithelium. The importance of understanding the molecular biology of apoptotic pathways in cancer therapy and future directions are also addressed.

  10. Task relevance regulates the interaction between reward expectation and emotion.

    Science.gov (United States)

    Wei, Ping; Kang, Guanlan

    2014-06-01

    In the present study, we investigated the impact of reward expectation on the processing of emotional facial expression using a cue-target paradigm. A cue indicating the reward condition of each trial (incentive vs. non-incentive) was followed by the presentation of a picture of an emotional face, the target. Participants were asked to discriminate the emotional expression of the target face in Experiment 1, to discriminate the gender of the target face in Experiment 2, and to judge a number superimposed on the center of the target face as even or odd in Experiment 3, rendering the emotional expression of the target face as task relevant in Experiment 1 but task irrelevant in Experiments 2 and 3. Faster reaction times (RTs) were observed in the monetary incentive condition than in the non-incentive condition, demonstrating the effect of reward on facilitating task concentration. Moreover, the reward effect (i.e., RTs in non-incentive conditions versus incentive conditions) was larger for emotional faces than for neutral faces when emotional expression was task relevant but not when it was task irrelevant. The findings suggest that top-down incentive motivation biased attentional processing toward task-relevant stimuli, and that task relevance played an important role in regulating the influence of reward expectation on the processing of emotional stimuli.

  11. Interactions between mitochondrial reactive oxygen species and cellular glucose metabolism

    NARCIS (Netherlands)

    Liemburg-Apers, D.C.; Willems, P.H.G.M.; Koopman, W.J.H.; Grefte, Sander

    2015-01-01

    Mitochondrial reactive oxygen species (ROS) production and detoxification are tightly balanced. Shifting this balance enables ROS to activate intracellular signaling and/or induce cellular damage and cell death. Increased mitochondrial ROS production is observed in a number of pathological condit

  12. The behavioral relevance of multisensory neural response interactions

    Directory of Open Access Journals (Sweden)

    Holger F Sperdin

    2010-05-01

    Full Text Available Sensory information can interact to impact perception and behavior. Foods are appreciated according to their appearance, smell, taste, and texture. Athletes and dancers combine visual, auditory, and somatosensory information to coordinate their movements. Under laboratory settings, detection and discrimination are likewise facilitated by multisensory signals. Research over the past several decades has shown both that the requisite anatomy exists to support interactions between sensory systems in regions canonically designated as exclusively unisensory in their function and more recently that neural response interactions occur within these same regions, including even primary cortices and thalamic nuclei, at early post-stimulus latencies. Here, we review evidence concerning direct links between early, low-level neural response interactions and behavioral measures of multisensory integration.

  13. Clinical relevance of drug-drug interactions - A structured assessment procedure

    NARCIS (Netherlands)

    van Roon, EN; Flikweert, S; le Comte, M; Langendijk, PNJ; Kwee-Zuiderwijk, WJM; Smits, P; Brouwers, JRBJ

    2005-01-01

    Introduction: Computerised drug interaction surveillance systems (CIS) may be helpful in detecting clinically significant drug interactions. Experience with CIS C, reveals that they often yield alerts with questionable clinical significance, fail to provide relevant information on risk factors for t

  14. Clinically relevant drug interactions between anticancer drugs and psychotropic agents.

    Science.gov (United States)

    Yap, K Y-L; Tay, W L; Chui, W K; Chan, A

    2011-01-01

    Drug interactions are commonly seen in the treatment of cancer patients. Psychotropics are often indicated for these patients since they may also suffer from pre-existing psychological disorders or experience insomnia and anxiety associated with cancer therapy. Thus, the risk of anticancer drug (ACD)-psychotropic drug-drug interactions (DDIs) is high. Drug interactions were compiled from the British National Formulary (53rd edn), Lexi-Comp's Drug Information Handbook (15th edn), Micromedex (v5.1), Hansten & Horn's Drug Interactions (2000) and Drug Interaction Facts (2008 edn). Product information of the individual drugs, as well as documented literature on ACD-psychotropic interactions from PubMed and other databases was also incorporated. This paper identifies clinically important ACD-psychotropic DDIs that are frequently observed. Pharmacokinetic DDIs were observed for tyrosine kinase inhibitors, corticosteroids and antimicrotubule agents due to their inhibitory or inductive effects on cytochrome P450 isoenzymes. Pharmacodynamic DDIs were identified for thalidomide with central nervous system depressants, procarbazine with antidepressants, myelosuppressive ACDs with clozapine and anthracyclines with QT-prolonging psychotropics. Clinicians should be vigilant when psychotropics are prescribed concurrently with ACDs. Close monitoring of plasma drug levels should be carried out to avoid toxicity in the patient, as well as to ensure adequate chemotherapeutic and psychotropic coverage.

  15. Reduced cellular DNA repair capacity after environmentally relevant arsenic exposure. Influence of Ogg1 deficiency.

    Science.gov (United States)

    Bach, Jordi; Peremartí, Jana; Annangi, Balasubramnayam; Marcos, Ricard; Hernández, Alba

    2015-09-01

    Inorganic arsenic (i-As) is a genotoxic and carcinogenic environmental contaminant known to affect millions of people worldwide. Our previous work demonstrated that chronic sub-toxic i-As concentrations were able to induce biologically significant levels of genotoxic and oxidative DNA damage that were strongly influenced by the Ogg1 genotype. In order to study the nature of the observed levels of damage and the observed differences between MEF Ogg1(+/+) and Ogg1(-/-) genetic backgrounds, the genotoxic and oxidative DNA repair kinetics of 18-weeks exposed MEF cells were evaluated by the comet assay. Results indicate that MEF Ogg1(+/+) and Ogg1(-/-) cells chronically exposed to i-As repair the DNA damage induced by arsenite, potassium bromide and UVC radiation less efficiently than control cells, being that observation clearly more pronounced in MEF Ogg1(-/-) cells. Consequently, exposed cells accumulate a higher percentage of unrepaired DNA damage at the end of the repair period. As an attempt to eliminate i-As associated toxicity, chronically exposed MEF Ogg1(-/-) cells overexpress the arsenic metabolizing enzyme As3mt. This adaptive response confers cells a significant resistance to i-As-induced cell death, but at expenses of accumulating high levels of DNA damage due to their repair impairment. Overall, the work presented here evidences that i-As chronic exposure disrupts the normal cellular repair function, and that oxidative DNA damage-and Ogg1 deficiency-exacerbates this phenomenon. The observed cell death resistance under a chronic scenario of genotoxic and oxidative stress may in turn contribute to the carcinogenic effects of i-As.

  16. Relevant aspects in the surface properties in titanium dental implants for the cellular viability.

    Science.gov (United States)

    Velasco-Ortega, E; Alfonso-Rodríguez, C A; Monsalve-Guil, L; España-López, A; Jiménez-Guerra, A; Garzón, I; Alaminos, M; Gil, F J

    2016-07-01

    Roughness and topographical features are the most relevant of the surface properties for a dental implant for its osseointegration. For that reason, we studied the four surfaces more used in titanium dental implants: machined, sandblasted, acid etching and sandblasted plus acid etching. The roughness and wettability (contact angle and surface free energy) was studied by means 3D-interferometric microscope and sessile drop method. Normal human gingival fibroblasts (HGF) were obtained from small oral mucosa biopsies and were used for cell cultures. To analyze cell integrity, we first quantified the total amount of DNA and LDH released from dead cells to the culture medium. Then, LIVE/DEAD assay was used as a combined method assessing cell integrity and metabolism. All experiments were carried out on each cell type cultured on each Ti material for 24h, 48h and 72h. To evaluate the in vivo cell adhesion capability of each Ti surface, the four types of discs were grafted subcutaneously in 5 Wistar rats. Sandblasted surfaces were significantly rougher than acid etching and machined. Wettability and surface free energy decrease when the roughness increases in sand blasted samples. This fact favors the protein adsorption. The DNA released by cells cultured on the four Ti surfaces did not differ from that of positive control cells (p>0.05). The number of cells per area was significantly lower (pimplants is able to significantly increase bone contact and bone growth with very good osseointegration results in vivo.

  17. Reduced cellular DNA repair capacity after environmentally relevant arsenic exposure. Influence of Ogg1 deficiency

    Energy Technology Data Exchange (ETDEWEB)

    Bach, Jordi; Peremartí, Jana; Annangi, Balasubramnayam [Grup de Mutagènesi, Departament de Genètica i de Microbiologia, Facultat de Biociències, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Barcelona (Spain); Marcos, Ricard, E-mail: ricard.marcos@uab.es [Grup de Mutagènesi, Departament de Genètica i de Microbiologia, Facultat de Biociències, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Barcelona (Spain); CIBER Epidemiología y Salud Pública, ISCIII, Madrid (Spain); Hernández, Alba, E-mail: alba.hernandez@uab.es [Grup de Mutagènesi, Departament de Genètica i de Microbiologia, Facultat de Biociències, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Barcelona (Spain); CIBER Epidemiología y Salud Pública, ISCIII, Madrid (Spain)

    2015-09-15

    Highlights: • Repair ability under long-term exposure to arsenic was tested using the comet assay. • Effects were measured under Ogg1 wild-type and deficient backgrounds. • Exposed cells repair less efficiency the DNA damage induced by SA, KBrO{sub 3}, MMA{sup III} or UVC radiation. • Oxidative damage and Ogg1 deficient background exacerbate repair deficiencies. • Overexpression of the arsenic metabolizing enzyme As3mt acts as adaptive mechanism. - Abstract: Inorganic arsenic (i-As) is a genotoxic and carcinogenic environmental contaminant known to affect millions of people worldwide. Our previous work demonstrated that chronic sub-toxic i-As concentrations were able to induce biologically significant levels of genotoxic and oxidative DNA damage that were strongly influenced by the Ogg1 genotype. In order to study the nature of the observed levels of damage and the observed differences between MEF Ogg1{sup +/+} and Ogg1{sup −/−} genetic backgrounds, the genotoxic and oxidative DNA repair kinetics of 18-weeks exposed MEF cells were evaluated by the comet assay. Results indicate that MEF Ogg1{sup +/+} and Ogg1{sup −/−} cells chronically exposed to i-As repair the DNA damage induced by arsenite, potassium bromide and UVC radiation less efficiently than control cells, being that observation clearly more pronounced in MEF Ogg1{sup −/−} cells. Consequently, exposed cells accumulate a higher percentage of unrepaired DNA damage at the end of the repair period. As an attempt to eliminate i-As associated toxicity, chronically exposed MEF Ogg1{sup −/−} cells overexpress the arsenic metabolizing enzyme As3mt. This adaptive response confers cells a significant resistance to i-As-induced cell death, but at expenses of accumulating high levels of DNA damage due to their repair impairment. Overall, the work presented here evidences that i-As chronic exposure disrupts the normal cellular repair function, and that oxidative DNA damage—and Ogg1 deficiency

  18. Phenomenology of soft hadron interactions and the relevant EAS data

    Science.gov (United States)

    Kalmykov, N. N.; Khristiansen, G. B.; Motova, M. V.

    1984-01-01

    The interpretation of the experimental data in superhigh energy cosmic rays requires the calculations using various models of elementary hadron interaction. One should prefer the models justified by accelerator data and giving definite predictions for superhigh energies. The model of quark-gluon pomeron strings (the QGPS models) satisfies this requirement.

  19. How relevant is social interaction in second language learning?

    Directory of Open Access Journals (Sweden)

    Laura eVerga

    2013-09-01

    Full Text Available Verbal language is the most widespread mode of human communication, and an intrinsically social activity. This claim is strengthen by evidence emerging from different fields, which clearly indicate that social interaction influences human communication, and more specifically, language learning. Indeed, research conducted with infants and children shows that interaction with a caregiver is necessary to acquire language. Further evidence on the influence of sociality on language comes from social and linguistic pathologies, in which deficits in social and linguistic abilities are tightly intertwined, as it is the case for Autism, for example. However, studies on adult second language learning have been mostly focused on individualistic approaches, partly because of methodological constraints especially of imaging methods. The question as to whether social interaction should be considered as a critical factor impacting upon adult language learning still remains underspecified. Here, we review evidence in support of the view that sociality plays a significant role in communication and language learning, in an attempt to emphasize factors that could facilitate this process in adult language learning. We suggest that sociality should be considered as a potentially influential factor in adult language learning and that future studies in this domain should explicitly target this factor.

  20. How relevant is social interaction in second language learning?

    Science.gov (United States)

    Verga, Laura; Kotz, Sonja A

    2013-09-03

    Verbal language is the most widespread mode of human communication, and an intrinsically social activity. This claim is strengthened by evidence emerging from different fields, which clearly indicates that social interaction influences human communication, and more specifically, language learning. Indeed, research conducted with infants and children shows that interaction with a caregiver is necessary to acquire language. Further evidence on the influence of sociality on language comes from social and linguistic pathologies, in which deficits in social and linguistic abilities are tightly intertwined, as is the case for Autism, for example. However, studies on adult second language (L2) learning have been mostly focused on individualistic approaches, partly because of methodological constraints, especially of imaging methods. The question as to whether social interaction should be considered as a critical factor impacting upon adult language learning still remains underspecified. Here, we review evidence in support of the view that sociality plays a significant role in communication and language learning, in an attempt to emphasize factors that could facilitate this process in adult language learning. We suggest that sociality should be considered as a potentially influential factor in adult language learning and that future studies in this domain should explicitly target this factor.

  1. Cooperativity in noncovalent interactions of biologically relevant molecules.

    Science.gov (United States)

    Antony, Jens; Brüske, Björn; Grimme, Stefan

    2009-10-14

    Using a recently published benchmark MP2 database of nucleic acid base trimers, the three-body contribution to the interaction energy (TBE, also termed (non)cooperativity) as a function of base composition and complex geometry is studied. In 28 out of 141 cases (or 20%), the counterpoise-corrected MP2/TZV(2df,2pd) TBE exceeds 1 kcal mol(-1). The TBE is below 1 kcal mol(-1) for all trimers in the benchmark set consisting of U, T, and A, irrespective of the geometrical arrangement in the database. The largest MP2/TZV(2df,2pd) cooperativity of -9 kcal mol(-1) is obtained for a hydrogen-bonded guanine trimer. The largest anti-cooperativity occurs for a protonated cytosine-guanine-cytosine trimer (6 kcal mol(-1)). Generally, the many-body non-additivity term is an order of magnitude smaller than the interaction energies (on average -33 kcal mol(-1)). Employing various density functionals (GGA, meta-GGA, and hybrid) and wave function methods up to third order perturbation theory, and using atomic-orbital basis sets of double-, triple-, and quadruple-zeta quality, we find that the non-additivity effects are almost independent of one particle basis set and method. To enable an interpretation of the TBE, the intermolecular interaction energy is subjected to an energy decomposition analysis (EDA) with a similar definition of the energy terms as the Morokuma decomposition scheme. We find that nonadditive effects are mainly due to the induction, while exchange repulsion, electrostatic, and dispersion contributions are essentially additive, the latter also beyond second order at the MP3/SV(d,p) level. The performance of dispersion-corrected density functional theory for the prediction of structures and binding energies is assessed. While an accurate reproduction of the MP2-optimized reference structures of the trimers can already be accomplished with modern density functionals, only the inclusion of the long-range (London) dispersion interaction provides a consistent picture

  2. Non-Chemical Distant Cellular Interactions as a potential confounder of Cell Biology Experiments

    Directory of Open Access Journals (Sweden)

    Ashkan eFarhadi

    2014-10-01

    Full Text Available Distant cells can communicate with each other through a variety of methods. Two such methods involve electrical and/or chemical mechanisms. Non-chemical, distant cellular interactions may be another method of communication that cells can use to modify the behavior of other cells that are mechanically separated. Moreover, non-chemical, distant cellular interactions may explain some cases of confounding effects in Cell Biology experiments. In this article, we review non-chemical, distant cellular interactions studies to try to shed light on the mechanisms in this highly unconventional field of cell biology. Despite the existence of several theories that try to explain the mechanism of non-chemical, distant cellular interactions, this phenomenon is still speculative. Among candidate mechanisms, electromagnetic waves appear to have the most experimental support. In this brief article, we try to answer a few key questions that may further clarify this mechanism.

  3. Clinical relevance of clopidogrel-proton pump inhibitors interaction

    Institute of Scientific and Technical Information of China (English)

    Stella; D; Bouziana; Konstantinos; Tziomalos

    2015-01-01

    Clopidogrel is a widely used antiplatelet agent for the secondary prevention of cardiovascular events in patients with stable coronary heart disease, acute coronary syndromes and ischemic stroke. Even though clopidogrel is safer than aspirin in terms of risk for gastrointestinal(GI) bleeding, the elderly, and patients with a history of prior GI bleeding, with Helicobacter pylori infection or those who are also treated with aspirin, anticoagulants, corticosteroids or nonsteroidal antiinflammatory drugs are at high risk for GI complications when treated with clopidogrel. Accordingly, proton pump inhibitors are frequently administered in combination with clopidogrel to reduce the risk for GI bleeding. Nevertheless, pharmacodynamic studies suggest that omeprazole might attenuate the antiplatelet effect of clopidogrel. However, in observational studies, this interaction does not appear to translate into increased cardiovascular risk in patients treated with this combination. Moreover, in the only randomized, double-blind study that assessed the cardiovascular implications of combining clopidogrel and omeprazole, patients treated with clopidogrel/omeprazole combination had reduced risk for GI events and similar risk for cardiovascular events than patients treated with clopidogrel and placebo. However, the premature interruption of the study and the lack of power analysis in terms of the cardiovascular endpoint do not allow definite conclusions regarding the cardiovascular safety of clopidogrel/omeprazole combination. Other proton pump inhibitors do not appear to interact with clopidogrel. Nevertheless, given the limitations of existing observational and interventional studies, the decision to administer proton pump inhibitors to patients treated with clopidogrel should be individualized based on the patient’s bleeding and cardiovascular risk.

  4. Interaction of tea tree oil with model and cellular membranes.

    Science.gov (United States)

    Giordani, Cristiano; Molinari, Agnese; Toccacieli, Laura; Calcabrini, Annarica; Stringaro, Annarita; Chistolini, Pietro; Arancia, Giuseppe; Diociaiuti, Marco

    2006-07-27

    Tea tree oil (TTO) is the essential oil steam-distilled from Melaleuca alternifolia, a species of northern New South Wales, Australia. It exhibits a broad-spectrum antimicrobial activity and an antifungal activity. Only recently has TTO been shown to inhibit the in vitro growth of multidrug resistant (MDR) human melanoma cells. It has been suggested that the effect of TTO on tumor cells could be mediated by its interaction with the plasma membrane, most likely by inducing a reorganization of lipid architecture. In this paper we report biophysical and structural results obtained using simplified planar model membranes (Langmuir films) mimicking lipid "rafts". We also used flow cytometry analysis (FCA) and freeze-fracturing transmission electron microscopy to investigate the effects of TTO on actual MDR melanoma cell membranes. Thermodynamic (compression isotherms and adsorption kinetics) and structural (Brewster angle microscopy) investigation of the lipid monolayers clearly indicates that TTO interacts preferentially with the less ordered DPPC "sea" and that it does not alter the more ordered lipid "rafts". Structural observations, performed by freeze fracturing, confirm that TTO interacts with the MDR melanoma cell plasma membrane. Moreover, experiments performed by FCA demonstrate that TTO does not interfere with the function of the MDR drug transporter P-gp. We therefore propose that the effect exerted on MDR melanoma cells is mediated by the interaction with the fluid DPPC phase, rather than with the more organized "rafts" and that this interaction preferentially influences the ATP-independent antiapoptotic activity of P-gp likely localized outside "rafts".

  5. Interactions between cyclodextrins and cellular components: Towards greener medical applications?

    Directory of Open Access Journals (Sweden)

    Loïc Leclercq

    2016-12-01

    Full Text Available In the field of host–guest chemistry, some of the most widely used hosts are probably cyclodextrins (CDs. As CDs are able to increase the water solubility of numerous drugs by inclusion into their hydrophobic cavity, they have been widespread used to develop numerous pharmaceutical formulations. Nevertheless, CDs are also able to interact with endogenous substances that originate from an organism, tissue or cell. These interactions can be useful for a vast array of topics including cholesterol manipulation, treatment of Alzheimer’s disease, control of pathogens, etc. In addition, the use of natural CDs offers the great advantage of avoiding or reducing the use of common petroleum-sourced drugs. In this paper, the general features and applications of CDs have been reviewed as well as their interactions with isolated biomolecules leading to the formation of inclusion or exclusion complexes. Finally, some potential medical applications are highlighted throughout several examples.

  6. Cellular zinc levels are modulated by TRPML1-TMEM163 interaction.

    Science.gov (United States)

    Cuajungco, Math P; Basilio, Luigi C; Silva, Joshua; Hart, Thomas; Tringali, Jonathan; Chen, Cheng-Chang; Biel, Martin; Grimm, Christian

    2014-11-01

    Mucolipidosis type IV (MLIV) is caused by loss of function mutations in the TRPML1 ion channel. We previously reported that tissue zinc levels in MLIV were abnormally elevated; however, the mechanism behind this pathologic accumulation remains unknown. Here, we identify transmembrane (TMEM)-163 protein, a putative zinc transporter, as a novel interacting partner for TRPML1. Evidence from yeast two-hybrid, tissue expression pattern, co-immunoprecipitation, mass spectrometry and confocal microscopy studies confirmed the physical association of TMEM163 with TRPML1. This interaction is disrupted when a part of TMEM163's N-terminus was deleted. Further studies to define the relevance of their interaction revealed that the plasma membrane (PM) levels of TMEM163 significantly decrease when TRPML1 is co-expressed in HEK-293 cells, while it mostly localizes within the PM when co-expressed with a mutant TRPML1 that distributes mostly in the PM. Meanwhile, co-expression of TMEM163 does not alter TRPML1 channel activity, but its expression levels in MLIV patient fibroblasts are reduced, which correlate with marked accumulation of zinc in lysosomes when these cells are acutely exposed to exogenous zinc (100 μM). When TMEM163 is knocked down or when TMEM163 and TRPML1 are co-knocked down in HEK-293 cells treated overnight with 100 nm zinc, the cells have significantly higher intracellular zinc levels than untreated control. Overall, these findings suggest that TMEM163 and TRPML1 proteins play a critical role in cellular zinc homeostasis, and thus possibly explain a novel mechanism for the pathological overload of zinc in MLIV disease.

  7. Social and emotional relevance in face processing: Happy faces of future interaction partners enhance the LPP

    Directory of Open Access Journals (Sweden)

    Florian eBublatzky

    2014-07-01

    Full Text Available Human face perception is modulated by both emotional valence and social relevance, but their interaction has rarely been examined. Event-related brain potentials (ERP to happy, neutral, and angry facial expressions with different degrees of social relevance were recorded. Social relevance was manipulated by presenting pictures of two specific face actors as future interaction partners (meet condition, whereas two other face actors remained non-relevant. As a further control condition all stimuli were presented without specific task instructions (passive viewing condition. A within-subject design (Facial Expression x Relevance x Task was implemented, where randomly ordered face stimuli of four actors (2 women, from the KDEF were presented for 1s to 26 participants (16 female. Results showed an augmented N170, early posterior negativity (EPN, and late positive potential (LPP for emotional in contrast to neutral facial expressions. Of particular interest, face processing varied as a function of instructed social relevance. Whereas the meet condition was accompanied with unspecific effects regardless of relevance (P1, EPN, viewing potential interaction partners was associated with increased LPP amplitudes. The LPP was specifically enhanced for happy facial expressions of the future interaction partners. This underscores that social relevance can impact face processing already at an early stage of visual processing. These findings are discussed within the framework of motivated attention and face processing theories.

  8. Cellular microbiology and molecular ecology of Legionella-amoeba interaction.

    Science.gov (United States)

    Richards, Ashley M; Von Dwingelo, Juanita E; Price, Christopher T; Abu Kwaik, Yousef

    2013-05-15

    Legionella pneumophila is an aquatic organism that interacts with amoebae and ciliated protozoa as the natural hosts, and this interaction plays a central role in bacterial ecology and infectivity. Upon transmission to humans, L. pneumophila infect and replicate within alveolar macrophages causing pneumonia. Intracellular proliferation of L. pneumophila within the two evolutionarily distant hosts is facilitated by bacterial exploitation of evolutionarily conserved host processes that are targeted by bacterial protein effectors injected into the host cell by the Dot/Icm type VIB translocation system. Although cysteine is semi-essential for humans and essential for amoeba, it is a metabolically favorable source of carbon and energy generation by L. pneumophila. To counteract host limitation of cysteine, L. pneumophila utilizes the AnkB Dot/Icm-translocated F-box effector to promote host proteasomal degradation of polyubiquitinated proteins within amoebae and human cells. Evidence indicates ankB and other Dot/Icm-translocated effector genes have been acquired through inter-kingdom horizontal gene transfer.

  9. Conserved BK channel-protein interactions reveal signals relevant to cell death and survival.

    Directory of Open Access Journals (Sweden)

    Bernd Sokolowski

    Full Text Available The large-conductance Ca(2+-activated K(+ (BK channel and its β-subunit underlie tuning in non-mammalian sensory or hair cells, whereas in mammals its function is less clear. To gain insights into species differences and to reveal putative BK functions, we undertook a systems analysis of BK and BK-Associated Proteins (BKAPS in the chicken cochlea and compared these results to other species. We identified 110 putative partners from cytoplasmic and membrane/cytoskeletal fractions, using a combination of coimmunoprecipitation, 2-D gel, and LC-MS/MS. Partners included 14-3-3γ, valosin-containing protein (VCP, stathmin (STMN, cortactin (CTTN, and prohibitin (PHB, of which 16 partners were verified by reciprocal coimmunoprecipitation. Bioinformatics revealed binary partners, the resultant interactome, subcellular localization, and cellular processes. The interactome contained 193 proteins involved in 190 binary interactions in subcellular compartments such as the ER, mitochondria, and nucleus. Comparisons with mice showed shared hub proteins that included N-methyl-D-aspartate receptor (NMDAR and ATP-synthase. Ortholog analyses across six species revealed conserved interactions involving apoptosis, Ca(2+ binding, and trafficking, in chicks, mice, and humans. Functional studies using recombinant BK and RNAi in a heterologous expression system revealed that proteins important to cell death/survival, such as annexinA5, γ-actin, lamin, superoxide dismutase, and VCP, caused a decrease in BK expression. This revelation led to an examination of specific kinases and their effectors relevant to cell viability. Sequence analyses of the BK C-terminus across 10 species showed putative binding sites for 14-3-3, RAC-α serine/threonine-protein kinase 1 (Akt, glycogen synthase kinase-3β (GSK3β and phosphoinositide-dependent kinase-1 (PDK1. Knockdown of 14-3-3 and Akt caused an increase in BK expression, whereas silencing of GSK3β and PDK1 had the opposite

  10. Cellular mechanisms regulating sperm-zona pellucida interaction

    Institute of Scientific and Technical Information of China (English)

    Andrew T Reid; Kate Redgrove; R John Aitken; Brett Nixon

    2011-01-01

    For mammalian spermatozoa to exhibit the ability to bind the zona pellucida(ZP)they must undergo three distinct phases of maturation,namely,spermatogenesis(testis),epididymal maturation(epididymis)and capacitation(female reproductive tract).An impressive array of spermatozoa surface remodeling events accompany these phases of maturation and appear critical for recognition and adhesion of the outer vestments of the oocyte,a structure known as the ZP.It is becoming increasingly apparent that species-specific zona adhesion is not mediated by a single receptor.Instead,compelling evidence now points toward models implicating a multiplicity of receptor-ligand interactions.This notion is in keeping with emerging research that has shown that there is a dynamic aggregation of proteins believed to be important in sperm-ZP recognition to the regions of sperm that mediate this binding event.Such remodeling may in turn facilitate the assembly of a multimeric zona recognition complex(MZRC).Though formation of MZRCs raises questions regarding the nature of the block to polyspermy,formation and assembly of such a structure would no doubt explain the strenuous maturation process that sperm endure on their sojourn to functional maturity.

  11. Interactions of the HSV-1 UL25 Capsid Protein with Cellular Microtubule-associated Protein

    Institute of Scientific and Technical Information of China (English)

    Lei GUO; Ying ZHANG; Yan-chun CHE; Wen-juan WU; Wei-zhong LI; Li-chun WANG; Yun LIAO; Long-ding LIU; Qi-han LI

    2008-01-01

    An interaction between the HSV-1 UL25 capsid protein and cellular microtubule-associated protein was found using a yeast two-hybrid screen and β-D-galactosidase activity assays. Immunofluorescence microscopy of the UL25 protein demonstrated its co-localization with cellular microtubule-associated protein in the plasma membrane. Further investigations with deletion mutants suggest that UL25 is likely to have a function in the nucleus.

  12. Mycosphaerella podagrariae - a necrotrophic phytopathogen forming a special cellular interaction with its host Aegopodium podagraria

    OpenAIRE

    Simon, U.K.; Groenewald, J.Z.; Stierhof, Y D; Crous, P.W.; Bauer, R

    2010-01-01

    We present a new kind of cellular interaction found between Mycosphaerella podagrariae and Aegopodium podagraria, which is remarkably different to the interaction type of the obligate biotrophic fungus Cymadothea trifolii, another member of the Mycosphaerellaceae (Capnodiales, Dothideomycetes, Ascomycota) which we have described earlier. Observations are based on both conventional and cryofixed material and show that some features of this particular interaction are better discernable after ch...

  13. Multiple cellular proteins interact with LEDGF/p75 through a conserved unstructured consensus motif.

    Science.gov (United States)

    Tesina, Petr; Čermáková, Kateřina; Hořejší, Magdalena; Procházková, Kateřina; Fábry, Milan; Sharma, Subhalakshmi; Christ, Frauke; Demeulemeester, Jonas; Debyser, Zeger; De Rijck, Jan; Veverka, Václav; Řezáčová, Pavlína

    2015-08-06

    Lens epithelium-derived growth factor (LEDGF/p75) is an epigenetic reader and attractive therapeutic target involved in HIV integration and the development of mixed lineage leukaemia (MLL1) fusion-driven leukaemia. Besides HIV integrase and the MLL1-menin complex, LEDGF/p75 interacts with various cellular proteins via its integrase binding domain (IBD). Here we present structural characterization of IBD interactions with transcriptional repressor JPO2 and domesticated transposase PogZ, and show that the PogZ interaction is nearly identical to the interaction of LEDGF/p75 with MLL1. The interaction with the IBD is maintained by an intrinsically disordered IBD-binding motif (IBM) common to all known cellular partners of LEDGF/p75. In addition, based on IBM conservation, we identify and validate IWS1 as a novel LEDGF/p75 interaction partner. Our results also reveal how HIV integrase efficiently displaces cellular binding partners from LEDGF/p75. Finally, the similar binding modes of LEDGF/p75 interaction partners represent a new challenge for the development of selective interaction inhibitors.

  14. CancerResource: a comprehensive database of cancer-relevant proteins and compound interactions supported by experimental knowledge.

    Science.gov (United States)

    Ahmed, Jessica; Meinel, Thomas; Dunkel, Mathias; Murgueitio, Manuela S; Adams, Robert; Blasse, Corinna; Eckert, Andreas; Preissner, Saskia; Preissner, Robert

    2011-01-01

    During the development of methods for cancer diagnosis and treatment, a vast amount of information is generated. Novel cancer target proteins have been identified and many compounds that activate or inhibit cancer-relevant target genes have been developed. This knowledge is based on an immense number of experimentally validated compound-target interactions in the literature, and excerpts from literature text mining are spread over numerous data sources. Our own analysis shows that the overlap between important existing repositories such as Comparative Toxicogenomics Database (CTD), Therapeutic Target Database (TTD), Pharmacogenomics Knowledge Base (PharmGKB) and DrugBank as well as between our own literature mining for cancer-annotated entries is surprisingly small. In order to provide an easy overview of interaction data, it is essential to integrate this information into a single, comprehensive data repository. Here, we present CancerResource, a database that integrates cancer-relevant relationships of compounds and targets from (i) our own literature mining and (ii) external resources complemented with (iii) essential experimental and supporting information on genes and cellular effects. In order to facilitate an overview of existing and supporting information, a series of novel information connections have been established. CancerResource addresses the spectrum of research on compound-target interactions in natural sciences as well as in individualized medicine; CancerResource is available at: http://bioinformatics.charite.de/cancerresource/.

  15. A pipeline for determining protein-protein interactions and proximities in the cellular milieu.

    Science.gov (United States)

    Subbotin, Roman I; Chait, Brian T

    2014-11-01

    It remains extraordinarily challenging to elucidate endogenous protein-protein interactions and proximities within the cellular milieu. The dynamic nature and the large range of affinities of these interactions augment the difficulty of this undertaking. Among the most useful tools for extracting such information are those based on affinity capture of target bait proteins in combination with mass spectrometric readout of the co-isolated species. Although highly enabling, the utility of affinity-based methods is generally limited by difficulties in distinguishing specific from nonspecific interactors, preserving and isolating all unique interactions including those that are weak, transient, or rapidly exchanging, and differentiating proximal interactions from those that are more distal. Here, we have devised and optimized a set of methods to address these challenges. The resulting pipeline involves flash-freezing cells in liquid nitrogen to preserve the cellular environment at the moment of freezing; cryomilling to fracture the frozen cells into intact micron chunks to allow for rapid access of a chemical reagent and to stabilize the intact endogenous subcellular assemblies and interactors upon thawing; and utilizing the high reactivity of glutaraldehyde to achieve sufficiently rapid stabilization at low temperatures to preserve native cellular interactions. In the course of this work, we determined that relatively low molar ratios of glutaraldehyde to reactive amines within the cellular milieu were sufficient to preserve even labile and transient interactions. This mild treatment enables efficient and rapid affinity capture of the protein assemblies of interest under nondenaturing conditions, followed by bottom-up MS to identify and quantify the protein constituents. For convenience, we have termed this approach Stabilized Affinity Capture Mass Spectrometry. Here, we demonstrate that Stabilized Affinity Capture Mass Spectrometry allows us to stabilize and elucidate

  16. Interaction of cellular-localized signature modules in response to prostate cancer

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Rapid progress in high-throughput biotechnologies (e. g. microarrays) and exponential accumulation of gene functional knowledge makes it promising for systematic understanding of complex human diseases at the functional modules level. Current modular categorizations can be defined and selected more specifically and precisely in terms of both biological processes and cellular locations, aiming at uncovering the modular molecular networks highly relevant to cancers. Based on Gene Ontology, we identifed the functional modules enriched with differentially expressed genes and characterized by biological processes and specific cellular locations. Then, according to the ranking of the disease discriminating abilities of the pre-selected functional modules, we further defined and filtered signature modules which have higher relevance to the cancer under study. Applications of the proposed method to the analysis of a prostate cancer dataset revealed insightful biological modules.

  17. Discovering the cellular-localized functional modules and modular interactions in response to liver cancer

    Institute of Scientific and Technical Information of China (English)

    Zhu Jing; Guo Zheng; Yang Da; Zhang Min; Wang Jing; Wang Chenguang

    2008-01-01

    In this paper, we firstly identify the functional modules enriched with differentially expressed genes (DEGs) and characterized by biological processes in specific cellular locations, based on gene ontology (GO) and microarray data. Then, we further define and filter disease relevant signature modules according to the ranking of the disease discriminating abilities of the pre-selected functional modules. At last, we analyze the potential way by which they cooperate towards human disease. Application of the proposed method to the analysis of a liver cancer dataset shows that, using the same false discovery rate (FDR) threshold, we can find more biologically meaningful and detailed processes by using the cellular localization information. Some biological evidences support the relevancy of our biological modules to the disease mechanism.

  18. THE RELEVANCE OF INTERACTIONS IN INNOVATION SYSTEMS: HOW TO CONSOLIDATE THE FRAMEWORK

    Directory of Open Access Journals (Sweden)

    Jon Mikel ZABALA-ITURRIAGAGOITIA

    2007-12-01

    Full Text Available Innovation Systems constitute an analysis framework which tries to identify the agents, and the interactions produced among them within an innovation system, endowing thus authorities of a tool for the definition of innovation policies. Accordingly, cooperation or interaction related practices become crucial. However, there is a need for the development and implementation of a more sophisticated measures and indicators as regards these interactive patterns, both from a theoretical and a quantitative approach. This papers aims at empirically contributing to highlight the relevance of these interactions. In order to do that, we first start by offering a clear taxonomy of the Spanish regions concerning R&D and innovation activities, to then analyse the extent to which interactions are relevant or not by considering in this case Spain as the unit of analysis between 1995-2002.

  19. A `Clicked' Tetrameric Hydroxamic Acid Glycopeptidomimetic Antagonizes Sugar-Lectin Interactions On The Cellular Level

    Science.gov (United States)

    Zhang, Hai-Lin; Zang, Yi; Xie, Juan; Li, Jia; Chen, Guo-Rong; He, Xiao-Peng; Tian, He

    2014-07-01

    A tetrameric N-acetyl galactosaminyl (GalNAc) peptidomimetic was constructed by N-acetylation of repeating proline-based hydroxamic acid units, followed by a convergent `click chemistry' coupling. This novel glycopeptidomimetic was determined to effectively antagonize the interaction between a transmembrane hepatic lectin and GalNAc on the cellular level.

  20. Dynamic circadian protein-protein interaction networks predict temporal organization of cellular functions.

    Directory of Open Access Journals (Sweden)

    Thomas Wallach

    2013-03-01

    Full Text Available Essentially all biological processes depend on protein-protein interactions (PPIs. Timing of such interactions is crucial for regulatory function. Although circadian (~24-hour clocks constitute fundamental cellular timing mechanisms regulating important physiological processes, PPI dynamics on this timescale are largely unknown. Here, we identified 109 novel PPIs among circadian clock proteins via a yeast-two-hybrid approach. Among them, the interaction of protein phosphatase 1 and CLOCK/BMAL1 was found to result in BMAL1 destabilization. We constructed a dynamic circadian PPI network predicting the PPI timing using circadian expression data. Systematic circadian phenotyping (RNAi and overexpression suggests a crucial role for components involved in dynamic interactions. Systems analysis of a global dynamic network in liver revealed that interacting proteins are expressed at similar times likely to restrict regulatory interactions to specific phases. Moreover, we predict that circadian PPIs dynamically connect many important cellular processes (signal transduction, cell cycle, etc. contributing to temporal organization of cellular physiology in an unprecedented manner.

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

    Energy Technology Data Exchange (ETDEWEB)

    Xie, Zhong-Ru; Chen, Jiawen; Wu, Yinghao, E-mail: yinghao.wu@einstein.yu.edu [Department of Systems and Computational Biology, Albert Einstein College of Medicine of Yeshiva University, 1300 Morris Park Avenue, Bronx, New York 10461 (United States)

    2014-02-07

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

  2. Beyond co-localization: inferring spatial interactions between sub-cellular structures from microscopy images

    Directory of Open Access Journals (Sweden)

    Paul Grégory

    2010-07-01

    Full Text Available Abstract Background Sub-cellular structures interact in numerous direct and indirect ways in order to fulfill cellular functions. While direct molecular interactions crucially depend on spatial proximity, other interactions typically result in spatial correlations between the interacting structures. Such correlations are the target of microscopy-based co-localization analysis, which can provide hints of potential interactions. Two complementary approaches to co-localization analysis can be distinguished: intensity correlation methods capitalize on pattern discovery, whereas object-based methods emphasize detection power. Results We first reinvestigate the classical co-localization measure in the context of spatial point pattern analysis. This allows us to unravel the set of implicit assumptions inherent to this measure and to identify potential confounding factors commonly ignored. We generalize object-based co-localization analysis to a statistical framework involving spatial point processes. In this framework, interactions are understood as position co-dependencies in the observed localization patterns. The framework is based on a model of effective pairwise interaction potentials and the specification of a null hypothesis for the expected pattern in the absence of interaction. Inferred interaction potentials thus reflect all significant effects that are not explained by the null hypothesis. Our model enables the use of a wealth of well-known statistical methods for analyzing experimental data, as demonstrated on synthetic data and in a case study considering virus entry into live cells. We show that the classical co-localization measure typically under-exploits the information contained in our data. Conclusions We establish a connection between co-localization and spatial interaction of sub-cellular structures by formulating the object-based interaction analysis problem in a spatial statistics framework based on nearest-neighbor distance

  3. Clinically relevant QTc prolongation due to overridden drug-drug interaction alerts: A retrospective cohort study

    NARCIS (Netherlands)

    I.H. van der Sijs (Heleen); R. Kowlesar (Ravi); A.P.J. Klootwijk (Peter); S.P. Nelwan (Stefan); A.G. Vulto (Arnold); T. van Gelder (Teun)

    2009-01-01

    textabstractAIMS: To investigate whether, in patients in whom drug-drug interaction (DDI) alerts on QTc prolongation were overridden, the physician had requested an electrocardiogram (ECG), and if these ECGs showed clinically relevant QTc prolongation. METHODS: For all patients with overridden DDI a

  4. Conserved Molecular and Epigenetic Determinants of Aromatase Gene Induction by the Herbicide Atrazine in Human and Rat Cellular Models Relevant to Breast Cancer Risk

    OpenAIRE

    2011-01-01

    AbstractConserved Molecular and Epigenetic Determinants of Aromatase Gene Induction by the Herbicide Atrazine in Human and Rat Cellular Models Relevant to Breast Cancer Risk ByTheresa Ryan StueveDoctor of Philosophy in Molecular ToxicologyUniversity of California, BerkeleyProfessor Gary Firestone, Co-ChairProfessor Dale Leitman, Co-ChairFall 2011The widely-applied herbicide atrazine (ATR) is a potent endocrine disruptor that elicits anti-androgenic and estrogenic effects, often at concentrat...

  5. ELF (extremely-low-frequency) field interactions at the animal, tissue and cellular levels

    Energy Technology Data Exchange (ETDEWEB)

    Tenforde, T.S.

    1990-10-01

    A description is given of the fundamental physical properties of extremely-low-frequency (ELF) electromagnetic fields, and the mechanisms through which these fields interact with the human body at a macroscopic level. Biological responses to ELF fields at the tissue, cellular and molecular levels are summarized, including new evidence that ELF field exposure produces alterations in gene expression and the cytoplasmic concentrations of specific proteins.

  6. A Quantum Cellular Automata architecture with nearest neighbor interactions using one quantum gate type

    CERN Document Server

    Ntalaperas, D

    2016-01-01

    We propose an architecture based on Quantum cellular Automata which allows the use of only one type of quantum gates per computational step in order to perform nearest neighbor interactions. The model is built in partial steps, each one of them analyzed using nearest neighbor interactions, starting with single qubit operations and continuing with two qubit ones. The effectiveness of the model is tested and valuated by developing a quantum circuit implementing the Quantum Fourier Transform. The important outcome of this validation was that the operations are performed in a local and controlled manner thus reducing the error rate of each computational step.

  7. Final Report: Laser-Material Interactions Relevant to Analytic Spectroscopy of Wide Band Gap Materials

    Energy Technology Data Exchange (ETDEWEB)

    Dickinson, J. T. [Washington State University

    2014-04-05

    We summarize our studies aimed at developing an understanding of the underlying physics and chemistry in terms of laser materials interactions relevant to laser-based sampling and chemical analysis of wide bandgap materials. This work focused on the determination of mechanisms for the emission of electrons, ions, atoms, and molecules from laser irradiation of surfaces. We determined the important role of defects on these emissions, the thermal, chemical, and physical interactions responsible for matrix effects and mass-dependent transport/detection. This work supported development of new techniques and technology for the determination of trace elements contained such as nuclear waste materials.

  8. Regression Trees Identify Relevant Interactions: Can This Improve the Predictive Performance of Risk Adjustment?

    Science.gov (United States)

    Buchner, Florian; Wasem, Jürgen; Schillo, Sonja

    2017-01-01

    Risk equalization formulas have been refined since their introduction about two decades ago. Because of the complexity and the abundance of possible interactions between the variables used, hardly any interactions are considered. A regression tree is used to systematically search for interactions, a methodologically new approach in risk equalization. Analyses are based on a data set of nearly 2.9 million individuals from a major German social health insurer. A two-step approach is applied: In the first step a regression tree is built on the basis of the learning data set. Terminal nodes characterized by more than one morbidity-group-split represent interaction effects of different morbidity groups. In the second step the 'traditional' weighted least squares regression equation is expanded by adding interaction terms for all interactions detected by the tree, and regression coefficients are recalculated. The resulting risk adjustment formula shows an improvement in the adjusted R(2) from 25.43% to 25.81% on the evaluation data set. Predictive ratios are calculated for subgroups affected by the interactions. The R(2) improvement detected is only marginal. According to the sample level performance measures used, not involving a considerable number of morbidity interactions forms no relevant loss in accuracy. Copyright © 2015 John Wiley & Sons, Ltd.

  9. Cellular uptake and transcytosis of lipid-based nanoparticles across the intestinal barrier: Relevance for oral drug delivery.

    Science.gov (United States)

    Neves, Ana Rute; Queiroz, Joana Fontes; Costa Lima, Sofia A; Figueiredo, Francisco; Fernandes, Rui; Reis, Salette

    2016-02-01

    Oral administration is the preferred route for drug delivery and nanosystems represent a promising tool for protection and transport of hardly soluble, chemically unstable and poorly permeable drugs through the intestinal barrier. In the present work, we have studied lipid nanoparticles cellular uptake, internalization pathways and transcytosis routes through Caco-2 cell monolayers. Both lipid nanosystems presented similar size (∼180nm) and surface charge (-30mV). Nanostructured lipid carriers showed a higher cellular uptake and permeability across the barrier, but solid lipid nanoparticles could enter cells faster than the former. The internalization of lipid nanoparticles occurs mainly through a clathrin-mediated endocytosis mechanism, although caveolae-mediated endocytosis is also involved in the uptake. Both lipid nanoparticles were able to cross the intestinal barrier by a preferential transcellular route. This work contributed to a better knowledge of the developed nanosystems for the oral delivery of a wide spectrum of drugs.

  10. Exploring Cellular Interactions of Liposomes Using Protein Corona Fingerprints and Physicochemical Properties.

    Science.gov (United States)

    Bigdeli, Arafeh; Palchetti, Sara; Pozzi, Daniela; Hormozi-Nezhad, Mohammad Reza; Baldelli Bombelli, Francesca; Caracciolo, Giulio; Mahmoudi, Morteza

    2016-03-22

    To control liposomes fate and transport upon contact with biofluids, it is essential to consider several parameters affecting the synthetic and biological identity of liposomes, as well as liposome-protein corona (PC) aspects. As a powerful tool in this data mining adventure, quantitative structure-activity relationship (QSAR) approach is used to correlate physicochemical properties of liposomes and their PC fingerprints to multiple quantified biological responses. In the present study, the relationship between cellular interactions of a set of structurally diverse liposomal formulations and their physicochemical and PC properties has been investigated via linear and nonlinear QSAR models. Significant parameters affecting cellular uptake and cell viability of liposomes in two important cancer cell lines (PC3 and HeLa) have been identified. The developed QSARs have the capacity to be implemented in advanced targeted delivery of liposomal drugs.

  11. Fungal-bacterial interactions and their relevance to oral health: linking the clinic and the bench

    Directory of Open Access Journals (Sweden)

    Patricia I Diaz

    2014-07-01

    Full Text Available High throughput sequencing has accelerated knowledge on the oral microbiome. While the bacterial component of oral communities has been extensively characterized, the role of the fungal microbiota in the oral cavity is largely unknown. Interactions among fungi and bacteria are likely to influence oral health as exemplified by the synergistic relationship between Candida albicans and oral streptococci. In this perspective, we discuss the current state of the field of fungal-bacterial interactions in the context of the oral cavity. We highlight the need to conduct longitudinal clinical studies to simultaneously characterize the bacterial and fungal components of the human oral microbiome in health and during disease progression. Such studies need to be coupled with investigations using disease-relevant models to mechanistically test the associations observed in humans and eventually identify fungal-bacterial interactions that could serve as preventive or therapeutic targets for oral diseases.

  12. Fungal-bacterial interactions and their relevance to oral health: linking the clinic and the bench.

    Science.gov (United States)

    Diaz, Patricia I; Strausbaugh, Linda D; Dongari-Bagtzoglou, Anna

    2014-01-01

    High throughput sequencing has accelerated knowledge on the oral microbiome. While the bacterial component of oral communities has been extensively characterized, the role of the fungal microbiota in the oral cavity is largely unknown. Interactions among fungi and bacteria are likely to influence oral health as exemplified by the synergistic relationship between Candida albicans and oral streptococci. In this perspective, we discuss the current state of the field of fungal-bacterial interactions in the context of the oral cavity. We highlight the need to conduct longitudinal clinical studies to simultaneously characterize the bacterial and fungal components of the human oral microbiome in health and during disease progression. Such studies need to be coupled with investigations using disease-relevant models to mechanistically test the associations observed in humans and eventually identify fungal-bacterial interactions that could serve as preventive or therapeutic targets for oral diseases.

  13. Clinically-relevant chemotherapy interactions with complementary and alternative medicines in patients with cancer.

    Science.gov (United States)

    Yap, Kevin Yi-Lwern; See, Cheng Shang; Chan, Alexandre

    2010-01-01

    Complementary and alternative medicines (CAMs), in particular herbal medicines, are commonly used by cancer patients in conjunction with chemotherapy treatment for their anticancer properties and supportive care. However, the effects of many of these herbs are not well-documented due to limited studies done on them. Severe herb-drug interactions (HDIs) have been recorded in some cases, and failure to recognize these harmful HDIs can lead to dire consequences in cancer patients. This study discusses clinically-relevant interactions between anticancer drugs (ACDs) and herbs classified into 7 categories: cancer treatment and prevention, immune-system-related, alopecia, nausea and vomiting, peripheral neuropathy and pain, inflammation, and fatigue. Some promising patents which contain these herbs and thus may manifest these interactions are also presented in this article. Pharmacokinetic interactions involved mainly induction or inhibition of the cytochrome P450 isozymes and p-glycoprotein, while pharmacodynamic interactions were related to increased risks of central nervous system-related effects, hepatotoxicity and bleeding, among others. Clinicians should be vigilant when treating cancer patients who take CAMs with concurrent chemotherapy since they face a high risk of HDIs. These HDIs can be minimized or avoided by selecting herb-drug pairs which are less likely to interact. Furthermore, close monitoring of pharmacological effects and plasma drug levels should be carried out to avoid toxicity and ensure adequate chemotherapeutic coverage in patients with cancer.

  14. The influence of silkworm species on cellular interactions with novel PVA/silk sericin hydrogels.

    Science.gov (United States)

    Lim, Khoon S; Kundu, Joydip; Reeves, April; Poole-Warren, Laura A; Kundu, Subhas C; Martens, Penny J

    2012-03-01

    Sericin peptides and PVA are chemically modified with methacrylate groups to produce a covalent PVA/sericin hydrogel. Preservation of the sericin bioactivity following methacrylation is confirmed, and PVA/sericin hydrogels are fabricated for both B. mori and A. mylitta sericin. Cell adhesion studies confirm the preservation of sericin bioactivity post incorporation in PVA gels. PVA/A. mylitta gels are observed to facilitate cell adhesion to a significantly greater degree than PVA/B. mori gels. Overall, the incorporation of sericin does not alter the physical properties of the PVA hydrogels but does result in significantly improved cellular interaction, particularly from A. mylitta gels.

  15. Inhibition of cytochrome P450 3A: relevant drug interactions in gastroenterology.

    Science.gov (United States)

    Sagir, A; Schmitt, M; Dilger, K; Häussinger, D

    2003-01-01

    Cytochrome P450 3A (CYP3A) is involved in biotransformation of more than half of all drugs currently available. Drug interactions by inhibition of CYP3A are of major interest in patients receiving combinations of drugs. Some interactions with CYP3A inhibitors also involve inhibition of the multidrug export pump, P-glycoprotein. An increasing number of adverse drug reactions might be avoided on the basis of knowledge about CYP3A substrates and inhibitors. This article summarizes some examples of such interactions relevant to gastroenterologists. Serious cases by coadministration of CYP3A inhibitors resulting in acute hepatitis, hypotension, rhabdomyolyis, torsade de pointes, sedation, or ergotism are presented: interactions with azole antifungals (ketoconazole, itraconazole, fluconazole), HIV protease inhibitors (ritonavir, indinavir, saquinavir, nelfinavir), macrolide antibiotics (clarithromycin, erythromycin), and grapefruit juice. In addition, 1 case is reported who presented the highest trough levels of the CYP3A substrate budesonide in serum ever measured. Practitioners have to be aware of the high potential of metabolic drug interactions when they prescribe a CYP3A inhibitor. It is wise to check carefully comedication in patients complaining of side effects with substrates of CYP3A.

  16. Interactions between glucocorticoid treatment and cis-regulatory polymorphisms contribute to cellular response phenotypes.

    Directory of Open Access Journals (Sweden)

    Joseph C Maranville

    2011-07-01

    Full Text Available Glucocorticoids (GCs mediate physiological responses to environmental stress and are commonly used as pharmaceuticals. GCs act primarily through the GC receptor (GR, a transcription factor. Despite their clear biomedical importance, little is known about the genetic architecture of variation in GC response. Here we provide an initial assessment of variability in the cellular response to GC treatment by profiling gene expression and protein secretion in 114 EBV-transformed B lymphocytes of African and European ancestry. We found that genetic variation affects the response of nearby genes and exhibits distinctive patterns of genotype-treatment interactions, with genotypic effects evident in either only GC-treated or only control-treated conditions. Using a novel statistical framework, we identified interactions that influence the expression of 26 genes known to play central roles in GC-related pathways (e.g. NQO1, AIRE, and SGK1 and that influence the secretion of IL6.

  17. Amorphous Silica Particles Relevant in Food Industry Influence Cellular Growth and Associated Signaling Pathways in Human Gastric Carcinoma Cells

    Directory of Open Access Journals (Sweden)

    Anja Wittig

    2017-01-01

    Full Text Available Nanostructured silica particles are commonly used in biomedical and biotechnical fields, as well as, in cosmetics and food industry. Thus, their environmental and health impacts are of great interest and effects after oral uptake are only rarely investigated. In the present study, the toxicological effects of commercially available nano-scaled silica with a nominal primary diameter of 12 nm were investigated on the human gastric carcinoma cell line GXF251L. Besides the analysis of cytotoxic and proliferative effects and the comparison with effects of particles with a nominal primary diameter of 200 nm, emphasis was also given to their influence on the cellular epidermal growth factor receptor (EGFR and mitogen-activated protein kinases (MAPK signaling pathways—both of them deeply involved in the regulation of cellular processes like cell cycle progression, differentiation or proliferation. The investigated silica nanoparticles (NPs were found to stimulate cell proliferation as measured by microscopy and the sulforhodamine B assay. In accordance, the nuclear level of the proliferation marker Ki-67 was enhanced in a concentration-dependent manner. At high particle concentrations also necrosis was induced. Finally, silica NPs affected the EGFR and MAPK pathways at various levels dependent on concentration and time. However, classical activation of the EGFR, to be reflected by enhanced levels of phosphorylation, could be excluded as major trigger of the proliferative stimulus. After 45 min of incubation the level of phosphorylated EGFR did not increase, whereas enhanced levels of total EGFR protein were observed. These results indicate interference with the complex homeostasis of the EGFR protein, whereby up to 24 h no impact on the transcription level was detected. In addition, downstream on the level of the MAP kinases ERK1/2 short term incubation appeared to affect total protein levels without clear increase in phosphorylation. Depending on the

  18. Amorphous Silica Particles Relevant in Food Industry Influence Cellular Growth and Associated Signaling Pathways in Human Gastric Carcinoma Cells.

    Science.gov (United States)

    Wittig, Anja; Gehrke, Helge; Del Favero, Giorgia; Fritz, Eva-Maria; Al-Rawi, Marco; Diabaté, Silvia; Weiss, Carsten; Sami, Haider; Ogris, Manfred; Marko, Doris

    2017-01-13

    Nanostructured silica particles are commonly used in biomedical and biotechnical fields, as well as, in cosmetics and food industry. Thus, their environmental and health impacts are of great interest and effects after oral uptake are only rarely investigated. In the present study, the toxicological effects of commercially available nano-scaled silica with a nominal primary diameter of 12 nm were investigated on the human gastric carcinoma cell line GXF251L. Besides the analysis of cytotoxic and proliferative effects and the comparison with effects of particles with a nominal primary diameter of 200 nm, emphasis was also given to their influence on the cellular epidermal growth factor receptor (EGFR) and mitogen-activated protein kinases (MAPK) signaling pathways-both of them deeply involved in the regulation of cellular processes like cell cycle progression, differentiation or proliferation. The investigated silica nanoparticles (NPs) were found to stimulate cell proliferation as measured by microscopy and the sulforhodamine B assay. In accordance, the nuclear level of the proliferation marker Ki-67 was enhanced in a concentration-dependent manner. At high particle concentrations also necrosis was induced. Finally, silica NPs affected the EGFR and MAPK pathways at various levels dependent on concentration and time. However, classical activation of the EGFR, to be reflected by enhanced levels of phosphorylation, could be excluded as major trigger of the proliferative stimulus. After 45 min of incubation the level of phosphorylated EGFR did not increase, whereas enhanced levels of total EGFR protein were observed. These results indicate interference with the complex homeostasis of the EGFR protein, whereby up to 24 h no impact on the transcription level was detected. In addition, downstream on the level of the MAP kinases ERK1/2 short term incubation appeared to affect total protein levels without clear increase in phosphorylation. Depending on the concentration

  19. Interactive breast cancer segmentation based on relevance feedback: from user-centered design to evaluation

    Science.gov (United States)

    Gouze, A.; Kieffer, S.; Van Brussel, C.; Moncarey, R.; Grivegnée, A.; Macq, B.

    2009-02-01

    Computer systems play an important role in medical imaging industry since radiologists depend on it for visualization, interpretation, communication and archiving. In particular, computer-aided diagnosis (CAD) systems help in lesion detection tasks. This paper presents the design and the development of an interactive segmentation tool for breast cancer screening and diagnosis. The tool conception is based upon a user-centered approach in order to ensure that the application is of real benefit to radiologists. The analysis of user expectations, workflow and decision-making practices give rise to the need for an interactive reporting system based on the BIRADS, that would not only include the numerical features extracted from the segmentation of the findings in a structured manner, but also support human relevance feedback as well. This way, the numerical results from segmentation can be either validated by end-users or enhanced thanks to domain-experts subjective interpretation. Such a domain-expert centered system requires the segmentation to be sufficiently accurate and locally adapted, and the features to be carefully selected in order to best suit user's knowledge and to be of use in enhancing segmentation. Improving segmentation accuracy with relevance feedback and providing radiologists with a user-friendly interface to support image analysis are the contributions of this work. The preliminary result is first the tool conception, and second the improvement of the segmentation precision.

  20. Clinical relevancy and risks of potential drug–drug interactions in intensive therapy

    Science.gov (United States)

    Rodrigues, Aline Teotonio; Stahlschmidt, Rebeca; Granja, Silvia; Falcão, Antonio Luis Eiras; Moriel, Patricia; Mazzola, Priscila Gava

    2014-01-01

    Purpose Evaluate the potential Drug–Drug Interactions (pDDI) found in prescription orders of adult Intensive Care Unit (ICU) of a Brazilian public health system hospital; quantify and qualify the pDDI regarding their severity and risks to the critical patient, using the database from Micromedex®. Methods Prospective study (January–December of 2011) collecting and evaluating 369 prescription orders (convenient sampling), one per patient. Results During the study 1844 pDDIs were identified and distributed in 405 pairs (medication A × medication B combination). There was an average of 5.00 ± 5.06 pDDIs per prescription order, the most prevalent being moderate and important interactions, present in 74% and 67% of prescription orders, respectively. In total, there were 9 contraindicated, 129 important and 204 moderate pDDIs. Among them 52 had as management recommendation to “avoid concomitant use” or “suspension of medication”, while 306 had as recommendation “continuous and adequate monitoring”. Conclusion The high number of pDDIs found in the study combined with the evaluation of the clinical relevancy of the most frequent pDDIs in the ICU shows that moderate and important interactions are highly incident. As the majority of them demand monitoring and adequate management, being aware of these interactions is major information for the safe and individualized risk management. PMID:27134536

  1. Functional Divergence of Hsp90 Genetic Interactions in Biofilm and Planktonic Cellular States.

    Directory of Open Access Journals (Sweden)

    Stephanie Diezmann

    Full Text Available Candida albicans is among the most prevalent opportunistic fungal pathogens. Its capacity to cause life-threatening bloodstream infections is associated with the ability to form biofilms, which are intrinsically drug resistant reservoirs for dispersal. A key regulator of biofilm drug resistance and dispersal is the molecular chaperone Hsp90, which stabilizes many signal transducers. We previously identified 226 C. albicans Hsp90 genetic interactors under planktonic conditions, of which 56 are involved in transcriptional regulation. Six of these transcriptional regulators have previously been implicated in biofilm formation, suggesting that Hsp90 genetic interactions identified in planktonic conditions may have functional significance in biofilms. Here, we explored the relationship between Hsp90 and five of these transcription factor genetic interactors: BCR1, MIG1, TEC1, TUP1, and UPC2. We deleted each transcription factor gene in an Hsp90 conditional expression strain, and assessed biofilm formation and morphogenesis. Strikingly, depletion of Hsp90 conferred no additional biofilm defect in the mutants. An interaction was observed in which deletion of BCR1 enhanced filamentation upon reduction of Hsp90 levels. Further, although Hsp90 modulates expression of TEC1, TUP1, and UPC2 in planktonic conditions, it has no impact in biofilms. Lastly, we probed for physical interactions between Hsp90 and Tup1, whose WD40 domain suggests that it might interact with Hsp90 directly. Hsp90 and Tup1 formed a stable complex, independent of temperature or developmental state. Our results illuminate a physical interaction between Hsp90 and a key transcriptional regulator of filamentation and biofilm formation, and suggest that Hsp90 has distinct genetic interactions in planktonic and biofilm cellular states.

  2. An ectromelia virus profilin homolog interacts with cellular tropomyosin and viral A-type inclusion protein

    Directory of Open Access Journals (Sweden)

    Burke Robert D

    2007-07-01

    Full Text Available Abstract Background Profilins are critical to cytoskeletal dynamics in eukaryotes; however, little is known about their viral counterparts. In this study, a poxviral profilin homolog, ectromelia virus strain Moscow gene 141 (ECTV-PH, was investigated by a variety of experimental and bioinformatics techniques to characterize its interactions with cellular and viral proteins. Results Profilin-like proteins are encoded by all orthopoxviruses sequenced to date, and share over 90% amino acid (aa identity. Sequence comparisons show highest similarity to mammalian type 1 profilins; however, a conserved 3 aa deletion in mammalian type 3 and poxviral profilins suggests that these homologs may be more closely related. Structural analysis shows that ECTV-PH can be successfully modelled onto both the profilin 1 crystal structure and profilin 3 homology model, though few of the surface residues thought to be required for binding actin, poly(L-proline, and PIP2 are conserved. Immunoprecipitation and mass spectrometry identified two proteins that interact with ECTV-PH within infected cells: alpha-tropomyosin, a 38 kDa cellular actin-binding protein, and the 84 kDa product of vaccinia virus strain Western Reserve (VACV-WR 148, which is the truncated VACV counterpart of the orthopoxvirus A-type inclusion (ATI protein. Western and far-western blots demonstrated that the interaction with alpha-tropomyosin is direct, and immunofluorescence experiments suggest that ECTV-PH and alpha-tropomyosin may colocalize to structures that resemble actin tails and cellular protrusions. Sequence comparisons of the poxviral ATI proteins show that although full-length orthologs are only present in cowpox and ectromelia viruses, an ~ 700 aa truncated ATI protein is conserved in over 90% of sequenced orthopoxviruses. Immunofluorescence studies indicate that ECTV-PH localizes to cytoplasmic inclusion bodies formed by both truncated and full-length versions of the viral ATI protein

  3. Plin2 inhibits cellular glucose uptake through interactions with SNAP23, a SNARE complex protein.

    Directory of Open Access Journals (Sweden)

    Subramanian Senthivinayagam

    Full Text Available Although a link between excess lipid storage and aberrant glucose metabolism has been recognized for many years, little is known what role lipid storage droplets and associated proteins such as Plin2 play in managing cellular glucose levels. To address this issue, the influence of Plin2 on glucose uptake was examined using 2-NBD-Glucose and [(3H]-2-deoxyglucose to show that insulin-mediated glucose uptake was decreased 1.7- and 1.8-fold, respectively in L cell fibroblasts overexpressing Plin2. Conversely, suppression of Plin2 levels by RNAi-mediated knockdown increased 2-NBD-Glucose uptake several fold in transfected L cells and differentiated 3T3-L1 cells. The effect of Plin2 expression on proteins involved in glucose uptake and transport was also examined. Expression of the SNARE protein SNAP23 was increased 1.6-fold while levels of syntaxin-5 were decreased 1.7-fold in Plin2 overexpression cells with no significant changes observed in lipid droplet associated proteins Plin1 or FSP27 or with the insulin receptor, GLUT1, or VAMP4. FRET experiments revealed a close proximity of Plin2 to SNAP23 on lipid droplets to within an intramolecular distance of 51 Å. The extent of targeting of SNAP23 to lipid droplets was determined by co-localization and co-immunoprecipitation experiments to show increased partitioning of SNAP23 to lipid droplets when Plin2 was overexpressed. Taken together, these results suggest that Plin2 inhibits glucose uptake by interacting with, and regulating cellular targeting of SNAP23 to lipid droplets. In summary, the current study for the first time provides direct evidence for the role of Plin2 in mediating cellular glucose uptake.

  4. Yeast mitochondrial protein-protein interactions reveal diverse complexes and disease-relevant functional relationships.

    Science.gov (United States)

    Jin, Ke; Musso, Gabriel; Vlasblom, James; Jessulat, Matthew; Deineko, Viktor; Negroni, Jacopo; Mosca, Roberto; Malty, Ramy; Nguyen-Tran, Diem-Hang; Aoki, Hiroyuki; Minic, Zoran; Freywald, Tanya; Phanse, Sadhna; Xiang, Qian; Freywald, Andrew; Aloy, Patrick; Zhang, Zhaolei; Babu, Mohan

    2015-02-06

    Although detailed, focused, and mechanistic analyses of associations among mitochondrial proteins (MPs) have identified their importance in varied biological processes, a systematic understanding of how MPs function in concert both with one another and with extra-mitochondrial proteins remains incomplete. Consequently, many questions regarding the role of mitochondrial dysfunction in the development of human disease remain unanswered. To address this, we compiled all existing mitochondrial physical interaction data for over 1200 experimentally defined yeast MPs and, through bioinformatic analysis, identified hundreds of heteromeric MP complexes having extensive associations both within and outside the mitochondria. We provide support for these complexes through structure prediction analysis, morphological comparisons of deletion strains, and protein co-immunoprecipitation. The integration of these MP complexes with reported genetic interaction data reveals substantial crosstalk between MPs and non-MPs and identifies novel factors in endoplasmic reticulum-mitochondrial organization, membrane structure, and mitochondrial lipid homeostasis. More than one-third of these MP complexes are conserved in humans, with many containing members linked to clinical pathologies, enabling us to identify genes with putative disease function through guilt-by-association. Although still remaining incomplete, existing mitochondrial interaction data suggests that the relevant molecular machinery is modular, yet highly integrated with non-mitochondrial processes.

  5. Gene and environment interaction: Is the differential susceptibility hypothesis relevant for obesity?

    Science.gov (United States)

    Dalle Molle, Roberta; Fatemi, Hajar; Dagher, Alain; Levitan, Robert D; Silveira, Patricia P; Dubé, Laurette

    2017-02-01

    The differential susceptibility model states that a given genetic variant is associated with an increased risk of pathology in negative environments but greater than average resilience in enriched ones. While this theory was first implemented in psychiatric-genetic research, it may also help us to unravel the complex ways that genes and environments interact to influence feeding behavior and obesity. We reviewed evidence on gene vs. environment interactions that influence obesity development, aiming to support the applicability of the differential susceptibility model for this condition, and propose that various environmental "layers" relevant for human development should be considered when bearing the differential susceptibility model in mind. Mother-child relationship, socioeconomic status and individual's response are important modifiers of BMI and food intake when interacting with gene variants, "for better and for worse". While only a few studies to date have investigated obesity outcomes using this approach, we propose that the differential susceptibility hypothesis is in fact highly applicable to the study of genetic and environmental influences on feeding behavior and obesity risk.

  6. Cellular Interactions and Signaling in neuroAIDS: Emerging Issues Colloquium.

    Science.gov (United States)

    Al-Harthi, Lena; Buch, Shilpa; Geiger, Jonathan D; Gendelman, Howard E; He, Johnny J; Jordan-Sciutto, Kelly L; Kolson, Dennis L; Rappaport, Jay; Roy, Sabita; Zheng, Jialin; Fox, Howard S

    2014-06-01

    On May 23, 2013 scientific leaders in the neuroAIDS community met at the University of Nebraska Medical Center to discuss cellular interaction and signaling for the third annual human immunodeficiency virus and neuroAIDS colloquium. The meeting continues a series of contemporary scientific issues related to how virus effects the nervous system. In 2011 the focus was on animal models and in 2012 in biomarkers. Here, our 2013 meeting featured ten presentations from outstanding scientists examining how inter- and intra-cellular processes contribute to neuropathogenesis. Talks highlighted emerging issues, findings, and potential therapies, followed by a panel discussion in which controversies in the field and gaps in our current knowledge were identified. The panel discussion was transcribed into the article and published as a field perspective. A link is available where all of the presentations and the concluding discussion can be seen and heard. The third annual University of Nebraska Medical Center (UNMC) colloquium on current issues in neuroAIDS was held on May 23, 2013. Following the presentations, which can be viewed at http://www.unmc.edu/pharmacology/CISN.htm . A panel discussion ensued. This discussion raised important topical issues. To disseminate this information, a transcript is provided below.

  7. Interacting factors and cellular localization of SR protein-specific kinase Dsk1

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Zhaohua, E-mail: ztang@jsd.claremont.edu [W.M. Keck Science Center, The Claremont Colleges, Claremont, CA 91711 (United States); Luca, Maria; Taggart-Murphy, Laura; Portillio, Jessica; Chang, Cathey; Guven, Ayse [W.M. Keck Science Center, The Claremont Colleges, Claremont, CA 91711 (United States); Lin, Ren-Jang [Department of Molecular and Cellular Biology, Beckman Research Institute of the City of Hope, Duarte, CA 91010 (United States); Murray, Johanne; Carr, Antony [Genome Damage and Stability Center, University of Sussex, Falmer, BN1 9RQ (United Kingdom)

    2012-10-01

    Schizosaccharomyces pombe Dsk1 is an SR protein-specific kinase (SRPK), whose homologs have been identified in every eukaryotic organism examined. Although discovered as a mitotic regulator with protein kinase activity toward SR splicing factors, it remains largely unknown about what and how Dsk1 contributes to cell cycle and pre-mRNA splicing. In this study, we investigated the Dsk1 function by determining interacting factors and cellular localization of the kinase. Consistent with its reported functions, we found that pre-mRNA processing and cell cycle factors are prominent among the proteins co-purified with Dsk1. The identification of these factors led us to find Rsd1 as a novel Dsk1 substrate, as well as the involvement of Dsk1 in cellular distribution of poly(A){sup +} RNA. In agreement with its role in nuclear events, we also found that Dsk1 is mainly localized in the nucleus during G{sub 2} phase and at mitosis. Furthermore, we revealed the oscillation of Dsk1 protein in a cell cycle-dependent manner. This paper marks the first comprehensive analysis of in vivo Dsk1-associated proteins in fission yeast. Our results reflect the conserved role of SRPK family in eukaryotic organisms, and provide information about how Dsk1 functions in pre-mRNA processing and cell-division cycle.

  8. Interactions of the p53 protein family in cellular stress response in gastrointestinal tumors.

    Science.gov (United States)

    Vilgelm, Anna E; Washington, Mary K; Wei, Jinxiong; Chen, Heidi; Prassolov, Vladimir S; Zaika, Alexander I

    2010-03-01

    p53, p63, and p73 are members of the p53 protein family involved in regulation of cell cycle, apoptosis, differentiation, and other critical cellular processes. Here, we investigated the contribution of the entire p53 family in chemotherapeutic drug response in gastrointestinal tumors. Real-time PCR and immunohistochemistry revealed complexity and variability of expression profiles of the p53 protein family. Using colon and esophageal cancer cells, we found that the integral transcription activity of the entire p53 family, as measured by the reporter analysis, associated with response to drug treatment in studied cells. We also found that p53 and p73, as well as p63 and p73, bind simultaneously to the promoters of p53 target genes. Taken together, our results support the view that the p53 protein family functions as an interacting network of proteins and show that cellular responses to chemotherapeutic drug treatment are determined by the total activity of the entire p53 family rather than p53 alone.

  9. An antiviral disulfide compound blocks interaction between arenavirus Z protein and cellular promyelocytic leukemia protein

    Energy Technology Data Exchange (ETDEWEB)

    Garcia, C.C. [Laboratory of Virology, Department of Biological Chemistry, School of Sciences, University of Buenos Aires, 1428 Buenos Aires (Argentina); Topisirovic, I. [Institute de Recherche en Immunologie et en Cancerologie, Universite de Montreal, Montreal, QC, Canada H3T 1J4 (Canada); Djavani, M. [Institute of Human Virology, School of Medicine, University of Maryland, Baltimore, MD 21201 (United States); Borden, K.L.B. [Institute de Recherche en Immunologie et en Cancerologie, Universite de Montreal, Montreal, QC, Canada H3T 1J4 (Canada); Damonte, E.B. [Laboratory of Virology, Department of Biological Chemistry, School of Sciences, University of Buenos Aires, 1428 Buenos Aires (Argentina); Salvato, M.S., E-mail: msalvato@ihv.umaryland.edu [Institute of Human Virology, School of Medicine, University of Maryland, Baltimore, MD 21201 (United States)

    2010-03-19

    The promyelocytic leukemia protein (PML) forms nuclear bodies (NB) that can be redistributed by virus infection. In particular, lymphocytic choriomeningitis virus (LCMV) influences disruption of PML NB through the interaction of PML with the arenaviral Z protein. In a previous report, we have shown that the disulfide compound NSC20625 has antiviral and virucidal properties against arenaviruses, inducing unfolding and oligomerization of Z without affecting cellular RING-containing proteins such as the PML. Here, we further studied the effect of the zinc-finger-reactive disulfide NSC20625 on PML-Z interaction. In HepG2 cells infected with LCMV or transiently transfected with Z protein constructs, treatment with NSC20625 restored PML distribution from a diffuse-cytoplasmic pattern to punctate, discrete NB which appeared identical to NB found in control, uninfected cells. Similar results were obtained in cells transfected with a construct expressing a Z mutant in zinc-binding site 2 of the RING domain, confirming that this Z-PML interaction requires the integrity of only one zinc-binding site. Altogether, these results show that the compound NSC20625 suppressed Z-mediated PML NB disruption and may be used as a tool for designing novel antiviral strategies against arenavirus infection.

  10. Dwell time of a Brownian interacting molecule in a cellular microdomain

    CERN Document Server

    Taflia, A; Taflia, Adi; Holcman, David

    2006-01-01

    The time spent by an interacting Brownian molecule inside a bounded microdomain has many applications in cellular biology, because the number of bounds is a quantitative signal, which can initiate a cascade of chemical reactions and thus has physiological consequences. In the present article, we propose to estimate the mean time spent by a Brownian molecule inside a microdomain $\\Omega$ which contains small holes on the boundary and agonist molecules located inside. We found that the mean time depends on several parameters such as the backward binding rate (with the agonist molecules), the mean escape time from the microdomain and the mean time a molecule reaches the binding sites (forward binding rate). In addition, we estimate the mean and the variance of the number of bounds made by a molecule before it exits $\\Omega$. These estimates rely on a boundary layer analysis of a conditional mean first passage time, solution of a singular partial differential equation. In particular, we apply the present results ...

  11. Cellular and molecular pathways of extremely-low-frequency electromagnetic field interactions with living systems

    Energy Technology Data Exchange (ETDEWEB)

    Tenforde, T.S.

    1992-06-01

    There is growing evidence that environmental electric and magnetic fields in the extremely-low-frequency (ELF) band below 300 Hz can influence biological functions by mechanisms that are only poorly understood at the present time. The primary objectives of this paper are to review the physical properties of ELF fields, their interactions with living systems at the tissue, cellular, and subcellular levels, and the key role of cell membranes ;in the transduction of signals from imposed ELF fields. Topics of discussion include signal-to-noise ratios for single cells and cell aggregates, resonance phenomena involving a combination of static and ELF magnetic fields, and the possible influence of ELF fields on molecular signaling pathways that involve membrane receptors and cytoplasmic second messengers.

  12. Evolution of altruism in spatial prisoner's dilemma: Intra- and inter-cellular interactions

    Science.gov (United States)

    Yokoi, Hiroki; Uehara, Takashi; Sakata, Tomoyuki; Naito, Hiromi; Morita, Satoru; Tainaka, Kei-ichi

    2014-12-01

    Iterated prisoner's dilemma game is carried out on lattice with “colony” structure. Each cell is regarded as a colony which contains plural players with an identical strategy. Both intra- and inter-cellular interactions are assumed. In the former a player plays with all other players in the same colony, while in the latter he plays with one player each from adjacent colonies. Spatial patterns among four typical strategies exhibit various dynamics and winners. Both theory and simulation reveal that All Cooperation (AC) wins, when the members of colony or the intensity of noise increases. This result explains the evolution of altruism in animal societies, even though errors easily occur in animal communications.

  13. DNA-controlled dynamic colloidal nanoparticle systems for mediating cellular interaction

    Science.gov (United States)

    Ohta, Seiichi; Glancy, Dylan; Chan, Warren C. W.

    2016-02-01

    Precise control of biosystems requires development of materials that can dynamically change physicochemical properties. Inspired by the ability of proteins to alter their conformation to mediate function, we explored the use of DNA as molecular keys to assemble and transform colloidal nanoparticle systems. The systems consist of a core nanoparticle surrounded by small satellites, the conformation of which can be transformed in response to DNA via a toe-hold displacement mechanism. The conformational changes can alter the optical properties and biological interactions of the assembled nanosystem. Photoluminescent signal is altered by changes in fluorophore-modified particle distance, whereas cellular targeting efficiency is increased 2.5 times by changing the surface display of targeting ligands. These concepts provide strategies for engineering dynamic nanotechnology systems for navigating complex biological environments.

  14. Biomaterial design for specific cellular interactions: Role of surface functionalization and geometric features

    Science.gov (United States)

    Kolhar, Poornima

    The areas of drug delivery and tissue engineering have experienced extraordinary growth in recent years with the application of engineering principles and their potential to support and improve the field of medicine. The tremendous progress in nanotechnology and biotechnology has lead to this explosion of research and development in biomedical applications. Biomaterials can now be engineered at a nanoscale and their specific interactions with the biological tissues can be modulated. Various design parameters are being established and researched for design of drug-delivery carriers and scaffolds to be implanted into humans. Nanoparticles made from versatile biomaterial can deliver both small-molecule drugs and various classes of bio-macromolecules, such as proteins and oligonucleotides. Similarly in the field of tissue engineering, current approaches emphasize nanoscale control of cell behavior by mimicking the natural extracellular matrix (ECM) unlike, traditional scaffolds. Drug delivery and tissue engineering are closely connected fields and both of these applications require materials with exceptional physical, chemical, biological, and biomechanical properties to provide superior therapy. In the current study the surface functionalization and the geometric features of the biomaterials has been explored. In particular, a synthetic surface for culture of human embryonic stem cells has been developed, demonstrating the importance of surface functionalization in maintaining the pluripotency of hESCs. In the second study, the geometric features of the drug delivery carriers are investigated and the polymeric nanoneedles mediated cellular permeabilization and direct cytoplasmic delivery is reported. In the third study, the combined effect of surface functionalization and geometric modification of carriers for vascular targeting is enunciated. These studies illustrate how the biomaterials can be designed to achieve various cellular behaviors and control the

  15. On the hydrogen-graphene layers interactions, relevance to the onboard storage problem.

    Science.gov (United States)

    Nechaev, Y S; Ochsner, A

    2012-10-01

    Empirical evaluations of fundamental characteristics of the physical and chemical interaction of hydrogen with graphene layers in different kinds of graphite and novel carbonaceous nanomaterials of graphene layer structure have been carried out. This was done by using the approaches of the thermodynamics of reversible and irreversible processes for analysis of the adsorption, absorption, diffusion, the temperature-programmed desorption (TPD) and other experimental data and comparing such analytical results with first-principles calculations. Such an analysis of a number of the known experimental and theoretical data has shown a real possibility of the multilayer specific adsorption (intercalation) of hydrogen between graphene layers in novel carbonaceous nanomaterials. This is of relevance for solving the bottle-neck problem of the hydrogen on-board storage in fuel-cell-powered vehicles, and other technical applications.

  16. The Importance of Physiologically Relevant Cell Lines for Studying Virus–Host Interactions

    Directory of Open Access Journals (Sweden)

    David Hare

    2016-11-01

    Full Text Available Viruses interact intimately with the host cell at nearly every stage of replication, and the cell model that is chosen to study virus infection is critically important. Although primary cells reflect the phenotype of healthy cells in vivo better than cell lines, their limited lifespan makes experimental manipulation challenging. However, many tumor-derived and artificially immortalized cell lines have defects in induction of interferon-stimulated genes and other antiviral defenses. These defects can affect virus replication, especially when cells are infected at lower, more physiologically relevant, multiplicities of infection. Understanding the selective pressures and mechanisms underlying the loss of innate signaling pathways is helpful to choose immortalized cell lines without impaired antiviral defense. We describe the trials and tribulations we encountered while searching for an immortalized cell line with intact innate signaling, and how directed immortalization of primary cells avoids many of the pitfalls of spontaneous immortalization.

  17. Metal oxide nanoparticles interact with immune cells and activate different cellular responses

    Directory of Open Access Journals (Sweden)

    Simón-Vázquez R

    2016-09-01

    Full Text Available Rosana Simón-Vázquez, Tamara Lozano-Fernández, Angela Dávila-Grana, Africa González-Fernández Immunology Laboratory, Biomedical Research Center (CINBIO and Institute of Biomedical Research of Ourense-Pontevedra-Vigo (IBI, University of Vigo, Campus Lagoas Marcosende, Vigo, Pontevedra, Spain Abstract: Besides cell death, nanoparticles (Nps can induce other cellular responses such as inflammation. The potential immune response mediated by the exposure of human lymphoid cells to metal oxide Nps (moNps was characterized using four different moNps (CeO2, TiO2, Al2O3, and ZnO to study the three most relevant mitogen-activated protein kinase subfamilies and the nuclear factor kappa-light-chain-enhancer of the activated B-cell inhibitor, IκBα, as well as the expression of several genes by immune cells incubated with these Nps. The moNps activated different signaling pathways and altered the gene expression in human lymphocyte cells. The ZnO Nps were the most active and the release of Zn2+ ions was the main mechanism of toxicity. CeO2 Nps induced the smallest changes in gene expression and in the IκBα protein. The effects of the particles were strongly dependent on the type and concentration of the Nps and on the cell activation status prior to Np exposure. Keywords: Jurkat, MAPK, NFκB, qPCR, inflammation, metabolism

  18. Cellular Interactions and Biocompatibility of Self-Assembling Diblock Polypeptide Hydrogels

    Science.gov (United States)

    Pakstis, Lisa; Ozbas, Bulent; Pochan, Darrin; Robinson, Clifford; Nowak, Andrew; Deming, Timothy

    2002-03-01

    Self-assembling peptide based hydrogels having a unique nano- and microscopic morphology are being studied for potential use as tissue engineering scaffolds. Low molecular weight ( ~20 kg/mol), amphiphilic, diblock polypeptides of hydrophilic lysine (K) or glutamic acid (E) and hydrophobic leucine (L) or valine (V) form hydrogels in aqueous solution at neutral pH and at very low volume fraction of polymer (vol. fraction polypeptide >=0.5 wt%). The morphology of these hydrogels has been characterized using laser confocal microscopy (LCM), small angle neutron scattering (SANS), and cryogenic transmission electron microscopy (cryoTEM) imaging. Studies of the interactions of the hydrogels with bacterial and mammalian cells reveal that these materials are non-cytotoxic and biocompatible. Hence, the chemistry of the assembled diblock polypeptides allows for cellular proliferation whereas the same chemistry in the homopolyeric form is cytotoxic. Current research is directed at the design and incorporation of binding sites within the polypeptide to specifically target interactions of the hydrogel with desired cells types.

  19. Cellular DDX3 regulates Japanese encephalitis virus replication by interacting with viral un-translated regions.

    Science.gov (United States)

    Li, Chen; Ge, Ling-ling; Li, Peng-peng; Wang, Yue; Dai, Juan-juan; Sun, Ming-xia; Huang, Li; Shen, Zhi-qiang; Hu, Xiao-chun; Ishag, Hassan; Mao, Xiang

    2014-01-20

    Japanese encephalitis virus is one of the most common causes for epidemic viral encephalitis in humans and animals. Herein we demonstrated that cellular helicase DDX3 is involved in JEV replication. DDX3 knockdown inhibits JEV replication. The helicase activity of DDX3 is crucial for JEV replication. GST-pulldown and co-immunoprecipitation experiments demonstrated that DDX3 could interact with JEV non-structural proteins 3 and 5. Co-immunoprecipitation and confocal microscopy analysis confirmed that DDX3 interacts and colocalizes with these viral proteins and viral RNA during the infection. We determined that DDX3 binds to JEV 5' and 3' un-translated regions. We used a JEV-replicon system to demonstrate that DDX3 positively regulates viral RNA translation, which might affect viral RNA replication at the late stage of virus infection. Collectively, we identified that DDX3 is necessary for JEV infection, suggesting that DDX3 might be a novel target to design new antiviral agents against JEV or other flavivirus infections.

  20. Improving protein-protein interactions prediction accuracy using protein evolutionary information and relevance vector machine model.

    Science.gov (United States)

    An, Ji-Yong; Meng, Fan-Rong; You, Zhu-Hong; Chen, Xing; Yan, Gui-Ying; Hu, Ji-Pu

    2016-10-01

    Predicting protein-protein interactions (PPIs) is a challenging task and essential to construct the protein interaction networks, which is important for facilitating our understanding of the mechanisms of biological systems. Although a number of high-throughput technologies have been proposed to predict PPIs, there are unavoidable shortcomings, including high cost, time intensity, and inherently high false positive rates. For these reasons, many computational methods have been proposed for predicting PPIs. However, the problem is still far from being solved. In this article, we propose a novel computational method called RVM-BiGP that combines the relevance vector machine (RVM) model and Bi-gram Probabilities (BiGP) for PPIs detection from protein sequences. The major improvement includes (1) Protein sequences are represented using the Bi-gram probabilities (BiGP) feature representation on a Position Specific Scoring Matrix (PSSM), in which the protein evolutionary information is contained; (2) For reducing the influence of noise, the Principal Component Analysis (PCA) method is used to reduce the dimension of BiGP vector; (3) The powerful and robust Relevance Vector Machine (RVM) algorithm is used for classification. Five-fold cross-validation experiments executed on yeast and Helicobacter pylori datasets, which achieved very high accuracies of 94.57 and 90.57%, respectively. Experimental results are significantly better than previous methods. To further evaluate the proposed method, we compare it with the state-of-the-art support vector machine (SVM) classifier on the yeast dataset. The experimental results demonstrate that our RVM-BiGP method is significantly better than the SVM-based method. In addition, we achieved 97.15% accuracy on imbalance yeast dataset, which is higher than that of balance yeast dataset. The promising experimental results show the efficiency and robust of the proposed method, which can be an automatic decision support tool for future

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

    Directory of Open Access Journals (Sweden)

    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

  2. RVMAB: Using the Relevance Vector Machine Model Combined with Average Blocks to Predict the Interactions of Proteins from Protein Sequences.

    Science.gov (United States)

    An, Ji-Yong; You, Zhu-Hong; Meng, Fan-Rong; Xu, Shu-Juan; Wang, Yin

    2016-01-01

    Protein-Protein Interactions (PPIs) play essential roles in most cellular processes. Knowledge of PPIs is becoming increasingly more important, which has prompted the development of technologies that are capable of discovering large-scale PPIs. Although many high-throughput biological technologies have been proposed to detect PPIs, there are unavoidable shortcomings, including cost, time intensity, and inherently high false positive and false negative rates. For the sake of these reasons, in silico methods are attracting much attention due to their good performances in predicting PPIs. In this paper, we propose a novel computational method known as RVM-AB that combines the Relevance Vector Machine (RVM) model and Average Blocks (AB) to predict PPIs from protein sequences. The main improvements are the results of representing protein sequences using the AB feature representation on a Position Specific Scoring Matrix (PSSM), reducing the influence of noise using a Principal Component Analysis (PCA), and using a Relevance Vector Machine (RVM) based classifier. We performed five-fold cross-validation experiments on yeast and Helicobacter pylori datasets, and achieved very high accuracies of 92.98% and 95.58% respectively, which is significantly better than previous works. In addition, we also obtained good prediction accuracies of 88.31%, 89.46%, 91.08%, 91.55%, and 94.81% on other five independent datasets C. elegans, M. musculus, H. sapiens, H. pylori, and E. coli for cross-species prediction. To further evaluate the proposed method, we compare it with the state-of-the-art support vector machine (SVM) classifier on the yeast dataset. The experimental results demonstrate that our RVM-AB method is obviously better than the SVM-based method. The promising experimental results show the efficiency and simplicity of the proposed method, which can be an automatic decision support tool. To facilitate extensive studies for future proteomics research, we developed a freely

  3. Identification of small peptides inhibiting the integrase-LEDGF/p75 interaction through targeting the cellular co-factor.

    Science.gov (United States)

    Cavalluzzo, Claudia; Christ, Frauke; Voet, Arnout; Sharma, Ajendra; Singh, Brajendra Kumar; Zhang, Kam Y J; Lescrinier, Eveline; De Maeyer, Marc; Debyser, Zeger; Van der Eycken, Erik

    2013-10-01

    The integration of the viral DNA into the host genome is one of the essential steps in the HIV replication cycle. This process is mediated by the viral enzyme integrase (IN) and lens epithelium-derived growth factor (LEDGF/p75). LEDGF/p75 has been identified as a crucial cellular co-factor of integration that acts by tethering IN to the cellular chromatin. Recently, circular peptides were identified that bind to the C-terminal domain of IN and disrupt the interaction with LEDGF/p75. Starting from the circular peptides, we identified a short peptidic sequence able to inhibit the LEDGF/p75-IN interaction at low μM concentration through its binding to the IN binding site of LEDGF/p75. This discovery can lead to the synthesis of peptidomimetics with high anti-HIV activity targeting the cellular co-factor LEDGF/p75 and not the viral protein IN.

  4. Characterization of cellular uptake and toxicity of aminosilane-coated iron oxide nanoparticles with different charges in central nervous system-relevant cell culture models

    Directory of Open Access Journals (Sweden)

    Sun Z

    2013-03-01

    Full Text Available Zhizhi Sun,1 Vinith Yathindranath,2 Matthew Worden,3 James A Thliveris,4 Stephanie Chu,1 Fiona E Parkinson,1 Torsten Hegmann,1–3 Donald W Miller1 1Department of Pharmacology and Therapeutics, 2Department of Chemistry, University of Manitoba, Winnipeg, Manitoba, Canada; 3Chemical Physics Interdisciplinary Program, Liquid Crystal Institute, Kent State University, Kent, OH, USA; 4Department of Human Anatomy and Cell Science, University of Manitoba, Winnipeg, Manitoba, Canada  Background: Aminosilane-coated iron oxide nanoparticles (AmS-IONPs have been widely used in constructing complex and multifunctional drug delivery systems. However, the biocompatibility and uptake characteristics of AmS-IONPs in central nervous system (CNS-relevant cells are unknown. The purpose of this study was to determine the effect of surface charge and magnetic field on toxicity and uptake of AmS-IONPs in CNS-relevant cell types. Methods: The toxicity and uptake profile of positively charged AmS-IONPs and negatively charged COOH-AmS-IONPs of similar size were examined using a mouse brain microvessel endothelial cell line (bEnd.3 and primary cultured mouse astrocytes and neurons. Cell accumulation of IONPs was examined using the ferrozine assay, and cytotoxicity was assessed by the 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay. Results: No toxicity was observed in bEnd.3 cells at concentrations up to 200 µg/mL for either AmS-IONPs or COOH-AmS-IONPs. AmS-IONPs at concentrations above 200 µg/mL reduced neuron viability by 50% in the presence or absence of a magnetic field, while only 20% reductions in viability were observed with COOH-AmS-IONPs. Similar concentrations of AmS-IONPs in astrocyte cultures reduced viability to 75% but only in the presence of a magnetic field, while exposure to COOH-AmS-IONPs reduced viability to 65% and 35% in the absence and presence of a magnetic field, respectively. Cellular accumulation of AmS-IONPs was greater

  5. Biomechanics and thermodynamics of nanoparticle interactions with plasma and endosomal membrane lipids in cellular uptake and endosomal escape.

    Science.gov (United States)

    Peetla, Chiranjeevi; Jin, Shihua; Weimer, Jonathan; Elegbede, Adekunle; Labhasetwar, Vinod

    2014-07-01

    To be effective for cytoplasmic delivery of therapeutics, nanoparticles (NPs) taken up via endocytic pathways must efficiently transport across the cell membrane and subsequently escape from the secondary endosomes. We hypothesized that the biomechanical and thermodynamic interactions of NPs with plasma and endosomal membrane lipids are involved in these processes. Using model plasma and endosomal lipid membranes, we compared the interactions of cationic NPs composed of poly(D,L-lactide-co-glycolide) modified with the dichain surfactant didodecyldimethylammonium bromide (DMAB) or the single-chain surfactant cetyltrimethylammonium bromide (CTAB) vs anionic unmodified NPs of similar size. We validated our hypothesis in doxorubicin-sensitive (MCF-7, with relatively fluid membranes) and resistant breast cancer cells (MCF-7/ADR, with rigid membranes). Despite their cationic surface charges, DMAB- and CTAB-modified NPs showed different patterns of biophysical interaction: DMAB-modified NPs induced bending of the model plasma membrane, whereas CTAB-modified NPs condensed the membrane, thereby resisted bending. Unmodified NPs showed no effects on bending. DMAB-modified NPs also induced thermodynamic instability of the model endosomal membrane, whereas CTAB-modified and unmodified NPs had no effect. Since bending of the plasma membrane and destabilization of the endosomal membrane are critical biophysical processes in NP cellular uptake and endosomal escape, respectively, we tested these NPs for cellular uptake and drug efficacy. Confocal imaging showed that in both sensitive and resistant cells DMAB-modified NPs exhibited greater cellular uptake and escape from endosomes than CTAB-modified or unmodified NPs. Further, paclitaxel-loaded DMAB-modified NPs induced greater cytotoxicity even in resistant cells than CTAB-modified or unmodified NPs or drug in solution, demonstrating the potential of DMAB-modified NPs to overcome the transport barrier in resistant cells. In

  6. Kinetic approach and estimation of the parameters of cellular interaction between the immunity system and a tumor.

    Science.gov (United States)

    Kuznetsov, V A; Zhivoglyadov, V P; Stepanova, L A

    1993-01-01

    A method is suggested to estimate multi component dynamic systems, which permits, with the help of the computer-calculated kinetic curves, to obtain information about the possible mechanisms of the system component interaction. The method is based on the structural and parametrical identification of mathematical models presented in the form of a system of nonlinear differential equations, using a multi-criterial approach. Using experimental data of studies on growth kinetics and regression of multicellular tumor EMT6 line spheroids in the mouse allogenic system and the immune system cell accumulation in spheroids a mathematical model has been developed of the cellular interaction process in a spheroid. It has been stated that the rate of macrophage and neutrophil accumulation in a spheroid depends on the amount of tumor cells and is determined by the hyperbolic law (as analogous to the Michaelis-Menthen kinetics), while the accumulation of immune lymphocytes in a tumor is determined besides that by the three-cellular cooperation of lymphocytes, macrophages and tumor cells. According to the model, the inhibition of the process of neutrophil and lymphocyte (but not of macrophages) accumulation is realized through the auto-suppression mechanism. The numerical values of the process parameters, which characterise the rates of accumulation, cellular death in a tumor and of local cellular interactions intensity are obtained.

  7. Enteropathogenic Escherichia coli, Samonella, Shigella and Yersinia: cellular aspects of host-bacteria interactions in enteric diseases

    Directory of Open Access Journals (Sweden)

    Reis Roberta

    2010-07-01

    Full Text Available Abstract A successful infection of the human intestine by enteropathogenic bacteria depends on the ability of bacteria to attach and colonize the intestinal epithelium and, in some cases, to invade the host cell, survive intracellularly and disseminate from cell to cell. To accomplish these processes bacteria have evolved an arsenal of molecules that are mostly secreted by dedicated type III secretion systems, and that interact with the host, subverting normal cellular functions. Here we overview the most important molecular strategies developed by enteropathogenic Escherichia coli, Salmonella enterica, Shigella flexneri, and Yersinia enterocolitica to cause enteric infections. Despite having evolved different effectors, these four microorganisms share common host cellular targets.

  8. Hyperthermic radiosensitization : mode of action and clinical relevance

    NARCIS (Netherlands)

    Kampinga, HH; Dikomey, E

    2001-01-01

    Purpose: To provide an update on the recent knowledge about the molecular mechanisms of thermal radiosensitization and its possible relevance to thermoradiotherapy. Summary: Hyperthermia is probably the most potent cellular radiosensitizer known to date. Heat interacts with radiation and potentiates

  9. Protein-protein interaction networks identify targets which rescue the MPP+ cellular model of Parkinson’s disease

    Science.gov (United States)

    Keane, Harriet; Ryan, Brent J.; Jackson, Brendan; Whitmore, Alan; Wade-Martins, Richard

    2015-11-01

    Neurodegenerative diseases are complex multifactorial disorders characterised by the interplay of many dysregulated physiological processes. As an exemplar, Parkinson’s disease (PD) involves multiple perturbed cellular functions, including mitochondrial dysfunction and autophagic dysregulation in preferentially-sensitive dopamine neurons, a selective pathophysiology recapitulated in vitro using the neurotoxin MPP+. Here we explore a network science approach for the selection of therapeutic protein targets in the cellular MPP+ model. We hypothesised that analysis of protein-protein interaction networks modelling MPP+ toxicity could identify proteins critical for mediating MPP+ toxicity. Analysis of protein-protein interaction networks constructed to model the interplay of mitochondrial dysfunction and autophagic dysregulation (key aspects of MPP+ toxicity) enabled us to identify four proteins predicted to be key for MPP+ toxicity (P62, GABARAP, GBRL1 and GBRL2). Combined, but not individual, knockdown of these proteins increased cellular susceptibility to MPP+ toxicity. Conversely, combined, but not individual, over-expression of the network targets provided rescue of MPP+ toxicity associated with the formation of autophagosome-like structures. We also found that modulation of two distinct proteins in the protein-protein interaction network was necessary and sufficient to mitigate neurotoxicity. Together, these findings validate our network science approach to multi-target identification in complex neurological diseases.

  10. The Environment for Professional Interaction and Relevant Practical Experience in AACSB-Accredited Accounting Programs.

    Science.gov (United States)

    Arlinghaus, Barry P.

    2002-01-01

    Responses from 276 of 1,128 faculty at Association to Advance Collegiate Schools of Business-accredited schools indicated that 231 were certified; only 96 served in professional associations; large numbers received financial support for professional activities, but only small numbers felt involvement or relevant experience (which are required for…

  11. Citations and references as keys to relevance ranking in interactive IR

    DEFF Research Database (Denmark)

    Ingwersen, Peter

    2012-01-01

    references (and thus citations) associated with relevance? 2) What are their potentials for IR? 3) What are their limitations? The presentation will propose a range of potentials and provide an initial research design. Selected cases are exemplified from the Web of Science database....

  12. Undergraduate Use of CD-ROM Databases: Observations of Human-Computer Interaction and Relevance Judgments.

    Science.gov (United States)

    Shaw, Debora

    1996-01-01

    Describes a study that observed undergraduates as they searched bibliographic databases on a CD-ROM local area network. Topics include related research, information needs, evolution of search topics, database selection, search strategies, relevance judgments, CD-ROM interfaces, and library instruction. (Author/LRW)

  13. The interaction of platinum-based drugs with native biologically relevant proteins

    NARCIS (Netherlands)

    Brauckmann, Christine; Wehe, Christoph A.; Kieshauer, Michael; Lanvers-Kaminsky, Claudia; Sperling, Michael; Karst, Uwe

    2013-01-01

    This study focuses on the identification of the products that are formed upon binding of therapeutically relevant platinum complexes to proteins like beta-lactoglobulin A (LGA), human serum albumin (HSA), or human hemoglobin (HB). The respective proteins were incubated with the platinum-based antica

  14. The interaction between Histoplasma capsulatum cell wall carbohydrates and host components: relevance in the immunomodulatory role of histoplasmosis

    Directory of Open Access Journals (Sweden)

    Patricia Gorocica

    2009-05-01

    Full Text Available Histoplasma capsulatum is an intracellular fungal pathogen that causes respiratory and systemic disease by proliferating within phagocytic cells. The binding of H. capsulatum to phagocytes may be mediated by the pathogen's cell wall carbohydrates, glucans, which consist of glucose homo and hetero-polymers and whose glycosydic linkage types differ between the yeast and mycelial phases. The ±-1,3-glucan is considered relevant for H. capsulatum virulence, whereas the ²-1,3-glucan is antigenic and participates in the modulation of the host immune response. H. capsulatum cell wall components with lectin-like activity seem to interact with the host cell surface, while host membrane lectin-like receptors can recognize a particular fungal carbohydrate ligand. This review emphasizes the relevance of the main H. capsulatum and host carbohydrate-driven interactions that allow for binding and internalization of the fungal cell into phagocytes and its subsequent avoidance of intracellular elimination.

  15. Syndecan-1 Acts as an Important Regulator of CXCL1 Expression and Cellular Interaction of Human Endometrial Stromal and Trophoblast Cells

    Directory of Open Access Journals (Sweden)

    Dunja Maria Baston-Buest

    2017-01-01

    Full Text Available Successful implantation of the embryo into the human receptive endometrium is substantial for the establishment of a healthy pregnancy. This study focusses on the role of Syndecan-1 at the embryo-maternal interface, the multitasking coreceptor influencing ligand concentration, release and receptor presentation, and cellular morphology. CXC motif ligand 1, being involved in chemotaxis and angiogenesis during implantation, is of special interest as a ligand of Syndecan-1. Human endometrial stromal cells with and without Syndecan-1 knock-down were decidualized and treated with specific inhibitors to evaluate signaling pathways regulating CXC ligand 1 expression. Western blot analyses of MAPK and Wnt members were performed, followed by analysis of spheroid interactions between human endometrial cells and extravillous trophoblast cells. By mimicking embryo contact using IL-1β, we showed less ERK and c-Jun activation by depletion of Syndecan-1 and less Frizzled 4 production as part of the canonical Wnt pathway. Additionally, more beta-catenin was phosphorylated and therefore degraded after depletion of Syndecan-1. Secretion of CXC motif ligand 1 depends on MEK-1 with respect to Syndecan-1. Regarding the interaction of endometrial and trophoblast cells, the spheroid center-to-center distances were smaller after depletion of Syndecan-1. Therefore, Syndecan-1 seems to affect signaling processes relevant to signaling and intercellular interaction at the trophoblast-decidual interface.

  16. The Interaction of the Gammaherpesvirus 68 orf73 Protein with Cellular BET Proteins Affects the Activation of Cell Cycle Promoters▿

    Science.gov (United States)

    Ottinger, Matthias; Pliquet, Daniel; Christalla, Thomas; Frank, Ronald; Stewart, James P.; Schulz, Thomas F.

    2009-01-01

    Infection of mice with murine gammaherpesvirus 68 (MHV-68) provides a valuable animal model for gamma-2 herpesvirus (rhadinovirus) infection and pathogenesis. The MHV-68 orf73 protein has been shown to be required for the establishment of viral latency in vivo. This study describes a novel transcriptional activation function of the MHV-68 orf73 protein and identifies the cellular bromodomain containing BET proteins Brd2/RING3, Brd3/ORFX, and BRD4 as interaction partners for the MHV-68 orf73 protein. BET protein members are known to interact with acetylated histones, and Brd2 and Brd4 have been implicated in fundamental cellular processes, including cell cycle regulation and transcriptional regulation. Using MHV-68 orf73 peptide array assays, we identified Brd2 and Brd4 interaction sites in the orf73 protein. Mutation of one binding site led to a loss of the interaction with Brd2/4 but not the retinoblastoma protein Rb, to impaired chromatin association, and to a decreased ability to activate the BET-responsive cyclin D1, D2, and E promoters. The results therefore pinpoint the binding site for Brd2/4 in a rhadinoviral orf73 protein and suggest that the recruitment of a member of the BET protein family allows the MHV-68 orf73 protein to activate the promoters of G1/S cyclins. These findings point to parallels between the transcriptional activator functions of rhadinoviral orf73 proteins and papillomavirus E2 proteins. PMID:19244327

  17. Investigating the Effects of Stress Interaction Using a Cellular-automaton Based Model in Fault Networks of Varying Complexity.

    Science.gov (United States)

    Hetherington, A. P.; Steacy, S.; McCloskey, J.

    2007-12-01

    Seismicity spatial and temporal patterns are strongly influenced by stress interaction between faults. However the effects of such interaction on earthquake statistics is not yet well understood. Computer models provide accurate, large and complete datasets to investigate this issue and also have the benefit of allowing direct comparison of seismicity behavior in time and space in networks, with and without fault interaction. We investigate the effect of such interaction on modeled real-world fault networks of varying complexity using a cellular-automata based model. Each 3-D fault within the fault network is modeled by a discrete cellular automaton. The cell size is 1 km square which allows for a minimum earthquake size of approximately Mw=4. The cell strength is distributed fractally across each fault and all cells are loaded by a remote tectonic stressing rate. When the stress on a cell exceeds its strength, the cell fails and stress is transferred to its nearest neighbors which may in turn cause them to break allowing the earthquake to grow. These stress transfer rules allow realistic stress concentrations to develop at the boundary of the rupture. If the extent of the rupture exceeds a user defined minimum length, and if interaction between faults is allowed, a boundary element method is used to calculate stress transfer to neighboring faults. Here we present results from four simulated fault networks based on active faults in the San Francisco Bay Area, California, the Northern Anatolian Fault, Turkey, Southern California, and the Marlborough Fault System, South Island, New Zealand. These are chosen for their varying level of fault complexity and we examine both interacting and non-interacting models in terms of their b-value and recurrence intervals for each region. Results will be compared and discussed.

  18. DGIdb 2.0: mining clinically relevant drug-gene interactions.

    Science.gov (United States)

    Wagner, Alex H; Coffman, Adam C; Ainscough, Benjamin J; Spies, Nicholas C; Skidmore, Zachary L; Campbell, Katie M; Krysiak, Kilannin; Pan, Deng; McMichael, Joshua F; Eldred, James M; Walker, Jason R; Wilson, Richard K; Mardis, Elaine R; Griffith, Malachi; Griffith, Obi L

    2016-01-01

    The Drug-Gene Interaction Database (DGIdb, www.dgidb.org) is a web resource that consolidates disparate data sources describing drug-gene interactions and gene druggability. It provides an intuitive graphical user interface and a documented application programming interface (API) for querying these data. DGIdb was assembled through an extensive manual curation effort, reflecting the combined information of twenty-seven sources. For DGIdb 2.0, substantial updates have been made to increase content and improve its usefulness as a resource for mining clinically actionable drug targets. Specifically, nine new sources of drug-gene interactions have been added, including seven resources specifically focused on interactions linked to clinical trials. These additions have more than doubled the overall count of drug-gene interactions. The total number of druggable gene claims has also increased by 30%. Importantly, a majority of the unrestricted, publicly-accessible sources used in DGIdb are now automatically updated on a weekly basis, providing the most current information for these sources. Finally, a new web view and API have been developed to allow searching for interactions by drug identifiers to complement existing gene-based search functionality. With these updates, DGIdb represents a comprehensive and user friendly tool for mining the druggable genome for precision medicine hypothesis generation.

  19. Metal oxide nanoparticles interact with immune cells and activate different cellular responses

    OpenAIRE

    Simón-Vázquez R; Lozano-Fernández T; Dávila-Grana A; González-Fernández A

    2016-01-01

    Rosana Simón-Vázquez, Tamara Lozano-Fernández, Angela Dávila-Grana, Africa González-Fernández Immunology Laboratory, Biomedical Research Center (CINBIO) and Institute of Biomedical Research of Ourense-Pontevedra-Vigo (IBI), University of Vigo, Campus Lagoas Marcosende, Vigo, Pontevedra, Spain Abstract: Besides cell death, nanoparticles (Nps) can induce other cellular responses such as inflammation. The potential immune respon...

  20. Cellular interactions of doxorubicin-loaded DNA-modified halloysite nanotubes

    Science.gov (United States)

    Lee, Yeonju; Jung, Goo-Eun; Cho, Sang Joon; Geckeler, Kurt E.; Fuchs, Harald

    2013-08-01

    Halloysite nanotube (HNT)-based supramolecular complexes are synthesized and evaluated with respect to their cytotoxicity and effects on cellular structures. As HNTs are water-insoluble, DNA is applied for wrapping the surface of HNTs to enhance their water-dispersibility. To investigate the potential of DNA-wrapped HNTs (HD) as a promising drug delivery carrier, doxorubicin (DOX) is introduced as a model anticancer agent and loaded onto HD. The DOX-loaded, DNA-wrapped HNTs (HDD) show sustained DOX release over two weeks without initial burst of DOX indicating delayed DOX release inside cells. In addition, effects of DNA-wrapped HNTs (HD) or HDD on the cytoskeleton organization of A549 cells are studied by visualizing the distribution of F-actin filaments using confocal laser scanning microscopy, and cellular morphological changes are observed by scanning electron microscopy and scanning ion conductance microscopy.Halloysite nanotube (HNT)-based supramolecular complexes are synthesized and evaluated with respect to their cytotoxicity and effects on cellular structures. As HNTs are water-insoluble, DNA is applied for wrapping the surface of HNTs to enhance their water-dispersibility. To investigate the potential of DNA-wrapped HNTs (HD) as a promising drug delivery carrier, doxorubicin (DOX) is introduced as a model anticancer agent and loaded onto HD. The DOX-loaded, DNA-wrapped HNTs (HDD) show sustained DOX release over two weeks without initial burst of DOX indicating delayed DOX release inside cells. In addition, effects of DNA-wrapped HNTs (HD) or HDD on the cytoskeleton organization of A549 cells are studied by visualizing the distribution of F-actin filaments using confocal laser scanning microscopy, and cellular morphological changes are observed by scanning electron microscopy and scanning ion conductance microscopy. Electronic supplementary information (ESI) available. See DOI: 10.1039/c3nr02665e

  1. Comparing the epidermal growth factor interaction with four different cell lines: intriguing effects imply strong dependency of cellular context.

    Directory of Open Access Journals (Sweden)

    Hanna Björkelund

    Full Text Available The interaction of the epidermal growth factor (EGF with its receptor (EGFR is known to be complex, and the common over-expression of EGF receptor family members in a multitude of tumors makes it important to decipher this interaction and the following signaling pathways. We have investigated the affinity and kinetics of (125I-EGF binding to EGFR in four human tumor cell lines, each using four culturing conditions, in real time by use of LigandTracer®.Highly repeatable and precise measurements show that the overall apparent affinity of the (125I-EGF - EGFR interaction is greatly dependent on cell line at normal culturing conditions, ranging from K(D ≈ 200 pM on SKBR3 cells to K(D≈8 nM on A431 cells. The (125I-EGF - EGFR binding curves (irrespective of cell line have strong signs of multiple simultaneous interactions. Furthermore, for the cell lines A431 and SKOV3, gefitinib treatment increases the (125I-EGF - EGFR affinity, in particular when the cells are starved. The (125I-EGF - EGFR interaction on cell line U343 is sensitive to starvation while as on SKBR3 it is insensitive to gefitinib and starvation.The intriguing pattern of the binding characteristics proves that the cellular context is important when deciphering how EGF interacts with EGFR. From a general perspective, care is advisable when generalizing ligand-receptor interaction results across multiple cell-lines.

  2. Recent advances in interactions of designed nanoparticles and cells with respect to cellular uptake, intracellular fate, degradation and cytotoxicity

    Science.gov (United States)

    Deng, Jun; Gao, Changyou

    2016-10-01

    The unique features of nanomaterials have led to their rapid development in the biomedical field. In particular, functionalized nanoparticles (NPs) are extensively used in the delivery of drugs and genes, bio-imaging and diagnosis. Hence, the interaction between NPs and cells is one of the most important issues towards understanding the true nature of the NP-mediated biological effects. Moreover, the intracellular safety concern of the NPs as a result of intracellular NP degradation remains to be clarified in detail. This review presents recent advances in the interactions of designed NPs and cells. The focus includes the governing factors on cellular uptake and the intracellular fate of NPs, and the degradation of NPs and its influence on nanotoxicity. Some basic consideration is proposed for optimizing the NP-cell interaction and designing NPs of better biocompatiblity for biomedical application.

  3. Possible Relevance of Receptor-Receptor Interactions between Viral- and Host-Coded Receptors for Viral-Induced Disease

    Directory of Open Access Journals (Sweden)

    Luigi F. Agnati

    2007-01-01

    Full Text Available It has been demonstrated that some viruses, such as the cytomegalovirus, code for G-protein coupled receptors not only to elude the immune system, but also to redirect cellular signaling in the receptor networks of the host cells. In view of the existence of receptor-receptor interactions, the hypothesis is introduced that these viral-coded receptors not only operate as constitutively active monomers, but also can affect other receptor function by interacting with receptors of the host cell. Furthermore, it is suggested that viruses could also insert not single receptors (monomers, but clusters of receptors (receptor mosaics, altering the cell metabolism in a profound way. The prevention of viral receptor-induced changes in host receptor networks may give rise to novel antiviral drugs that counteract viral-induced disease.

  4. Plant-Herbivore Interaction: Dissection of the Cellular Pattern of Tetranychus urticae Feeding on the Host Plant

    Science.gov (United States)

    Bensoussan, Nicolas; Santamaria, M. Estrella; Zhurov, Vladimir; Diaz, Isabel; Grbić, Miodrag; Grbić, Vojislava

    2016-01-01

    The two-spotted spider mite, Tetranychus urticae Koch (Acari: Tetranychidae), is one of the most polyphagous herbivores feeding on cell contents of over 1100 plant species including more than 150 crops. It is being established as a model for chelicerate herbivores with tools that enable tracking of reciprocal responses in plant-spider mite interactions. However, despite their important pest status and a growing understanding of the molecular basis of interactions with plant hosts, knowledge of the way mites interface with the plant while feeding and the plant damage directly inflicted by mites is lacking. Here, utilizing histology and microscopy methods, we uncovered several key features of T. urticae feeding. By following the stylet path within the plant tissue, we determined that the stylet penetrates the leaf either in between epidermal pavement cells or through a stomatal opening, without damaging the epidermal cellular layer. Our recordings of mite feeding established that duration of the feeding event ranges from several minutes to more than half an hour, during which time mites consume a single mesophyll cell in a pattern that is common to both bean and Arabidopsis plant hosts. In addition, this study determined that leaf chlorotic spots, a common symptom of mite herbivory, do not form as an immediate consequence of mite feeding. Our results establish a cellular context for the plant-spider mite interaction that will support our understanding of the molecular mechanisms and cell signaling associated with spider mite feeding. PMID:27512397

  5. Plant-herbivore interaction: dissection of the cellular pattern of Tetranychus urticae feeding on the host plant

    Directory of Open Access Journals (Sweden)

    Nicolas Bensoussan

    2016-07-01

    Full Text Available The two-spotted spider mite, Tetranychus urticae Koch (Acari: Tetranychidae, is one of the most polyphagous herbivores feeding on cell contents of over 1,100 plant species including more than 150 crops. It is being established as a model for chelicerate herbivores with tools that enable tracking of reciprocal responses in plant-spider mite interactions. However, despite their important pest status and a growing understanding of the molecular basis of interactions with plant hosts, knowledge of the way mites interface with the plant while feeding and the plant damage directly inflicted by mites is lacking. Here, utilizing histology and microscopy methods, we uncovered several key features of T. urticae feeding. By following the stylet path within the plant tissue, we determined that the stylet penetrates the leaf either in between epidermal pavement cells or through a stomatal opening, without damaging the epidermal cellular layer. Our recordings of mite feeding established that duration of the feeding event ranges from several minutes to more than half an hour, during which time mites consume a single mesophyll cell in a pattern that is common to both bean and Arabidopsis plant hosts. In addition, this study determined that leaf chlorotic spots, a common symptom of mite herbivory, do not form as an immediate consequence of mite feeding. Our results establish a cellular context for the plant-spider mite interaction that will support our understanding of the molecular mechanisms and cell signaling associated with spider mite feeding.

  6. Plant-Herbivore Interaction: Dissection of the Cellular Pattern of Tetranychus urticae Feeding on the Host Plant.

    Science.gov (United States)

    Bensoussan, Nicolas; Santamaria, M Estrella; Zhurov, Vladimir; Diaz, Isabel; Grbić, Miodrag; Grbić, Vojislava

    2016-01-01

    The two-spotted spider mite, Tetranychus urticae Koch (Acari: Tetranychidae), is one of the most polyphagous herbivores feeding on cell contents of over 1100 plant species including more than 150 crops. It is being established as a model for chelicerate herbivores with tools that enable tracking of reciprocal responses in plant-spider mite interactions. However, despite their important pest status and a growing understanding of the molecular basis of interactions with plant hosts, knowledge of the way mites interface with the plant while feeding and the plant damage directly inflicted by mites is lacking. Here, utilizing histology and microscopy methods, we uncovered several key features of T. urticae feeding. By following the stylet path within the plant tissue, we determined that the stylet penetrates the leaf either in between epidermal pavement cells or through a stomatal opening, without damaging the epidermal cellular layer. Our recordings of mite feeding established that duration of the feeding event ranges from several minutes to more than half an hour, during which time mites consume a single mesophyll cell in a pattern that is common to both bean and Arabidopsis plant hosts. In addition, this study determined that leaf chlorotic spots, a common symptom of mite herbivory, do not form as an immediate consequence of mite feeding. Our results establish a cellular context for the plant-spider mite interaction that will support our understanding of the molecular mechanisms and cell signaling associated with spider mite feeding.

  7. Analysis and Identification of Aptamer-Compound Interactions with a Maximum Relevance Minimum Redundancy and Nearest Neighbor Algorithm

    Directory of Open Access Journals (Sweden)

    ShaoPeng Wang

    2016-01-01

    Full Text Available The development of biochemistry and molecular biology has revealed an increasingly important role of compounds in several biological processes. Like the aptamer-protein interaction, aptamer-compound interaction attracts increasing attention. However, it is time-consuming to select proper aptamers against compounds using traditional methods, such as exponential enrichment. Thus, there is an urgent need to design effective computational methods for searching effective aptamers against compounds. This study attempted to extract important features for aptamer-compound interactions using feature selection methods, such as Maximum Relevance Minimum Redundancy, as well as incremental feature selection. Each aptamer-compound pair was represented by properties derived from the aptamer and compound, including frequencies of single nucleotides and dinucleotides for the aptamer, as well as the constitutional, electrostatic, quantum-chemical, and space conformational descriptors of the compounds. As a result, some important features were obtained. To confirm the importance of the obtained features, we further discussed the associations between them and aptamer-compound interactions. Simultaneously, an optimal prediction model based on the nearest neighbor algorithm was built to identify aptamer-compound interactions, which has the potential to be a useful tool for the identification of novel aptamer-compound interactions. The program is available upon the request.

  8. Interactions between hepatic iron and lipid metabolism with possible relevance to steatohepatitis

    Institute of Scientific and Technical Information of China (English)

    Umbreen Ahmed; Patricia S Latham; Phillip S Oates

    2012-01-01

    The liver is an important site for iron and lipid metabolism and the main site for the interactions between these two metabolic pathways.Although conflicting results have been obtained,most studies support the hypothesis that iron plays a role in hepatic lipogenesis.Iron is an integral part of some enzymes and transporters involved in lipid metabolism and,as such,may exert a direct effect on hepatic lipid load,intrahepatic metabolic pathways and hepatic lipid secretion.On the other hand,iron in its ferrous form may indirectly affect lipid metabolism through its ability to induce oxidative stress and inflammation,a hypothesis which is currently the focus of much research in the field of nonalcoholic fatty liver disease/non-alcoholic steatohepatitis (NAFLD/NASH).The present review will first discuss how iron might directly interact with the metabolism of hepatic lipids and then consider a new perspective on the way in which iron may have a role in the two hit hypothesis for the progression of NAFLD via ferroportin and the iron regulatory molecule hepcidin.The review concludes that iron has important interactions with lipid metabolism in the liver that can impact on the development of NAFLD/NASH.More defined studies are required to improve our understanding of these effects.

  9. A cellular genetics approach identifies gene-drug interactions and pinpoints drug toxicity pathway nodes

    Directory of Open Access Journals (Sweden)

    Oscar Takeo Suzuki

    2014-08-01

    Full Text Available New approaches to toxicity testing have incorporated high-throughput screening across a broad-range of in vitro assays to identify potential key events in response to chemical or drug treatment. To date, these approaches have primarily utilized repurposed drug discovery assays. In this study, we describe an approach that combines in vitro screening with genetic approaches for the experimental identification of genes and pathways involved in chemical or drug toxicity. Primary embryonic fibroblasts isolated from 32 genetically-characterized inbred mouse strains were treated in concentration-response format with 65 compounds, including pharmaceutical drugs, environmental chemicals, and compounds with known modes-of-action. Integrated cellular responses were measured at 24 and 72 hours using high-content imaging and included cell loss, membrane permeability, mitochondrial function, and apoptosis. Genetic association analysis of cross-strain differences in the cellular responses resulted in a collection of candidate loci potentially underlying the variable strain response to each chemical. As a demonstration of the approach, one candidate gene involved in rotenone sensitivity, Cybb, was experimentally validated in vitro and in vivo. Pathway analysis on the combined list of candidate loci across all chemicals identified a number of over-connected nodes that may serve as core regulatory points in toxicity pathways.

  10. Analysis and prediction of drug-drug interaction by minimum redundancy maximum relevance and incremental feature selection.

    Science.gov (United States)

    Liu, Lili; Chen, Lei; Zhang, Yu-Hang; Wei, Lai; Cheng, Shiwen; Kong, Xiangyin; Zheng, Mingyue; Huang, Tao; Cai, Yu-Dong

    2017-02-01

    Drug-drug interaction (DDI) defines a situation in which one drug affects the activity of another when both are administered together. DDI is a common cause of adverse drug reactions and sometimes also leads to improved therapeutic effects. Therefore, it is of great interest to discover novel DDIs according to their molecular properties and mechanisms in a robust and rigorous way. This paper attempts to predict effective DDIs using the following properties: (1) chemical interaction between drugs; (2) protein interactions between the targets of drugs; and (3) target enrichment of KEGG pathways. The data consisted of 7323 pairs of DDIs collected from the DrugBank and 36,615 pairs of drugs constructed by randomly combining two drugs. Each drug pair was represented by 465 features derived from the aforementioned three categories of properties. The random forest algorithm was adopted to train the prediction model. Some feature selection techniques, including minimum redundancy maximum relevance and incremental feature selection, were used to extract key features as the optimal input for the prediction model. The extracted key features may help to gain insights into the mechanisms of DDIs and provide some guidelines for the relevant clinical medication developments, and the prediction model can give new clues for identification of novel DDIs.

  11. Genome-wide Mapping of Cellular Protein-RNA Interactions Enabled by Chemical Crosslinking

    Institute of Scientific and Technical Information of China (English)

    Xiaoyu Li; Jinghui Song; Chengqi Yi

    2014-01-01

    RNA-protein interactions influence many biological processes. Identifying the binding sites of RNA-binding proteins (RBPs) remains one of the most fundamental and important chal-lenges to the studies of such interactions. Capturing RNA and RBPs via chemical crosslinking allows stringent purification procedures that significantly remove the non-specific RNA and protein interactions. Two major types of chemical crosslinking strategies have been developed to date, i.e., UV-enabled crosslinking and enzymatic mechanism-based covalent capture. In this review, we com-pare such strategies and their current applications, with an emphasis on the technologies themselves rather than the biology that has been revealed. We hope such methods could benefit broader audi-ence and also urge for the development of new methods to study RNA RBP interactions.

  12. Interaction of ANS with human serum albumin under confinement: Important insights and relevance

    Energy Technology Data Exchange (ETDEWEB)

    Malik, Ashima; Kundu, Jayanta; Karmakar, Sandip; Lai, Sima; Chowdhury, Pramit K., E-mail: pramitc@chemistry.iitd.ac.in

    2015-11-15

    Human serum albumin (HSA) has been extensively studied over the years not only as a model protein but also as an important small molecule carrier with its ability to bind a variety of ligands. This study focuses on the modulation in the conformational disposition of HSA within the confinement of water pools of AOT reverse micelles, and its interactions with 1-anilinonapthelenesulfonate (ANS), the latter serving as a drug moiety. Circular dichroism studies show that while on one hand the incorporation of the protein in the reverse micelles leads to significant distortion in its secondary structure, however, at the same time, addition of ANS leads to a marked increase in helicity of HSA. A combination of FRET studies, time resolved anisotropy measurements and global analyses of temperature dependent spectra reveal little or no significant interaction between HSA and ANS inside the AOT water pools, this being expected, based on the observed distortion of the protein secondary structure on reverse micelle entrapment (the latter resulting in disruption of the binding pockets available to ANS). Taken together our data show possible insights into how HSA releases its bound species (when interacting with membranes or charged confined spaces) and thereby remains a viable drug carrier. - Highlights: • Perturbation of the native structure of HSA in reverse micelles was investigated. • The thermal transition of HSA was quite non-cooperative inside the water pools. • 1-ANS was use to check whether it was binding to HSA inside the water pools. • Our analyses show the HSA subdomain cavities to be perturbed not allowing ANS to bind. • This we propose is a manner that HSA can release its bound molecules.

  13. The mechanisms responsible for garlic - drug interactions and their in vivo relevance.

    Science.gov (United States)

    Berginc, Katja; Kristl, Albin

    2013-01-01

    Garlic phytochemicals and garlic supplements influence the pharmacokinetic and pharmacodynamic behavior of concomitantly ingested drugs. In this paper we have summarized the mechanisms responsible for first-pass intestinal pharmacokinetic interactions by investigating the intestinal permeability of some cardiovascular, antiviral drugs, their transport with hepatic transporters and CYP3A4 metabolism. Transporter-enzyme interplay was studied with several in vitro models of varying complexity: rat small intestine and Caco-2 cell monolayers were used in studies of intestinal processes, and hepatic pharmacokinetics was monitored in HepG2 cells, isolated rat hepatocytes and rat liver slices. Garlic phytochemicals from aged garlic extract modified the activities of secretory and absorptive transporters in both intestine and liver and competitively inhibited CYP3A4 enzyme. The increased activities of the most important intestinal efflux (P-glycoprotein - Pgp, Multidrug Resistance Associated Protein 2 - MRP-2, Breast Cancer Resistance Protein - BCRP) and uptake (MonoCarboxylate Transporter 1 - MCT1, Organic Anion Transporting Polypeptide - OATP, Peptide transporter 1 - PepT1) transporters were caused by changes in electrophysiological membrane properties and by allosteric modifications. Because clinical studies investigating interactions between garlic and human immunodeficiency virus protease inhibitors saquinavir and ritonavir have already been performed, we used these in vivo data to evaluate the in vitro results and the reliability of the models employed as screening tools for forecasting the potential of first-pass intestinal metabolism changes. We also assessed the probability of pharmacokinetic interactions with garlic of the novel drug darunavir and other cardiovascular drugs. Finally, selected garlic phytochemicals were tested for their ability to influence P-glycoprotein and CYP3A4 activities.

  14. Theory of coupled electromagnetic circuits, the connection to quantum mechanical resonance interactions and relevance to chronobiology

    CERN Document Server

    Ulmer, W; Halberg, F; Schwarzkopff, O

    2011-01-01

    The existence of specific biorhythms and the role of geomagnetic and/or solar magnetic activities are well-established by appropriate correlations in chronobiology. From a physical viewpoint, there are two different accesses to biorhythms to set up connections to molecular processes: 1. Diffusion of charged molecules in magnetic fields. 2. Quantum mechanical perturbation theoretical methods and their resonance dominators to characterize specific interactions between constituents. The methods of point 2 permit the treatment of molecular processes by circuits with characteristic resonances and 'beat-frequencies', which result from the primarily fast physical processes. As examples the tunneling processes between DNA base pairs (H bonds) and the ATP decomposition are considered.

  15. Emotion and Attention Interaction: a trade-off between stimuli relevance, motivation and individual differences

    Directory of Open Access Journals (Sweden)

    Leticia eOliveira

    2013-07-01

    Full Text Available Mounting evidence suggests that the neural processing of emotional stimuli is prioritized. However, whether the processing of emotional stimuli is dependent on attention remains debatable. Several studies have investigated this issue by testing the capacity of emotional distracters to divert processing resources from an attentional main task. The attentional load theory postulates that the perceptual load of the main task determines the selective processing of the distracter. Although we agree with this theory, we also suggest that other factors could be important in determining the association between the load of the main task and distracter processing, namely, (1 the relevance of the to-be ignored stimuli and (2 the engagement in the main task resulting from motivation. We postulate that these factors function as opposite forces to influence distracter processing. In addition, we propose that this trade-off is modulated by individual differences. In summary, we suggest that the relationship between emotion and attention is flexible rather than rigid and depends on several factors. Considering this perspective may help us to understand the divergence in the results described by several studies in this field.

  16. Molecular interactions of the aryl hydrocarbon receptor and its biological and toxicological relevance for reproduction.

    Science.gov (United States)

    Pocar, P; Fischer, B; Klonisch, T; Hombach-Klonisch, S

    2005-04-01

    The dioxin/aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor responsive to both natural and man-made environmental compounds. AhR and its nuclear partner ARNT are expressed in the female reproductive tract in a variety of species and several indications suggest that the AhR might play a pivotal role in the physiology of reproduction. Furthermore, it appears to be the mediator of most, if not all, the adverse effects on reproduction of a group of highly potent environmental pollutants collectively called aryl hydrocarbons (AHs), including the highly toxic compound 2,3,7,8-tetrachlor-odibenzo-p-dioxin (TCDD). Although a large body of recent literature has implicated AhR in multiple signal transduction pathways, the mechanisms of action resulting in a wide spectrum of effects on female reproduction are largely unknown. Here we summarize the major types of molecular cross-talks that have been identified for the AhR and linked cell signaling pathways and that are relevant for the understanding of the role of this transcription factor in female reproduction.

  17. Direct protein-protein interactions and substrate channeling between cellular retinoic acid binding proteins and CYP26B1.

    Science.gov (United States)

    Nelson, Cara H; Peng, Chi-Chi; Lutz, Justin D; Yeung, Catherine K; Zelter, Alex; Isoherranen, Nina

    2016-08-01

    Cellular retinoic acid binding proteins (CRABPs) bind all-trans-retinoic acid (atRA) tightly. This study aimed to determine whether atRA is channeled directly to cytochrome P450 (CYP) CYP26B1 by CRABPs, and whether CRABPs interact directly with CYP26B1. atRA bound to CRABPs (holo-CRABP) was efficiently metabolized by CYP26B1. Isotope dilution experiments showed that delivery of atRA to CYP26B1 in solution was similar with or without CRABP. Holo-CRABPs had higher affinity for CYP26B1 than free atRA, but both apo-CRABPs inhibited the formation of 4-OH-RA by CYP26B1. Similar protein-protein interactions between soluble binding proteins and CYPs may be important for other lipophilic CYP substrates.

  18. The telomeric protein AKTIP interacts with A- and B-type lamins and is involved in regulation of cellular senescence

    Science.gov (United States)

    Burla, Romina; Carcuro, Mariateresa; Torre, Mattia La; Fratini, Federica; Crescenzi, Marco; D'Apice, Maria Rosaria; Spitalieri, Paola; Raffa, Grazia Daniela; Astrologo, Letizia; Lattanzi, Giovanna; Cundari, Enrico; Raimondo, Domenico; Biroccio, Annamaria; Gatti, Maurizio

    2016-01-01

    AKTIP is a shelterin-interacting protein required for replication of telomeric DNA. Here, we show that AKTIP biochemically interacts with A- and B-type lamins and affects lamin A, but not lamin C or B, expression. In interphase cells, AKTIP localizes at the nuclear rim and in discrete regions of the nucleoplasm just like lamins. Double immunostaining revealed that AKTIP partially co-localizes with lamin B1 and lamin A/C in interphase cells, and that proper AKTIP localization requires functional lamin A. In mitotic cells, AKTIP is enriched at the spindle poles and at the midbody of late telophase cells similar to lamin B1. AKTIP-depleted cells show senescence-associated markers and recapitulate several aspects of the progeroid phenotype. Collectively, our results indicate that AKTIP is a new player in lamin-related processes, including those that govern nuclear architecture, telomere homeostasis and cellular senescence. PMID:27512140

  19. Lactose-Functionalized Dendrimers Arbitrate the Interaction of Galectin-3/MUC1 Mediated Cancer Cellular Aggregation

    Science.gov (United States)

    Michel, Anna K.; Nangia-Makker, Pratima; Raz, Avraham

    2015-01-01

    By using lactose-functionalized poly(amidoamine) dendrimers as a tunable multivalent platform, we studied cancer cell aggregation in three different cell lines (A549, DU-145, and HT-1080) with galectin-3. We found that small lactose-functionalized G(2)-dendrimer 1 inhibited galectin-3-induced aggregation of the cancer cells. In contrast, dendrimer 4 (a larger, generation 6 dendrimer with 100 carbohydrate end groups) caused cancer cells to aggregate through a galectin-3 pathway. This study indicates that inhibition of cellular aggregation occurred because 1 provided competitive binding sites for galectin-3 (compared to its putative cancer cell ligand, TF-antigen on MUC1). Dendrimer 4, in contrast, provided an excess of ligands for galectin-3 binding; this caused crosslinking and aggregation of cells to be increased. PMID:25138772

  20. Cellular immunity and pathogen strategies in combative interactions involving Drosophila hosts and their endoparasitic wasps

    Directory of Open Access Journals (Sweden)

    AJ Nappi

    2010-09-01

    Full Text Available Various cellular innate immune responses protect invertebrates from attack by eukaryotic pathogens. In insects, assessments of the factor(s causing, or contributing to, pathogen mortality have long considered as toxic components certain molecules associated with enzyme-mediated melanogenesis. In Drosophila hosts, observations that have prompted additional or alternative considerations are those that document either the survival of certain endoparasitic wasps despite melanotic encapsulation, or the destruction of the parasite with no evidence of this type of host response. Investigations of the production of some reactive intermediates of oxygen and nitrogen during infection provide a basis for proposing that these molecules constitute important elements of the immune arsenal of Drosophila. Studies of the target specificity of virulence factors injected by female wasps during infection that suppress the host immune response will likely facilitate identification of the toxic host molecules, and contribute to a more detailed understanding of the cell-signaling pathways that regulate their synthesis.

  1. A grounded theory: seeking relief from flatus as relevant client-nurse action and interaction.

    Science.gov (United States)

    Annells, Merilyn

    2007-01-01

    Flatus problems are not uncommon among gastroenterological clients and those in other care settings. Yet what clients and nurses do productively about those problems in regard to their actions and interactions and why they do so has not previously been the focus of research. Holistic health management requires trustworthy qualitative evidence to guide best practice in this regard. This study systematically developed a substantive grounded theory that details and explains the trajectory of the basic social process: seeking relief from being discommoded (inconvenienced, troubled) by flatus in the situational context of client-nurse interactions. In the theory, there is also a focus on the context of nursing care situations, possible constraints, and likely outcomes. Grounded theory method was applied. Data were collected through semistructured individual interviews, nonparticipant observation, and document analysis regarding incidents and situations involving 38 participants-clients and registered nurses. The results show that clients, when trying to do something about the situation, can be severely discommoded by flatus problems and are hampered by embarrassment and the social taboo about admitting that one is bothered by flatus. The individual may or may not disclose the problem to a nurse, and nurses may or may not be attuned to these problems. There are ways for nurses to be helpful in these situations and possible remedies are identified in this article.

  2. Antiparallel Self-Association of a γ,α-Hybrid Peptide: More Relevance of Weak Interactions.

    Science.gov (United States)

    Venugopalan, Paloth; Kishore, Raghuvansh

    2015-08-01

    To learn how a preorganized peptide-based molecular template, together with diverse weak non-covalent interactions, leads to an effective self-association, we investigated the conformational characteristics of a simple γ,α-hybrid model peptide, Boc-γ-Abz-Gly-OMe. The single-crystal X-ray diffraction analysis revealed the existence of a fully extended β-strand-like structure stabilized by two non-conventional C-H⋅⋅⋅O=C intramolecular H-bonds. The 2D (1) H NMR ROESY experiment led us to propose that the flat topology of the urethane-γ-Abz-amide moiety is predominantly preserved in a non-polar environment. The self-association of the energetically more favorable antiparallel β-strand-mimic in solid-state engenders an unusual 'flight of stairs' fabricated through face-to-face and edge-to-edge Ar⋅⋅⋅Ar interactions. In conjunction with FT-IR spectroscopic analysis in chloroform, we highlight that conformationally semi-rigid γ-Abz foldamer in appositely designed peptides may encourage unusual β-strand or β-sheet-like self-association and supramolecular organization stabilized via weak attractive forces.

  3. Biochemical and Molecular Mechanisms of Plant-Microbe-Metal Interactions: Relevance for Phytoremediation

    Science.gov (United States)

    Ma, Ying; Oliveira, Rui S.; Freitas, Helena; Zhang, Chang

    2016-01-01

    Plants and microbes coexist or compete for survival and their cohesive interactions play a vital role in adapting to metalliferous environments, and can thus be explored to improve microbe-assisted phytoremediation. Plant root exudates are useful nutrient and energy sources for soil microorganisms, with whom they establish intricate communication systems. Some beneficial bacteria and fungi, acting as plant growth promoting microorganisms (PGPMs), may alleviate metal phytotoxicity and stimulate plant growth indirectly via the induction of defense mechanisms against phytopathogens, and/or directly through the solubilization of mineral nutrients (nitrogen, phosphate, potassium, iron, etc.), production of plant growth promoting substances (e.g., phytohormones), and secretion of specific enzymes (e.g., 1-aminocyclopropane-1-carboxylate deaminase). PGPM can also change metal bioavailability in soil through various mechanisms such as acidification, precipitation, chelation, complexation, and redox reactions. This review presents the recent advances and applications made hitherto in understanding the biochemical and molecular mechanisms of plant–microbe interactions and their role in the major processes involved in phytoremediation, such as heavy metal detoxification, mobilization, immobilization, transformation, transport, and distribution. PMID:27446148

  4. Modeling the interaction between quinolinate and the receptor for advanced glycation end products (RAGE: relevance for early neuropathological processes.

    Directory of Open Access Journals (Sweden)

    Iris N Serratos

    Full Text Available The receptor for advanced glycation end products (RAGE is a pattern-recognition receptor involved in neurodegenerative and inflammatory disorders. RAGE induces cellular signaling upon binding to a variety of ligands. Evidence suggests that RAGE up-regulation is involved in quinolinate (QUIN-induced toxicity. We investigated the QUIN-induced toxic events associated with early noxious responses, which might be linked to signaling cascades leading to cell death. The extent of early cellular damage caused by this receptor in the rat striatum was characterized by image processing methods. To document the direct interaction between QUIN and RAGE, we determined the binding constant (Kb of RAGE (VC1 domain with QUIN through a fluorescence assay. We modeled possible binding sites of QUIN to the VC1 domain for both rat and human RAGE. QUIN was found to bind at multiple sites to the VC1 dimer, each leading to particular mechanistic scenarios for the signaling evoked by QUIN binding, some of which directly alter RAGE oligomerization. This work contributes to the understanding of the phenomenon of RAGE-QUIN recognition, leading to the modulation of RAGE function.

  5. Interaction of Actinide Species with Microorganisms & Microbial Chelators: Cellular Uptake, Toxicity, & Implications for Bioremediation of Soil & Ground Water.

    Energy Technology Data Exchange (ETDEWEB)

    Hakim Boukhalfa

    2006-03-28

    Microorganisms influence the natural cycle of major elements, including C, N, P, S, and transition metals such as Mn and Fe. Bacterial processes can also influence the behavior of actinides in soil and ground water. While radionuclides have no known biological utility, they have the potential to interact with microorganisms and to interfere with processes involving other elements such as Fe and Mn. These interactions can transform radionuclides and affect their fate and transport. Organic acids, extruded by-products of cell metabolism, can solubilize radionuclides and facilitate their transport. The soluble complexes formed can be taken up by the cells and incorporated into biofilm structures. We have examined the interactions of Pu species with bacterial metabolites, studied Pu uptake by microorganisms and examined the toxicity of Pu and other toxic metals to environmentally relevant bacteria. We have also studied the speciation of Pu(IV) in the presence of natural and synthetic chelators.

  6. Metacomprehension for educationally relevant materials: dramatic effects of encoding-retrieval interactions.

    Science.gov (United States)

    Thomas, Ayanna K; McDaniel, Mark A

    2007-04-01

    As the metacomprehension literature has grown, important discoveries pertinent to education havebeen made. For example, as students are better able to assess their knowledge and implement appropriate study strategies, presumably their acquisition and retention of course material improves. Accordingly, we consider the metacomprehension literature with an emphasis on factors that impact metacomprehension accuracy. Several studies have demonstrated that metacomprehension prediction accuracy will improve to the extent that people engage in enriched-encoding activities. More recently, research by Thomas and McDaniel (in press) has suggested that enriched-encoding manipulations interact with retrieval to impact both retention and metacomprehension and, in turn, the effectiveness of controlling subsequent study. Thus, matching enriched-encoding activities with the criterial test plays a critical role in metacomprehension accuracy and control of studying.

  7. CALCIFICATION OF SUBCUTANEOUSLY IMPLANTED COLLAGENS IN RELATION TO CYTOTOXICITY, CELLULAR INTERACTIONS AND CROSS-LINKING

    NARCIS (Netherlands)

    VANLUYN, MJA; VANWACHEM, PB; DIJKSTRA, PJ; DAMINK, LHHO; FEIJEN, J

    1995-01-01

    In general, calcification of biomaterials occurs through an interaction of host and implanted material factors, but up to now the real origin of pathologic calcification is unknown. In this study we aimed to investigate incidence of calcification of (crosslinked) dermal sheep collagens (DSCs) with r

  8. Molecular and cellular aspects of the bidirectional interaction between probiotic bacteria and the host

    NARCIS (Netherlands)

    van Bergenhenegouwen, B.J.

    2015-01-01

    Accumulating evidence suggests that intestinal microbial imbalance, or dysbiosis, and the associated changes in microbe-host interactions might contribute to the prevalence of disease. Dysbiosis is associated with a loss of beneficial bacteria and has triggered research into the potential preventive

  9. Host- and Strain-Specific Regulation of Influenza Virus Polymerase Activity by Interacting Cellular Proteins

    NARCIS (Netherlands)

    Bortz, Eric; Westera, Liset; Maamary, Jad; Steel, John; Albrecht, Randy A.; Manicassamy, Balaji; Chase, Geoffrey; Martinez-Sobrido, Luis; Schwemmle, Martin; Garcia-Sastre, Adolfo

    2011-01-01

    Highly pathogenic avian influenza A (HPAI) viruses of the H5N1 subtype have recently emerged from avian zoonotic reservoirs to cause fatal human disease. Adaptation of HPAI virus RNA-dependent RNA polymerase (PB1, PB2, and PA proteins) and nucleoprotein (NP) to interactions with mammalian host prote

  10. Interactions between dodecyl phosphates and hydroxyapatite or tooth enamel: relevance to inhibition of dental erosion.

    Science.gov (United States)

    Jones, Siân B; Barbour, Michele E; Shellis, R Peter; Rees, Gareth D

    2014-05-01

    Tooth surface modification is a potential method of preventing dental erosion, a form of excessive tooth wear facilitated by softening of tooth surfaces through the direct action of acids, mainly of dietary origin. We have previously shown that dodecyl phosphates (DPs) effectively inhibit dissolution of native surfaces of hydroxyapatite (the type mineral for dental enamel) and show good substantivity. However, adsorbed saliva also inhibits dissolution and DPs did not augment this effect, which suggests that DPs and saliva interact at the hydroxyapatite surface. In the present study the adsorption and desorption of potassium and sodium dodecyl phosphates or sodium dodecyl sulphate (SDS) to hydroxyapatite and human tooth enamel powder, both native and pre-treated with saliva, were studied by high performance liquid chromatography-mass Spectrometry. Thermo gravimetric analysis was used to analyse residual saliva and surfactant on the substrates. Both DPs showed a higher affinity than SDS for both hydroxyapatite and enamel, and little DP was desorbed by washing with water. SDS was readily desorbed from hydroxyapatite, suggesting that the phosphate head group is essential for strong binding to this substrate. However, SDS was not desorbed from enamel, so that this substrate has surface properties different from those of hydroxyapatite. The presence of a salivary coating had little or no effect on adsorption of the DPs, but treatment with DPs partly desorbed saliva; this could account for the failure of DPs to increase the dissolution inhibition due to adsorbed saliva.

  11. The relevance of the cross-wavelet transform in the analysis of human interaction - a tutorial.

    Science.gov (United States)

    Issartel, Johann; Bardainne, Thomas; Gaillot, Philippe; Marin, Ludovic

    2014-01-01

    This article sheds light on a quantitative method allowing psychologists and behavioral scientists to take into account the specific characteristics emerging from the interaction between two sets of data in general and two individuals in particular. The current article outlines the practical elements of the cross-wavelet transform (CWT) method, highlighting WHY such a method is important in the analysis of time-series in psychology. The idea is (1) to bridge the gap between physical measurements classically used in physiology - neuroscience and psychology; (2) and demonstrates how the CWT method can be applied in psychology. One of the aims is to answer three important questions WHO could use this method in psychology, WHEN it is appropriate to use it (suitable type of time-series) and HOW to use it. Throughout these explanations, an example with simulated data is used. Finally, data from real life application are analyzed. This data corresponds to a rating task where the participants had to rate in real time the emotional expression of a person. The objectives of this practical example are (i) to point out how to manipulate the properties of the CWT method on real data, (ii) to show how to extract meaningful information from the results, and (iii) to provide a new way to analyze psychological attributes.

  12. Host-microbe interactions in distal airways: relevance to chronic airway diseases.

    Science.gov (United States)

    Martin, Clémence; Burgel, Pierre-Régis; Lepage, Patricia; Andréjak, Claire; de Blic, Jacques; Bourdin, Arnaud; Brouard, Jacques; Chanez, Pascal; Dalphin, Jean-Charles; Deslée, Gaetan; Deschildre, Antoine; Gosset, Philippe; Touqui, Lhousseine; Dusser, Daniel

    2015-03-01

    This article is the summary of a workshop, which took place in November 2013, on the roles of microorganisms in chronic respiratory diseases. Until recently, it was assumed that lower airways were sterile in healthy individuals. However, it has long been acknowledged that microorganisms could be identified in distal airway secretions from patients with various respiratory diseases, including cystic fibrosis (CF) and non-CF bronchiectasis, chronic obstructive pulmonary disease, asthma and other chronic airway diseases (e.g. post-transplantation bronchiolitis obliterans). These microorganisms were sometimes considered as infectious agents that triggered host immune responses and contributed to disease onset and/or progression; alternatively, microorganisms were often considered as colonisers, which were considered unlikely to play roles in disease pathophysiology. These concepts were developed at a time when the identification of microorganisms relied on culture-based methods. Importantly, the majority of microorganisms cannot be cultured using conventional methods, and the use of novel culture-independent methods that rely on the identification of microorganism genomes has revealed that healthy distal airways display a complex flora called the airway microbiota. The present article reviews some aspects of current literature on host-microbe (mostly bacteria and viruses) interactions in healthy and diseased airways, with a special focus on distal airways.

  13. Host–microbe interactions in distal airways: relevance to chronic airway diseases

    Directory of Open Access Journals (Sweden)

    Clémence Martin

    2015-03-01

    Full Text Available This article is the summary of a workshop, which took place in November 2013, on the roles of microorganisms in chronic respiratory diseases. Until recently, it was assumed that lower airways were sterile in healthy individuals. However, it has long been acknowledged that microorganisms could be identified in distal airway secretions from patients with various respiratory diseases, including cystic fibrosis (CF and non-CF bronchiectasis, chronic obstructive pulmonary disease, asthma and other chronic airway diseases (e.g. post-transplantation bronchiolitis obliterans. These microorganisms were sometimes considered as infectious agents that triggered host immune responses and contributed to disease onset and/or progression; alternatively, microorganisms were often considered as colonisers, which were considered unlikely to play roles in disease pathophysiology. These concepts were developed at a time when the identification of microorganisms relied on culture-based methods. Importantly, the majority of microorganisms cannot be cultured using conventional methods, and the use of novel culture-independent methods that rely on the identification of microorganism genomes has revealed that healthy distal airways display a complex flora called the airway microbiota. The present article reviews some aspects of current literature on host–microbe (mostly bacteria and viruses interactions in healthy and diseased airways, with a special focus on distal airways.

  14. Oscillatory Shear Rheology in Examining the Drug-Polymer Interactions Relevant in Hot Melt Extrusion.

    Science.gov (United States)

    Aho, Johanna; Edinger, Magnus; Botker, Johan; Baldursdottir, Stefania; Rantanen, Jukka

    2016-01-01

    The flow properties of drug-polymer mixtures have a significant influence on their processability when using techniques such as hot melt extrusion (HME). Suitable extrusion temperature and screw speed to be used in laboratory scale HME were evaluated for mixtures containing 30% of paracetamol (PRC), ibuprofen (IBU), or indomethacin (IND), and 70% of polyethylene oxide, by using small amplitude oscillatory shear rheology. The initial evaluation of the drug:polyethylene oxide solubility was estimated by differential scanning calorimetry of the physical mixtures containing a wide range of weight fractions of the drug substances. Consecutively, the mixtures were extruded, and the maximum plasticizing weight fraction of each drug was determined by means of rheological measurements. IBU was found to have an efficient plasticizing functionality, decreasing the viscosity of the mixtures even above its apparent saturation solubility, whereas IND and PRC initially lowered the viscosity of the mixture slightly but increased it significantly with increasing drug load. The main reason for the enhanced plasticization effect seems to be the lower melting temperature of IBU, which is closer to the used HME temperature, compared to PRC and IND. This study highlights the importance of rheological investigation in understanding the drug-polymer interactions in melt processing.

  15. Augmented cellular uptake of nanoparticles using tea catechins: effect of surface modification on nanoparticle-cell interaction

    Science.gov (United States)

    Lu, Yi-Ching; Luo, Pei-Chun; Huang, Chun-Wan; Leu, Yann-Lii; Wang, Tzu-Hao; Wei, Kuo-Chen; Wang, Hsin-Ell; Ma, Yunn-Hwa

    2014-08-01

    Nanoparticles may serve as carriers in targeted therapeutics; interaction of the nanoparticles with a biological system may determine their targeting effects and therapeutic efficacy. Epigallocatechin-3-gallate (EGCG), a major component of tea catechins, has been conjugated with nanoparticles and tested as an anticancer agent. We investigated whether EGCG may enhance nanoparticle uptake by tumor cells. Cellular uptake of a dextran-coated magnetic nanoparticle (MNP) was determined by confocal microscopy, flow cytometry or a potassium thiocyanate colorimetric method. We demonstrated that EGCG greatly enhanced interaction and/or internalization of MNPs (with or without polyethylene glycol) by glioma cells, but not vascular endothelial cells. The enhancing effects are both time- and concentration-dependent. Such effects may be induced by a simple mix of MNPs with EGCG at a concentration as low as 1-3 μM, which increased MNP uptake 2- to 7-fold. In addition, application of magnetic force further potentiated MNP uptake, suggesting a synergetic effect of EGCG and magnetic force. Because the effects of EGCG were preserved at 4 °C, but not when EGCG was removed from the culture medium prior to addition of MNPs, a direct interaction of EGCG and MNPs was implicated. Use of an MNP-EGCG composite produced by adsorption of EGCG and magnetic separation also led to an enhanced uptake. The results reveal a novel interaction of a food component and nanocarrier system, which may be potentially amenable to magnetofection, cell labeling/tracing, and targeted therapeutics.

  16. Requirement of cellular DDX3 for hepatitis C virus replication is unrelated to its interaction with the viral core protein.

    Science.gov (United States)

    Angus, Allan G N; Dalrymple, David; Boulant, Steeve; McGivern, David R; Clayton, Reginald F; Scott, Martin J; Adair, Richard; Graham, Susan; Owsianka, Ania M; Targett-Adams, Paul; Li, Kui; Wakita, Takaji; McLauchlan, John; Lemon, Stanley M; Patel, Arvind H

    2010-01-01

    The cellular DEAD-box protein DDX3 was recently shown to be essential for hepatitis C virus (HCV) replication. Prior to that, we had reported that HCV core binds to DDX3 in yeast-two hybrid and transient transfection assays. Here, we confirm by co-immunoprecipitation that this interaction occurs in cells replicating the JFH1 virus. Consistent with this result, immunofluorescence staining of infected cells revealed a dramatic redistribution of cytoplasmic DDX3 by core protein to the virus assembly sites around lipid droplets. Given this close association of DDX3 with core and lipid droplets, and its involvement in virus replication, we investigated the importance of this host factor in the virus life cycle. Mutagenesis studies located a single amino acid in the N-terminal domain of JFH1 core that when changed to alanine significantly abrogated this interaction. Surprisingly, this mutation did not alter infectious virus production and RNA replication, indicating that the core-DDX3 interaction is dispensable in the HCV life cycle. Consistent with previous studies, siRNA-led knockdown of DDX3 lowered virus production and RNA replication levels of both WT JFH1 and the mutant virus unable to bind DDX3. Thus, our study shows for the first time that the requirement of DDX3 for HCV replication is unrelated to its interaction with the viral core protein.

  17. Augmented cellular uptake of nanoparticles using tea catechins: effect of surface modification on nanoparticle-cell interaction.

    Science.gov (United States)

    Lu, Yi-Ching; Luo, Pei-Chun; Huang, Chun-Wan; Leu, Yann-Lii; Wang, Tzu-Hao; Wei, Kuo-Chen; Wang, Hsin-Ell; Ma, Yunn-Hwa

    2014-09-07

    Nanoparticles may serve as carriers in targeted therapeutics; interaction of the nanoparticles with a biological system may determine their targeting effects and therapeutic efficacy. Epigallocatechin-3-gallate (EGCG), a major component of tea catechins, has been conjugated with nanoparticles and tested as an anticancer agent. We investigated whether EGCG may enhance nanoparticle uptake by tumor cells. Cellular uptake of a dextran-coated magnetic nanoparticle (MNP) was determined by confocal microscopy, flow cytometry or a potassium thiocyanate colorimetric method. We demonstrated that EGCG greatly enhanced interaction and/or internalization of MNPs (with or without polyethylene glycol) by glioma cells, but not vascular endothelial cells. The enhancing effects are both time- and concentration-dependent. Such effects may be induced by a simple mix of MNPs with EGCG at a concentration as low as 1-3 μM, which increased MNP uptake 2- to 7-fold. In addition, application of magnetic force further potentiated MNP uptake, suggesting a synergetic effect of EGCG and magnetic force. Because the effects of EGCG were preserved at 4 °C, but not when EGCG was removed from the culture medium prior to addition of MNPs, a direct interaction of EGCG and MNPs was implicated. Use of an MNP-EGCG composite produced by adsorption of EGCG and magnetic separation also led to an enhanced uptake. The results reveal a novel interaction of a food component and nanocarrier system, which may be potentially amenable to magnetofection, cell labeling/tracing, and targeted therapeutics.

  18. Revealing the sequence and resulting cellular morphology of receptor-ligand interactions during Plasmodium falciparum invasion of erythrocytes.

    Directory of Open Access Journals (Sweden)

    Greta E Weiss

    2015-02-01

    Full Text Available During blood stage Plasmodium falciparum infection, merozoites invade uninfected erythrocytes via a complex, multistep process involving a series of distinct receptor-ligand binding events. Understanding each element in this process increases the potential to block the parasite's life cycle via drugs or vaccines. To investigate specific receptor-ligand interactions, they were systematically blocked using a combination of genetic deletion, enzymatic receptor cleavage and inhibition of binding via antibodies, peptides and small molecules, and the resulting temporal changes in invasion and morphological effects on erythrocytes were filmed using live cell imaging. Analysis of the videos have shown receptor-ligand interactions occur in the following sequence with the following cellular morphologies; 1 an early heparin-blockable interaction which weakly deforms the erythrocyte, 2 EBA and PfRh ligands which strongly deform the erythrocyte, a process dependant on the merozoite's actin-myosin motor, 3 a PfRh5-basigin binding step which results in a pore or opening between parasite and host through which it appears small molecules and possibly invasion components can flow and 4 an AMA1-RON2 interaction that mediates tight junction formation, which acts as an anchor point for internalization. In addition to enhancing general knowledge of apicomplexan biology, this work provides a rational basis to combine sequentially acting merozoite vaccine candidates in a single multi-receptor-blocking vaccine.

  19. Nutrient-Gene Interaction in Colon Cancer, from the Membrane to Cellular Physiology.

    Science.gov (United States)

    Hou, Tim Y; Davidson, Laurie A; Kim, Eunjoo; Fan, Yang-Yi; Fuentes, Natividad R; Triff, Karen; Chapkin, Robert S

    2016-07-17

    The International Agency for Research on Cancer recently released an assessment classifying red and processed meat as "carcinogenic to humans" on the basis of the positive association between increased consumption and risk for colorectal cancer. Diet, however, can also decrease the risk for colorectal cancer and be used as a chemopreventive strategy. Bioactive dietary molecules, such as n-3 polyunsaturated fatty acids, curcumin, and fermentable fiber, have been proposed to exert chemoprotective effects, and their molecular mechanisms have been the focus of research in the dietary/chemoprevention field. Using these bioactives as examples, this review surveys the proposed mechanisms by which they exert their effects, from the nucleus to the cellular membrane. In addition, we discuss emerging technologies involving the culturing of colonic organoids to study the physiological effects of dietary bioactives. Finally, we address future challenges to the field regarding the identification of additional molecular mechanisms and other bioactive dietary molecules that can be utilized in our fight to reduce the incidence of colorectal cancer.

  20. iGPCR-drug: a web server for predicting interaction between GPCRs and drugs in cellular networking.

    Directory of Open Access Journals (Sweden)

    Xuan Xiao

    Full Text Available Involved in many diseases such as cancer, diabetes, neurodegenerative, inflammatory and respiratory disorders, G-protein-coupled receptors (GPCRs are among the most frequent targets of therapeutic drugs. It is time-consuming and expensive to determine whether a drug and a GPCR are to interact with each other in a cellular network purely by means of experimental techniques. Although some computational methods were developed in this regard based on the knowledge of the 3D (dimensional structure of protein, unfortunately their usage is quite limited because the 3D structures for most GPCRs are still unknown. To overcome the situation, a sequence-based classifier, called "iGPCR-drug", was developed to predict the interactions between GPCRs and drugs in cellular networking. In the predictor, the drug compound is formulated by a 2D (dimensional fingerprint via a 256D vector, GPCR by the PseAAC (pseudo amino acid composition generated with the grey model theory, and the prediction engine is operated by the fuzzy K-nearest neighbour algorithm. Moreover, a user-friendly web-server for iGPCR-drug was established at http://www.jci-bioinfo.cn/iGPCR-Drug/. For the convenience of most experimental scientists, a step-by-step guide is provided on how to use the web-server to get the desired results without the need to follow the complicated math equations presented in this paper just for its integrity. The overall success rate achieved by iGPCR-drug via the jackknife test was 85.5%, which is remarkably higher than the rate by the existing peer method developed in 2010 although no web server was ever established for it. It is anticipated that iGPCR-Drug may become a useful high throughput tool for both basic research and drug development, and that the approach presented here can also be extended to study other drug - target interaction networks.

  1. Cellular Zinc Levels are Modulated by Trpml1-Tmem163 Interaction

    OpenAIRE

    2014-01-01

    Mucolipidosis type IV (MLIV) is caused by loss of function mutations in the TRPML1 ion channel. We previously reported that tissue zinc levels in MLIV were abnormally elevated; however, the mechanism behind this pathologic accumulation remains unknown. Here, we identify transmembrane (TMEM)-163 protein, a putative zinc transporter, as a novel interacting partner for TRPML1. Evidence from yeast two-hybrid, tissue expression pattern, co-immunoprecipitation, mass spectrometry, and...

  2. Experimental and computational analysis of cellular interactions with nylon-3-bearing substrates.

    Science.gov (United States)

    Liu, Runhui; Vang, Kang Z; Kreeger, Pamela K; Gellman, Samuel H; Masters, Kristyn S

    2012-10-01

    The ability to design biomaterials that interact with biological environments in a predictable manner necessitates an improved understanding of how surface chemistry influences events such as protein adsorption and cell adhesion. In this work, we examined mechanisms governing the interactions between 3T3 fibroblasts and nylon-3 polymers, which have a protein-like polyamide backbone and are highly amenable to tuning of chemical and physical properties. Protein adsorption and cell adhesion to a library of nylon-3 polymers were characterized and analyzed by partial least squares regression. This analysis revealed that specific chemical features of the nylon-3 polymers correlated with the extent of protein adsorption, which, in turn, correlated with cell adhesion in a serum-containing environment. In contrast, in a serum-free environment, cell adhesion could be predicted solely from chemical properties. Enzymatic treatments of 3T3 cells before plating indicated that proteins bound to the cell surface mediated cell-nylon-3 polymer interactions under serum-free conditions, with additional analysis suggesting that cell-associated fibronectin played a dominant role in adhesion in the absence of serum. The mechanistic insight gained from these studies can be used to inform the design of new polymer structures in addition to providing a basis for continued development of nylon-3 copolymers for tissue engineering applications.

  3. The relationship between passibility, agency and social interaction and its relevance for research and pedagogy

    Science.gov (United States)

    Kirch, Susan A.; Ma, Jasmine Y.

    2016-12-01

    The interaction analysis presented by Kim and Roth examines nine students, their teachers, the learning task and materials in a mixed second and third grade science classroom during the school day. In the research narrative readers are introduced to two resourceful and creative groups of students as they work on a task assigned by their teacher—to cantilever a pizza box over the edge of a student desk. Readers are given glimpses (through images and transcripts) of the inventive ways each group solved the cantilever problem. Sometimes the children disregarded the design constraints, but even after compliance they managed to successfully solve the problem. The point of the learning task was not clearly stated, but readers are told the unit focused on investigating forces, forces in equilibrium, and structures as well as different forces (push, pull, etc.), properties of materials, and the relations between weight and balance while building structures. Kim and Roth were specifically interested in using this session to investigate and resolve the problem of learning as described by socio-cultural theorists as, how does a learner orient toward a learning outcome when they cannot do that until they have learned it? To answer this question Kim and Roth argued that learners (in engineering design) learn when and because: (1) they are open to be affected by the responses of materials to student action (i.e. student and material agency and physical touch) (2) their bodies are endowed with the capacity to be affected (i.e. passibility), and (3) knowledge and understanding emerge as and in social relations first. In their analysis, Kim and Roth argued that knowledge and knowing-how depend on these three universal processes. The authors further theorized the concept of passibility. Included in their theory of passibility was the claim that passibility is necessary for agency. After reading this paper we found we had many questions about Kim and Roth's analysis, context, and

  4. The relationship between passibility, agency and social interaction and its relevance for research and pedagogy

    Science.gov (United States)

    Kirch, Susan A.; Ma, Jasmine Y.

    2016-02-01

    The interaction analysis presented by Kim and Roth examines nine students, their teachers, the learning task and materials in a mixed second and third grade science classroom during the school day. In the research narrative readers are introduced to two resourceful and creative groups of students as they work on a task assigned by their teacher—to cantilever a pizza box over the edge of a student desk. Readers are given glimpses (through images and transcripts) of the inventive ways each group solved the cantilever problem. Sometimes the children disregarded the design constraints, but even after compliance they managed to successfully solve the problem. The point of the learning task was not clearly stated, but readers are told the unit focused on investigating forces, forces in equilibrium, and structures as well as different forces (push, pull, etc.), properties of materials, and the relations between weight and balance while building structures. Kim and Roth were specifically interested in using this session to investigate and resolve the problem of learning as described by socio-cultural theorists as, how does a learner orient toward a learning outcome when they cannot do that until they have learned it? To answer this question Kim and Roth argued that learners (in engineering design) learn when and because: (1) they are open to be affected by the responses of materials to student action (i.e. student and material agency and physical touch) (2) their bodies are endowed with the capacity to be affected (i.e. passibility), and (3) knowledge and understanding emerge as and in social relations first. In their analysis, Kim and Roth argued that knowledge and knowing-how depend on these three universal processes. The authors further theorized the concept of passibility. Included in their theory of passibility was the claim that passibility is necessary for agency. After reading this paper we found we had many questions about Kim and Roth's analysis, context, and

  5. Molecular and Cellular Interactions between Mother and Fetus. Pregnancy as a Rejuvenating Factor.

    Science.gov (United States)

    Popkov, V A; Silachev, D N; Jankauskas, S S; Zorova, L D; Pevzner, I B; Babenko, V A; Plotnikov, E Y; Zorov, D B

    2016-12-01

    Aging is associated with a decline of various body functions, including ability to regenerate. Over recent decades, it has been demonstrated that some of these changes could be reversed in response to factors originating from a young organism, for example, fetal stem cells or "young blood" in models of heterochronic parabiosis. Pregnancy might be considered as parabiotic model of the interaction between two organisms of different age. In this work, we analyzed and summarized data on the effects of pregnancy on the maternal organism that confirm the hypothesis that pregnancy rejuvenates the mother's organism or slows its aging.

  6. iNR-Drug: Predicting the Interaction of Drugs with Nuclear Receptors in Cellular Networking

    Directory of Open Access Journals (Sweden)

    Yue-Nong Fan

    2014-03-01

    Full Text Available Nuclear receptors (NRs are closely associated with various major diseases such as cancer, diabetes, inflammatory disease, and osteoporosis. Therefore, NRs have become a frequent target for drug development. During the process of developing drugs against these diseases by targeting NRs, we are often facing a problem: Given a NR and chemical compound, can we identify whether they are really in interaction with each other in a cell? To address this problem, a predictor called “iNR-Drug” was developed. In the predictor, the drug compound concerned was formulated by a 256-D (dimensional vector derived from its molecular fingerprint, and the NR by a 500-D vector formed by incorporating its sequential evolution information and physicochemical features into the general form of pseudo amino acid composition, and the prediction engine was operated by the SVM (support vector machine algorithm. Compared with the existing prediction methods in this area, iNR-Drug not only can yield a higher success rate, but is also featured by a user-friendly web-server established at http://www.jci-bioinfo.cn/iNR-Drug/, which is particularly useful for most experimental scientists to obtain their desired data in a timely manner. It is anticipated that the iNR-Drug server may become a useful high throughput tool for both basic research and drug development, and that the current approach may be easily extended to study the interactions of drug with other targets as well.

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

    Science.gov (United States)

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

    2012-01-01

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

  8. Cellular interactions and photoprotective effects of idebenone-loaded nanostructured lipid carriers stabilized using PEG-free surfactant.

    Science.gov (United States)

    Kyadarkunte, Abhay Y; Patole, Milind S; Pokharkar, Varsha B

    2015-02-01

    In past years, nanostructured lipid carriers (NLCs) have emerged as novel topical antioxidant delivery systems because of combined positive features of liposomes and polymeric nanoparticles. Here, we seek to unlock the possibility of idebenone (IDB; an antioxidant)-loaded NLCs (IDB-NLCs) cellular interactions such as, viability and uptake, and its photoprotective effects against Ultraviolet-B (UVB)-mediated oxidative stress in immortal human keratinocyte cell line (HaCaT). The two-step preformulation strategy followed by three-level, three-variable, L9 (3(3)) Taguchi robust orthogonal design employed was important in improving IDB-NLCs key physicochemical aspects such as, entrapment efficiency, drug release (sustained), occlusion, skin deposition and physical stability. UV crosslinker, confocal microscopy and flow cytometry techniques were used to (1) mediate oxidative stress in HaCaT cells, (2) study a qualitative cellular uptake, (3) measure intracellular reactive oxygen species (ROS), and mitochondrial membrane potential, respectively. NLCs markedly improved biocompatibility of IDB under normal as well as stress conditions. Quantitative and qualitative cell uptake studies demonstrated a significant uptake of IDB-NLCs (3-fold increase) and nile red-labeled IDB-NLCs (NR-IDB-NLCs) at 2 h, respectively, hence exerted improved photoprotective effects.

  9. Clinical relevancy and determinants of potential drug–drug interactions in chronic kidney disease patients: results from a retrospective analysis

    Directory of Open Access Journals (Sweden)

    Saleem A

    2017-02-01

    Full Text Available Ahsan Saleem,1,2 Imran Masood,1 Tahir Mehmood Khan3 1Department of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur, Pakistan; 2Pharmacy Services Department, Integrated Medical Center, The Aga Khan University Hospital, Lahore, Pakistan; 3School of Pharmacy, Monash University, Sunway Campus, Selangor, Malaysia Background: Chronic kidney disease (CKD alters the pharmacokinetic and pharmacodynamic responses of various renally excreted drugs and increases the risk of drug-related problems, such as drug–drug interactions.Objectives: To assess the pattern, determinants, and clinical relevancy of potential drug–drug interactions (pDDIs in CKD patients.Materials and methods: This study retrospectively reviewed medical charts of all CKD patients admitted in the nephrology unit of a tertiary care hospital in Pakistan from January 2013 to December 2014. The Micromedex Drug-Reax® system was used to screen patient profiles for pDDIs, and IBM SPSS version 20 was used to carry out statistical analysis.Results: We evaluated 209 medical charts and found pDDIs in nearly 78.5% CKD patients. Overall, 541 pDDIs were observed, of which, nearly 60.8% patients had moderate, 41.1% had minor, 27.8% had major, and 13.4% had contraindicated interactions. Among those interactions, 49.4% had good evidence, 44.0% had fair, 6.3% had excellent evidence, and 35.5% interactions had delayed onset of action. The potential adverse outcomes of pDDIs included postural hypotension, QT prolongation, ceftriaxone–calcium precipitation, cardiac arrhythmias, and reduction in therapeutic effectiveness. The occurrence of pDDIs was found strongly associated with the age of <60 years, number of prescribed medicines ≥5, hypertension, and the lengthy hospitalization of patients.Conclusion: The occurrence of pDDIs was high in CKD patients. It was observed that CKD patients with an older age, higher number of prescribed medicines, lengthy hospitalization, and hypertension were at

  10. KIR/HLA interactions negatively affect rituximab- but not GA101 (obinutuzumab)-induced antibody-dependent cellular cytotoxicity.

    Science.gov (United States)

    Terszowski, Grzegorz; Klein, Christian; Stern, Martin

    2014-06-15

    Ab-dependent cellular cytotoxicity (ADCC) mediated by NK cells is regulated by inhibitory killer cell Ig-like receptors (KIRs), which interact with target cell HLA class I. We analyzed how KIR/HLA interactions influence ADCC induced by rituximab and by GA101, a novel type II CD20 Ab glycoengineered for increased FcgRIII binding and ADCC capacity. We found that KIR/HLA interactions strongly and selectively inhibit rituximab-induced in vitro ADCC toward target cells expressing cognate HLA KIR ligands. NK cells of donors carrying all three ligands to inhibitory KIR showed weak activation and target cell depletion capacity when incubated with rituximab and KIR-ligand matched target B cells. In contrast, NK cells from individuals missing one or more KIR ligands activated more strongly and depleted KIR ligand-matched target B cells more efficiently in the presence of rituximab. NK cells expressing a KIR for which the ligand was absent were the main effectors of ADCC in these donors. Notably, the influence of KIR/HLA interactions on NK cell activation was synergistic with the effect of the V158F FCGR3A single nucleotide polymorphism. In contrast, GA101 induced activation of NK cells irrespective of inhibitory KIR expression, and efficiency of target cell depletion was not negatively affected by KIR/HLA interactions. These data show that modification of the Fc fragment to enhance ADCC can be an effective strategy to augment the efficacy of therapeutic mAbs by recruiting NK cells irrespective of their inhibitory KIR expression.

  11. Lineage Specification of Ovarian Theca Cells Requires Multi-Cellular Interactions via Oocyte and Granulosa Cells

    Science.gov (United States)

    Liu, Chang; Peng, Jia; Matzuk, Martin M.; Yao, Humphrey H-C

    2015-01-01

    Organogenesis of the ovary is a highly orchestrated process involving multiple lineage determinations of ovarian surface epithelium, granulosa cells, and theca cells. While the sources of ovarian surface epithelium and granulosa cells are known, the origin(s) of theca progenitor cells have not been definitively identified. Here we show that theca cells derive from two sources: Wt1+ cells indigenous to the ovary and Gli1+ mesenchymal cells migrated from the mesonephros. These progenitors acquire theca lineage marker Gli1 in response to paracrine signals Desert hedgehog (Dhh) and Indian hedgehog (Ihh) from granulosa cells. Ovaries lacking Dhh/Ihh exhibit theca layer loss, blunted steroid production, arrested folliculogenesis, and failure to form corpora lutea. Production of Dhh/Ihh in granulosa cells requires Growth differentiation factor 9 (GDF9) from the oocyte. Our studies provide the first genetic evidence for the origins of theca cells and reveal a multicellular interaction critical for the formation of a functional theca. PMID:25917826

  12. The EHV-1 UL4 protein that tempers viral gene expression interacts with cellular transcription factors.

    Science.gov (United States)

    Zhang, Yunfei; Charvat, Robert A; Kim, Seong K; O'Callaghan, Dennis J

    2014-01-20

    The UL4 gene is conserved within the genome of defective interfering particles of equine herpesvirus type 1 (EHV-1) that mediate persistent infection. Here, we show that the UL4 protein inhibits EHV-1 reporter gene expression by decreasing the level of transcribed mRNA. The UL4 protein did not bind any gene class of EHV-1 promoters in electromobility or chromatin immunoprecipitation assays, but directly interacted with the TATA box-binding protein (TBP) and the carboxy-terminal domain of RNA polymerase II both in vitro (GST-pulldown assays) and in infected cells (coimmunoprecipitation analyses). Microarray analyses of the expression of the 78 EHV-1 genes revealed that viral late genes important for virion assembly displayed enhanced expression in cells infected with UL4-null virus as compared to wild-type or UL4-restored EHV-1. Quantitative PCR analyses showed that viral DNA replication was not retarded in cells infected with the UL4-null virus as compared to wild-type EHV-1.

  13. Mechanism of Laser/light beam interaction at cellular and tissue level and study of the influential factors for the application of low level laser therapy

    OpenAIRE

    2016-01-01

    After the discovery of laser therapy it was realized it has useful application of wound healing and reduce pain, but due to the poor understanding of the mechanism and dose response this technique remained to be controversial for therapeutic applications. In order to understand the working and effectiveness different experiments were performed to determine the laser beam effect at the cellular and tissue level. This article discusses the mechanism of beam interaction at tissues and cellular l...

  14. High-Aspect Ratio Bio-Metallic Nanocomposites for Cellular Interactions

    Science.gov (United States)

    Deodhar, Sneha; Huckaby, Justin; Delahoussaye, Miles; DeCoster, Mark A.

    2014-08-01

    We synthesized high aspect ratio composites with biological and metal components. Scanning electron microscopy (SEM) and Transmission Electron Microscopy (TEM) revealed linear morphology and smooth surface texture. SEM, TEM and light microscopy showed that composites have scalable dimensions from nano- to micro-, with diameters as low as 60 nm, lengths exceeding 150 pm, and average aspect ratio of 100. The structures are stable, remaining intact for over one year in dried form and in liquid, and did not aggregate, in contrast to metal nanoparticles such as iron and copper. Many metal nanoparticles are toxic to cells, limiting their use for biological applications. The bio-metallic composites characterized here showed lower toxicity compared to their precursor metal nanoparticles in brain tumor cell cultures. Due to these more biocompatible properties, we tested the ability of the composites to interact with cells. Zeta potential analysis indicated that composites carry a net negative charge (-24.3 ± 2.2 mV), while the starting metal nanoparticles measured (43.3 ± 2.4 mV). We labeled the composites with poly-l-lysine fluorescein isothiocyanate (PLL-FITC), which shifted the potential to 3.5 ± 2.9 mV. It was observed by fluorescence microscopy that composites smaller than cells were internalized by some cells and larger composites remained outside. Cells became fluorescent over time due to leakage of PLL-FITC from the composites which lost fluorescence over time. Higher biocompatibility, low aggregation, and ability to control size distribution of the linear composites may make them ideal vehicles to deliver drugs or other materials to cells, and may be used as a scaffolding material for cells.

  15. Cellular interactions of the cytolethal distending toxins from Escherichia coli and Haemophilus ducreyi.

    Science.gov (United States)

    Gargi, Amandeep; Tamilselvam, Batcha; Powers, Brendan; Prouty, Michael G; Lincecum, Tommie; Eshraghi, Aria; Maldonado-Arocho, Francisco J; Wilson, Brenda A; Bradley, Kenneth A; Blanke, Steven R

    2013-03-15

    The cytolethal distending toxins (CDTs) compose a subclass of intracellularly acting genotoxins produced by many Gram-negative pathogenic bacteria that disrupt the normal progression of the eukaryotic cell cycle. Here, the intoxication mechanisms of CDTs from Escherichia coli (Ec-CDT) and Haemophilus ducreyi (Hd-CDT), which share limited amino acid sequence homology, were directly compared. Ec-CDT and Hd-CDT shared comparable in vitro DNase activities of the CdtB subunits, saturable cell surface binding with comparable affinities, and the requirement for an intact Golgi complex to induce cell cycle arrest. In contrast, disruption of endosome acidification blocked Hd-CDT-mediated cell cycle arrest and toxin transport to the endoplasmic reticulum and nucleus, while having no effects on Ec-CDT. Phosphorylation of the histone protein H2AX, as well as nuclear localization, was inhibited for Hd-CdtB, but not Ec-CdtB, in cells expressing dominant negative Rab7 (T22N), suggesting that Hd-CDT, but not Ec-CDT, is trafficked through late endosomal vesicles. In support of this idea, significantly more Hd-CdtB than Ec-CdtB co-localized with Rab9, which is enriched in late endosomal compartments. Competitive binding studies suggested that Ec-CDT and Hd-CDT bind to discrete cell surface determinants. These results suggest that Ec-CDT and Hd-CDT are transported within cells by distinct pathways, possibly mediated by their interaction with different receptors at the cell surface.

  16. Modeling Laser-Plasma Interactions at Direct-Drive Ignition-Relevant Plasma Conditions at the National Ignition Facility

    Science.gov (United States)

    Solodov, A. A.; Rosenberg, M. J.; Myatt, J. F.; Epstein, R.; Seka, W.; Hohenberger, M.; Short, R. W.; Shaw, J. G.; Regan, S. P.; Froula, D. H.; Radha, P. B.; Bates, J. W.; Schmitt, A. J.; Michel, P.; Moody, J. D.; Ralph, J. E.; Turnbull, D. P.; Barrios, M. A.

    2016-10-01

    Laser-plasma interaction instabilities, such as two-plasmon decay (TPD) and stimulated Raman scattering (SRS), can be detrimental for direct-drive inertial confinement fusion because of target preheat by generated high-energy electrons. The radiation-hydrodynamics code DRACO has been used to design planar-target experiments that generate plasma and interaction conditions relevant to direct-drive-ignition designs (IL 1015 W / cm 2 , Te > 3 KeV density gradient scale lengths of Ln 600 μm) . The hot-electron temperature of 40to50keV and the fraction of laser energy converted to hot electrons of 0.5to were inferred based on comparing the simulated and experimentally observed x-ray emission when the laser intensity at the quarter-critical surface increased from 6 to 15 ×1014 W / cm 2 . The measured SRS energy was sufficient to explain the observed total energy in hot electrons. Implications for ignition-scale direct-drive experiments and hot-electron preheat mitigation using mid- Z ablators will be discussed. This material is based upon work supported by the Department of Energy National Nuclear Security Administration under Award Number DE-NA0001944.

  17. The Protein Corona of Plant Virus Nanoparticles Influences their Dispersion Properties, Cellular Interactions, and In Vivo Fates.

    Science.gov (United States)

    Pitek, Andrzej S; Wen, Amy M; Shukla, Sourabh; Steinmetz, Nicole F

    2016-04-06

    Biomolecules in bodily fluids such as plasma can adsorb to the surface of nanoparticles and influence their biological properties. This phenomenon, known as the protein corona, is well established in the field of synthetic nanotechnology but has not been described in the context of plant virus nanoparticles (VNPs). The interaction between VNPs derived from Tobacco mosaic virus (TMV) and plasma proteins is investigated, and it is found that the VNP protein corona is significantly less abundant compared to the corona of synthetic particles. The formed corona is dominated by complement proteins and immunoglobulins, the binding of which can be reduced by PEGylating the VNP surface. The impact of the VNP protein corona on molecular recognition and cell targeting in the context of cancer and thrombosis is investigated. A library of functionalized TMV rods with polyethylene glycol (PEG) and peptide ligands targeting integrins or fibrin(ogen) show different dispersion properties, cellular interactions, and in vivo fates depending on the properties of the protein corona, influencing target specificity, and non-specific scavenging by macrophages. Our results provide insight into the in vivo properties of VNPs and suggest that the protein corona effect should be considered during the development of efficacious, targeted VNP formulations.

  18. Genomic amplification of Fanconi anemia complementation group A (FancA) in head and neck squamous cell carcinoma (HNSCC): Cellular mechanisms of radioresistance and clinical relevance.

    Science.gov (United States)

    Hess, Julia; Unger, Kristian; Orth, Michael; Schötz, Ulrike; Schüttrumpf, Lars; Zangen, Verena; Gimenez-Aznar, Igor; Michna, Agata; Schneider, Ludmila; Stamp, Ramona; Selmansberger, Martin; Braselmann, Herbert; Hieber, Ludwig; Drexler, Guido A; Kuger, Sebastian; Klein, Diana; Jendrossek, Verena; Friedl, Anna A; Belka, Claus; Zitzelsberger, Horst; Lauber, Kirsten

    2017-02-01

    Radio (chemo) therapy is a crucial treatment modality for head and neck squamous cell carcinoma (HNSCC), but relapse is frequent, and the underlying mechanisms remain largely elusive. Therefore, novel biomarkers are urgently needed. Previously, we identified gains on 16q23-24 to be associated with amplification of the Fanconi anemia A (FancA) gene and to correlate with reduced progression-free survival after radiotherapy. Here, we analyzed the effects of FancA on radiation sensitivity in vitro, characterized the underlying mechanisms, and evaluated their clinical relevance. Silencing of FancA expression in HNSCC cell lines with genomic gains on 16q23-24 resulted in significantly impaired clonogenic survival upon irradiation. Conversely, overexpression of FancA in immortalized keratinocytes conferred increased survival accompanied by improved DNA repair, reduced accumulation of chromosomal translocations, but no hyperactivation of the FA/BRCA-pathway. Downregulation of interferon signaling as identified by microarray analyses, enforced irradiation-induced senescence, and elevated production of the senescence-associated secretory phenotype (SASP) appeared to be candidate mechanisms contributing to FancA-mediated radioresistance. Data of the TCGA HNSCC cohort confirmed the association of gains on 16q24.3 with FancA overexpression and impaired overall survival. Importantly, transcriptomic alterations similar to those observed upon FancA overexpression in vitro strengthened the clinical relevance. Overall, FancA amplification and overexpression appear to be crucial for radiotherapeutic failure in HNSCC.

  19. NMDA and PACAP receptor signaling interact to mediate retinal-induced scn cellular rhythmicity in the absence of light.

    Directory of Open Access Journals (Sweden)

    Ian C Webb

    Full Text Available The "core" region of the suprachiasmatic nucleus (SCN, a central clock responsible for coordinating circadian rhythms, shows a daily rhythm in phosphorylation of extracellular regulated kinase (pERK. This cellular rhythm persists under constant darkness and, despite the absence of light, is dependent upon inputs from the eye. The neural signals driving this rhythmicity remain unknown and here the roles of glutamate and PACAP are examined. First, rhythmic phosphorylation of the NR1 NMDA receptor subunit (pNR1, a marker for receptor activation was shown to coincide with SCN core pERK, with a peak at circadian time (CT 16. Enucleation and intraocular TTX administration attenuated the peak in the pERK and pNR1 rhythms, demonstrating that activation of the NMDA receptor and ERK in the SCN core at CT16 are dependent on retinal inputs. In contrast, ERK and NR1 phosphorylation in the SCN shell region were unaffected by these treatments. Intraventricular administration of the NMDA receptor antagonist MK-801 also attenuated the peak in SCN core pERK, indicating that ERK phosphorylation in this region requires NMDA receptor activation. As PACAP is implicated in photic entrainment and is known to modulate glutamate signaling, the effects of a PAC1 receptor antagonist (PACAP 6-38 on SCN core pERK and pNR1 also were examined. PACAP 6-38 administration attenuated SCN core pERK and pNR1, suggesting that PACAP induces pERK directly, and indirectly via a modulation of NMDA receptor signaling. Together, these data indicate that, in the absence of light, retinal-mediated NMDA and PAC1 receptor activation interact to induce cellular rhythms in the SCN core. These results highlight a novel function for glutamate and PACAP release in the hamster SCN apart from their well-known roles in the induction of photic circadian clock resetting.

  20. Graphene nanoplatelets spontaneously translocate into the cytosol and physically interact with cellular organelles in the fish cell line PLHC-1

    Energy Technology Data Exchange (ETDEWEB)

    Lammel, Tobias; Navas, José M., E-mail: jmnavas@inia.es

    2014-05-01

    Highlights: • We assessed the cytotoxicity and uptake of graphene nanomaterials in PLHC-1 cells. • GO and CXYG nanoplatelets caused physical injury of the plasma membrane. • GO and CXYG accumulated in the cytosol and interacted with cellular organelles. • PLHC-1 cells exposed to GO/CXYG demonstrated high ROS levels but low cytotoxicity. • ROS formation was related with GO/CXYG-induced structural damage of mitochondria. - Abstract: Graphene and graphene derivatives constitute a novel class of carbon-based nanomaterials being increasingly produced and used in technical and consumer applications. Release of graphene nanoplatelets during the life cycle of these applications may result in human and environmental exposure calling for assessment of their potential to cause harm to humans and wildlife. This study aimed to assess the toxicity of graphene oxide (GO) and carboxyl graphene (CXYG) nanoplatelets to non-mammalian species using the fish cell line PLHC-1 as in vitro model. The cytotoxicity of GO and CXYG was assessed using different assays measuring alterations in plasma membrane integrity, metabolic activity, and lysosomal and mitochondrial function. The induction of oxidative stress was assessed by measuring intracellular reactive oxygen species (ROS) levels. Interaction with the plasma membrane and internalization of nanoplatelets were investigated by electron microscopy. Graphene nanoplatelets spontaneously penetrated through the plasma membrane and accumulated in the cytosol, where they further interacted with mitochondrial and nuclear membranes. PLHC-1 cells demonstrated significantly reduced mitochondrial membrane potential (MMP) and increased ROS levels at 16 μg/ml GO and CXYG (72 h), but barely any decrease in cell viability. The observation of intracellular graphene accumulations not enclosed by membranes suggests that GO and CXYG internalization in fish hepatoma cells occurs through an endocytosis-independent mechanism.

  1. Planar Laser-Plasma Interaction Experiments at Direct-Drive Ignition-Relevant Scale Lengths at the National Ignition Facility

    Science.gov (United States)

    Rosenberg, M. J.; Solodov, A. A.; Seka, W.; Myatt, J. F.; Regan, S. P.; Hohenberger, M.; Epstein, R.; Froula, D. H.; Radha, P. B.; Michel, P. A.; Moody, J. D.; Masse, L.; Goyon, C.; Turnbull, D. P.; Barrios, M. A.; Bates, J. W.; Schmitt, A. J.

    2016-10-01

    The first experiments at the National Ignition Facility to probe laser-plasma interactions and the hot electron production at scale lengths relevant to direct-drive ignition are reported. The irradiation on one side of planar CH foils generated a plasma at the quarter-critical surface with predicted density scale lengths of Ln 600 μm, measured electron temperatures of Te 3.5 to 4.0 keV, and overlapped laser intensities of I 6 to 15 ×1014W/cm2. Optical emission from stimulated Raman scattering (SRS) and at ω/2 are correlated with the time-dependent hard x-ray signal. The fraction of laser energy converted to hot electrons increased from 0.5 % to 2.3 % as the laser intensity increased from 6 to 15 ×1014W/cm2, while the hot electron temperature was nearly constant around 40 to 50 keV. Only a sharp red-shifted feature is observed around ω/2, and both refracted and sidescattered SRS are detected, suggesting that multibeam SRS contributes to, and may even dominate, hot-electron production. These results imply a diminished presence of two-plasmon decay relative to SRS at these conditions, which has implications for hot-electron preheat mitigation strategies for direct-drive ignition. This work is supported by the DOE NNSA under Award Number DE-NA0001944.

  2. Hierarchthis: An Interactive Interface for Identifying Mission-Relevant Components of the Advanced Multi-Mission Operations System

    Science.gov (United States)

    Litomisky, Krystof

    2012-01-01

    Even though NASA's space missions are many and varied, there are some tasks that are common to all of them. For example, all spacecraft need to communicate with other entities, and all spacecraft need to know where they are. These tasks use tools and services that can be inherited and reused between missions, reducing systems engineering effort and therefore reducing cost.The Advanced Multi-Mission Operations System, or AMMOS, is a collection of multimission tools and services, whose development and maintenance are funded by NASA. I created HierarchThis, a plugin designed to provide an interactive interface to help customers identify mission-relevant tools and services. HierarchThis automatically creates diagrams of the AMMOS database, and then allows users to show/hide specific details through a graphical interface. Once customers identify tools and services they want for a specific mission, HierarchThis can automatically generate a contract between the Multimission Ground Systems and Services Office, which manages AMMOS, and the customer. The document contains the selected AMMOS components, along with their capabilities and satisfied requirements. HierarchThis reduces the time needed for the process from service selections to having a mission-specific contract from the order of days to the order of minutes.

  3. Interaction of cadmium and zinc on accumulation and sub-cellular distribution in leaves of hyperaccumulator Potentilla griffithii

    Energy Technology Data Exchange (ETDEWEB)

    Qiu Rongliang, E-mail: eesqrl@mail.sysu.edu.cn [School of Environmental Science and Engineering, Sun Yat-Sen University, Guangzhou 510275 (China); Guangdong Provincial Key Lab of Environmental Pollution Control and Remediation Technology, Guangzhou 510275 (China); Thangavel, Palaniswamy; Hu Pengjie; Senthilkumar, Palaninaicker; Ying Rongrong [School of Environmental Science and Engineering, Sun Yat-Sen University, Guangzhou 510275 (China); Tang Yetao [School of Environmental Science and Engineering, Sun Yat-Sen University, Guangzhou 510275 (China); Guangdong Provincial Key Lab of Environmental Pollution Control and Remediation Technology, Guangzhou 510275 (China)

    2011-02-28

    Potentilla griffithii Hook is a newly found hyperaccumulator plant capable of high tolerance and accumulation of Zn and Cd. We investigated the interactive effects between Cd and Zn on accumulation and vacuolar sequestration in P. griffithii. Stimulatory effect of growth was noted at 0.2 mM Cd and 1.25 and 2.5 mM Zn tested. Accumulation of Zn and Cd in roots, petioles and leaves were increased significantly with addition of these metals individually. However, the Zn supplement decreased root Cd accumulation but increased the concentration of Cd in petioles and leaves. The results from sub-cellular distribution showed that up to 94% and 70% of the total Zn and Cd in the leaves were present in the protoplasts, and more than 90% Cd and Zn in the protoplasts were localized in the vacuoles. Nearly, 88% and 85% of total Cd and Zn were extracted in the cell sap of the leaves suggesting that most of the Cd and Zn in the leaves were available in soluble form. The present results indicate that Zn supplement significantly enhanced the petiole accumulation of Cd and further vacuolar sequestration plays an important role in tolerance, detoxification and hyperaccumulation of these metals in P. griffithii.

  4. Cellular Interactions and Biological Responses to Titanium Dioxide Nanoparticles in HepG2 and BEAS-2B Cells: Role of Cell Culture Media

    Science.gov (United States)

    ABSTRACT We have shown previously that the composition of the biological medium used in vitro can affect the cellular interaction and biological response of titanium dioxide nanoparticles (nano-TiO2) in human lung epithelial cells. However, it is unclear if these effects are co...

  5. The cellular prion protein interacts with the tissue non-specific alkaline phosphatase in membrane microdomains of bioaminergic neuronal cells.

    Directory of Open Access Journals (Sweden)

    Myriam Ermonval

    Full Text Available BACKGROUND: The cellular prion protein, PrP(C, is GPI anchored and abundant in lipid rafts. The absolute requirement of PrP(C in neurodegeneration associated to prion diseases is well established. However, the function of this ubiquitous protein is still puzzling. Our previous work using the 1C11 neuronal model, provided evidence that PrP(C acts as a cell surface receptor. Besides a ubiquitous signaling function of PrP(C, we have described a neuronal specificity pointing to a role of PrP(C in neuronal homeostasis. 1C11 cells, upon appropriate induction, engage into neuronal differentiation programs, giving rise either to serotonergic (1C11(5-HT or noradrenergic (1C11(NE derivatives. METHODOLOGY/PRINCIPAL FINDINGS: The neuronal specificity of PrP(C signaling prompted us to search for PrP(C partners in 1C11-derived bioaminergic neuronal cells. We show here by immunoprecipitation an association of PrP(C with an 80 kDa protein identified by mass spectrometry as the tissue non-specific alkaline phosphatase (TNAP. This interaction occurs in lipid rafts and is restricted to 1C11-derived neuronal progenies. Our data indicate that TNAP is implemented during the differentiation programs of 1C11(5-HT and 1C11(NE cells and is active at their cell surface. Noteworthy, TNAP may contribute to the regulation of serotonin or catecholamine synthesis in 1C11(5-HT and 1C11(NE bioaminergic cells by controlling pyridoxal phosphate levels. Finally, TNAP activity is shown to modulate the phosphorylation status of laminin and thereby its interaction with PrP. CONCLUSION/SIGNIFICANCE: The identification of a novel PrP(C partner in lipid rafts of neuronal cells favors the idea of a role of PrP in multiple functions. Because PrP(C and laminin functionally interact to support neuronal differentiation and memory consolidation, our findings introduce TNAP as a functional protagonist in the PrP(C-laminin interplay. The partnership between TNAP and PrP(C in neuronal cells may

  6. Mechanism of Laser/light beam interaction at cellular and tissue level and study of the influential factors for the application of low level laser therapy

    CERN Document Server

    Khalid, Muhammad Zeeshan

    2016-01-01

    After the discovery of laser therapy it was realized it has useful application of wound healing and reduce pain, but due to the poor understanding of the mechanism and dose response this technique remained to be controversial for therapeutic applications. In order to understand the working and effectiveness different experiments were performed to determine the laser beam effect at the cellular and tissue level. This article discusses the mechanism of beam interaction at tissues and cellular level with different light sources and dosimetry principles for clinical application of low level laser therapy. Different application techniques and methods currently in use for clinical treatment has also been reviewed.

  7. The interaction of the cellular export adaptor protein Aly/REF with ICP27 contributes to the efficiency of herpes simplex virus 1 mRNA export.

    Science.gov (United States)

    Tian, Xiaochen; Devi-Rao, Gayathri; Golovanov, Alexander P; Sandri-Goldin, Rozanne M

    2013-07-01

    Herpes simplex virus 1 (HSV-1) protein ICP27 enables viral mRNA export by accessing the cellular mRNA export receptor TAP/NXF, which guides mRNA through the nuclear pore complex. ICP27 binds viral mRNAs and interacts with TAP/NXF, providing a link to the cellular mRNA export pathway. ICP27 also interacts with the mRNA export adaptor protein Aly/REF, which binds cellular mRNAs and also interacts with TAP/NXF. Studies using small interfering RNA (siRNA) knockdown indicated that Aly/REF is not required for cellular mRNA export, and similar knockdown studies during HSV-1 infection led us to conclude that Aly/REF may be dispensable for viral RNA export. Recently, the structural basis of the interaction of ICP27 with Aly/REF was elucidated at atomic resolution, and it was shown that three ICP27 residues, W105, R107, and L108, interface with the RNA recognition motif (RRM) domain of Aly/REF. Here, to determine the role the interaction of ICP27 and Aly/REF plays during infection, these residues were mutated to alanine, and a recombinant virus, WRL-A, was constructed. Virus production was reduced about 10-fold during WRL-A infection, and export of ICP27 protein and most viral mRNAs was less efficient. We conclude that interaction of ICP27 with Aly/REF contributes to efficient viral mRNA export.

  8. 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.

  9. The terrestrial isopod microbiome: An all-in-one toolbox for animal-microbe interactions of ecological relevance

    Directory of Open Access Journals (Sweden)

    Didier Bouchon

    2016-09-01

    Full Text Available Bacterial symbionts represent essential drivers of arthropod ecology and evolution, influencing host traits such as nutrition, reproduction, immunity and speciation. However, the majority of work on arthropod microbiota has been conducted in insects and more studies in non-model species across different ecological niches will be needed to complete our understanding of host-microbiota interactions. In this review, we present terrestrial isopod crustaceans as an emerging model organism to investigate symbiotic associations with potential relevance to ecosystem functioning. Terrestrial isopods comprise a group of crustaceans that have evolved a terrestrial lifestyle and represent keystone species in terrestrial ecosystems, contributing to the decomposition of organic matter and regulating the microbial food web. Since their nutrition is based on plant detritus, it has long been suspected that bacterial symbionts located in the digestive tissues might play an important role in host nutrition via the provisioning of digestive enzymes, thereby enabling the utilization of recalcitrant food compounds (e.g. cellulose or lignins. If this were the case, then (i the acquisition of these bacteria might have been an important evolutionary prerequisite for the colonization of land by isopods, and (ii these bacterial symbionts would directly mediate the role of their hosts in ecosystem functioning. Several bacterial symbionts have indeed been discovered in the midgut caeca of terrestrial isopods and some of them might be specific to this group of animals (i.e. Candidatus Hepatoplasma crinochetorum, Candidatus Hepatincola porcellionum and Rhabdochlamydia porcellionis, while others are well-known intracellular pathogens (Rickettsiella spp. or reproductive parasites (Wolbachia sp.. Moreover, a recent investigation of the microbiota in Armadillidium vulgare has revealed that this species harbors a highly diverse bacterial community which varies between host

  10. The Terrestrial Isopod Microbiome: An All-in-One Toolbox for Animal–Microbe Interactions of Ecological Relevance

    Science.gov (United States)

    Bouchon, Didier; Zimmer, Martin; Dittmer, Jessica

    2016-01-01

    Bacterial symbionts represent essential drivers of arthropod ecology and evolution, influencing host traits such as nutrition, reproduction, immunity, and speciation. However, the majority of work on arthropod microbiota has been conducted in insects and more studies in non-model species across different ecological niches will be needed to complete our understanding of host–microbiota interactions. In this review, we present terrestrial isopod crustaceans as an emerging model organism to investigate symbiotic associations with potential relevance to ecosystem functioning. Terrestrial isopods comprise a group of crustaceans that have evolved a terrestrial lifestyle and represent keystone species in terrestrial ecosystems, contributing to the decomposition of organic matter and regulating the microbial food web. Since their nutrition is based on plant detritus, it has long been suspected that bacterial symbionts located in the digestive tissues might play an important role in host nutrition via the provisioning of digestive enzymes, thereby enabling the utilization of recalcitrant food compounds (e.g., cellulose or lignins). If this were the case, then (i) the acquisition of these bacteria might have been an important evolutionary prerequisite for the colonization of land by isopods, and (ii) these bacterial symbionts would directly mediate the role of their hosts in ecosystem functioning. Several bacterial symbionts have indeed been discovered in the midgut caeca of terrestrial isopods and some of them might be specific to this group of animals (i.e., Candidatus Hepatoplasma crinochetorum, Candidatus Hepatincola porcellionum, and Rhabdochlamydia porcellionis), while others are well-known intracellular pathogens (Rickettsiella spp.) or reproductive parasites (Wolbachia sp.). Moreover, a recent investigation of the microbiota in Armadillidium vulgare has revealed that this species harbors a highly diverse bacterial community which varies between host populations

  11. A cellular stress response (CSR) that interacts with NADPH-P450 reductase (NPR) is a new regulator of hypoxic response.

    Science.gov (United States)

    Oguro, Ami; Koyama, Chika; Xu, Jing; Imaoka, Susumu

    2014-02-28

    NADPH-P450 reductase (NPR) was previously found to contribute to the hypoxic response of cells, but the mechanism was not clarified. In this study, we identified a cellular stress response (CSR) as a new factor interacting with NPR by a yeast two-hybrid system. Overexpression of CSR enhanced the induction of erythropoietin and hypoxia response element (HRE) activity under hypoxia in human hepatocarcinoma cell lines (Hep3B), while knockdown of CSR suppressed them. This new finding regarding the interaction of NPR with CSR provides insight into the function of NPR in hypoxic response.

  12. The interaction of short-chain fatty acids with adipose tissue : relevance for prevention of type 2 diabetes

    NARCIS (Netherlands)

    Roelofsen, H.; Priebe, M. G.; Vonk, R. J.

    2010-01-01

    Short chain fatty acids (SCFA) are the main bacterial metabolites of colonic fermentation processes. The physiological relevance of the SCFA for the host outside the gastrointestinal tract is getting increased attention. In this review we will focus on the effect of SCFA on inflammation processes in

  13. The influence of surface charge on serum protein interaction and cellular uptake: studies with dendritic polyglycerols and dendritic polyglycerol-coated gold nanoparticles

    Science.gov (United States)

    Bewersdorff, Tony; Vonnemann, Jonathan; Kanik, Asiye; Haag, Rainer; Haase, Andrea

    2017-01-01

    Nanoparticles (NPs) have gained huge interest in the medical field, in particular for drug delivery purposes. However, binding of proteins often leads to fast NP uptake and rapid clearance, thereby hampering medical applications. Thus, it is essential to determine and control the bio–nano interface. This study investigated the serum protein interactions of dendritic polyglycerols (dPGs), which are promising drug delivery candidates by means of two dimensional gel electrophoresis (2DE) in combination with mass spectrometry. In order to investigate the influence of surface charge, sulfated (sulfated dendritic polyglycerol [dPGS]) and non-sulfated (dPGOH) surfaces were applied, which were synthesized on a gold core allowing for easier separation from unbound biomolecules through centrifugation. Furthermore, two different sizes for dPGS were included. Although size had only a minor influence, considerable differences were detected in protein affinity for dPGS versus dPGOH surfaces, with dPGOH binding much less proteins. Cellular uptake into human CD14+ monocytes was analyzed by flow cytometry, and dPGOH was taken up to a much lower extent compared to dPGS. By using a pull-down approach, possible cellular interaction partners of serum pre-incubated dPGS-Au20 NPs from the membrane fraction of THP-1 cells could be identified such as for instance the transferrin receptor or an integrin. Clathrin-mediated endocytosis was further investigated using chlorpromazine as an inhibitor, which resulted in a 50% decrease of the cellular uptake of dPGS. This study could confirm the influence of surface charge on protein interactions and cellular uptake of dPGS. Furthermore, the approach allowed for the identification of possible uptake receptors and insights into the uptake mechanism. PMID:28352171

  14. Incidence rate and pattern of clinically relevant potential drug-drug interactions in a large outpatient population of a developing country

    Directory of Open Access Journals (Sweden)

    Ehsan Nabovati

    2016-01-01

    Full Text Available The objective of this study was to determine incidence rate, type, and pattern of clinically relevant potential drug-drug interactions (pDDIs in a large outpatient population of a developing country. A retrospective, descriptive cross-sectional study was conducted on outpatients’ prescriptions in Khorasan Razavi province, Iran, over 12 months. A list of 25 clinically relevant DDIs, which are likely to occur in the outpatient setting, was used as the reference. Most frequent clinically relevant pDDIs, most common drugs contributing to the pDDIs, and the pattern of pDDIs for each medical specialty were determined. Descriptive statistics were used to report the results. In total, out of 8,169,142 prescriptions, 6,096 clinically relevant pDDIs were identified. The most common identified pDDIs were theophyllines-quinolones, warfarin-nonsteroidal anti-inflammatory drugs, benzodiazepines-azole antifungal agents, and anticoagulants-thyroid hormones. The most common drugs contributing to the identified pDDIs were ciprofloxacin, theophylline, warfarin, aminophylline, alprazolam, levothyroxine, and selegiline. While the incidence rate of clinically relevant pDDIs in prescriptions of general practitioners, internists, and cardiologists was the highest, the average pDDI incidence per 10,000 prescriptions of pulmonologists, infectious disease specialists, and cardiologists was highest. Although a small proportion of the analyzed prescriptions contained drug pairs with potential for clinically relevant DDIs, a significant number of outpatients have been exposed to the adverse effects associated with these interactions. It is recommended that in addition to training physicians and pharmacists, other effective interventions such as computerized alerting systems and electronic prescribing systems be designed and implemented.

  15. Surface-supported Ag islands stabilized by a quantum size effect: Their interaction with small molecules relevant to ethylene epoxidation

    Energy Technology Data Exchange (ETDEWEB)

    Shao, Dahai [Iowa State Univ., Ames, IA (United States)

    2013-05-15

    This dissertation focuses on how QSE-stabilized, surface-supported Ag nanoclusters will interact with ethylene or oxygen. Experiments are performed to determine whether the QSE-mediated Ag islands react differently toward adsorption of ethylene or oxygen, or whether the adsorption of these small molecules will affect the QSE-mediated stability of Ag islands. Studies of the interaction of oxygen with Ag/Si(111)-7×7 were previously reported, but these studies were performed at a low Ag coverage where 3D Ag islands were not formed. So the study of such a system at a higher Ag coverage will be a subject of this work. The interaction of ethylene with Ag/Si(111)-7×7, as well as the interaction of oxygen with Ag/NiAl(110) are also important parts of this study.

  16. Interactions of metal ions with DNA, its constituents and derivatives, which may be relevant for anticancer research.

    Science.gov (United States)

    Turel, Iztok; Kljun, Jakob

    2011-01-01

    In this review several types of interactions between metal ions and DNA are given, starting from basic binding to the use of metal complexes in cancer treatment and diagnostics. Metal cations help to neutralize the negative charge of DNA and thus enable the normal functions of DNA but many other interactions are also possible and are discussed in this paper. Various consequences of such interactions can be reversible (e. g. conformational changes) or irreversible (e. g. cleavage). It is known that some metal ions can also damage DNA which can provoke mutations and in some cases leads to cancer. It is clear that we know a lot about metal-DNA interactions but much more information is needed to understand the role of metal ions completely and to use this knowledge successfully.

  17. Accumulated SET protein up-regulates and interacts with hnRNPK, increasing its binding to nucleic acids, the Bcl-xS repression, and cellular proliferation.

    Science.gov (United States)

    Almeida, Luciana O; Garcia, Cristiana B; Matos-Silva, Flavia A; Curti, Carlos; Leopoldino, Andréia M

    2014-02-28

    SET and hnRNPK are proteins involved in gene expression and regulation of cellular signaling. We previously demonstrated that SET accumulates in head and neck squamous cell carcinoma (HNSCC); hnRNPK is a prognostic marker in cancer. Here, we postulate that SET and hnRNPK proteins interact to promote tumorigenesis. We performed studies in HEK293 and HNSCC (HN6, HN12, and HN13) cell lines with SET/hnRNPK overexpression and knockdown, respectively. We found that SET and/or hnRNPK protein accumulation increased cellular proliferation. SET accumulation up-regulated hnRNPK mRNA and total/phosphorylated protein, promoted hnRNPK nuclear location, and reduced Bcl-x mRNA levels. SET protein directly interacted with hnRNPK, increasing both its binding to nucleic acids and Bcl-xS repression. We propose that hnRNPK should be a new target of SET and that SET-hnRNPK interaction, in turn, has potential implications in cell survival and malignant transformation.

  18. Accumulated SET protein up-regulates and interacts with hnRNPK, increasing its binding to nucleic acids, the Bcl-xS repression, and cellular proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Almeida, Luciana O.; Garcia, Cristiana B.; Matos-Silva, Flavia A. [Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP (Brazil); Curti, Carlos [Department of Physics and Chemistry, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP (Brazil); Leopoldino, Andréia M., E-mail: andreiaml@usp.br [Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP (Brazil)

    2014-02-28

    Highlights: • hnRNPK is a new target of SET. • SET regulates hnRNPK. • SET and hnRNPK accumulation promotes tumorigenesis. • SET accumulation is a potential model to study genes regulated by SET-hnRNPK. - Abstract: SET and hnRNPK are proteins involved in gene expression and regulation of cellular signaling. We previously demonstrated that SET accumulates in head and neck squamous cell carcinoma (HNSCC); hnRNPK is a prognostic marker in cancer. Here, we postulate that SET and hnRNPK proteins interact to promote tumorigenesis. We performed studies in HEK293 and HNSCC (HN6, HN12, and HN13) cell lines with SET/hnRNPK overexpression and knockdown, respectively. We found that SET and/or hnRNPK protein accumulation increased cellular proliferation. SET accumulation up-regulated hnRNPK mRNA and total/phosphorylated protein, promoted hnRNPK nuclear location, and reduced Bcl-x mRNA levels. SET protein directly interacted with hnRNPK, increasing both its binding to nucleic acids and Bcl-xS repression. We propose that hnRNPK should be a new target of SET and that SET–hnRNPK interaction, in turn, has potential implications in cell survival and malignant transformation.

  19. The MnSOD Ala16Val SNP: relevance to human diseases and interaction with environmental factors.

    Science.gov (United States)

    Bresciani, G; Cruz, I B M; de Paz, J A; Cuevas, M J; González-Gallego, J

    2013-10-01

    The relevance of reactive oxygen species (ROS) production relies on the dual role shown by these molecules in aerobes. ROS are known to modulate several physiological phenomena, such as immune response and cell growth and differentiation; on the other hand, uncontrolled ROS production may cause important tissue and cell damage, such as deoxyribonucleic acid oxidation, lipid peroxidation, and protein carbonylation. The manganese superoxide dismutase (MnSOD) antioxidant enzyme affords the major defense against ROS within the mitochondria, which is considered the main ROS production locus in aerobes. Structural and/or functional single nucleotide polymorphisms (SNP) within the MnSOD encoding gene may be relevant for ROS detoxification. Specifically, the MnSOD Ala16Val SNP has been shown to alter the enzyme localization and mitochondrial transportation, affecting the redox status balance. Oxidative stress may contribute to the development of type 2 diabetes, cardiovascular diseases, various inflammatory conditions, or cancer. The Ala16Val MnSOD SNP has been associated with these and other chronic diseases; however, inconsistent findings between studies have made difficult drawing definitive conclusions. Environmental factors, such as dietary antioxidant intake and exercise have been shown to affect ROS metabolism through antioxidant enzyme regulation and may contribute to explain inconsistencies in the literature. Nevertheless, whether environmental factors may be associated to the Ala16Val genotypes in human diseases still needs to be clarified.

  20. Cu(II)-vitamin D interaction leads to free radical-mediated cellular DNA damage: a novel putative mechanism for its selective cytotoxic action against malignant cells.

    Science.gov (United States)

    Rizvi, Asim; Chibber, Sandesh; Naseem, Imrana

    2015-03-01

    Vitamin D (vit D) is a known anticancer molecule, and cancer cells are reported to have elevated levels of Cu(II) ions. In this study, we show that interaction of vit D and Cu(II) leads to the formation of hydroxyl free radicals, superoxide anion and hydrogen peroxide, which causes severe oxidative stress, selectively in malignant cells. We show that the production of these reactive oxygen species causes cellular DNA fragmentation which may cause cell death. A novel putative chemical mechanism explaining how vit D causes cell death by DNA damage, selectively in malignant cells, is proposed.

  1. Is glutathione the major cellular target of cisplatin? A study of the interactions of cisplatin with cancer cell extracts.

    Science.gov (United States)

    Kasherman, Yonit; Sturup, Stefan; Gibson, Dan

    2009-07-23

    Cisplatin is an anticancer drug whose efficacy is limited because tumors develop resistance to the drug. Resistant cells often have elevated levels of cellular glutathione (GSH), believed to be the major cellular target of cisplatin that inactivates the drug by binding to it irreversibly, forming [Pt(SG)(2)] adducts. We show by [(1)H,(15)N] HSQC that the half-life of (15)N labeled cisplatin in whole cell extracts is approximately 75 min, but no Pt-GSH adducts were observed. When the low molecular mass fraction (cisplatin, binding to GSH was observed probably due to removal of high molecular mass platinophiles. Two-thirds of the Pt adducts formed in whole cell extracts, had a molecular mass >3 kDa. [Pt(SG)(2)] cannot account for more than 20% of the Pt adducts. The concentration of reduced thiols in the high molecular mass fraction of the extracts is six times higher than in the low molecular mass fraction.

  2. Relevancies of multiple-interaction events and signal-to-noise ratio for Anger-logic based PET detector designs

    Science.gov (United States)

    Peng, Hao

    2015-10-01

    A fundamental challenge for PET block detector designs is to deploy finer crystal elements while limiting the number of readout channels. The standard Anger-logic scheme including light sharing (an 8 by 8 crystal array coupled to a 2×2 photodetector array with an optical diffuser, multiplexing ratio: 16:1) has been widely used to address such a challenge. Our work proposes a generalized model to study the impacts of two critical parameters on spatial resolution performance of a PET block detector: multiple interaction events and signal-to-noise ratio (SNR). The study consists of the following three parts: (1) studying light output profile and multiple interactions of 511 keV photons within crystal arrays of different crystal widths (from 4 mm down to 1 mm, constant height: 20 mm); (2) applying the Anger-logic positioning algorithm to investigate positioning/decoding uncertainties (i.e., "block effect") in terms of peak-to-valley ratio (PVR), with light sharing, multiple interactions and photodetector SNR taken into account; and (3) studying the dependency of spatial resolution on SNR in the context of modulation transfer function (MTF). The proposed model can be used to guide the development and evaluation of a standard Anger-logic based PET block detector including: (1) selecting/optimizing the configuration of crystal elements for a given photodetector SNR; and (2) predicting to what extent additional electronic multiplexing may be implemented to further reduce the number of readout channels.

  3. Relevancies of multiple-interaction events and signal-to-noise ratio for Anger-logic based PET detector designs

    Energy Technology Data Exchange (ETDEWEB)

    Peng, Hao, E-mail: penghao@mcmaster.ca [Department of Medical Physics, McMaster University, Canada L8S 4K1 (Canada); Department of Electrical and Computer Engineering, McMaster University, Canada L8S 4K1 (Canada)

    2015-10-21

    A fundamental challenge for PET block detector designs is to deploy finer crystal elements while limiting the number of readout channels. The standard Anger-logic scheme including light sharing (an 8 by 8 crystal array coupled to a 2×2 photodetector array with an optical diffuser, multiplexing ratio: 16:1) has been widely used to address such a challenge. Our work proposes a generalized model to study the impacts of two critical parameters on spatial resolution performance of a PET block detector: multiple interaction events and signal-to-noise ratio (SNR). The study consists of the following three parts: (1) studying light output profile and multiple interactions of 511 keV photons within crystal arrays of different crystal widths (from 4 mm down to 1 mm, constant height: 20 mm); (2) applying the Anger-logic positioning algorithm to investigate positioning/decoding uncertainties (i.e., “block effect”) in terms of peak-to-valley ratio (PVR), with light sharing, multiple interactions and photodetector SNR taken into account; and (3) studying the dependency of spatial resolution on SNR in the context of modulation transfer function (MTF). The proposed model can be used to guide the development and evaluation of a standard Anger-logic based PET block detector including: (1) selecting/optimizing the configuration of crystal elements for a given photodetector SNR; and (2) predicting to what extent additional electronic multiplexing may be implemented to further reduce the number of readout channels.

  4. Interactions between mobilized radionuclides and secondary phases in final repository-relevant formation aquifers. Final report; Wechselwirkung mobilisierter Radionuklide mit sekundaeren Phasen in endlagerrelevanten Formationswaessern. Abschlussbericht

    Energy Technology Data Exchange (ETDEWEB)

    Curtius, H.; Kaiser, G.; Paparigas, Z.; Hansen, B.; Neumann, A.; Klinkenberg, M.; Mueller, E.; Bruecher, H.; Bosbach, D.

    2010-10-15

    The report on interactions between mobilized radionuclides and secondary phases in final repository-relevant formation aquifers covers the following issues: scope of study, leaching experiments, secondary phases, incorporation and sorption studies, summary and prospects. The results show that the investigated spent fuels dissolve instantaneously in contact with the repository-relevant aquifers in presence of iron ions. For the elements Cs and Sr no re-immobilization was observed. These elements have to be considered as mobile species in the radionuclide source term. The secondary phases due to corrosion processes are radionuclide sinks, i.e. actinides are re-immobilized, the retention mechanisms were clarified. The studies with irradiated nuclear fuel show that the uranium/silicon containing phases effect the molar solubility of actinides.

  5. Cellular and molecular-genetic mechanisms of symbiosis and associative interaction of microorganisms with plants in rhizosphere

    Directory of Open Access Journals (Sweden)

    Lioshina L. G.

    2009-02-01

    Full Text Available The review contains the results of research on symbiotic and associative interaction of microorganisms and plants in rhizosphere. A special attention is given to the process of contact association of microorganisms and plants tissues including the concrete molecular structures and dominant role pertaining to protein-carbohydrate interaction. There are common features and distinctions at formation of arbuscular mycorhiza, rhizobia– legume symbiosis and association of non-leguminous plants with Azospirillum

  6. iDrug-Target: predicting the interactions between drug compounds and target proteins in cellular networking via benchmark dataset optimization approach.

    Science.gov (United States)

    Xiao, Xuan; Min, Jian-Liang; Lin, Wei-Zhong; Liu, Zi; Cheng, Xiang; Chou, Kuo-Chen

    2015-01-01

    Information about the interactions of drug compounds with proteins in cellular networking is very important for drug development. Unfortunately, all the existing predictors for identifying drug-protein interactions were trained by a skewed benchmark data-set where the number of non-interactive drug-protein pairs is overwhelmingly larger than that of the interactive ones. Using this kind of highly unbalanced benchmark data-set to train predictors would lead to the outcome that many interactive drug-protein pairs might be mispredicted as non-interactive. Since the minority interactive pairs often contain the most important information for drug design, it is necessary to minimize this kind of misprediction. In this study, we adopted the neighborhood cleaning rule and synthetic minority over-sampling technique to treat the skewed benchmark datasets and balance the positive and negative subsets. The new benchmark datasets thus obtained are called the optimized benchmark datasets, based on which a new predictor called iDrug-Target was developed that contains four sub-predictors: iDrug-GPCR, iDrug-Chl, iDrug-Ezy, and iDrug-NR, specialized for identifying the interactions of drug compounds with GPCRs (G-protein-coupled receptors), ion channels, enzymes, and NR (nuclear receptors), respectively. Rigorous cross-validations on a set of experiment-confirmed datasets have indicated that these new predictors remarkably outperformed the existing ones for the same purpose. To maximize users' convenience, a public accessible Web server for iDrug-Target has been established at http://www.jci-bioinfo.cn/iDrug-Target/ , by which users can easily get their desired results. It has not escaped our notice that the aforementioned strategy can be widely used in many other areas as well.

  7. Identification of cellular proteins that interact with Newcastle Disease Virus and human Respiratory Syncytial Virus by a two-dimensional virus overlay protein binding assay (VOPBA).

    Science.gov (United States)

    Holguera, Javier; Villar, Enrique; Muñoz-Barroso, Isabel

    2014-10-13

    Although it is well documented that the initial attachment receptors for Newcastle Disease Virus (NDV) and Respiratory Syncytial Virus (RSV) are sialic acid-containing molecules and glycosaminoglycans respectively, the exact nature of the receptors for both viruses remains to be deciphered. Moreover, additional molecules at the host cell surface might be involved in the entry mechanism. With the aim of identifying the cellular proteins that interact with NDV and RSV at the cell surface, we performed a virus overlay protein binding assay (VOPBA). Cell membrane lysates were separated by two dimensional (2D) gel electrophoresis and electrotransferred to PVDF membranes, after which they were probed with high viral concentrations. NDV interacted with a Protein Disulfide Isomerase from chicken fibroblasts. In the case of RSV, we detected 15 reactive spots, which were identified as six different proteins, of which nucleolin was outstanding. We discuss the possible role of PDI and nucleolin in NDV and RSV entry, respectively.

  8. Clinical relevance of the small intestine as an organ of drug elimination: drug-fruit juice interactions.

    Science.gov (United States)

    Paine, Mary F; Oberlies, Nicholas H

    2007-02-01

    Most drugs are taken orally. For those intended to act systemically, a significant fraction of the dose can be eliminated during its first passage through a sequence of organs before entry into the general circulation. For some drugs, the degree of first-pass elimination can be large enough such that oral bioavailability is significantly reduced, with the consequent potential for a reduced clinical response. Of these first-pass eliminating organs, the small intestine and liver are the most commonly implicated, in part because they express the highest levels of drug-metabolizing enzymes. For several drugs whose major route of elimination occurs via CYP3A-mediated metabolism, the extent of first-pass metabolism in the small intestine can rival that in the liver. As such, alterations in enteric CYP3A activity alone can significantly influence oral bioavailability. The most extensively studied xenobiotic shown to inhibit only enteric CYP3A is grapefruit juice, the consequences of which can be clinically significant. Although much information has been gained regarding the grapefruit juice effect, progress in the relatively understudied area of drug-diet interactions continues to be sluggish and reactive. In stark contrast, the potential for drug-drug interactions involving any new therapeutic agent must be evaluated, prospectively, before market introduction. To prospectively elucidate mechanisms underlying drug-diet interactions, a multidisciplinary, translational research approach is required, which capitalizes on the collective expertise of drug metabolism scientists and natural products chemists. Such an approach would allow proper between-study comparisons, and ultimately provide conclusive information as to whether specific dietary substances can be taken safely with certain medications.

  9. Distinct interactions with cellular E-cadherin of the two virulent metalloproteinases encoded by a Bacteroides fragilis pathogenicity island.

    Science.gov (United States)

    Remacle, Albert G; Shiryaev, Sergey A; Strongin, Alex Y

    2014-01-01

    Bacteroides fragilis causes the majority of Gram-negative anaerobic infections in the humans. The presence of a short, 6-kb, pathogenicity island in the genome is linked to enterotoxigenic B. fragilis (ETBF). The role of the enterotoxin in B. fragilis virulence, however, remains to be determined, as the majority of clinical isolates lack ETBF genes and healthy individuals carry enterotoxin-positive B. fragilis. The island encodes secretory metalloproteinase II (MPII) and one of three homologous enterotoxigenic fragilysin isoenzymes (FRA; also termed B. fragilis toxin or BFT). The secretory metalloproteinases expressed from the genes on the B. fragilis pathogenicity island may have pathological importance within the gut, not linked to diarrhea. MPII and FRA are counter-transcribed in the bacterial genome, implying that regardless of their structural similarity and overlapping cleavage preferences these proteases perform distinct and highly specialized functions in the course of B. fragilis infection. The earlier data by us and others have demonstrated that FRA cleaves cellular E-cadherin, an important adherens junction protein, and weakens cell-to-cell contacts. Using E-cadherin-positive and E-cadherin-deficient cancer cells, and the immunostaining, direct cell binding and pull-down approaches, we, however, demonstrated that MPII via its catalytic domain efficiently binds, rather than cleaves, E-cadherin. According to our results, E-cadherin is an adherens junction cellular receptor, rather than a proteolytic target, of the B. fragilis secretory MPII enzyme. As a result of the combined FRA and MPII proteolysis, cell-to-cell contacts and adherens junctions are likely to weaken further.

  10. Interactions between HIF-1α and AMPK in the regulation of cellular hypoxia adaptation in chronic kidney disease.

    Science.gov (United States)

    Li, Hui; Satriano, Joseph; Thomas, Joanna L; Miyamoto, Satoshi; Sharma, Kumar; Pastor-Soler, Núria M; Hallows, Kenneth R; Singh, Prabhleen

    2015-09-01

    Renal hypoxia contributes to chronic kidney disease (CKD) progression, as validated in experimental and human CKD. In the early stages, increased oxygen consumption causes oxygen demand/supply mismatch, leading to hypoxia. Hence, early targeting of the determinants and regulators of oxygen consumption in CKD may alter the disease course before permanent damage ensues. Here, we focus on hypoxia inducible factor-1α (HIF-1α) and AMP-activated protein kinase (AMPK) and on the mechanisms by which they may facilitate cellular hypoxia adaptation. We found that HIF-1α activation in the subtotal nephrectomy (STN) model of CKD limits protein synthesis, inhibits apoptosis, and activates autophagy, presumably for improved cell survival. AMPK activation was diminished in the STN kidney and was remarkably restored by HIF-1α activation, demonstrating a novel role for HIF-1α in the regulation of AMPK activity. We also investigated the independent and combined effects of HIF-1α and AMPK on cell survival and death pathways by utilizing pharmacological and knockdown approaches in cell culture models. We found that the effect of HIF-1α activation on autophagy is independent of AMPK, but on apoptosis it is partially AMPK dependent. The effects of HIF-1α and AMPK activation on inhibiting protein synthesis via the mTOR pathway appear to be additive. These various effects were also observed under hypoxic conditions. In conclusion, HIF-1α and AMPK appear to be linked at a molecular level and may act as components of a concerted cellular response to hypoxic stress in the pathophysiology of CKD.

  11. Interaction of fluorescence dyes with 5-fluorouracil: A photoinduced electron transfer study in bulk and biologically relevant water

    Science.gov (United States)

    Kuchlyan, Jagannath; Banik, Debasis; Kundu, Niloy; Roy, Arpita; Sarkar, Nilmoni

    2014-10-01

    The interactions of widely used chemotherapeutic drug, 5-fluorouracil (5FU) with coumarin dyes have been investigated for the first time using steady-state and time-resolved fluorescence spectroscopic measurements. The fluorescence quenching along with the decrease in lifetimes of excited state of coumarin derivatives with gradual addition of 5FU is explained by photoinduced electron transfer (PET) mechanism. Our studies were performed in bulk water and confined water of AOT (aerosol OT) reverse micelle to investigate the effect of confinement on PET dynamics. The feasibility of PET reaction for coumarin-5FU systems is investigated calculating the standard free energy changes using the Rehm-Weller equation.

  12. The relevance of chemical interactions with CYP17 enzyme activity: Assessment using a novel in vitro assay

    Energy Technology Data Exchange (ETDEWEB)

    Roelofs, Maarke J.E., E-mail: m.j.e.roelofs@uu.nl [Endocrine Toxicology Research Group, Institute for Risk Assessment Sciences (IRAS), Utrecht University, P.O. Box 80.177, NL-3508 TD Utrecht (Netherlands); Center for Health Protection, National Institute for Public Health and the Environment (RIVM), P.O. Box 1, 3720 BA Bilthoven (Netherlands); Piersma, Aldert H. [Endocrine Toxicology Research Group, Institute for Risk Assessment Sciences (IRAS), Utrecht University, P.O. Box 80.177, NL-3508 TD Utrecht (Netherlands); Center for Health Protection, National Institute for Public Health and the Environment (RIVM), P.O. Box 1, 3720 BA Bilthoven (Netherlands); Berg, Martin van den; Duursen, Majorie B.M. van [Endocrine Toxicology Research Group, Institute for Risk Assessment Sciences (IRAS), Utrecht University, P.O. Box 80.177, NL-3508 TD Utrecht (Netherlands)

    2013-05-01

    The steroidogenic cytochrome P450 17 (CYP17) enzyme produces dehydroepiandrosterone (DHEA), which is the most abundant circulating endogenous sex steroid precursor. DHEA plays a key role in e.g. sexual functioning and development. To date, no rapid screening assay for effects on CYP17 is available. In this study, a novel assay using porcine adrenal cortex microsomes (PACMs) was described. Effects of twenty-eight suggested endocrine disrupting compounds (EDCs) on CYP17 activity were compared with effects in the US EPA validated H295R (human adrenocorticocarcinoma cell line) steroidogenesis assay. In the PACM assay DHEA production was higher compared with the H295R assay (4.4 versus 2.2 nmol/h/mg protein). To determine the additional value of a CYP17 assay, all compounds were also tested for interaction with CYP19 (aromatase) using human placental microsomes (HPMs) and H295R cells. 62.5% of the compounds showed enzyme inhibition in at least one of the microsomal assays. Only the cAMP inducer forskolin induced CYP17 activity, while CYP19 was induced by four test compounds in the H295R assay. These effects remained unnoticed in the PACM and HPM assays. Diethylstilbestrol and tetrabromobisphenol A inhibited CYP17 but not CYP19 activity, indicating different mechanisms for the inhibition of these enzymes. From our results it becomes apparent that CYP17 can be a target for EDCs and that this interaction differs from interactions with CYP19. Our data strongly suggest that research attention should focus on validating a specific assay for CYP17 activity, such as the PACM assay, that can be included in the EDC screening battery. - Highlights: ► DHEA, produced by CYP17, plays a key role in sexual functioning and development. ► No rapid screening assay for effects on CYP17 is available yet. ► A novel assay using porcine adrenal cortex microsomes (PACMs) was described. ► Endocrine disrupting compounds (EDCs) targeting CYP17 interact differently with CYP19. ► A

  13. Interaction of Impurity (Li, Be, B and C)and Hydrogen Isotope Pellet Injection with Reactor-relevant Plasmas

    Institute of Scientific and Technical Information of China (English)

    Deng Baiquan(邓柏权); J.P.Allain; Peng Lilin(彭利林); Wang Xiaoyu(王晓宇); Chen Zhi(陈志); Yan Jiancheng(严建成)

    2005-01-01

    Based on the two-dimensional kinetic ablation theory of the hydrogen pellet ablation developed by Kuteev [B.V. Kuteev, Nuclear Fusion, 35 (1995) 431], an algorithm of erosion speed and ablation rate calculations for Li, Be, and B impurity pellets in reactor-relevant plasma has been derived. Results show compatibilities of lithium pellet injection used in α-particle diagnostics are positive in comparison with other solid impurity pellets (e.g. Be, B and C). Using the 2-D Kuteev lentil model, including kinetic effects, we find that currently existing pellet injection techniques will not meet core-fueling requirements for ITER-FEAT. A pressure as high as 254 MPa must be applied to a pellet accelerator with a 200 cm-long single-stage pneumatic gun, in order to accelerate a pellet with a radius rp0 =0.5 cm to a velocity of Vp0, 24×105 cm/s penetrating 100 cm into the ITER plasma core. Comparisons of pellet velocity- and radius-dependent penetration depth between the Neutral Gas Shielding and the Kuteev's models are made. However, we find that the isotopic effects can lead to a 33% lower pellet speed for solid DT, compared to an identical H2 pellet penetrating the same length in ITER-FEAT plasma, and our calculations show that HFS injection will much improve core fueling efficiency.

  14. Epstein–Barr virus glycoprotein gM can interact with the cellular protein p32 and knockdown of p32 impairs virus

    Energy Technology Data Exchange (ETDEWEB)

    Changotra, Harish; Turk, Susan M. [Department of Microbiology and Immunology, Center for Molecular and Tumor Virology and Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center, Shreveport, LA (United States); Artigues, Antonio [Department of Biochemistry, University of Kansas Medical Center, Kansas City, KS (United States); Thakur, Nagendra; Gore, Mindy; Muggeridge, Martin I. [Department of Microbiology and Immunology, Center for Molecular and Tumor Virology and Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center, Shreveport, LA (United States); Hutt-Fletcher, Lindsey M., E-mail: lhuttf@lsuhsc.edu [Department of Microbiology and Immunology, Center for Molecular and Tumor Virology and Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center, Shreveport, LA (United States)

    2016-02-15

    The Epstein–Barr virus glycoprotein complex gMgN has been implicated in assembly and release of fully enveloped virus, although the precise role that it plays has not been elucidated. We report here that the long predicted cytoplasmic tail of gM is not required for complex formation and that it interacts with the cellular protein p32, which has been reported to be involved in nuclear egress of human cytomegalovirus and herpes simplex virus. Although redistribution of p32 and colocalization with gM was not observed in virus infected cells, knockdown of p32 expression by siRNA or lentivirus-delivered shRNA recapitulated the phenotype of a virus lacking expression of gNgM. A proportion of virus released from cells sedimented with characteristics of virus lacking an intact envelope and there was an increase in virus trapped in nuclear condensed chromatin. The observations suggest the possibility that p32 may also be involved in nuclear egress of Epstein–Barr virus. - Highlights: • The predicted cytoplasmic tail of gM is not required to complex with gN. • Cellular p32 can interact with the predicted cytoplasmic tail of EBV gM. • Knockdown of p32 recapitulates the phenotype of virus lacking the gNgM complex.

  15. Compound C prevents Hypoxia-Inducible Factor-1α protein stabilization by regulating the cellular oxygen availability via interaction with Mitochondrial Complex I

    Directory of Open Access Journals (Sweden)

    Hagen Thilo

    2011-04-01

    Full Text Available Abstract The transcription factor Hypoxia-Inducible Factor-1α is a master regulator of the cellular response to low oxygen concentration. Compound C, an inhibitor of AMP-activated kinase, has been reported to inhibit hypoxia dependent Hypoxia-Inducible Factor-1α activation via a mechanism that is independent of AMP-activated kinase but dependent on its interaction with the mitochondrial electron transport chain. The objective of this study is to characterize the interaction of Compound C with the mitochondrial electron transport chain and to determine the mechanism through which the drug influences the stability of the Hypoxia-Inducible Factor-1α protein. We found that Compound C functions as an inhibitor of complex I of the mitochondrial electron transport chain as demonstrated by its effect on mitochondrial respiration. It also prevents hypoxia-induced Hypoxia-Inducible Factor-1α stabilization in a dose dependent manner. In addition, Compound C does not have significant effects on reactive oxygen species production from complex I via both forward and reverse electron flux. This study provides evidence that similar to other mitochondrial electron transport chain inhibitors, Compound C regulates Hypoxia-Inducible Factor-1α stability by controlling the cellular oxygen concentration.

  16. Basic research on interactions of heavy metals with pharmaceutical substances with relevance to the environment and residual toxicology

    Energy Technology Data Exchange (ETDEWEB)

    Gaede, W.; Kuehnert, M.

    1986-01-01

    Studies were conducted into interactions between long-time exposure of rats to subtoxic doses of lead and copper and humic acids orally applied to them in parallel. Tests were based on established activities of erythrocytic delta-aminolaevulinic acid dehydratase and on the length of hexobarbital-induced sleep. Also investigated were the effects of heavy metal on the blood level of a sulphonamide (sulphaclomide). Lead and copper interactions under the impact of pharmaceutical substances (humic acids and sulphaclomide) produced affirmative evidence to the well-known depression of activity of delta-aminolaevulinic acid dehydratase. There was also a high probability that cytochrome-P-450 had been induced by lead and copper and, perhaps, by humic acids, as well. Enteral absorption of sulphaclomide was clearly affected by protein-denaturing and permeability-reducing action of heavy metals on the gastro-intestinal mucosa. That locally delimited action of lead and copper was widely offset under the impact of humic acids, and sulphaclomide levels in the blood were renormalised. The above findings are likely to suggest that in the context of environmental toxicology long-time exposure of warm-blooded animals to heavy metals may impair the therapeutic effectiveness of pharmaceuticals (sulphaclomide in this case).

  17. FE65 regulates and interacts with the Bloom syndrome protein in dynamic nuclear spheres - potential relevance to Alzheimer's disease.

    Science.gov (United States)

    Schrötter, Andreas; Mastalski, Thomas; Nensa, Fabian M; Neumann, Martin; Loosse, Christina; Pfeiffer, Kathy; Magraoui, Fouzi El; Platta, Harald W; Erdmann, Ralf; Theiss, Carsten; Uszkoreit, Julian; Eisenacher, Martin; Meyer, Helmut E; Marcus, Katrin; Müller, Thorsten

    2013-06-01

    The intracellular domain of the amyloid precursor protein (AICD) is generated following cleavage of the precursor by the γ-secretase complex and is involved in membrane to nucleus signaling, for which the binding of AICD to the adapter protein FE65 is essential. Here we show that FE65 knockdown causes a downregulation of the protein Bloom syndrome protein (BLM) and the minichromosome maintenance (MCM) protein family and that elevated nuclear levels of FE65 result in stabilization of the BLM protein in nuclear mobile spheres. These spheres are able to grow and fuse, and potentially correspond to the nuclear domain 10. BLM plays a role in DNA replication and repair mechanisms and FE65 was also shown to play a role in DNA damage response in the cell. A set of proliferation assays in our work revealed that FE65 knockdown in HEK293T cells reduced cell replication. On the basis of these results, we hypothesize that nuclear FE65 levels (nuclear FE65/BLM containing spheres) may regulate cell cycle re-entry in neurons as a result of increased interaction of FE65 with BLM and/or an increase in MCM protein levels. Thus, FE65 interactions with BLM and MCM proteins may contribute to the neuronal cell cycle re-entry observed in brains affected by Alzheimer's disease.

  18. Perceptions of document relevance

    Directory of Open Access Journals (Sweden)

    Peter eBruza

    2014-07-01

    Full Text Available This article presents a study of how humans perceive the relevance of documents.Humans are adept at making reasonably robust and quick decisions about what information is relevant to them, despite the ever increasing complexity and volume of their surrounding information environment. The literature on document relevance has identified various dimensions of relevance (e.g., topicality, novelty, etc., however little is understood about how these dimensions may interact.We performed a crowdsourced study of how human subjects judge two relevance dimensions in relation to document snippets retrieved from an internet search engine.The order of the judgement was controlled.For those judgements exhibiting an order effect, a q-test was performed to determine whether the order effects can be explained by a quantum decision model based on incompatible decision perspectives.Some evidence of incompatibility was found which suggests incompatible decision perspectives is appropriate for explaining interacting dimensions of relevance.

  19. Studies of Sociosexual Interactions in Rats in an Externally Valid Procedure: Are They Relevant for Understanding Human Sexual Behavior?

    Directory of Open Access Journals (Sweden)

    Xi Chu

    2016-09-01

    Full Text Available When a prolonged observation of groups of rats in a seminatural environment is used as testing procedure, different behavioral patterns are shown compared with what observed in a pair housed in a small cage. Males and females copulate simultaneously, they show a promiscuously and random copulatory pattern. Females remain completely receptive from the first lordosis displayed in the period of behavioral estrus until the last. There is no reduction in paracopulatory behaviors and no increase in rejections towards the end of estrus. Female paracopulatory behavior and receptivity change in a most abrupt way at both initiation and termination of behavioral estrus. It appears that, in the seminatural environment, males copulate in bouts, and males do not pursue the females unless they are fully receptive. Non-sexual, social behavior including affiliative and nonaffiliative interaction among rats is rather unrelated to sexual activities in both sex.

  20. Interaction of carbonylcyanide p-trifluoromethoxyphenylhydrazone (FCCP) with lipid membrane systems: a biophysical approach with relevance to mitochondrial uncoupling.

    Science.gov (United States)

    Monteiro, João P; Martins, André F; Lúcio, Marlene; Reis, Salette; Geraldes, Carlos F G C; Oliveira, Paulo J; Jurado, Amália S

    2011-06-01

    FCCP (carbonylcyanide p-trifluoromethoxyphenylhydrazone), a classical uncoupler of mitochondrial oxidative phosphorylation, is used in this study as a model to clarify how interactions of uncouplers with membrane lipid bilayers may influence membrane biophysics and their protonophoric activity itself. In order to disclose putative effects that may be important when considering using uncouplers for pharmacological purposes, an extensive characterization of FCCP membrane lipid interactions using accurate biophysical approaches and simple model lipid systems was carried out. Differential scanning calorimetry studies showed that FCCP molecules disturb lipid bilayers and favor lateral phase separation in mixed lipid systems. (31)P NMR assays indicated that FCCP alters the curvature elastic properties of membrane models containing non-bilayer lipids, favoring lamellar/H(II) transition, probably by alleviation of hydrocarbon-packing constraints in the inverted hexagonal phase. Taking advantage of FCCP quenching effects on the fluorescent probes DPH (1,6-diphenyl-1,3,5-hexatriene) and DPH-PA (3-(p-(6-phenyl)-1,3,5-hexatrienyl)phenylpropionic acid), it is demonstrated that FCCP distributes across the bilayer thickness in both a single and a ternary lipid system mimicking the inner mitochondrial membrane. This behavior is consistent with the ability of the compound to migrate through the thickness of the inner mitochondrial membrane, an event required for its protonophoric activity. Finally, the study of the membrane fluidity in different lipid systems, as reported by the rotational correlation time (θ) of DPH or DPH-PA, showed that the extension at which FCCP disturbs membrane properties associated with the dynamics and the order of lipid molecules depends on the lipid composition of the model lipid system assayed.

  1. PCNA-interacting peptides reduce Akt phosphorylation and TLR-mediated cytokine secretion suggesting a role of PCNA in cellular signaling.

    Science.gov (United States)

    Olaisen, Camilla; Müller, Rebekka; Nedal, Aina; Otterlei, Marit

    2015-07-01

    Proliferating cell nuclear antigen (PCNA), commonly known as a nuclear protein essential for regulation of DNA replication, DNA repair, and epigenetics, has recently been associated with multiple cytosolic functions. Many proteins containing one of the two known PCNA-interacting motifs, the AlkB homologue 2 PCNA interacting motif (APIM) and the PCNA-interacting peptide (PIP)-box, are considered to be mainly cytosolic. APIM is found in more than 20 kinases and/or associated proteins including several direct or indirect members of the mitogen-activated protein kinase (MAPK) and PI3K/Akt pathways. Mass spectrometry analysis of PCNA-pull downs verified that many cytosolic proteins involved in the MAPK and PI3K/Akt pathways are in complex with PCNA. Furthermore, treatment of cells with a PCNA-interacting APIM-containing peptide (APIM-peptide) reduced Akt phosphorylation in human peripheral blood monocytes and a human keratinocyte cell line (HaCaT). Additionally, the APIM-peptide strongly reduced the cytokine secretion from monocytes stimulated with toll like receptor (TLR) ligands and potentiated the effects of MAPK and PI3K/Akt inhibitors. Interestingly, the protein level of the APIM-containing PKR/RIG-1 activator protein (PACT) was initially strongly reduced in HaCaT cells stimulated with APIM-peptide in combination with the TLR ligand polyinosinic-polycytidylic acid (polyIC). Our results suggest that PCNA has a platform role in cytosol affecting cellular signaling.

  2. The Hd, Hj, and Hz66 flagella variants of Salmonella enterica serovar Typhi modify host responses and cellular interactions.

    Science.gov (United States)

    Schreiber, Fernanda; Kay, Sally; Frankel, Gad; Clare, Simon; Goulding, David; van de Vosse, Esther; van Dissel, Jaap T; Strugnell, Richard; Thwaites, Guy; Kingsley, Robert A; Dougan, Gordon; Baker, Stephen

    2015-01-22

    Salmonella Typhi, the causative agent of typhoid fever, is a monophyletic, human-restricted bacterium that exhibits limited phenotypic variation. S. Typhi from Indonesia are a notable exception, with circulating strains expressing diverse flagella antigens including Hj, Hd and Hz66. Hypothesizing that S. Typhi flagella plays a key role during infection, we constructed an S. Typhi fliC mutant and otherwise isogenic S. Typhi strains expressing the Hj, Hd, Hz66 flagella antigens. Phenotyping revealed differences in flagellum structure, strain motility and immunogenicity, but not in the ability of flagellated isolates to induce TLR5 activity. Invasion assays using epithelial and macrophage cell lines revealed differences in the ability of these S. Typhi derivatives to invade cells or induce cellular restructuring in the form of ruffles. Notably, the Hj variant induced substantial ruffles that were not fully dependent on the GTPases that contribute to this process. These data highlight important differences in the phenotypic properties of S. Typhi flagella variation and how they impact on the pathogenesis of S. Typhi.

  3. Surface interactions with compartmentalized cellular phosphates explain rare earth oxide nanoparticle hazard and provide opportunities for safer design.

    Science.gov (United States)

    Li, Ruibin; Ji, Zhaoxia; Chang, Chong Hyun; Dunphy, Darren R; Cai, Xiaoming; Meng, Huan; Zhang, Haiyuan; Sun, Bingbing; Wang, Xiang; Dong, Juyao; Lin, Sijie; Wang, Meiying; Liao, Yu-Pei; Brinker, C Jeffrey; Nel, Andre; Xia, Tian

    2014-02-25

    Growing international exploitation of rare earth oxides (REOs) for commercial and biological use has increased the possibility of human exposure and adverse health effects. Occupational exposure to rare earth materials in miners and polishers leads to a severe form of pneumoconiosis, while gadolinium-containing MRI contrast agents cause nephrogenic systemic fibrosis in patients with renal impairment. The mechanisms for inducing these adverse pro-fibrogenic effects are of considerable importance for the safety assessment of REO particles as well as presenting opportunities for safer design. In this study, using a well-prepared REO library, we obtained a mechanistic understanding of how REOs induce cellular and pulmonary damage by a compartmentalized intracellular biotransformation process in lysosomes that results in pro-fibrogenic growth factor production and lung fibrosis. We demonstrate that rare earth oxide ion shedding in acidifying macrophage lysosomes leads to biotic phosphate complexation that results in organelle damage due to stripping of phosphates from the surrounding lipid bilayer. This results in nanoparticle biotransformation into urchin shaped structures and setting in motion a series of events that trigger NLRP3 inflammasome activation, IL-1β release, TGF-β1 and PDGF-AA production. However, pretreatment of REO nanoparticles with phosphate in a neutral pH environment prevents biological transformation and pro-fibrogenic effects. This can be used as a safer design principle for producing rare earth nanoparticles for biological use.

  4. Incidence of potential drug interactions in a transplant centre setting and relevance of electronic alerts for clinical practice support

    Directory of Open Access Journals (Sweden)

    Piera Polidori

    2013-09-01

    Full Text Available Background Adverse drug events may occur as a result of drug–drug interactions (DDIs. Information technology (IT systems can be an important decision-making tool for healthcare workers to identify DDIs.Objective The aim of the study is to analyse drug prescriptions in our main hospital units, in order to measure the incidence and severity of potential DDIs. The utility of clinical decision-support systems (CDSSs and computerised physician order entry (CPOE in term of alerts adherence was also assessed. DDIs were assessed using a Micromedex healthcare series database.Methods The system, adopted by the hospital, generates alerts for prescriptions with negative interactions and thanks to an ’acknowledgement function’ it is possible to verify physician adherence to alerts. This function, although used previously, became mandatory from September 2010. Physician adherence to alerts and mean monthly incidence of potential DDIs in analysed units, before and after the mandatory ‘acknowledgement function’, were calculated.Results The intensive care unit (ICU registered the greatest incidence of potential DDIs (49.0%, followed by the abdominal surgery unit and dialysis (43.4 and 42.0%, respectively. The cardiothoracic surgery unit (41.6%, step-down unit (38.3% and post-anaesthesia care unit (30.0% were comparable. The operating theatre and endoscopy registered the fewest potential DDIs (28.2 and 22.7%, respectively. Adherence to alerts after the ‘acknowledgement function’ increased by 25.0% in the ICU, 54.0% in the cardiothoracic surgery unit, 52.5% in the abdominal surgery unit, 58.0% in the stepdown unit, 67.0% in dialysis, 51.0% in endoscopy and 48.0% in the post-anaesthesia care unit. In the operating theatre, adherence to alerts decreased from 34.0 to 30.0%. The incidence of potential DDIs after mandatory use of the ’acknowledgement function’ decreased slightly in endoscopy (–2.9%, the abdominal surgery unit (–2.7%, dialysis (

  5. Cellular Response to Irradiation

    Institute of Scientific and Technical Information of China (English)

    LIU Bo; YAN Shi-Wei

    2011-01-01

    To explore the nonlinear activities of the cellular signaling system composed of one transcriptional arm and one protein-interaction arm, we use an irradiation-response module to study the dynamics of stochastic interactions.It is shown that the oscillatory behavior could be described in a unified way when the radiation-derived signal and noise are incorporated.

  6. Interactions of AChE with Aβ Aggregates in Alzheimer’s Brain: Therapeutic Relevance of IDN 5706

    Directory of Open Access Journals (Sweden)

    Francisco Javier Carvajal

    2011-09-01

    Full Text Available Acetylcholinesterase (AChE; EC 3.1.1.7 plays a crucial role in the rapid hydrolysis of the neurotransmitter acetylcholine, in the central and peripheral nervous system and might also participate in non-cholinergic mechanism related to neurodegenerative diseases. Alzheimer’s disease (AD is a neurodegenerative disorder characterized by a progressive deterioration of cognitive abilities, amyloid-β peptide (Aβ accumulation and synaptic alterations. We have previously shown that AChE is able to accelerate the Aβ peptide assembly into Alzheimer-type aggregates increasing its neurotoxicity. Furthermore, AChE activity is altered in brain and blood of Alzheimer’s patients. The enzyme associated to amyloid plaques changes its enzymatic and pharmacological properties, as well as, increases its resistant to low pH, inhibitors and excess of substrate. Here, we reviewed the effects of IDN 5706, a hyperforin derivative that has potential preventive effects on the development of AD. Our results show that treatment with IDN5706 for 10 weeks increases brain AChE activity in seven month-old double transgenic mice (APPswe - PS1 and decreases the content of AChE associated with different types of amyloid plaques in this Alzheimer’s model. We concluded that early treatment with IDN 5706 decreases AChE-Aβ interaction and this effect might be of therapeutic interest in the treatment of AD.

  7. Interactions of AChE with Aβ Aggregates in Alzheimer’s Brain: Therapeutic Relevance of IDN 5706

    Science.gov (United States)

    Carvajal, Francisco J.; Inestrosa, Nibaldo C.

    2011-01-01

    Acetylcholinesterase (AChE; EC 3.1.1.7) plays a crucial role in the rapid hydrolysis of the neurotransmitter acetylcholine, in the central and peripheral nervous system and might also participate in non-cholinergic mechanism related to neurodegenerative diseases. Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by a progressive deterioration of cognitive abilities, amyloid-β (Aβ) peptide accumulation and synaptic alterations. We have previously shown that AChE is able to accelerate the Aβ peptide assembly into Alzheimer-type aggregates increasing its neurotoxicity. Furthermore, AChE activity is altered in brain and blood of Alzheimer’s patients. The enzyme associated to amyloid plaques changes its enzymatic and pharmacological properties, as well as, increases its resistant to low pH, inhibitors and excess of substrate. Here, we reviewed the effects of IDN 5706, a hyperforin derivative that has potential preventive effects on the development of AD. Our results show that treatment with IDN 5706 for 10 weeks increases brain AChE activity in 7-month-old double transgenic mice (APPSWE–PS1) and decreases the content of AChE associated with different types of amyloid plaques in this Alzheimer’s model. We concluded that early treatment with IDN 5706 decreases AChE–Aβ interaction and this effect might be of therapeutic interest in the treatment of AD. PMID:21949501

  8. Relevance of in vitro and clinical data for predicting CYP3A4-mediated herb-drug interactions in cancer patients.

    Science.gov (United States)

    Goey, Andrew K L; Mooiman, Kim D; Beijnen, Jos H; Schellens, Jan H M; Meijerman, Irma

    2013-11-01

    The use of complementary and alternative medicines (CAM) by cancer patients is increasing. Concomitant use of CAM and anticancer drugs could lead to serious safety issues in patients. CAM have the potential to cause pharmacokinetic interactions with anticancer drugs, leading to either increased or decreased plasma levels of anticancer drugs. This could result in unexpected toxicities or a reduced efficacy. Significant pharmacokinetic interactions have already been shown between St. John's Wort (SJW) and the anticancer drugs imatinib and irinotecan. Most pharmacokinetic CAM-drug interactions, involve drug metabolizing cytochrome P450 (CYP) enzymes, in particular CYP3A4. The effect of CAM on CYP3A4 activity and expression can be assessed in vitro. However, no data have been reported yet regarding the relevance of these in vitro data for the prediction of CAM-anticancer drug interactions in clinical practice. To address this issue, a literature research was performed to evaluate the relevance of in vitro data to predict clinical effects of CAM frequently used by cancer patients: SJW, milk thistle, garlic and Panax ginseng (P. ginseng). Furthermore, in clinical studies the sensitive CYP3A4 substrate probe midazolam is often used to determine pharmacokinetic interactions. Results of these clinical studies with midazolam are used to predict pharmacokinetic interactions with other drugs metabolized by CYP3A4. Therefore, this review also explored whether clinical trials with midazolam are useful to predict clinical pharmacokinetic CAM-anticancer drug interactions. In vitro data of SJW have shown CYP3A4 inhibition after short-term exposure and induction after long-term exposure. In clinical studies using midazolam or anticancer drugs (irinotecan and imatinib) as known CYP3A4 substrates in combination with SJW, decreased plasma levels of these drugs were observed, which was expected as a consequence of CYP3A4 induction. For garlic, no effect on CYP3A4 has been shown in vitro

  9. Cellular automata

    CERN Document Server

    Codd, E F

    1968-01-01

    Cellular Automata presents the fundamental principles of homogeneous cellular systems. This book discusses the possibility of biochemical computers with self-reproducing capability.Organized into eight chapters, this book begins with an overview of some theorems dealing with conditions under which universal computation and construction can be exhibited in cellular spaces. This text then presents a design for a machine embedded in a cellular space or a machine that can compute all computable functions and construct a replica of itself in any accessible and sufficiently large region of t

  10. Herpes Simplex Virus-2 Glycoprotein Interaction with HVEM Influences Virus-Specific Recall Cellular Responses at the Mucosa

    Directory of Open Access Journals (Sweden)

    Sarah J. Kopp

    2012-01-01

    Full Text Available Infection of susceptible cells by herpes simplex virus (HSV requires the interaction of the HSV gD glycoprotein with one of two principal entry receptors, herpes virus entry mediator (HVEM or nectins. HVEM naturally functions in immune signaling, and the gD-HVEM interaction alters innate signaling early after mucosal infection. We investigated whether the gD-HVEM interaction during priming changes lymphocyte recall responses in the murine intravaginal model. Mice were primed with attenuated HSV-2 expressing wild-type gD or mutant gD unable to engage HVEM and challenged 32 days later with virulent HSV-2 expressing wild-type gD. HSV-specific CD8+ T cells were decreased at the genital mucosa during the recall response after priming with virus unable to engage HVEM but did not differ in draining lymph nodes. CD4+ T cells, which are critical for entry of HSV-specific CD8+ T cells into mucosa in acute infection, did not differ between the two groups in either tissue. An inverse association between Foxp3+ CD4+ regulatory T cells and CD8+ infiltration into the mucosa was not statistically significant. CXCR3 surface expression was not significantly different among different lymphocyte subsets. We conclude that engagement of HVEM during the acute phase of HSV infection influences the antiviral CD8+ recall response by an unexplained mechanism.

  11. A cellular automaton simulation model for pedestrian and vehicle interaction behaviors at unsignalized mid-block crosswalks.

    Science.gov (United States)

    Lu, Lili; Ren, Gang; Wang, Wei; Chan, Ching-Yao; Wang, Jian

    2016-10-01

    At unsignalized crosswalks, interactions between pedestrians and vehicles often lead to traffic safety hazards due to absence of traffic control and unclear right-of-ways. To address this safety problem, there is a need to understand the interaction behaviors of pedestrians and vehicles that are complicated by a variety of traffic and roadway attributes. The prime objective of this study is to establish a reliable simulation model to represent the vehicle yielding and pedestrian crossing behaviors at unsignalized crosswalks in a realistic way. The model is calibrated with detailed behavioral data collected and extracted from field observations. The capability of the calibrated model in predicting the pedestrian-interaction events as well as estimating the driver yielding rate and pedestrian delay are also tested and demonstrated. Meanwhile, the traffic dynamics in the vicinity of the crosswalk can be meaningfully represented with simulation results based on the model. Moreover, with the definitions of the vehicle-pedestrian conflicts, the proposed model is capable to evaluate the pedestrian safety. Thereby, the simulation model has the potential to serve as a useful tool for assessing safety performance and traffic operations at existing facilities. Furthermore, the model can enable the evaluation of policy effectiveness and the selection of engineering treatments at unsignalized crosswalks to improve safety and efficiency of pedestrian crossing.

  12. A Saccharomyces cerevisiae assay system to investigate ligand/AdipoR1 interactions that lead to cellular signaling.

    Directory of Open Access Journals (Sweden)

    Mustapha Aouida

    Full Text Available Adiponectin is a mammalian hormone that exerts anti-diabetic, anti-cancer and cardioprotective effects through interaction with its major ubiquitously expressed plasma membrane localized receptors, AdipoR1 and AdipoR2. Here, we report a Saccharomyces cerevisiae based method for investigating agonist-AdipoR interactions that is amenable for high-throughput scale-up and can be used to study both AdipoRs separately. Agonist-AdipoR1 interactions are detected using a split firefly luciferase assay based on reconstitution of firefly luciferase (Luc activity due to juxtaposition of its N- and C-terminal fragments, NLuc and CLuc, by ligand induced interaction of the chimeric proteins CLuc-AdipoR1 and APPL1-NLuc (adaptor protein containing pleckstrin homology domain, phosphotyrosine binding domain and leucine zipper motif 1-NLuc in a S. cerevisiae strain lacking the yeast homolog of AdipoRs (Izh2p. The assay monitors the earliest known step in the adiponectin-AdipoR anti-diabetic signaling cascade. We demonstrate that reconstituted Luc activity can be detected in colonies or cells using a CCD camera and quantified in cell suspensions using a microplate reader. AdipoR1-APPL1 interaction occurs in absence of ligand but can be stimulated specifically by agonists such as adiponectin and the tobacco protein osmotin that was shown to have AdipoR-dependent adiponectin-like biological activity in mammalian cells. To further validate this assay, we have modeled the three dimensional structures of receptor-ligand complexes of membrane-embedded AdipoR1 with cyclic peptides derived from osmotin or osmotin-like plant proteins. We demonstrate that the calculated AdipoR1-peptide binding energies correlate with the peptides' ability to behave as AdipoR1 agonists in the split luciferase assay. Further, we demonstrate agonist-AdipoR dependent activation of protein kinase A (PKA signaling and AMP activated protein kinase (AMPK phosphorylation in S. cerevisiae, which are

  13. Characterization of L1 ORF1p self-interaction and cellular localization using a mammalian two-hybrid system.

    Directory of Open Access Journals (Sweden)

    Mark Sokolowski

    Full Text Available Long INterspersed Element-1 (LINE-1, L1 is an active retrotransposon that mobilizes using a ribonucleoprotein particle (RNP intermediate composed of the full-length bicistronic L1 mRNA and the two proteins (ORF1p and ORF2p encoded by that mRNA. ORF1p and ORF2p demonstrate cis-preference for their encoding mRNA. Previous studies of ORF1p, purified from bacterial and insect cells demonstrated that this protein forms trimers in vitro. While valuable for understanding ORF1p function, these in vitro approaches do not provide any information on ORF1p self-interaction in the context of mammalian cells. We used a mammalian two-hybrid (M2H system in order to study L1 ORF1p self-interaction in human and mouse cells. We demonstrate that the M2H system successfully detects human and mouse ORF1p self-interactions in transiently transfected mammalian cells. We also generated mouse and human ORF1p-specific antibodies to characterize the expression of ORF1p fusion proteins used in the M2H system. Using these antibodies, we demonstrate that ORF1p interaction in trans leads to the formation of heterodimers that are expected to produce a positive signal in the M2H system. Although the role for L1 ORF1p cis-preference in L1 mobilization is established, the impact of ability of ORF1pto interact in trans on the L1 replication cycle is not known. Furthermore, western blot analysis of ORF1p generated by a full-length L1, wild type ORF1, or a codon-optimized ORF1 expression vector is detected in the nucleus. In contrast, the addition of a tag to the N-terminus of the mouse and human ORF1 proteins can significantly alter the subcellular localization in a tag-specific manner. These data support that nuclear localization of ORF1p may contribute to L1 (and potentially the SINE Alu RNP nuclear access in the host cell.

  14. A Saccharomyces cerevisiae Assay System to Investigate Ligand/AdipoR1 Interactions That Lead to Cellular Signaling

    KAUST Repository

    Aouida, Mustapha

    2013-06-07

    Adiponectin is a mammalian hormone that exerts anti-diabetic, anti-cancer and cardioprotective effects through interaction with its major ubiquitously expressed plasma membrane localized receptors, AdipoR1 and AdipoR2. Here, we report a Saccharomyces cerevisiae based method for investigating agonist-AdipoR interactions that is amenable for high-throughput scale-up and can be used to study both AdipoRs separately. Agonist-AdipoR1 interactions are detected using a split firefly luciferase assay based on reconstitution of firefly luciferase (Luc) activity due to juxtaposition of its N- and C-terminal fragments, NLuc and CLuc, by ligand induced interaction of the chimeric proteins CLuc-AdipoR1 and APPL1-NLuc (adaptor protein containing pleckstrin homology domain, phosphotyrosine binding domain and leucine zipper motif 1-NLuc) in a S. cerevisiae strain lacking the yeast homolog of AdipoRs (Izh2p). The assay monitors the earliest known step in the adiponectin-AdipoR anti-diabetic signaling cascade. We demonstrate that reconstituted Luc activity can be detected in colonies or cells using a CCD camera and quantified in cell suspensions using a microplate reader. AdipoR1-APPL1 interaction occurs in absence of ligand but can be stimulated specifically by agonists such as adiponectin and the tobacco protein osmotin that was shown to have AdipoR-dependent adiponectin-like biological activity in mammalian cells. To further validate this assay, we have modeled the three dimensional structures of receptor-ligand complexes of membrane-embedded AdipoR1 with cyclic peptides derived from osmotin or osmotin-like plant proteins. We demonstrate that the calculated AdipoR1-peptide binding energies correlate with the peptides\\' ability to behave as AdipoR1 agonists in the split luciferase assay. Further, we demonstrate agonist-AdipoR dependent activation of protein kinase A (PKA) signaling and AMP activated protein kinase (AMPK) phosphorylation in S. cerevisiae, which are homologous to

  15. Interaction of Frequency Allocation Schemes and Beam Forming on the Performance of Cellular Communication Systems Based on OFDM

    Directory of Open Access Journals (Sweden)

    R. Gholami

    2013-03-01

    Full Text Available In this study, the interaction of Beam Forming and frequency allocation schemes on an OFDM-based system such as LTE or WiMAX is investigated in order to support the maximum capacity and minimum outage probability. The results of simulation show that rank1 precode scheme based on MISO channel, according to what considered in LTE standard, along with the cell region division in order to allocate OFDM frequency carriers lead to a Considerable interest in the total capacity of the network in different traffics.

  16. Intra-cellular transport by single-headed kinesin KIF1A: effects of single-motor mechano-chemistry and steric interactions

    CERN Document Server

    Greulich, P; Garai, A; Nishinari, K; Schadschneider, A; Chowdhury, Debashish; Garai, Ashok; Greulich, Philip; Nishinari, Katsuhiro; Schadschneider, Andreas

    2006-01-01

    In eukaryotic cells, many motor proteins can move simultaneously on a single microtubule track. This leads to interesting collective phenomena like jamming. Recently we reported ({\\it Phys. Rev. Lett. {\\bf 95}, 118101 (2005)}) a lattice-gas model which describes traffic of unconventional (single-headed) kinesins KIF1A. Here we generalize this model, introducing a novel interaction parameter $c$, to account for an interesting mechano-chemical process which has not been considered in any earlier model. We have been able to extract all the parameters of the model, except $c$, from experimentally measured quantities. In contrast to earlier models of intra-cellular molecular motor traffic, our model assigns distinct ``chemical'' (or, conformational) states to each kinesin to account for the hydrolysis of ATP, the chemical fuel of the motor. Our model makes experimentally testable theoretical predictions. We determine the phase diagram of the model in planes spanned by experimentally controllable parameters, namely...

  17. 特发性肺纤维化的细胞学研究进展%Cells and cellular interactions in the pathogenesis of idiopathic pulmonary fibrosis

    Institute of Scientific and Technical Information of China (English)

    夏婷婷; 张丽婷(综述); 陈芳; 宋康(审校)

    2016-01-01

    特发性肺纤维化( idiopathic pulmonary fibrosis, IPF)是一种病因未明的间质性肺疾病,其发病率逐年升高,且致残率、病死率高,极具侵袭性。目前IPF的发病机制尚未完全阐明,但是细胞及其相互作用对肺泡炎和纤维化的发生起到了决定性作用。文中通过分析近年来研究较多的IPF相关细胞(免疫细胞、成纤维细胞、纤维细胞、肌成纤维细胞、内皮细胞和肺泡上皮细胞),总结IPF细胞学发病机制,探索新的研究方向和治疗靶点。%Idiopathic pulmonary fibrosis ( IPF) is a kind of Interstitial lung disease with cause unknown,which is aggressive for its increasing prevalence and high morbidity and mortality.At present the pathogenesis of IPF is not entirely clear, but cells and cel-lular interactions play a decisive role on the alveolar inflammation and fibrosis results.We review IPF related cells of interest ( immune competent cells and fibroblast, fibrocyte, myofibroblast, endothelial and alveolar epithelial cells) , to summarize cells and cellular in-teractions in the pathogenesis of IPF,and discuss new research directions and therapeutic targets.

  18. Lipid-based liquid crystalline nanoparticles as oral drug delivery vehicles for poorly water-soluble drugs: cellular interaction and in vivo absorption

    Directory of Open Access Journals (Sweden)

    Zeng N

    2012-07-01

    Full Text Available Ni Zeng,1,3,* Xiaoling Gao,2,* Quanyin Hu,1 Qingxiang Song,2 Huimin Xia,1 Zhongyang Liu,1 Guangzhi Gu,1 Mengyin Jiang,1,4 Zhiqing Pang,1 Hongzhuan Chen,2 Jun Chen,1 Liang Fang3 1Key Laboratory of Smart Drug Delivery, Ministry of Education and PLA, School of Pharmacy, Fudan University, Shanghai, 2Department of Pharmacology, Institute of Medical Sciences, Shanghai Jiaotong University School of Medicine, Shanghai, 3Department of Pharmaceutical Science, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning, 4School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, Shandong People's Republic of China, *These authors contributed equally to this workBackground: Lipid-based liquid crystalline nanoparticles (LCNPs have attracted growing interest as novel drug-delivery systems for improving the bioavailability of both hydrophilic and hydrophobic drugs. However, their cellular interaction and in vivo behavior have not been fully developed and characterized.Methods: In this study, self-assembled LCNPs prepared from soy phosphatidylcholine and glycerol dioleate were developed as a platform for oral delivery of paclitaxel. The particle size of empty LCNPs and paclitaxel-loaded LCNPs was around 80 nm. The phase behavior of the liquid crystalline matrix was characterized using crossed polarized light microscopy and small-angle X-ray scattering, and showed both reversed cubic and hexagonal phase in the liquid crystalline matrix. Transmission electron microscopy and cryofield emission scanning electron microscopy analysis revealed an inner winding water channel in LCNPs and a "ball-like"/"hexagonal" morphology.Results: Cellular uptake of LCNPs in Caco-2 cells was found to be concentration-dependent and time-dependent, with involvement of both clathrin and caveolae/lipid raft-mediated endocytosis. Under confocal laser scanning microscopy, soy phosphatidylcholine was observed to segregate from the internalized LCNPs and

  19. The Influence of Receptor-Mediated Interactions on Reaction-Diffusion Mechanisms of Cellular Self-organisation

    KAUST Repository

    Klika, Václav

    2011-11-10

    Understanding the mechanisms governing and regulating self-organisation in the developing embryo is a key challenge that has puzzled and fascinated scientists for decades. Since its conception in 1952 the Turing model has been a paradigm for pattern formation, motivating numerous theoretical and experimental studies, though its verification at the molecular level in biological systems has remained elusive. In this work, we consider the influence of receptor-mediated dynamics within the framework of Turing models, showing how non-diffusing species impact the conditions for the emergence of self-organisation. We illustrate our results within the framework of hair follicle pre-patterning, showing how receptor interaction structures can be constrained by the requirement for patterning, without the need for detailed knowledge of the network dynamics. Finally, in the light of our results, we discuss the ability of such systems to pattern outside the classical limits of the Turing model, and the inherent dangers involved in model reduction. © 2011 Society for Mathematical Biology.

  20. Multi-parametric cytometry from a complex cellular sample: Improvements and limits of manual versus computational-based interactive analyses.

    Science.gov (United States)

    Gondois-Rey, F; Granjeaud, S; Rouillier, P; Rioualen, C; Bidaut, G; Olive, D

    2016-05-01

    The wide possibilities opened by the developments of multi-parametric cytometry are limited by the inadequacy of the classical methods of analysis to the multi-dimensional characteristics of the data. While new computational tools seemed ideally adapted and were applied successfully, their adoption is still low among the flow cytometrists. In the purpose to integrate unsupervised computational tools for the management of multi-stained samples, we investigated their advantages and limits by comparison to manual gating on a typical sample analyzed in immunomonitoring routine. A single tube of PBMC, containing 11 populations characterized by different sizes and stained with 9 fluorescent markers, was used. We investigated the impact of the strategy choice on manual gating variability, an undocumented pitfall of the analysis process, and we identified rules to optimize it. While assessing automatic gating as an alternate, we introduced the Multi-Experiment Viewer software (MeV) and validated it for merging clusters and annotating interactively populations. This procedure allowed the finding of both targeted and unexpected populations. However, the careful examination of computed clusters in standard dot plots revealed some heterogeneity, often below 10%, that was overcome by increasing the number of clusters to be computed. MeV facilitated the identification of populations by displaying both the MFI and the marker signature of the dataset simultaneously. The procedure described here appears fully adapted to manage homogeneously high number of multi-stained samples and allows improving multi-parametric analyses in a way close to the classic approach. © 2016 International Society for Advancement of Cytometry.

  1. Cellular Prion Protein and Caveolin-1 Interaction in a Neuronal Cell Line Precedes Fyn/Erk 1/2 Signal Transduction

    Directory of Open Access Journals (Sweden)

    Mattia Toni

    2006-01-01

    Full Text Available It has been reported that cellular prion protein (PrPc is enriched in caveolae or caveolae-like domains with caveolin-1 (Cav-1 participating to signal transduction events by Fyn kinase recruitment. By using the Glutathione-S-transferase (GST-fusion proteins assay, we observed that PrPc strongly interacts in vitro with Cav-1. Thus, we ascertained the PrPc caveolar localization in a hypothalamic neuronal cell line (GN11, by confocal microscopy analysis, flotation on density gradient, and coimmunoprecipitation experiments. Following the anti-PrPc antibody-mediated stimulation of live GN11 cells, we observed that PrPc clustered on plasma membrane domains rich in Cav-1 in which Fyn kinase converged to be activated. After these events, a signaling cascade through p42/44 MAP kinase (Erk 1/2 was triggered, suggesting that following translocations from rafts to caveolae or caveolae-like domains PrPc could interact with Cav-1 and induce signal transduction events.

  2. Characterization of a 20 kW helicon source for fusion relevant plasma-surface interactions using microwave and electrostic diagnostics

    Science.gov (United States)

    Caneses, Juan Francisco; Blackwell, Boyd; Guenette, Mathew; Corr, Cormac

    2013-10-01

    The MAGnetized Plasma Interaction Experiment (MAGPIE) is a non-uniform axial magnetic field helicon source built to study fusion relevant plasma-surface interactions. In this work we describe its operation with a new 20 kW pulsed RF source in H2 and He under various discharge configurations. Diagnostics such as RF double probes and a 140 GHz heterodyne Michelson microwave interferometer are used to characterize the performance of the device over a wide range of operational regimes. During initial characterization we have measured plasma densities in excess of 1 × 1019 m-3 in H2 at 12 kW of RF power. Finally, we report on recent work conducted in MAGPIE in close collaboration with the Australian Nuclear Science and Technology Organisation (ANSTO) and the Plasma Research Laboratory (PRL) where biased material samples are subjected to H2 plasma. These samples are then analyzed ex-suti using a variety of material characterization techniques. Materials being investigated include graphite, diamond and tungsten.

  3. Molecular kinesis in cellular function and plasticity.

    Science.gov (United States)

    Tiedge, H; Bloom, F E; Richter, D

    2001-06-19

    Intracellular transport and localization of cellular components are essential for the functional organization and plasticity of eukaryotic cells. Although the elucidation of protein transport mechanisms has made impressive progress in recent years, intracellular transport of RNA remains less well understood. The National Academy of Sciences Colloquium on Molecular Kinesis in Cellular Function and Plasticity therefore was devised as an interdisciplinary platform for participants to discuss intracellular molecular transport from a variety of different perspectives. Topics covered at the meeting included RNA metabolism and transport, mechanisms of protein synthesis and localization, the formation of complex interactive protein ensembles, and the relevance of such mechanisms for activity-dependent regulation and synaptic plasticity in neurons. It was the overall objective of the colloquium to generate momentum and cohesion for the emerging research field of molecular kinesis.

  4. Cellular Telephone

    Institute of Scientific and Technical Information of China (English)

    杨周

    1996-01-01

    Cellular phones, used in automobiles, airliners, and passenger trains, are basically low-power radiotelephones. Calls go through radio transmitters that are located within small geographical units called cells. Because each cell’s signals are too weak to interfere with those of other cells operating on the same fre-

  5. Cellular interactions and biological responses to titanium dioxide nanoparticles in HepG2 and BEAS-2B cells: role of cell culture media.

    Science.gov (United States)

    Prasad, Raju Y; Simmons, Steven O; Killius, Micaela G; Zucker, Robert M; Kligerman, Andrew D; Blackman, Carl F; Fry, Rebecca C; Demarini, David M

    2014-05-01

    We showed previously that exposure of human lung cells (BEAS-2B) to TiO2 nanoparticles (nano-TiO2 ) produced micronuclei (MN) only when the final concentration of protein in the cell-culture medium was at least 1%. Nanoparticles localize in the liver; thus, we exposed human liver cells (HepG2) to nano-TiO2 and found the same requirement for MN induction. Nano-TiO2 also formed small agglomerates in medium containing as little as 1% protein and caused cellular interaction as measured by side scatter by flow cytometry and DNA damage (comet assay) in HepG2 cells. Nano-TiO2 also increased the activity of the inflammatory factor NFkB but not of AP1 in a reporter-gene HepG2 cell line. Suspension of nano-TiO2 in medium containing 0.1% protein was sufficient for induction of MN by the nanoparticles in either BEAS-2B or HepG2 cells as long the final concentration of protein in the cell-culture medium was at least 1%.

  6. Information Needs/Relevance

    OpenAIRE

    Wildemuth, Barbara M.

    2009-01-01

    A user's interaction with a DL is often initiated as the result of the user experiencing an information need of some kind. Aspects of that experience and how it might affect the user's interactions with the DL are discussed in this module. In addition, users continuously make decisions about and evaluations of the materials retrieved from a DL, relative to their information needs. Relevance judgments, and their relationship to the user's information needs, are discussed in this module. Draft

  7. Targeting Cells With MR Imaging Probes: Cellular Interaction And Intracellular Magnetic Iron Oxide Nanoparticles Uptake In Brain Capillary Endothelial and Choroidal Plexus Epithelial Cells

    Science.gov (United States)

    Cambianica, I.; Bossi, M.; Gasco, P.; Gonzalez, W.; Idee, J. M.; Miserocchi, G.; Rigolio, R.; Chanana, M.; Morjan, I.; Wang, D.; Sancini, G.

    2010-10-01

    Magnetic iron oxide nanoparticles (NPs) are considered for various diagnostic and therapeutic applications in brain including their use as contrast agent for magnetic resonance imaging. In delivery application, the critical step is the transport across cell layers and the internalization of NPs into specific cells, a process often limited by poor targeting specificity and low internalization efficiency. The development of the models of brain endothelial cells and choroidal plexus epithelial cells in culture has allowed us to investigate into these mechanisms. Our strategy is aimed at exploring different routes to the entrapment of iron oxide NPs in these brain related cells. Here we demonstrated that not only cells endowed with a good phagocytic activity like activated macrophages but also endothelial brain capillary and choroidal plexus epithelial cells do internalize iron oxide NPs. Our study of the intracellular trafficking of NPs by TEM, and confocal microscopy revealed that NPs are mainly internalized by the endocytic pathway. Iron oxide NPs were dispersed in water and coated with 3,4-dihydroxyl-L-phenylalanine (L-DOPA) using standard procedures. Magnetic lipid NPs were prepared by NANOVECTOR: water in oil in water (W/O/W) microemulsion process has been applied to directly coat different iron based NPs by lipid layer or to encapsulate them into Solid Lipid Nanoparticles (SLNs). By these coating/loading the colloidal stability was improved without strong alteration of the particle size distribution. Magnetic lipid NPs could be reconstituted after freeze drying without appreciable changes in stability. L-DOPA coated NPs are stable in PBS and in MEM (Modified Eagle Medium) medium. The magnetic properties of these NPs were not altered by the coating processes. We investigated the cellular uptake, cytotoxicity, and interaction of these NPs with rat brain capillary endothelial (REB4) and choroidal plexus epithelial (Z310) cells. By means of widefield, confocal

  8. Hydrophilic interaction liquid chromatography-tandem mass spectrometry quantitative method for the cellular analysis of varying structures of gemini surfactants designed as nanomaterial drug carriers.

    Science.gov (United States)

    Donkuru, McDonald; Michel, Deborah; Awad, Hanan; Katselis, George; El-Aneed, Anas

    2016-05-13

    Diquaternary gemini surfactants have successfully been used to form lipid-based nanoparticles that are able to compact, protect, and deliver genetic materials into cells. However, what happens to the gemini surfactants after they have released their therapeutic cargo is unknown. Such knowledge is critical to assess the quality, safety, and efficacy of gemini surfactant nanoparticles. We have developed a simple and rapid liquid chromatography electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) method for the quantitative determination of various structures of gemini surfactants in cells. Hydrophilic interaction liquid chromatography (HILIC) was employed allowing for a short simple isocratic run of only 4min. The lower limit of detection (LLOD) was 3ng/mL. The method was valid to 18 structures of gemini surfactants belonging to two different structural families. A full method validation was performed for two lead compounds according to USFDA guidelines. The HILIC-MS/MS method was compatible with the physicochemical properties of gemini surfactants that bear a permanent positive charge with both hydrophilic and hydrophobic elements within their molecular structure. In addition, an effective liquid-liquid extraction method (98% recovery) was employed surpassing previously used extraction methods. The analysis of nanoparticle-treated cells showed an initial rise in the analyte intracellular concentration followed by a maximum and a somewhat more gradual decrease of the intracellular concentration. The observed intracellular depletion of the gemini surfactants may be attributable to their bio-transformation into metabolites and exocytosis from the host cells. Obtained cellular data showed a pattern that grants additional investigations, evaluating metabolite formation and assessing the subcellular distribution of tested compounds.

  9. Ephrin-B-dependent thymic epithelial cell-thymocyte interactions are necessary for correct T cell differentiation and thymus histology organization: relevance for thymic cortex development.

    Science.gov (United States)

    Cejalvo, Teresa; Munoz, Juan J; Tobajas, Esther; Fanlo, Lucía; Alfaro, David; García-Ceca, Javier; Zapata, Agustín

    2013-03-15

    Previous analysis on the thymus of erythropoietin-producing hepatocyte kinases (Eph) B knockout mice and chimeras revealed that Eph-Eph receptor-interacting proteins (ephrins) are expressed both on T cells and thymic epithelial cells (TECs) and play a role in defining the thymus microenvironments. In the current study, we have used the Cre-LoxP system to selectively delete ephrin-B1 and/or ephrin-B2 in either thymocytes (EfnB1(thy/thy), EfnB2(thy/thy), and EfnB1(thy/thy)EfnB2(thy/thy) mice) or TECs (EfnB1(tec/tec), EfnB2(tec/tec), and EfnB1(tec/tec)EfnB2(tec/tec) mice) and determine the relevance of these Eph ligands in T cell differentiation and thymus histology. Our results indicate that ephrin-B1 and ephrin-B2 expressed on thymocytes play an autonomous role in T cell development and, expressed on TECs, their nonautonomous roles are partially overlapping. The effects of the lack of ephrin-B1 and/or ephrin-B2 on either thymocytes or TECs are more severe and specific on thymic epithelium, contribute to the cell intermingling necessary for thymus organization, and affect cortical TEC subpopulation phenotype and location. Moreover, ephrin-B1 and ephrin-B2 seem to be involved in the temporal appearance of distinct cortical TECs subsets defined by different Ly51 levels of expression on the ontogeny.

  10. Cellular systems biology profiling applied to cellular models of disease.

    Science.gov (United States)

    Giuliano, Kenneth A; Premkumar, Daniel R; Strock, Christopher J; Johnston, Patricia; Taylor, Lansing

    2009-11-01

    Building cellular models of disease based on the approach of Cellular Systems Biology (CSB) has the potential to improve the process of creating drugs as part of the continuum from early drug discovery through drug development and clinical trials and diagnostics. This paper focuses on the application of CSB to early drug discovery. We discuss the integration of protein-protein interaction biosensors with other multiplexed, functional biomarkers as an example in using CSB to optimize the identification of quality lead series compounds.

  11. Creating a Model of Acceptance: Preservice Teachers Interact with Non-English-Speaking Latino Parents Using Culturally Relevant Mathematics and Science Activities at Family Learning Events

    Science.gov (United States)

    Ramirez, Olga; McCollough, Cherie A.; Diaz, Zulmaris

    2016-01-01

    The following describes a culturally relevant mathematics and science content program implemented by preservice teachers (PSTs) at Family Math/Science Learning Events (FM/SLEs) conducted through two different university programs in south Texas. These experiences are required course activities designed to inform PSTs of the importance of…

  12. Interactive effects of CO₂ and trace metals on the proteasome activity and cellular stress response of marine bivalves Crassostrea virginica and Mercenaria mercenaria

    Energy Technology Data Exchange (ETDEWEB)

    Götze, Sandra [Alfred Wegener Institute, Helmholtz Centre for Polar, Marine Research, Functional Ecology, 27570 Bremerhaven (Germany); Department of Biology, University of North Carolina at Charlotte, Charlotte, NC 28223 (United States); Matoo, Omera B. [Department of Biology, University of North Carolina at Charlotte, Charlotte, NC 28223 (United States); Beniash, Elia [Department of Oral Biology, University of Pittsburgh, Pittsburgh, PA (United States); Saborowski, Reinhard [Alfred Wegener Institute, Helmholtz Centre for Polar, Marine Research, Functional Ecology, 27570 Bremerhaven (Germany); Sokolova, Inna M., E-mail: isokolov@uncc.edu [Department of Biology, University of North Carolina at Charlotte, Charlotte, NC 28223 (United States)

    2014-04-01

    Highlights: • Elevated PCO₂ enhanced accumulation of Cu and Cd in the gills of mollusks. • The proteasome activities were affected by metals but robust to elevated PCO₂. • Exposure to Cd and Cu had opposite effects on the proteasome activity. • Combined exposure to Cu and elevated PCO₂ negatively affected energy status. - Abstract: Increased anthropogenic emission of CO₂ changes the carbonate chemistry and decreases the pH of the ocean. This can affect the speciation and the bioavailability of metals in polluted habitats such as estuaries. However, the effects of acidification on metal accumulation and stress response in estuarine organisms including bivalves are poorly understood. We studied the interactive effects of CO₂ and two common metal pollutants, copper (Cu) and cadmium (Cd), on metal accumulation, intracellular ATP/ubiquitin-dependent protein degradation, stress response and energy metabolism in two common estuarine bivalves—Crassostrea virginica (eastern oyster) and Mercenaria mercenaria (hard shell clam). Bivalves were exposed for 4–5 weeks to clean seawater (control) and to either 50 μg L⁻¹ Cu or 50 μg L⁻¹ Cd at one of three partial pressures of CO₂ PCO₂ ~395, ~800 and ~1500 μatm) representative of the present-day conditions and projections of the Intergovernmental Panel for Climate Change (IPCC) for the years 2100 and 2250, respectively. Clams accumulated lower metal burdens than oysters, and elevated PCO₂ enhanced the Cd and Cu accumulation in mantle tissues in both species. Higher Cd and Cu burdens were associated with elevated mRNA expression of metal binding proteins metallothionein and ferritin. In the absence of added metals, proteasome activities of clams and oysters were robust to elevated PCO₂, but PCO₂ modulated the proteasome response to metals. Cd exposure stimulated the chymotrypsin-like activity of the oyster proteasome

  13. From Cnn Dynamics to Cellular Wave Computers

    Science.gov (United States)

    Roska, Tamas

    2013-01-01

    Embedded in a historical overview, the development of the Cellular Wave Computing paradigm is presented, starting from the standard CNN dynamics. The theoretical aspects, the physical implementation, the innovation process, as well as the biological relevance are discussed in details. Finally, the latest developments, the physical versus virtual cellular machines, as well as some open questions are presented.

  14. Bioceramics for osteogenesis, molecular and cellular advances.

    Science.gov (United States)

    Demirkiran, Hande

    2012-01-01

    The remarkable need for bone tissue replacement in clinical situations, its limited availability and some major drawbacks of autologous (from the patient) and allogeneic (from a donor) bone grafts are driving researchers to search for alternative approaches for bone repair. In order to develop an appropriate bone substitute, one should understand bone structure and properties and its growth, which will guide researchers to select the optimal conditions for tissue culture and implantation. It's well accepted that bioceramics are excellent candidates as bone replacement with osteogenesis, osteoinduction and osteoconduction capacity. Therefore, the molecular and cellular interactions that take place at the surface of bioceramics and their relevance in osteogenesis excites many researchers to delve deeper into this line of research.

  15. The "true" pore size of textile filter media and its relevance for the filtration process with respect to the interaction with apparatus and suspension

    OpenAIRE

    Anlauf, Harald

    2016-01-01

    The success of a filtration process depends on the filter medium itself but also on the apparatus design and the process conditions. Here the discussion is focussed on woven media for cake filtration, but the principle findings seem to be transferable to vleeces depth filter media or membranes. Particle retention and the flow resistance are representing the main properties of a filter medium relevant for the filtration process. For an optimal filter operation further properties like mechanica...

  16. Putative adverse outcome pathways relevant to neurotoxicity

    Science.gov (United States)

    Bal-Price, Anna; Crofton, Kevin M.; Sachana, Magdalini; Shafer, Timothy J.; Behl, Mamta; Forsby, Anna; Hargreaves, Alan; Landesmann, Brigitte; Lein, Pamela J.; Louisse, Jochem; Monnet-Tschudi, Florianne; Paini, Alicia; Rolaki, Alexandra; Schrattenholz, André; Suñol, Cristina; van Thriel, Christoph; Whelan, Maurice; Fritsche, Ellen

    2016-01-01

    The Adverse Outcome Pathway (AOP) framework provides a template that facilitates understanding of complex biological systems and the pathways of toxicity that result in adverse outcomes (AOs). The AOP starts with an molecular initiating event (MIE) in which a chemical interacts with a biological target(s), followed by a sequential series of KEs, which are cellular, anatomical, and/or functional changes in biological processes, that ultimately result in an AO manifest in individual organisms and populations. It has been developed as a tool for a knowledge-based safety assessment that relies on understanding mechanisms of toxicity, rather than simply observing its adverse outcome. A large number of cellular and molecular processes are known to be crucial to proper development and function of the central (CNS) and peripheral nervous systems (PNS). However, there are relatively few examples of well-documented pathways that include causally linked MIEs and KEs that result in adverse outcomes in the CNS or PNS. As a first step in applying the AOP framework to adverse health outcomes associated with exposure to exogenous neurotoxic substances, the EU Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM) organized a workshop (March 2013, Ispra, Italy) to identify potential AOPs relevant to neurotoxic and developmental neurotoxic outcomes. Although the AOPs outlined during the workshop are not fully described, they could serve as a basis for further, more detailed AOP development and evaluation that could be useful to support human health risk assessment in a variety of ways. PMID:25605028

  17. Multiuser Cellular Network

    CERN Document Server

    Bao, Yi; Chen, Ming

    2011-01-01

    Modern radio communication is faced with a problem about how to distribute restricted frequency to users in a certain space. Since our task is to minimize the number of repeaters, a natural idea is enlarging coverage area. However, coverage has restrictions. First, service area has to be divided economically as repeater's coverage is limited. In this paper, our fundamental method is to adopt seamless cellular network division. Second, underlying physics content in frequency distribution problem is interference between two close frequencies. Consequently, we choose a proper frequency width of 0.1MHz and a relevantly reliable setting to apply one frequency several times. We make a few general assumptions to simplify real situation. For instance, immobile users yield to homogenous distribution; repeaters can receive and transmit information in any given frequency in duplex operation; coverage is mainly decided by antenna height. Two models are built up to solve 1000 users and 10000 users situations respectively....

  18. The Interaction Between the Adjustment of Land Use Control and the Actions of Relevant Actors%土地用途管制调整与权益主体行为研究

    Institute of Scientific and Technical Information of China (English)

    罗罡辉; 李贵才; 仝德

    2013-01-01

      研究目的:基于财产权的视角,研究土地用途管制决策与土地权益主体行为的互动关系。研究方法:文献资料法、实证法和博弈论。研究结果:土地用途管制的调整影响财产权结构的变化,政府和相关土地权益主体可通过协商互动达成权益平衡。研究结论:土地用途管制决策应开放更多权益主体参与论证,协调发展过程中的矛盾。%  The purpose of this paper is to explore the interaction between the adjustment of land use control and the actions of relevant actors from the perspective of property rights. Methods employed are documentation, empirical study and game theory. The results indicate that the adjustment of land use control affects the structure of property rights. Government and the relevant actors can reach agreements through consultation and interaction. The paper concludes that the decision-making of land use control shall be more open, allowing more participation of relevant stakeholders so as to coordinate the contradictions in the development process.

  19. Apoptosis in Cellular Society: Communication between Apoptotic Cells and Their Neighbors

    Directory of Open Access Journals (Sweden)

    Yuhei Kawamoto

    2016-12-01

    Full Text Available Apoptosis is one of the cell-intrinsic suicide programs and is an essential cellular behavior for animal development and homeostasis. Traditionally, apoptosis has been regarded as a cell-autonomous phenomenon. However, recent in vivo genetic studies have revealed that apoptotic cells actively influence the behaviors of surrounding cells, including engulfment, proliferation, and production of mechanical forces. Such interactions can be bidirectional, and apoptosis is non-autonomously induced in a cellular community. Of note, it is becoming evident that active communication between apoptotic cells and living cells contributes to physiological processes during tissue remodeling, regeneration, and morphogenesis. In this review, we focus on the mutual interactions between apoptotic cells and their neighbors in cellular society and discuss issues relevant to future studies of apoptosis.

  20. Cancer Stem Cells: Cellular Plasticity, Niche, and its Clinical Relevance.

    Science.gov (United States)

    Lee, Gina; Hall, Robert R; Ahmed, Atique U

    2016-10-01

    Cancer handles an estimated 7.6 million deaths worldwide per annum. A recent theory focuses on the role Cancer Stem Cells (CSCs) in driving tumorigenesis and disease progression. This theory hypothesizes that a population of the tumor cell with similar functional and phenotypic characteristics as normal tissue stem cells are responsible for formation and advancement of many human cancers. The CSCs subpopulation can differentiate into non-CSC tumor cells and promote phenotypic and functional heterogeneity within the tumor. The presence of CSCs has been reported in a number of human cancers including blood, breast, brain, colon, lung, pancreas prostate and liver. Although the origin of CSCs remains a mystery, recent reports suggest that the phenotypic characteristics of CSCs may be plastic and are influenced by the microenvironment specific for the individual tumor. Such factors unique to each tumor preserve the dynamic balance between CSCs to non-CSCs cell fate, as well as maintain the proper equilibrium. Alternating such equilibrium via dedifferentiation can result in aggressiveness, as CSCs are considered to be more resistant to the conventional cancer treatments of chemotherapy and radiation. Understanding how the tumoral microenvironment affects the plasticity driven CSC niche will be critical for developing a more effective treatment for cancer by eliminating its aggressive and recurring nature that now is believed to be perpetuated by CSCs.

  1. 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...

  2. An SH3 binding motif within the nucleocapsid protein of porcine reproductive and respiratory syndrome virus interacts with the host cellular signaling proteins STAMI, TXK, Fyn, Hck, and cortactin.

    Science.gov (United States)

    Kenney, Scott P; Meng, Xiang-Jin

    2015-06-02

    Porcine reproductive and respiratory syndrome virus (PRRSV) causes an economically important global swine disease, and has a complicated virus-host immunomodulation that often leads to a weak Th2 immune response and viral persistence. In this study, we identified a Src homology 3 (SH3) binding motif, PxxPxxP, that is conserved within the N protein of PRRSV strains. Subsequently, we identified five host cellular proteins [signal transducing adaptor molecule (STAM)I, TXK tyrosine kinase (TXK), protein tyrosine kinase fyn (Fyn), hematopoietic cell kinase (Hck), and cortactin] that interact with this SH3 motif. We demonstrated that binding of SH3 proteins with PRRSV N protein depends on at least one intact PxxP motif as disruption of P53 within the motif significantly reduced interaction of each of the 5 proteins. The first PxxP motif appears to be more important for STAMI-N protein interactions whereas the second PxxP motif was more important for Hck interaction. Both STAMI and Hck interactions with PRRSV N protein required an unhindered C-terminal domain as the interaction was only observed with STAMI and Hck proteins with N-terminal but not C-terminal fluorescent tags. We showed that the P56 residue within the SH3 motif is critical for virus lifecycle as mutation resulted in a loss of virus infectivity, however the P50 and P53 mutations did not abolish virus infectivity suggesting that these highly conserved proline residues within the SH3 motif may provide a selective growth advantage through interactions with the host rather than a vital functional element. These results have important implications in understanding PRRSV-host interactions.

  3. Intestinal transporters for endogenic and pharmaceutical organic anions: The challenges of deriving in-vitro kinetic parameters for the prediction of clinically relevant drug-drug interactions

    DEFF Research Database (Denmark)

    Grandvuinet, Anne Sophie; Vestergaard, Henrik Tang; Rapin, Nicolas

    2012-01-01

    Objectives This review provides an overview of intestinal human transporters for organic anions and stresses the need for standardization of the various in-vitro methods presently employed in drug-drug interaction (DDI) investigations. Key findings Current knowledge on the intestinal expression o...... the involvement of other transporters than P-glycoprotein. Moreover, the interplay between various processes that a drug is subject to in-vivo such as translocation by several transporters and dissolution should be considered. © 2012 Royal Pharmaceutical Society....

  4. Interaction of Mycobacterium leprae with the HaCaT human keratinocyte cell line: new frontiers in the cellular immunology of leprosy.

    Science.gov (United States)

    Lyrio, Eloah C D; Campos-Souza, Ivy C; Corrêa, Luiz C D; Lechuga, Guilherme C; Verícimo, Maurício; Castro, Helena C; Bourguignon, Saulo C; Côrte-Real, Suzana; Ratcliffe, Norman; Declercq, Wim; Santos, Dilvani O

    2015-07-01

    Leprosy is a chronic granulomatous disease caused by Mycobacterium leprae affecting the skin and peripheral nerves. Despite M. leprae invasion of the skin and keratinocytes importance in innate immunity, the interaction of these cells in vitro during M. leprae infection is poorly understood. Conventional and fluorescence optical microscopy, transmission electronic microscopy, flow cytometry and ELISA were used to study the in vitro interaction of M. leprae with the HaCaT human keratinocyte cell line. Keratinocytes uptake of M. leprae is described, and modulation of the surface expression of CD80 and CD209, cathelicidin expression and TNF-α and IL-1β production of human keratinocytes are compared with dendritic cells and macrophages during M. leprae interaction. This study demonstrated that M. leprae interaction with human keratinocytes enhanced expression of cathelicidin and greatly increased TNF-α production. The highest spontaneous expression of cathelicidin was by dendritic cells which are less susceptible to M. leprae infection. In contrast, keratinocytes displayed low spontaneous cathelicidin expression and were more susceptible to M. leprae infection than dendritic cells. The results show, for the first time, an active role for keratinocytes during infection by irradiated whole cells of M. leprae and the effect of vitamin D on this process. They also suggest that therapies which target cathelicidin modulation may provide novel approaches for treatment of leprosy.

  5. Screening of cellular proteins that interact with the classical swine fever virus non-structural protein 5A by yeast two-hybrid analysis

    Indian Academy of Sciences (India)

    Chengcheng Zhang; Lei He; Kai Kang; Heng Chen; Lei Xu; Yanming Zhang

    2014-03-01

    Classical swine fever virus (CSFV), the pathogen of classical swine fever (CSF), causes severe hemorrhagic fever and vascular necrosis in domestic pigs and wild boar. A large number of evidence has proven that non-structural 5A (NS5A) is not only a very important part of viral replication complex, but also can regulate host cell’s function; however, the underlying mechanisms remain poorly understood. In the current study, aiming to find more clues in understanding the molecular mechanisms of CSFV NS5A’s function, the yeast two-hybrid (Y2H) system was adopted to screen for CSFV NS5A interactive proteins in the cDNA library of the swine umbilical vein endothelial cell (SUVEC). Alignment with the NCBI database revealed 16 interactive proteins: DDX5, PSMC3, NAV1, PHF5A, GNB2L1, CSDE1, HSPA8, BRMS1, PPP2R3C, AIP, TMED10, POLR1C, TMEM70, METAP2, CHORDC1 and COPS6. These proteins are mostly related to gene transcription, protein folding, protein degradation and metabolism. The interactions detected by the Y2H system should be considered as preliminary results. Since identifying novel pathways and host targets, which play essential roles during infection, may provide potential targets for therapeutic development. The finding of proteins obtained from the SUVEC cDNA library that interact with the CSFV NS5A protein provide valuable information for better understanding the interactions between this viral protein and the host target proteins.

  6. Liquid chromatography-inductively coupled plasma-based metallomic approaches to probe health-relevant interactions between xenobiotics and mammalian organisms.

    Science.gov (United States)

    Gómez-Ariza, José Luis; Jahromi, Elham Zeini; González-Fernández, Macarena; García-Barrera, Tamara; Gailer, Jürgen

    2011-06-01

    In mammals, the transport of essential elements from the gastrointestinal tract to organs is orchestrated by biochemical mechanisms which have evolved over millions of years. The subsequent organ-based assembly of sufficient amounts of metalloproteins is a prerequisite to maintain mammalian health and well-being. The chronic exposure of various human populations to environmentally abundant toxic metals/metalloid compounds and/or the deliberate administration of medicinal drugs, however, can adversely affect these processes which may eventually result in disease. A better understanding of the perturbation of these processes has the potential to advance human health, but their visualization poses a major problem. Nonetheless, liquid chromatography-inductively coupled plasma-based 'metallomics' methods, however, can provide much needed insight. Size-exclusion chromatography-inductively coupled plasma atomic emission spectrometry, for example, can be used to visualize changes that toxic metals/medicinal drugs exert at the metalloprotein level when they are added to plasma in vitro. In addition, size-exclusion chromatography-inductively coupled plasma mass spectrometry can be employed to analyze organs from toxic metal/medicinal drug-exposed organisms for metalloproteins to gain insight into the biochemical changes that are associated with their acute or chronic toxicity. The execution of such studies-from the selection of an appropriate model organism to the generation of accurate analytical data-is littered with potential pitfalls that may result in artifacts. Drawing on recent lessons that were learned by two research groups, this tutorial review is intended to provide relevant information with regard to the experimental design and the practical application of these aforementioned metallomics tools in applied health research.

  7. Corresponding-states behavior of a dipolar model fluid with variable dispersion interactions and its relevance to the anomalies of hydrogen fluoride.

    Science.gov (United States)

    Weiss, Volker C; Leroy, Frédéric

    2016-06-14

    More than two decades ago, the elusiveness of a liquid-vapor equilibrium and a corresponding critical point in simulations of the supposedly simple model of dipolar hard spheres came as a surprise to many liquid matter theorists. van Leeuwen and Smit [Phys. Rev. Lett. 71, 3991 (1993)] showed that a minimum of attractive dispersion interactions among the dipolar particles may be needed to observe regular fluid behavior. Here, we adopt their approach and use an only slightly modified model, in which the original point dipole is replaced by a dipole moment produced by charges that are separated in space, to study the influence of dispersion interactions of variable strength on the coexistence and interfacial properties of a polar fluid. The thermophysical properties are discussed in terms of Guggenheim's corresponding-states approach. In this way, the coexistence curve, the critical compressibility factor, the surface tension, Guggenheim's ratio, and modifications of Guldberg's and Trouton's rules (related to the vapor pressure and the enthalpy of vaporization) are analyzed. As the importance of dispersion is decreased, a crossover from simple-fluid behavior to that characteristic of strongly dipolar systems takes place; for some properties, this transition is monotonic, but for others it occurs non-monotonically. For strongly dipolar systems, the reduced surface tension is very low, whereas Guggenheim's ratio and Guldberg's ratio are found to be high. The critical compressibility factor is smaller, and the coexistence curve is wider and more skewed than for simple fluids. For very weak dispersion, liquid-vapor equilibrium is still observable, but the interfacial tension is extremely low and may, eventually, vanish marking the end of the existence of a liquid phase. We discuss the implications of our findings for real fluids, in particular, for hydrogen fluoride.

  8. Synthesis and Structural Investigation of New Bio-Relevant Complexes of Lanthanides with 5-Hydroxyflavone: DNA Binding and Protein Interaction Studies

    Directory of Open Access Journals (Sweden)

    Alexandra-Cristina Munteanu

    2016-12-01

    Full Text Available In the present work, we attempted to develop new metal coordination complexes of the natural flavonoid 5-hydroxyflavone with Sm(III, Eu(III, Gd(III, Tb(III. The resultant hydroxo complexes have been characterized by a variety of spectroscopic techniques, including fluorescence, FT-IR, UV-Vis, EPR and mass spectral studies. The general chemical formula of the complexes is [Ln(C15H9O33(OH2(H2Ox]·nH2O, where Ln is the lanthanide cation and x = 0 for Sm(III, x = 1 for Eu(III, Gd(III, Tb(III and n = 0 for Sm(III, Gd(III, Tb(III, n = 1 for Eu(III, respectively. The proposed structures of the complexes were optimized by DFT calculations. Theoretical calculations and experimental determinations sustain the proposed structures of the hydroxo complexes, with two molecules of 5-hydroxyflavone acting as monoanionic bidentate chelate ligands. The interaction of the complexes with calf thymus DNA has been explored by fluorescence titration and UV-Vis absorption binding studies, and revealed that the synthesized complexes interact with DNA with binding constants (Kb ~ 104. Human serum albumin (HSA and transferrin (Tf binding studies have also been performed by fluorescence titration techniques (fluorescence quenching studies, synchronous fluorescence spectra. The apparent association constants (Ka and thermodynamic parameters have been calculated from the fluorescence quenching experiment at 299 K, 308 K, and 318 K. The quenching curves indicate that the complexes bind to HSA with smaller affinity than the ligand, but to Tf with higher binding affinities than the ligand.

  9. Corresponding-states behavior of a dipolar model fluid with variable dispersion interactions and its relevance to the anomalies of hydrogen fluoride

    Science.gov (United States)

    Weiss, Volker C.; Leroy, Frédéric

    2016-06-01

    More than two decades ago, the elusiveness of a liquid-vapor equilibrium and a corresponding critical point in simulations of the supposedly simple model of dipolar hard spheres came as a surprise to many liquid matter theorists. van Leeuwen and Smit [Phys. Rev. Lett. 71, 3991 (1993)] showed that a minimum of attractive dispersion interactions among the dipolar particles may be needed to observe regular fluid behavior. Here, we adopt their approach and use an only slightly modified model, in which the original point dipole is replaced by a dipole moment produced by charges that are separated in space, to study the influence of dispersion interactions of variable strength on the coexistence and interfacial properties of a polar fluid. The thermophysical properties are discussed in terms of Guggenheim's corresponding-states approach. In this way, the coexistence curve, the critical compressibility factor, the surface tension, Guggenheim's ratio, and modifications of Guldberg's and Trouton's rules (related to the vapor pressure and the enthalpy of vaporization) are analyzed. As the importance of dispersion is decreased, a crossover from simple-fluid behavior to that characteristic of strongly dipolar systems takes place; for some properties, this transition is monotonic, but for others it occurs non-monotonically. For strongly dipolar systems, the reduced surface tension is very low, whereas Guggenheim's ratio and Guldberg's ratio are found to be high. The critical compressibility factor is smaller, and the coexistence curve is wider and more skewed than for simple fluids. For very weak dispersion, liquid-vapor equilibrium is still observable, but the interfacial tension is extremely low and may, eventually, vanish marking the end of the existence of a liquid phase. We discuss the implications of our findings for real fluids, in particular, for hydrogen fluoride.

  10. Why relevance theory is relevant for lexicography

    DEFF Research Database (Denmark)

    Bothma, Theo; Tarp, Sven

    2014-01-01

    , socio-cognitive and affective relevance. It then shows, at the hand of examples, why relevance is important from a user perspective in the extra-lexicographical pre- and post-consultation phases and in the intra-lexicographical consultation phase. It defines an additional type of subjective relevance...... that is very important for lexicography as well as for information science, viz. functional relevance. Since all lexicographic work is ultimately aimed at satisfying users’ information needs, the article then discusses why the lexicographer should take note of all these types of relevance when planning a new...... dictionary project, identifying new tasks and responsibilities of the modern lexicographer. The article furthermore discusses how relevance theory impacts on teaching dictionary culture and reference skills. By integrating insights from lexicography and information science, the article contributes to new...

  11. Hydrodynamic interactions between nearby slender filaments

    CERN Document Server

    Man, Yi; Lauga, Eric

    2016-01-01

    Cellular biology abound with filaments interacting through fluids, from intracellular microtubules, to rotating flagella and beating cilia. While previous work has demonstrated the complexity of capturing nonlocal hydrodynamic interactions between moving filaments, the problem remains difficult theoretically. We show here that when filaments are closer to each other than their relevant length scale, the integration of hydrodynamic interactions can be approximately carried out analytically. This leads to a set of simplified local equations, illustrated on a simple model of two interacting filaments, which can be used to tackle theoretically a range of problems in biology and physics.

  12. An Analysis of Bubble Deformation by a Sphere Relevant to the Measurements of Bubble-Particle Contact Interaction and Detachment Forces.

    Science.gov (United States)

    Sherman, H; Nguyen, A V; Bruckard, W

    2016-11-22

    Atomic force microscopy makes it possible to measure the interacting forces between individual colloidal particles and air bubbles, which can provide a measure of the particle hydrophobicity. To indicate the level of hydrophobicity of the particle, the contact angle can be calculated, assuming that no interfacial deformation occurs with the bubble retaining a spherical profile. Our experimental results obtained using a modified sphere tensiometry apparatus to detach submillimeter spherical particles show that deformation of the bubble interface does occur during particle detachment. We also develop a theoretical model to describe the equilibrium shape of the bubble meniscus at any given particle position, based on the minimization of the free energy of the system. The developed model allows us to analyze high-speed video captured during detachment. In the system model deformation of the bubble profile is accounted for by the incorporation of a Lagrange multiplier into both the Young-Laplace equation and the force balance. The solution of the bubble profile matched to the high-speed video allows us to accurately calculate the contact angle and determine the total force balance as a function of the contact point of the bubble on the particle surface.

  13. Microbial dissolution of hematite and associated cellular fossilization by reduced iron phases: a study of ancient microbe-mineral surface interactions.

    Science.gov (United States)

    Kolo, Kamal; Konhauser, Kurt; Krumbein, Wolfgang Elisabeth; Ingelgem, Yves Van; Hubin, Annick; Claeys, Philippe

    2009-10-01

    We report here on magnetite- and wustite-encrusted and geometrically oriented microbial-like structures (MLS) attached to the surfaces of hematite (alpha-Fe(2)O(3)) crystals in a banded iron formation. Field emission scanning electron microscope (FE-SEM) and scanning electron microscope (SEM) imaging showed a 3-D network of MLS arranged in 1 microm x approximately 20 microm coccoidal-like chains (CLC) of various geometrical shapes: dichotomous and budding-like protrusions, parallel, intersecting, triangular, or sinusoidal. Individual spheroidal forms ( approximately 1 mum in diameter), some displaying what appears to be division, were also abundant. In addition to their size, morphology, and preferred orientations, a microbial origin of these chains and single spheroidal forms is inferred by the presence of material that resembles extracellular polymeric substances (EPS) extending from the base of the chains along the mineral surface: the attachment sites show circular dissolution pits of about 100 nm diameter. Other thin structures protruding from the CLC are reminiscent of bacterial "nanowires." We were, however, unable to find any extant cells, organic carbon, or even recover DNA from the MLS, which suggests that they, if microbial, are possibly mineralogically replaced casts or mineral encrustations of cells. It is further speculated that, given the nature of the substrate upon which the forms are attached and their preferential orientations, it seems plausible that the "original cells" may have been Fe(III)-reducing bacteria that exploited structural imperfections in the crystal lattice. Importantly, the preservation of the ancient microbial shapes in mineral casts of magnetite, wustite, or both may be an overlooked means by which cellular features in the rock record are retained.

  14. Complex interactions between dioxin-like and non-dioxin-like compounds for in vitro cellular responses: implications for the identification of dioxin exposure biomarkers.

    Science.gov (United States)

    O'Kane, Anthony A; Elliott, Chris T; Mooney, Mark H

    2014-02-17

    Despite considerable advances in reducing the production of dioxin-like toxicants in recent years, contamination of the food chain still occasionally occurs resulting in huge losses to the agri-food sector and risk to human health through exposure. Dioxin-like toxicity is exhibited by a range of stable and bioaccumulative compounds including polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs), produced by certain types of combustion, and man-made coplanar polychlorinated biphenyls (PCBs), as found in electrical transformer oils. While dioxinergic compounds act by a common mode of action making exposure detection biomarker based techniques a potentially useful tool, the influence of co-contaminating toxicants on such approaches needs to be considered. To assess the impact of possible interactions, the biological responses of H4IIE cells to challenge by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in combination with PCB-52 and benzo-a-pyrene (BaP) were evaluated by a number of methods in this study. Ethoxyresorufin-O-deethylase (EROD) induction in TCDD exposed cells was suppressed by increasing concentrations of PCB-52, PCB-153, or BaP up to 10 μM. BaP levels below 1 μM suppressed TCDD stimulated EROD induction, but at higher concentrations, EROD induction was greater than the maximum observed when cells were treated with TCDD alone. A similar biphasic interaction of BaP with TCDD co-exposure was noted in the AlamarBlue assay and to a lesser extent with PCB-52. Surface enhanced laser desorption/ionization-time of flight mass spectrometry (SELDI-TOF) profiling of peptidomic responses of cells exposed to compound combinations was compared. Cells co-exposed to TCDD in the presence of BaP or PCB-52 produced the most differentiated spectra with a substantial number of non-additive interactions observed. These findings suggest that interactions between dioxin and other toxicants create novel, additive, and non-additive effects, which may be more indicative

  15. Relevance theory and pragmatic impairment.

    Science.gov (United States)

    Leinonen, E; Kerbel, D

    1999-01-01

    This paper summarizes aspects of relevance theory that are useful for exploring impairment of pragmatic comprehension in children. It explores data from three children with pragmatic language difficulties within this framework. Relevance theory is seen to provide a means of explaining why, in a given context, a particular utterance is problematic. It thus enables one to move on from mere description of problematic behaviours towards their explanation. The theory provides a clearer delineation between the explicit and the implicit, and hence between semantics and pragmatics. This enables one to place certain difficulties more firmly within semantics and others within pragmatics. Relevance, and its maximization in communication, are squarely placed within human cognition, which suggests a close connection between pragmatic and cognitive (dis)functioning. Relevance theory thus emerges as a powerful tool in the exploration and understanding of pragmatic language difficulties in children and offers therapeutically valuable insight into the nature of interactions involving individuals with such impairments.

  16. INCURVATA2 Encodes the Catalytic Subunit of DNA Polymerase α and Interacts with Genes Involved in Chromatin-Mediated Cellular Memory in Arabidopsis thaliana

    Science.gov (United States)

    Barrero, José María; González-Bayón, Rebeca; del Pozo, Juan Carlos; Ponce, María Rosa; Micol, José Luis

    2007-01-01

    Cell type–specific gene expression patterns are maintained by the stable inheritance of transcriptional states through mitosis, requiring the action of multiprotein complexes that remodel chromatin structure. Genetic and molecular interactions between chromatin remodeling factors and components of the DNA replication machinery have been identified in Schizosaccharomyces pombe, indicating that some epigenetic marks are replicated simultaneously to DNA with the participation of the DNA replication complexes. This model of epigenetic inheritance might be extended to the plant kingdom, as we report here with the positional cloning and characterization of INCURVATA2 (ICU2), which encodes the putative catalytic subunit of the DNA polymerase α of Arabidopsis thaliana. The strong icu2-2 and icu2-3 insertional alleles caused fully penetrant zygotic lethality when homozygous and incompletely penetrant gametophytic lethality, probably because of loss of DNA polymerase activity. The weak icu2-1 allele carried a point mutation and caused early flowering, leaf incurvature, and homeotic transformations of sepals into carpels and of petals into stamens. Further genetic analyses indicated that ICU2 interacts with TERMINAL FLOWER2, the ortholog of HETEROCHROMATIN PROTEIN1 of animals and yeasts, and with the Polycomb group (PcG) gene CURLY LEAF. Another PcG gene, EMBRYONIC FLOWER2, was found to be epistatic to ICU2. Quantitative RT-PCR analyses indicated that a number of regulatory genes were derepressed in the icu2-1 mutant, including genes associated with flowering time, floral meristem, and floral organ identity. PMID:17873092

  17. INCURVATA2 encodes the catalytic subunit of DNA Polymerase alpha and interacts with genes involved in chromatin-mediated cellular memory in Arabidopsis thaliana.

    Science.gov (United States)

    Barrero, José María; González-Bayón, Rebeca; del Pozo, Juan Carlos; Ponce, María Rosa; Micol, José Luis

    2007-09-01

    Cell type-specific gene expression patterns are maintained by the stable inheritance of transcriptional states through mitosis, requiring the action of multiprotein complexes that remodel chromatin structure. Genetic and molecular interactions between chromatin remodeling factors and components of the DNA replication machinery have been identified in Schizosaccharomyces pombe, indicating that some epigenetic marks are replicated simultaneously to DNA with the participation of the DNA replication complexes. This model of epigenetic inheritance might be extended to the plant kingdom, as we report here with the positional cloning and characterization of INCURVATA2 (ICU2), which encodes the putative catalytic subunit of the DNA polymerase alpha of Arabidopsis thaliana. The strong icu2-2 and icu2-3 insertional alleles caused fully penetrant zygotic lethality when homozygous and incompletely penetrant gametophytic lethality, probably because of loss of DNA polymerase activity. The weak icu2-1 allele carried a point mutation and caused early flowering, leaf incurvature, and homeotic transformations of sepals into carpels and of petals into stamens. Further genetic analyses indicated that ICU2 interacts with TERMINAL FLOWER2, the ortholog of HETEROCHROMATIN PROTEIN1 of animals and yeasts, and with the Polycomb group (PcG) gene CURLY LEAF. Another PcG gene, EMBRYONIC FLOWER2, was found to be epistatic to ICU2. Quantitative RT-PCR analyses indicated that a number of regulatory genes were derepressed in the icu2-1 mutant, including genes associated with flowering time, floral meristem, and floral organ identity.

  18. Molecular Interaction and Cellular Location of RecA and CheW Proteins in Salmonella enterica during SOS Response and Their Implication in Swarming

    Science.gov (United States)

    Irazoki, Oihane; Aranda, Jesús; Zimmermann, Timo; Campoy, Susana; Barbé, Jordi

    2016-01-01

    In addition to its role in DNA damage repair and recombination, the RecA protein, through its interaction with CheW, is involved in swarming motility, a form of flagella-dependent movement across surfaces. In order to better understand how SOS response modulates swarming, in this work the location of RecA and CheW proteins within the swarming cells has been studied by using super-resolution microscopy. Further, and after in silico docking studies, the specific RecA and CheW regions associated with the RecA-CheW interaction have also been confirmed by site-directed mutagenesis and immunoprecipitation techniques. Our results point out that the CheW distribution changes, from the cell poles to foci distributed in a helical pattern along the cell axis when SOS response is activated or RecA protein is overexpressed. In this situation, the CheW presents the same subcellular location as that of RecA, pointing out that the previously described RecA storage structures may be modulators of swarming motility. Data reported herein not only confirmed that the RecA-CheW pair is essential for swarming motility but it is directly involved in the CheW distribution change associated to SOS response activation. A model explaining not only the mechanism by which DNA damage modulates swarming but also how both the lack and the excess of RecA protein impair this motility is proposed. PMID:27766091

  19. Sponging of Cellular Proteins by Viral RNAs

    OpenAIRE

    Charley, Phillida A.; Wilusz, Jeffrey

    2014-01-01

    Viral RNAs accumulate to high levels during infection and interact with a variety of cellular factors including miRNAs and RNA-binding proteins. Although many of these interactions exist to directly modulate replication, translation and decay of viral transcripts, evidence is emerging that abundant viral RNAs may in certain cases serve as a sponge to sequester host non coding RNAs and proteins. By effectively reducing the ability of cellular RNA binding proteins to regulate host cell gene exp...

  20. Unique cellular events occurring during the initial interaction of macrophages with matrix-retained or methylated aggregated low density lipoprotein (LDL). Prolonged cell-surface contact during which ldl-cholesteryl ester hydrolysis exceeds ldl protein degradation.

    Science.gov (United States)

    Buton, X; Mamdouh, Z; Ghosh, R; Du, H; Kuriakose, G; Beatini, N; Grabowski, G A; Maxfield, F R; Tabas, I

    1999-11-05

    A critical event in atherogenesis is the interaction of arterial wall macrophages with subendothelial lipoproteins. Although most studies have investigated this interaction by incubating cultured macrophages with monomeric lipoproteins dissolved in media, arterial wall macrophages encounter lipoproteins that are mostly bound to subendothelial extracellular matrix, and these lipoproteins are often aggregated or fused. Herein, we utilize a specialized cell-culture system to study the initial interaction of macrophages with aggregated low density lipoprotein (LDL) bound to extracellular matrix. The aggregated LDL remains extracellular for a relatively prolonged period of time and becomes lodged in invaginations in the surface of the macrophages. As expected, the degradation of the protein moiety of the LDL was very slow. Remarkably, however, hydrolysis of the cholesteryl ester (CE) moiety of the LDL was 3-7-fold higher than that of the protein moiety, in stark contrast to the situation with receptor-mediated endocytosis of acetyl-LDL. Similar results were obtained using another experimental system in which the degradation of aggregated LDL protein was delayed by LDL methylation rather than by retention on matrix. Additional experiments indicated the following properties of this interaction: (a) LDL-CE hydrolysis is catalyzed by lysosomal acid lipase; (b) neither scavenger receptors nor the LDL receptor appear necessary for the excess LDL-CE hydrolysis; and (c) LDL-CE hydrolysis in this system is resistant to cellular potassium depletion, which further distinguishes this process from receptor-mediated endocytosis. In summary, experimental systems specifically designed to mimic the in vivo interaction of arterial wall macrophages with subendothelial lipoproteins have demonstrated an initial period of prolonged cell-surface contact in which CE hydrolysis exceeds protein degradation.

  1. Old age and the associated impairment of bones' adaptation to loading are associated with transcriptomic changes in cellular metabolism, cell-matrix interactions and the cell cycle.

    Science.gov (United States)

    Galea, Gabriel L; Meakin, Lee B; Harris, Marie A; Delisser, Peter J; Lanyon, Lance E; Harris, Stephen E; Price, Joanna S

    2017-01-30

    In old animals, bone's ability to adapt its mass and architecture to functional load-bearing requirements is diminished, resulting in bone loss characteristic of osteoporosis. Here we investigate transcriptomic changes associated with this impaired adaptive response. Young adult (19-week-old) and aged (19-month-old) female mice were subjected to unilateral axial tibial loading and their cortical shells harvested for microarray analysis between 1h and 24h following loading (36 mice per age group, 6 mice per loading group at 6 time points). In non-loaded aged bones, down-regulated genes are enriched for MAPK, Wnt and cell cycle components, including E2F1. E2F1 is the transcription factor most closely associated with genes down-regulated by ageing and is down-regulated at the protein level in osteocytes. Genes up-regulated in aged bone are enriched for carbohydrate metabolism, TNFα and TGFβ superfamily components. Loading stimulates rapid and sustained transcriptional responses in both age groups. However, genes related to proliferation are predominantly up-regulated in the young and down-regulated in the aged following loading, whereas those implicated in bioenergetics are down-regulated in the young and up-regulated in the aged. Networks of inter-related transcription factors regulated by E2F1 are loading-responsive in both age groups. Loading regulates genes involved in similar signalling cascades in both age groups, but these responses are more sustained in the young than aged. From this we conclude that cells in aged bone retain the capability to sense and transduce loading-related stimuli, but their ability to translate acute responses into functionally relevant outcomes is diminished.

  2. Investigating the consequences of eIF4E2 (4EHP interaction with 4E-transporter on its cellular distribution in HeLa cells.

    Directory of Open Access Journals (Sweden)

    Dorota Kubacka

    Full Text Available In addition to the canonical eIF4E cap-binding protein, eukaryotes have evolved sequence-related variants with distinct features, some of which have been shown to negatively regulate translation of particular mRNAs, but which remain poorly characterised. Mammalian eIF4E proteins have been divided into three classes, with class I representing the canonical cap-binding protein eIF4E1. eIF4E1 binds eIF4G to initiate translation, and other eIF4E-binding proteins such as 4E-BPs and 4E-T prevent this interaction by binding eIF4E1 with the same consensus sequence YX 4Lϕ. We investigate here the interaction of human eIF4E2 (4EHP, a class II eIF4E protein, which binds the cap weakly, with eIF4E-transporter protein, 4E-T. We first show that ratios of eIF4E1:4E-T range from 50:1 to 15:1 in HeLa and HEK293 cells respectively, while those of eIF4E2:4E-T vary from 6:1 to 3:1. We next provide evidence that eIF4E2 binds 4E-T in the yeast two hybrid assay, as well as in pull-down assays and by recruitment to P-bodies in mammalian cells. We also show that while both eIF4E1 and eIF4E2 bind 4E-T via the canonical YX 4Lϕ sequence, nearby downstream sequences also influence eIF4E:4E-T interactions. Indirect immunofluorescence was used to demonstrate that eIF4E2, normally homogeneously localised in the cytoplasm, does not redistribute to stress granules in arsenite-treated cells, nor to P-bodies in Actinomycin D-treated cells, in contrast to eIF4E1. Moreover, eIF4E2 shuttles through nuclei in a Crm1-dependent manner, but in an 4E-T-independent manner, also unlike eIF4E1. Altogether we conclude that while both cap-binding proteins interact with 4E-T, and can be recruited by 4E-T to P-bodies, eIF4E2 functions are likely to be distinct from those of eIF4E1, both in the cytoplasm and nucleus, further extending our understanding of mammalian class I and II cap-binding proteins.

  3. Protein arginine methyltransferase 1 and 8 interact with FUS to modify its sub-cellular distribution and toxicity in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Chiara Scaramuzzino

    Full Text Available Amyotrophic lateral sclerosis (ALS is a late onset and progressive motor neuron disease. Mutations in the gene coding for fused in sarcoma/translocated in liposarcoma (FUS are responsible for some cases of both familial and sporadic forms of ALS. The mechanism through which mutations of FUS result in motor neuron degeneration and loss is not known. FUS belongs to the family of TET proteins, which are regulated at the post-translational level by arginine methylation. Here, we investigated the impact of arginine methylation in the pathogenesis of FUS-related ALS. We found that wild type FUS (FUS-WT specifically interacts with protein arginine methyltransferases 1 and 8 (PRMT1 and PRMT8 and undergoes asymmetric dimethylation in cultured cells. ALS-causing FUS mutants retained the ability to interact with both PRMT1 and PRMT8 and undergo asymmetric dimethylation similar to FUS-WT. Importantly, PRMT1 and PRMT8 localized to mutant FUS-positive inclusion bodies. Pharmacologic inhibition of PRMT1 and PRMT8 activity reduced both the nuclear and cytoplasmic accumulation of FUS-WT and ALS-associated FUS mutants in motor neuron-derived cells and in cells obtained from an ALS patient carrying the R518G mutation. Genetic ablation of the fly homologue of human PRMT1 (DART1 exacerbated the neurodegeneration induced by overexpression of FUS-WT and R521H FUS mutant in a Drosophila model of FUS-related ALS. These results support a role for arginine methylation in the pathogenesis of FUS-related ALS.

  4. INTERACT

    DEFF Research Database (Denmark)

    Jochum, Elizabeth; Borggreen, Gunhild; Murphey, TD

    This paper considers the impact of visual art and performance on robotics and human-computer interaction and outlines a research project that combines puppetry and live performance with robotics. Kinesics—communication through movement—is the foundation of many theatre and performance traditions...... interaction between a human operator and an artificial actor or agent. We can apply insights from puppetry to develop culturally-aware robots. Here we describe the development of a robotic marionette theatre wherein robotic controllers assume the role of human puppeteers. The system has been built, tested...

  5. Cellular bioluminescence imaging.

    Science.gov (United States)

    Welsh, David K; Noguchi, Takako

    2012-08-01

    Bioluminescence imaging of live cells has recently been recognized as an important alternative to fluorescence imaging. Fluorescent probes are much brighter than bioluminescent probes (luciferase enzymes) and, therefore, provide much better spatial and temporal resolution and much better contrast for delineating cell structure. However, with bioluminescence imaging there is virtually no background or toxicity. As a result, bioluminescence can be superior to fluorescence for detecting and quantifying molecules and their interactions in living cells, particularly in long-term studies. Structurally diverse luciferases from beetle and marine species have been used for a wide variety of applications, including tracking cells in vivo, detecting protein-protein interactions, measuring levels of calcium and other signaling molecules, detecting protease activity, and reporting circadian clock gene expression. Such applications can be optimized by the use of brighter and variously colored luciferases, brighter microscope optics, and ultrasensitive, low-noise cameras. This article presents a review of how bioluminescence differs from fluorescence, its applications to cellular imaging, and available probes, optics, and detectors. It also gives practical suggestions for optimal bioluminescence imaging of single cells.

  6. Flat Cellular (UMTS) Networks

    NARCIS (Netherlands)

    Bosch, H.G.P.; Samuel, L.G.; Mullender, S.J.; Polakos, P.; Rittenhouse, G.

    2007-01-01

    Traditionally, cellular systems have been built in a hierarchical manner: many specialized cellular access network elements that collectively form a hierarchical cellular system. When 2G and later 3G systems were designed there was a good reason to make system hierarchical: from a cost-perspective i

  7. Plant viral nanoparticles-based HER2 vaccine: Immune response influenced by differential transport, localization and cellular interactions of particulate carriers.

    Science.gov (United States)

    Shukla, Sourabh; Myers, Jay T; Woods, Sarah E; Gong, Xingjian; Czapar, Anna E; Commandeur, Ulrich; Huang, Alex Y; Levine, Alan D; Steinmetz, Nicole F

    2017-03-01

    Cancer vaccines are designed to elicit an endogenous adaptive immune response that can successfully recognize and eliminate residual or recurring tumors. Such approaches can potentially overcome shortcomings of passive immunotherapies by generating long-lived therapeutic effects and immune memory while limiting systemic toxicities. A critical determinant of vaccine efficacy is efficient transport and delivery of tumor-associated antigens to professional antigen presenting cells (APCs). Plant viral nanoparticles (VNPs) with natural tropism for APCs and a high payload carrying capacity may be particularly effective vaccine carriers. The applicability of VNP platform technologies is governed by stringent structure-function relationships. We compare two distinct VNP platforms: icosahedral cowpea mosaic virus (CPMV) and filamentous potato virus X (PVX). Specifically, we evaluate in vivo capabilities of engineered VNPs delivering human epidermal growth factor receptor 2 (HER2) epitopes for therapy and prophylaxis of HER2(+) malignancies. Our results corroborate the structure-function relationship where icosahedral CPMV particles showed significantly enhanced lymph node transport and retention, and greater uptake by/activation of APCs compared to filamentous PVX particles. These enhanced immune cell interactions and transport properties resulted in elevated HER2-specific antibody titers raised by CPMV- vs. PVX-based peptide vaccine. The 'synthetic virology' field is rapidly expanding with numerous platforms undergoing development and preclinical testing; our studies highlight the need for systematic studies to define rules guiding the design and rational choice of platform, in the context of peptide-vaccine display technologies.

  8. Epstein–Barr virus nuclear antigen 3C interact with p73: Interplay between a viral oncoprotein and cellular tumor suppressor

    Energy Technology Data Exchange (ETDEWEB)

    Sahu, Sushil Kumar; Mohanty, Suchitra; Kumar, Amit [Division of Infectious Disease Biology, Institute of Life Sciences, Nalco Square, Chandrasekharpur, Bhubaneswar 751023 (India); Kundu, Chanakya N. [School of Biotechnology, KIIT University, Bhubaneswar (India); Verma, Subhash C. [Department of Microbiology and Immunology, University of Nevada, School of Medicine, Reno, NV 89557 (United States); Choudhuri, Tathagata, E-mail: tatha@ils.res.in [Division of Infectious Disease Biology, Institute of Life Sciences, Nalco Square, Chandrasekharpur, Bhubaneswar 751023 (India); Department of Biotechnology, Siksha Bhavana, Visva Bharati, Santiniketan, Bolpur (India)

    2014-01-05

    The p73 protein has structural and functional homology with the tumor suppressor p53, which plays an important role in cell cycle regulation, apoptosis, and DNA repair. The p73 locus encodes both a tumor suppressor (TAp73) and a putative oncogene (ΔNp73). p73 May play a significant role in p53-deficient lymphomas infected with Epstein–Barr virus (EBV). EBV produces an asymptomatic infection in the majority of the global population, but it is associated with several human B-cell malignancies. The EBV-encoded Epstein–Barr virus nuclear antigen 3C (EBNA3C) is thought to disrupt the cell cycle checkpoint by interacting directly with p53 family proteins. Doxorubicin, a commonly used chemotherapeutic agent, induces apoptosis through p53 and p73 signaling such that the lowΔNp73 level promotes the p73-mediated intrinsic pathway of apoptosis. In this report, we investigated the mechanism by which EBV infection counters p73α-induced apoptosis through EBNA3C. - Highlights: • EBV-encoded EBNA3C suppresses doxorubicin-induced apoptosis in B-cell lymphomas. • EBNA3C binds to p73 to suppress its apoptotic effect. • EBNA3C maintains latency by regulating downstream mitochondrial pathways.

  9. Suppressing activity of tributyrin on hepatocarcinogenesis is associated with inhibiting the p53-CRM1 interaction and changing the cellular compartmentalization of p53 protein.

    Science.gov (United States)

    Ortega, Juliana F; de Conti, Aline; Tryndyak, Volodymyr; Furtado, Kelly S; Heidor, Renato; Horst, Maria Aderuza; Fernandes, Laura Helena Gasparini; Tavares, Paulo Eduardo Latorre Martins; Pogribna, Marta; Shpyleva, Svitlana; Beland, Frederick A; Pogribny, Igor P; Moreno, Fernando Salvador

    2016-04-26

    Hepatocellular carcinoma (HCC), an aggressive and the fastest growing life-threatening cancer worldwide, is often diagnosed at intermediate or advanced stages of the disease, which substantially limits therapeutic approaches for its successful treatment. This indicates that the prevention of hepatocarcinogenesis is probably the most promising approach to reduce both the HCC incidence and cancer-related mortality. In previous studies, we demonstrated a potent chemopreventive effect of tributyrin, a butyric acid prodrug, on experimental hepatocarcinogenesis. The cancer-inhibitory effect of tributyrin was linked to the suppression of sustained cell proliferation and induction of apoptotic cell death driven by an activation of the p53 apoptotic signaling pathway. The goal of the present study was to investigate the underlying molecular mechanisms linked to tributyrin-mediated p53 activation. Using in vivo and in vitro models of liver cancer, we demonstrate that an increase in the level of p53 protein in nuclei, a decrease in the level of cytoplasmic p53, and, consequently, an increase in the ratio of nuclear/cytoplasmic p53 in rat preneoplastic livers and in rat and human HCC cell lines caused by tributyrin or sodium butyrate treatments was associated with a marked increase in the level of nuclear chromosome region maintenance 1 (CRM1) protein. Mechanistically, the increase in the level of nuclear p53 protein was associated with a substantially reduced binding interaction between CRM1 and p53. The results demonstrate that the cancer-inhibitory activity of sodium butyrate and its derivatives on liver carcinogenesis may be attributed to retention of p53 and CRM1 proteins in the nucleus, an event that may trigger activation of p53-mediated apoptotic cell death in neoplastic cells.

  10. Interactions

    DEFF Research Database (Denmark)

    The main theme of this anthology is the unique interaction between mathematics, physics and philosophy during the beginning of the 20th century. Seminal theories of modern physics and new fundamental mathematical structures were discovered or formed in this period. Significant physicists such as ...... also key figures in the philosophical discussions of nature and science - from philosophical tendencies like logical empiricism via critical rationalism to various neo-Kantian trends....

  11. Phosphorylation of eIF4E Confers Resistance to Cellular Stress and DNA-Damaging Agents through an Interaction with 4E-T: A Rationale for Novel Therapeutic Approaches.

    Directory of Open Access Journals (Sweden)

    Alba Martínez

    Full Text Available Phosphorylation of the eukaryotic translation initiation factor eIF4E is associated with malignant progression and poor cancer prognosis. Accordingly, here we have analyzed the association between eIF4E phosphorylation and cellular resistance to oxidative stress, starvation, and DNA-damaging agents in vitro. Using immortalized and cancer cell lines, retroviral expression of a phosphomimetic (S209D form of eIF4E, but not phospho-dead (S209A eIF4E or GFP control, significantly increased cellular resistance to stress induced by DNA-damaging agents (cisplatin, starvation (glucose+glutamine withdrawal, and oxidative stress (arsenite. De novo accumulation of eIF4E-containing cytoplasmic bodies colocalizing with the eIF4E-binding protein 4E-T was observed after expression of phosphomimetic S209D, but not S209A or wild-type eIF4E. Increased resistance to cellular stress induced by eIF4E-S209D was lost upon knockdown of endogenous 4E-T or use of an eIF4E-W73A-S209D mutant unable to bind 4E-T. Cancer cells treated with the Mnk1/2 inhibitor CGP57380 to prevent eIF4E phosphorylation and mouse embryonic fibroblasts derived from Mnk1/2 knockout mice were also more sensitive to arsenite and cisplatin treatment. Polysome analysis revealed an 80S peak 2 hours after arsenite treatment in cells overexpressing phosphomimetic eIF4E, indicating translational stalling. Nonetheless, a selective increase was observed in the synthesis of some proteins (cyclin D1, HuR, and Mcl-1. We conclude that phosphorylation of eIF4E confers resistance to various cell stressors and that a direct interaction or regulation of 4E-T by eIF4E is required. Further delineation of this process may identify novel therapeutic avenues for cancer treatment, and these results support the use of modern Mnk1/2 inhibitors in conjunction with standard therapy.

  12. Deep learning relevance

    DEFF Research Database (Denmark)

    Lioma, Christina; Larsen, Birger; Petersen, Casper

    2016-01-01

    train a Recurrent Neural Network (RNN) on existing relevant information to that query. We then use the RNN to "deep learn" a single, synthetic, and we assume, relevant document for that query. We design a crowdsourcing experiment to assess how relevant the "deep learned" document is, compared......What if Information Retrieval (IR) systems did not just retrieve relevant information that is stored in their indices, but could also "understand" it and synthesise it into a single document? We present a preliminary study that makes a first step towards answering this question. Given a query, we...... to existing relevant documents. Users are shown a query and four wordclouds (of three existing relevant documents and our deep learned synthetic document). The synthetic document is ranked on average most relevant of all....

  13. A Computation in a Cellular Automaton Collider Rule 110

    CERN Document Server

    Martinez, Genaro J; McIntosh, Harold V

    2016-01-01

    A cellular automaton collider is a finite state machine build of rings of one-dimensional cellular automata. We show how a computation can be performed on the collider by exploiting interactions between gliders (particles, localisations). The constructions proposed are based on universality of elementary cellular automaton rule 110, cyclic tag systems, supercolliders, and computing on rings.

  14. Differences between disease-associated endoplasmic reticulum aminopeptidase 1 (ERAP1) isoforms in cellular expression, interactions with tumour necrosis factor receptor 1 (TNF-R1) and regulation by cytokines.

    Science.gov (United States)

    Yousaf, N; Low, W Y; Onipinla, A; Mein, C; Caulfield, M; Munroe, P B; Chernajovsky, Y

    2015-05-01

    Endoplasmic reticulum aminopeptidase 1 (ERAP1) processes peptides for major histocompatibility complex (MHC) class I presentation and promotes cytokine receptor ectodomain shedding. These known functions of ERAP1 may explain its genetic association with several autoimmune inflammatory diseases. In this study, we identified four novel alternatively spliced variants of ERAP1 mRNA, designated as ΔExon-11, ΔExon-13, ΔExon-14 and ΔExon-15. We also observed a rapid and differential modulation of ERAP1 mRNA levels and spliced variants in different cell types pretreated with lipopolysaccharide (LPS). We have studied three full-length allelic forms of ERAP1 (R127-K528, P127-K528, P127-R528) and one spliced variant (ΔExon-11) and assessed their interactions with tumour necrosis factor receptor 1 (TNF-R1) in transfected cells. We observed variation in cellular expression of different ERAP1 isoforms, with R127-K528 being expressed at a much lower level. Furthermore, the cellular expression of full-length P127-K528 and ΔExon-11 spliced variant was enhanced significantly when co-transfected with TNF-R1. Isoforms P127-K528, P127-R528 and ΔExon-11 spliced variant associated with TNF-R1, and this interaction occurred in a region within the first 10 exons of ERAP1. Supernatant-derived vesicles from transfected cells contained the full-length and ectodomain form of soluble TNF-R1, as well as carrying the full-length ERAP1 isoforms. We observed marginal differences between TNF-R1 ectodomain levels when co-expressed with individual ERAP1 isoforms, and treatment of transfected cells with tumour necrosis factor (TNF), interleukin (IL)-1β and IL-10 exerted variable effects on TNF-R1 ectodomain cleavage. Our data suggest that ERAP1 isoforms may exhibit differential biological properties and inflammatory mediators could play critical roles in modulating ERAP1 expression, leading to altered functional activities of this enzyme.

  15. ADENOVIRUS INTERACTION WITH ITS CELLULAR RECEPTOR CAR.

    Energy Technology Data Exchange (ETDEWEB)

    HOWITT,J.; ANDERSON,C.W.; FREIMUTH,P.

    2001-08-01

    The mechanism of adenovirus attachment to the host cell plasma membrane has been revealed in detail by research over the past 10 years. It has long been known that receptor binding activity is associated with the viral fibers, trimeric spike proteins that protrude radially from the vertices of the icosahedral capsid (Philipson et al. 1968). In some adenovirus serotypes, fiber and other virus structural proteins are synthesized in excess and accumulate in the cell nucleus during late stages of infection. Fiber protein can be readily purified from lysates of cells infected with subgroup C viruses, for example Ad2 and Ad5 (Boulanger and Puvion 1973). Addition of purified fiber protein to virus suspensions during adsorption strongly inhibits infection, indicating that fiber and intact virus particles compete for binding sites on host cells (Philipson et al. 1968; Hautala et al. 1998). Cell binding studies using purified radiolabeled fiber demonstrated that fiber binds specifically and with high affinity to the cell plasma membrane, and that cell lines typically used for laboratory propagation of adenovirus have approximately 10{sup 4} high-affinity receptor sites per cell (Persson et al. 1985; Freimuth 1996). Similar numbers of high-affinity binding sites for radiolabeled intact virus particles also were observed (Seth et al. 1994).

  16. Cellular polarity and interactions in plant graviperception

    Science.gov (United States)

    Sack, Fred D.

    1993-01-01

    Presented are results of studies on the mechanisms of gravitropic sensing in higher and lower plants. Gravitropic roots of the aquatic angiosperm, Limnobium, were found to have sedimented amyloplasts in their elongation zone but not in their rootcap; nuclei were found to sediment in the elongation zone as well. Another study attempted to understand how plastid sedimentation occurs in vertical Ceratodon cells and how this sedimentation is regulated. To determine whether the cytoskeleton restricts plastid sedimentation, the effects of amiprophos-methyl (APM) and cytochalasin (CD) on plastid position were qualified. Results suggest that microtubules restrict the sedimentation of plastids along the length of the cell and that microtubules are load-bearing for all the plastids in the apical cell, demonstrating the importance of the cytoskeleton in maintaining organelle position and cell organization against the force of gravity. Physcomitrella and Funaria were also studied. Results suggest that gravitropism may be relatively common in moss protonemata and reinforce the idea that amyloplast mass functions in gravitropic sensing.

  17. Interactions of Rodent Coronaviruses with Cellular Receptors

    Science.gov (United States)

    2016-05-08

    porcine transmissible gastroenteris vi rus; Cell , canine coronavi rus; FECI/ , feline enteric coronavlrus; FIPV. fel ine infectious peritonitis ...bluecomb disease). b. Other diseases caused by corooaviruses inc lude infectious peritonitis , r!¥lting, nephritis , pancreatitis, parotitis, and...first described in 1961 (Innes and Stanton, 1961). Rat coronaviruses are highly infectious but the disease they cause is self limiting and rarely

  18. Fuzziness and Relevance Theory

    Institute of Scientific and Technical Information of China (English)

    Grace Qiao Zhang

    2005-01-01

    This paper investigates how the phenomenon of fuzzy language, such as `many' in `Mary has many friends', can be explained by Relevance Theory. It is concluded that fuzzy language use conforms with optimal relevance in that it can achieve the greatest positive effect with the least processing effort. It is the communicators themselves who decide whether or not optimal relevance is achieved, rather than the language form (fuzzy or non-fuzzy) used. People can skillfully adjust the deployment of different language forms or choose appropriate interpretations to suit different situations and communication needs. However, there are two challenges to RT: a. to extend its theory from individual relevance to group relevance; b. to embrace cultural considerations (because when relevance principles and cultural protocols are in conflict, the latter tends to prevail).

  19. Relevance Theory in Translation

    Institute of Scientific and Technical Information of China (English)

    Shao Jun; Jiang Min

    2008-01-01

    In perspective of relevance theory, translation is regarded as communication. According to relevance theory, communication not only requires encoding, transfer and decoding processes, but also involves inference in addition. As communication, translation decision-making is also based on the human beings' inferential mental faculty. Concentrating on relevance theory, this paper tries to analyze and explain some translation phenomena in two English versions of Cai Gen Tan-My Crude Philosophy of Life.

  20. Cellular modelling using P systems and process algebra

    Institute of Scientific and Technical Information of China (English)

    Francisco J.Romero-Campero; Marian Gheorghe; Gabriel Ciobanu; John M. Auld; Mario J. Pérez-Jiménez

    2007-01-01

    In this paper various molecular chemical interactions are modelled under different computational paradigms. P systems and π-calculus are used to describe intra-cellular reactions like protein-protein interactions and gene regulation control.

  1. Reversible quantum cellular automata

    CERN Document Server

    Schumacher, B

    2004-01-01

    We define quantum cellular automata as infinite quantum lattice systems with discrete time dynamics, such that the time step commutes with lattice translations and has strictly finite propagation speed. In contrast to earlier definitions this allows us to give an explicit characterization of all local rules generating such automata. The same local rules also generate the global time step for automata with periodic boundary conditions. Our main structure theorem asserts that any quantum cellular automaton is structurally reversible, i.e., that it can be obtained by applying two blockwise unitary operations in a generalized Margolus partitioning scheme. This implies that, in contrast to the classical case, the inverse of a nearest neighbor quantum cellular automaton is again a nearest neighbor automaton. We present several construction methods for quantum cellular automata, based on unitaries commuting with their translates, on the quantization of (arbitrary) reversible classical cellular automata, on quantum c...

  2. Making Science Relevant

    Science.gov (United States)

    Eick, Charles; Deutsch, Bill; Fuller, Jennifer; Scott, Fletcher

    2008-01-01

    Science teachers are always looking for ways to demonstrate the relevance of science to students. By connecting science learning to important societal issues, teachers can motivate students to both enjoy and engage in relevant science (Bennet, Lubben, and Hogarth 2007). To develop that connection, teachers can help students take an active role in…

  3. The Prion Protein N1 and N2 Cleavage Fragments Bind to Phosphatidylserine and Phosphatidic Acid; Relevance to Stress-Protection Responses.

    Directory of Open Access Journals (Sweden)

    Cathryn L Haigh

    Full Text Available Internal cleavage of the cellular prion protein generates two well characterised N-terminal fragments, N1 and N2. These fragments have been shown to bind to anionic phospholipids at low pH. We sought to investigate binding with other lipid moieties and queried how such interactions could be relevant to the cellular functions of these fragments. Both N1 and N2 bound phosphatidylserine (PS, as previously reported, and a further interaction with phosphatidic acid (PA was also identified. The specificity of this interaction required the N-terminus, especially the proline motif within the basic amino acids at the N-terminus, together with the copper-binding region (unrelated to copper saturation. Previously, the fragments have been shown to be protective against cellular stresses. In the current study, serum deprivation was used to induce changes in the cellular lipid environment, including externalisation of plasma membrane PS and increased cellular levels of PA. When copper-saturated, N2 could reverse these changes, but N1 could not, suggesting that direct binding of N2 to cellular lipids may be part of the mechanism by which this peptide signals its protective response.

  4. Tuning Cellular Uptake of Molecular Probes by Rational Design of Their Assembly into Supramolecular Nanoprobes.

    Science.gov (United States)

    Lock, Lye Lin; Reyes, Claudia D; Zhang, Pengcheng; Cui, Honggang

    2016-03-16

    Intracellular sensing of pathologically relevant biomolecules could provide essential information for accurate evaluation of disease staging and progression, yet the poor cellular uptake of water-soluble molecular probes limits their use as protease sensors. In other cases such as extracellular sensing, cellular uptake should be effectively inhibited. Self-assembly of molecular probes into supramolecular nanoprobes presents a potential strategy to alter their interaction mechanisms with cells to promote or reduce their cellular uptake. Here, we report on the design, synthesis, and assembly of peptide-based molecular beacons into supramolecular protease sensors of either spherical or filamentous shapes. We found that positively charged spherical nanobeacons demonstrate much higher cellular uptake efficiency than its monomeric form, thus making them most suitable for intracellular sensing of the lysosomal protease cathepsin B. Our results also suggest that assembly into filamentous nanobeacons significantly reduces their internalization by cancer cells, an important property that can be utilized for probing extracellular protease activities. These studies provide important guiding principles for rational design of supramolecular nanoprobes with tunable cellular uptake characteristics.

  5. 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

  6. Resveratrol and calcium signaling: molecular mechanisms and clinical relevance.

    Science.gov (United States)

    McCalley, Audrey E; Kaja, Simon; Payne, Andrew J; Koulen, Peter

    2014-06-05

    Resveratrol is a naturally occurring compound contributing to cellular defense mechanisms in plants. Its use as a nutritional component and/or supplement in a number of diseases, disorders, and syndromes such as chronic diseases of the central nervous system, cancer, inflammatory diseases, diabetes, and cardiovascular diseases has prompted great interest in the underlying molecular mechanisms of action. The present review focuses on resveratrol, specifically its isomer trans-resveratrol, and its effects on intracellular calcium signaling mechanisms. As resveratrol's mechanisms of action are likely pleiotropic, its effects and interactions with key signaling proteins controlling cellular calcium homeostasis are reviewed and discussed. The clinical relevance of resveratrol's actions on excitable cells, transformed or cancer cells, immune cells and retinal pigment epithelial cells are contrasted with a review of the molecular mechanisms affecting calcium signaling proteins on the plasma membrane, cytoplasm, endoplasmic reticulum, and mitochondria. The present review emphasizes the correlation between molecular mechanisms of action that have recently been identified for resveratrol and their clinical implications.

  7. Nanostructured cellular networks.

    Science.gov (United States)

    Moriarty, P; Taylor, M D R; Brust, M

    2002-12-01

    Au nanocrystals spin-coated onto silicon from toluene form cellular networks. A quantitative statistical crystallography analysis shows that intercellular correlations drive the networks far from statistical equilibrium. Spin-coating from hexane does not produce cellular structure, yet a strong correlation is retained in the positions of nanocrystal aggregates. Mechanisms based on Marangoni convection alone cannot account for the variety of patterns observed, and we argue that spinodal decomposition plays an important role in foam formation.

  8. Environmental Factors Impacting Bone-Relevant Chemokines

    Science.gov (United States)

    Smith, Justin T.; Schneider, Andrew D.; Katchko, Karina M.; Yun, Chawon; Hsu, Erin L.

    2017-01-01

    Chemokines play an important role in normal bone physiology and the pathophysiology of many bone diseases. The recent increased focus on the individual roles of this class of proteins in the context of bone has shown that members of the two major chemokine subfamilies—CC and CXC—support or promote the formation of new bone and the remodeling of existing bone in response to a myriad of stimuli. These chemotactic molecules are crucial in orchestrating appropriate cellular homing, osteoblastogenesis, and osteoclastogenesis during normal bone repair. Bone healing is a complex cascade of carefully regulated processes, including inflammation, progenitor cell recruitment, differentiation, and remodeling. The extensive role of chemokines in these processes and the known links between environmental contaminants and chemokine expression/activity leaves ample opportunity for disruption of bone healing by environmental factors. However, despite increased clinical awareness, the potential impact of many of these environmental factors on bone-related chemokines is still ill defined. A great deal of focus has been placed on environmental exposure to various endocrine disruptors (bisphenol A, phthalate esters, etc.), volatile organic compounds, dioxins, and heavy metals, though mainly in other tissues. Awareness of the impact of other less well-studied bone toxicants, such as fluoride, mold and fungal toxins, asbestos, and chlorine, is also reviewed. In many cases, the literature on these toxins in osteogenic models is lacking. However, research focused on their effects in other tissues and cell lines provides clues for where future resources could be best utilized. This review aims to serve as a current and exhaustive resource detailing the known links between several classes of high-interest environmental pollutants and their interaction with the chemokines relevant to bone healing. PMID:28261155

  9. Criticisms of Relevance Theory

    Institute of Scientific and Technical Information of China (English)

    尚静; 孟晔; 焦丽芳

    2006-01-01

    This paper briefly introduces first the notion of Sperber and Wilson's Relevance Theory. Then, the motivation of S & W putting forward their RT is also mentioned. Secondly, the paper gives some details about the methodology of RT, in which ostensive-inferential communication, context and optimal relevance are highlighted. Thirdly, the paper focuses on the criticisms of RT from different areas of research on human language and communication. Finally, the paper draws a conclusion on the great importance of RT in pragmatics.

  10. Dispersion Behaviour of Silica Nanoparticles in Biological Media and Its Influence on Cellular Uptake.

    Science.gov (United States)

    Halamoda-Kenzaoui, Blanka; Ceridono, Mara; Colpo, Pascal; Valsesia, Andrea; Urbán, Patricia; Ojea-Jiménez, Isaac; Gioria, Sabrina; Gilliland, Douglas; Rossi, François; Kinsner-Ovaskainen, Agnieszka

    2015-01-01

    Given the increasing variety of manufactured nanomaterials, suitable, robust, standardized in vitro screening methods are needed to study the mechanisms by which they can interact with biological systems. The in vitro evaluation of interactions of nanoparticles (NPs) with living cells is challenging due to the complex behaviour of NPs, which may involve dissolution, aggregation, sedimentation and formation of a protein corona. These variable parameters have an influence on the surface properties and the stability of NPs in the biological environment and therefore also on the interaction of NPs with cells. We present here a study using 30 nm and 80 nm fluorescently-labelled silicon dioxide NPs (Rubipy-SiO2 NPs) to evaluate the NPs dispersion behaviour up to 48 hours in two different cellular media either supplemented with 10% of serum or in serum-free conditions. Size-dependent differences in dispersion behaviour were observed and the influence of the living cells on NPs stability and deposition was determined. Using flow cytometry and fluorescence microscopy techniques we studied the kinetics of the cellular uptake of Rubipy-SiO2 NPs by A549 and CaCo-2 cells and we found a correlation between the NPs characteristics in cell media and the amount of cellular uptake. Our results emphasize how relevant and important it is to evaluate and to monitor the size and agglomeration state of nanoparticles in the biological medium, in order to interpret correctly the results of the in vitro toxicological assays.

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

    Directory of Open Access Journals (Sweden)

    Michael E. Hasselmo

    2008-01-01

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

  12. Astrobiological Complexity with Probabilistic Cellular Automata

    CERN Document Server

    Vukotić, B

    2012-01-01

    Search for extraterrestrial life and intelligence constitutes one of the major endeavors in science, but has yet been quantitatively modeled only rarely and in a cursory and superficial fashion. We argue that probabilistic cellular automata (PCA) represent the best quantitative framework for modeling astrobiological history of the Milky Way and its Galactic Habitable Zone. The relevant astrobiological parameters are to be modeled as the elements of the input probability matrix for the PCA kernel. With the underlying simplicity of the cellular automata constructs, this approach enables a quick analysis of large and ambiguous input parameters' space. We perform a simple clustering analysis of typical astrobiological histories and discuss the relevant boundary conditions of practical importance for planning and guiding actual empirical astrobiological and SETI projects. In addition to showing how the present framework is adaptable to more complex situations and updated observational databases from current and ne...

  13. Organization of cellular receptors into a nanoscale junction during HIV-1 adhesion.

    Directory of Open Access Journals (Sweden)

    Terrence M Dobrowsky

    Full Text Available The fusion of the human immunodeficiency virus type 1 (HIV-1 with its host cell is the target for new antiretroviral therapies. Viral particles interact with the flexible plasma membrane via viral surface protein gp120 which binds its primary cellular receptor CD4 and subsequently the coreceptor CCR5. However, whether and how these receptors become organized at the adhesive junction between cell and virion are unknown. Here, stochastic modeling predicts that, regarding binding to gp120, cellular receptors CD4 and CCR5 form an organized, ring-like, nanoscale structure beneath the virion, which locally deforms the plasma membrane. This organized adhesive junction between cell and virion, which we name the viral junction, is reminiscent of the well-characterized immunological synapse, albeit at much smaller length scales. The formation of an organized viral junction under multiple physiopathologically relevant conditions may represent a novel intermediate step in productive infection.

  14. Organization of cellular receptors into a nanoscale junction during HIV-1 adhesion.

    Science.gov (United States)

    Dobrowsky, Terrence M; Daniels, Brian R; Siliciano, Robert F; Sun, Sean X; Wirtz, Denis

    2010-07-15

    The fusion of the human immunodeficiency virus type 1 (HIV-1) with its host cell is the target for new antiretroviral therapies. Viral particles interact with the flexible plasma membrane via viral surface protein gp120 which binds its primary cellular receptor CD4 and subsequently the coreceptor CCR5. However, whether and how these receptors become organized at the adhesive junction between cell and virion are unknown. Here, stochastic modeling predicts that, regarding binding to gp120, cellular receptors CD4 and CCR5 form an organized, ring-like, nanoscale structure beneath the virion, which locally deforms the plasma membrane. This organized adhesive junction between cell and virion, which we name the viral junction, is reminiscent of the well-characterized immunological synapse, albeit at much smaller length scales. The formation of an organized viral junction under multiple physiopathologically relevant conditions may represent a novel intermediate step in productive infection.

  15. Cellular Automation of Galactic Habitable Zone

    CERN Document Server

    Vukotic, Branislav

    2010-01-01

    We present a preliminary results of our Galactic Habitable Zone (GHZ) 2D probabilistic cellular automata models. The relevant time-scales (emergence of life, it's diversification and evolution influenced with the global risk function) are modeled as the probability matrix elements and are chosen in accordance with the Copernican principle to be well-represented by the data inferred from the Earth's fossil record. With Fermi's paradox as a main boundary condition the resulting histories of astrobiological landscape are discussed.

  16. The Limits to Relevance

    Science.gov (United States)

    Averill, M.; Briggle, A.

    2006-12-01

    Science policy and knowledge production lately have taken a pragmatic turn. Funding agencies increasingly are requiring scientists to explain the relevance of their work to society. This stems in part from mounting critiques of the "linear model" of knowledge production in which scientists operating according to their own interests or disciplinary standards are presumed to automatically produce knowledge that is of relevance outside of their narrow communities. Many contend that funded scientific research should be linked more directly to societal goals, which implies a shift in the kind of research that will be funded. While both authors support the concept of useful science, we question the exact meaning of "relevance" and the wisdom of allowing it to control research agendas. We hope to contribute to the conversation by thinking more critically about the meaning and limits of the term "relevance" and the trade-offs implicit in a narrow utilitarian approach. The paper will consider which interests tend to be privileged by an emphasis on relevance and address issues such as whose goals ought to be pursued and why, and who gets to decide. We will consider how relevance, narrowly construed, may actually limit the ultimate utility of scientific research. The paper also will reflect on the worthiness of research goals themselves and their relationship to a broader view of what it means to be human and to live in society. Just as there is more to being human than the pragmatic demands of daily life, there is more at issue with knowledge production than finding the most efficient ways to satisfy consumer preferences or fix near-term policy problems. We will conclude by calling for a balanced approach to funding research that addresses society's most pressing needs but also supports innovative research with less immediately apparent application.

  17. Epigenetics and Cellular Metabolism

    Science.gov (United States)

    Xu, Wenyi; Wang, Fengzhong; Yu, Zhongsheng; Xin, Fengjiao

    2016-01-01

    Living eukaryotic systems evolve delicate cellular mechanisms for responding to various environmental signals. Among them, epigenetic machinery (DNA methylation, histone modifications, microRNAs, etc.) is the hub in transducing external stimuli into transcriptional response. Emerging evidence reveals the concept that epigenetic signatures are essential for the proper maintenance of cellular metabolism. On the other hand, the metabolite, a main environmental input, can also influence the processing of epigenetic memory. Here, we summarize the recent research progress in the epigenetic regulation of cellular metabolism and discuss how the dysfunction of epigenetic machineries influences the development of metabolic disorders such as diabetes and obesity; then, we focus on discussing the notion that manipulating metabolites, the fuel of cell metabolism, can function as a strategy for interfering epigenetic machinery and its related disease progression as well. PMID:27695375

  18. Architected Cellular Materials

    Science.gov (United States)

    Schaedler, Tobias A.; Carter, William B.

    2016-07-01

    Additive manufacturing enables fabrication of materials with intricate cellular architecture, whereby progress in 3D printing techniques is increasing the possible configurations of voids and solids ad infinitum. Examples are microlattices with graded porosity and truss structures optimized for specific loading conditions. The cellular architecture determines the mechanical properties and density of these materials and can influence a wide range of other properties, e.g., acoustic, thermal, and biological properties. By combining optimized cellular architectures with high-performance metals and ceramics, several lightweight materials that exhibit strength and stiffness previously unachievable at low densities were recently demonstrated. This review introduces the field of architected materials; summarizes the most common fabrication methods, with an emphasis on additive manufacturing; and discusses recent progress in the development of architected materials. The review also discusses important applications, including lightweight structures, energy absorption, metamaterials, thermal management, and bioscaffolds.

  19. A Quantum Relativistic Prisoner's Dilemma Cellular Automaton

    Science.gov (United States)

    Alonso-Sanz, Ramón; Carvalho, Márcio; Situ, Haozhen

    2016-10-01

    The effect of variable entangling on the dynamics of a spatial quantum relativistic formulation of the iterated prisoner's dilemma game is studied in this work. The game is played in the cellular automata manner, i.e., with local and synchronous interaction. The game is assessed in fair and unfair contests.

  20. Cellular blue naevus

    Directory of Open Access Journals (Sweden)

    Mittal R

    2001-01-01

    Full Text Available A 31-year-old man had asymptomatic, stationary, 1.5X2 cm, shiny, smooth, dark blue nodule on dorsum of right hand since 12-14 years. In addition he had developed extensive eruption of yellow to orange papulonodular lesions on extensors of limbs and buttocks since one and half months. Investigations confirmed that yellow papules were xanthomatosis and he had associated diabetes mellitus and hyperlipidaemia. Biopsy of blue nodule confirmed the clinical diagnosis of cellular blue naevus. Cellular blue naevus is rare and its association with xanthomatosis and diabetes mellitus were interesting features of above patients which is being reported for its rarity.

  1. Is Information Still Relevant?

    Science.gov (United States)

    Ma, Lia

    2013-01-01

    Introduction: The term "information" in information science does not share the characteristics of those of a nomenclature: it does not bear a generally accepted definition and it does not serve as the bases and assumptions for research studies. As the data deluge has arrived, is the concept of information still relevant for information…

  2. The Relevance of Literature.

    Science.gov (United States)

    Dunham, L. L.

    1971-01-01

    The "legacy" of the humanities is discussed in terms of relevance, involvement, and other philosophical considerations. Reasons for studying foreign literature in language classes are developed in the article. Comment is also made on attitudes and ideas culled from the writings of Clifton Fadiman, Jean Paul Sartre, and James Baldwin. (RL)

  3. Relevant Subspace Clustering

    DEFF Research Database (Denmark)

    Müller, Emmanuel; Assent, Ira; Günnemann, Stephan;

    2009-01-01

    Subspace clustering aims at detecting clusters in any subspace projection of a high dimensional space. As the number of possible subspace projections is exponential in the number of dimensions, the result is often tremendously large. Recent approaches fail to reduce results to relevant subspace c...

  4. Cellular rehabilitation of photobiomodulation

    Science.gov (United States)

    Liu, Timon Cheng-Yi; Yuan, Jian-Qin; Wang, Yan-Fang; Xu, Xiao-Yang; Liu, Song-Hao

    2007-05-01

    Homeostasis is a term that refers to constancy in a system. A cell in homeostasis normally functions. There are two kinds of processes in the internal environment and external environment of a cell, the pathogenic processes (PP) which disrupts the old homeostasis (OH), and the sanogenetic processes (SP) which restores OH or establishes a new homeostasis (NH). Photobiomodualtion (PBM), the cell-specific effects of low intensity monochromatic light or low intensity laser irradiation (LIL) on biological systems, is a kind of modulation on PP or SP so that there is no PBM on a cell in homeostasis. There are two kinds of pathways mediating PBM, the membrane endogenetic chromophores mediating pathways which often act through reactive oxygen species, and membrane proteins mediating pathways which often enhance cellular SP so that it might be called cellular rehabilitation. The cellular rehabilitation of PBM will be discussed in this paper. It is concluded that PBM might modulate the disruption of cellular homeostasis induced by pathogenic factors such as toxin until OH has been restored or NH has been established, but can not change homeostatic processes from one to another one.

  5. Protein-protein and protein-lipid interactions in domain-assembly : Lessons from giant unilamellar vesicles

    NARCIS (Netherlands)

    Kahya, Nicoletta

    2010-01-01

    Giant Unilamellar Vesicles (GUVs) provide a key model membrane system to study lipid-lipid and lipid-protein interactions, which are relevant to vital cellular processes, by (single-molecule) optical microscopy. Here, we review the work on reconstitution techniques for membrane proteins and other pr

  6. The Cellular Proteins Grb2 and DDX3 Are Increased upon Human Cytomegalovirus Infection and Act in a Proviral Fashion.

    Science.gov (United States)

    Cavignac, Yolaine; Lieber, Diana; Laib Sampaio, Kerstin; Madlung, Johannes; Lamkemeyer, Tobias; Jahn, Gerhard; Nordheim, Alfred; Sinzger, Christian

    2015-01-01

    While it is well established that human cytomegalovirus (HCMV) upregulates many cellular proteins and incorporates several of them into its virion, little is known about the functional relevance of such virus-host interactions. Two cellular proteins, Grb2 and DDX3, gained our interest as they appeared enriched in virion particles and this incorporation depended on the viral tegument protein pp65, suggesting a functional relevance. We therefore tested whether the level of these proteins is altered upon HCMV infection and whether they support viral replication. Immunoblotting analyses of cellular fractions showed increased levels of both proteins in infected cells with a maximum at 2 d p.i. and a reduction of the soluble Grb2 fraction. Knockdown of either gene by transfection of siRNAs reduced viral spread not only of the cell culture adapted HCMV strain TB40/E but also of recent clinical isolates. Apparently, Grb2 and DDX3 are proviral cellular factors that are upregulated in infected cells.

  7. The Cellular Proteins Grb2 and DDX3 Are Increased upon Human Cytomegalovirus Infection and Act in a Proviral Fashion.

    Directory of Open Access Journals (Sweden)

    Yolaine Cavignac

    Full Text Available While it is well established that human cytomegalovirus (HCMV upregulates many cellular proteins and incorporates several of them into its virion, little is known about the functional relevance of such virus-host interactions. Two cellular proteins, Grb2 and DDX3, gained our interest as they appeared enriched in virion particles and this incorporation depended on the viral tegument protein pp65, suggesting a functional relevance. We therefore tested whether the level of these proteins is altered upon HCMV infection and whether they support viral replication. Immunoblotting analyses of cellular fractions showed increased levels of both proteins in infected cells with a maximum at 2 d p.i. and a reduction of the soluble Grb2 fraction. Knockdown of either gene by transfection of siRNAs reduced viral spread not only of the cell culture adapted HCMV strain TB40/E but also of recent clinical isolates. Apparently, Grb2 and DDX3 are proviral cellular factors that are upregulated in infected cells.

  8. Extent of structural asymmetry in homodimeric proteins: prevalence and relevance.

    Directory of Open Access Journals (Sweden)

    Lakshmipuram Seshadri Swapna

    Full Text Available Most homodimeric proteins have symmetric structure. Although symmetry is known to confer structural and functional advantage, asymmetric organization is also observed. Using a non-redundant dataset of 223 high-resolution crystal structures of biologically relevant homodimers, we address questions on the prevalence and significance of asymmetry. We used two measures to quantify global and interface asymmetry, and assess the correlation of several molecular and structural parameters with asymmetry. We have identified rare cases (11/223 of biologically relevant homodimers with pronounced global asymmetry. Asymmetry serves as a means to bring about 2:1 binding between the homodimer and another molecule; it also enables cellular signalling arising from asymmetric macromolecular ligands such as DNA. Analysis of these cases reveals two possible mechanisms by which possible infinite array formation is prevented. In case of homodimers associating via non-topologically equivalent surfaces in their tertiary structures, ligand-dependent mechanisms are used. For stable dimers binding via large surfaces, ligand-dependent structural change regulates polymerisation/depolymerisation; for unstable dimers binding via smaller surfaces that are not evolutionarily well conserved, dimerisation occurs only in the presence of the ligand. In case of homodimers associating via interaction surfaces with parts of the surfaces topologically equivalent in the tertiary structures, steric hindrance serves as the preventive mechanism of infinite array. We also find that homodimers exhibiting grossly symmetric organization rarely exhibit either perfect local symmetry or high local asymmetry. Binding of small ligands at the interface does not cause any significant variation in interface asymmetry. However, identification of biologically relevant interface asymmetry in grossly symmetric homodimers is confounded by the presence of similar small magnitude changes caused due to

  9. Korrek, volledig, relevant

    DEFF Research Database (Denmark)

    Bergenholtz, Henning; Gouws, Rufus

    2007-01-01

    as detrimental to the status of a dictionary as a container of linguistic knowledge. This paper shows that, from a lexicographic perspective, such a distinction is not relevant. What is important is that definitions should contain information that is relevant to and needed by the target users of that specific......In explanatory dictionaries, both general language dictionaries and dictionaries dealing with languages for special purposes, the lexicographic definition is an important item to present the meaning of a given lemma. Due to a strong linguistic bias, resulting from an approach prevalent in the early...... phases of the development of theoretical lexicography, a distinction is often made between encyclopaedic information and semantic information in dictionary definitions, and dictionaries had often been criticized when their definitions were dominated by an encyclopaedic approach. This used to be seen...

  10. Relevance model in information retrieval based on information science perspective

    Science.gov (United States)

    Zeng, Dan

    2011-10-01

    Relevance models in relevance research is the main research issue in information retrieval and information science. Relevance research of information retrieval can be divided into the system-oriented school and the user-oriented schoo1.The evaluation of relevance is closely related to user's experiences, cognitive status and thinking, and includes the interaction of several level. On this basis, a four-dimension model (information resource, representation of user problem time and components) and an interactive model are critically illuminated. A better understanding of the cognitive model, the episode model and the stratified model is of great importance to the interactive model.

  11. Insights Into Quantitative Biology: analysis of cellular adaptation

    OpenAIRE

    Agoni, Valentina

    2013-01-01

    In the last years many powerful techniques have emerged to measure protein interactions as well as gene expression. Many progresses have been done since the introduction of these techniques but not toward quantitative analysis of data. In this paper we show how to study cellular adaptation and how to detect cellular subpopulations. Moreover we go deeper in analyzing signal transduction pathways dynamics.

  12. [Clinical relevance of cardiopulmonary reflexes in anesthesiology].

    Science.gov (United States)

    Guerri-Guttenberg, R A; Siaba-Serrate, F; Cacheiro, F J

    2013-10-01

    The baroreflex, chemoreflex, pulmonary reflexes, Bezold-Jarisch and Bainbridge reflexes and their interaction with local mechanisms, are a demonstration of the richness of cardiovascular responses that occur in human beings. As well as these, the anesthesiologist must contend with other variables that interact by attenuating or accentuating cardiopulmonary reflexes such as, anesthetic drugs, surgical manipulation, and patient positioning. In the present article we review these reflexes and their clinical relevance in anesthesiology.

  13. 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 ...

  14. Environment Aware Cellular Networks

    KAUST Repository

    Ghazzai, Hakim

    2015-02-01

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

  15. Asymptotic Behavior of Excitable Cellular Automata

    CERN Document Server

    Durrett, R; Durrett, Richard; Griffeath, David

    1993-01-01

    Abstract: We study two families of excitable cellular automata known as the Greenberg-Hastings Model (GHM) and the Cyclic Cellular Automaton (CCA). Each family consists of local deterministic oscillating lattice dynamics, with parallel discrete-time updating, parametrized by the range of interaction, the "shape" of its neighbor set, threshold value for contact updating, and number of possible states per site. GHM and CCA are mathematically tractable prototypes for the spatially distributed periodic wave activity of so-called excitable media observed in diverse disciplines of experimental science. Earlier work by Fisch, Gravner, and Griffeath studied the ergodic behavior of these excitable cellular automata on Z^2, and identified two distinct (but closely-related) elaborate phase portraits as the parameters vary. In particular, they noted the emergence of asymptotic phase diagrams (and Euclidean dynamics) in a well-defined threshold-range scaling limit. In this study we present several rigorous results and som...

  16. Crack Propagation in Bamboo's Hierarchical Cellular Structure

    Science.gov (United States)

    Habibi, Meisam K.; Lu, Yang

    2014-07-01

    Bamboo, as a natural hierarchical cellular material, exhibits remarkable mechanical properties including excellent flexibility and fracture toughness. As far as bamboo as a functionally graded bio-composite is concerned, the interactions of different constituents (bamboo fibers; parenchyma cells; and vessels.) alongside their corresponding interfacial areas with a developed crack should be of high significance. Here, by using multi-scale mechanical characterizations coupled with advanced environmental electron microscopy (ESEM), we unambiguously show that fibers' interfacial areas along with parenchyma cells' boundaries were preferred routes for crack growth in both radial and longitudinal directions. Irrespective of the honeycomb structure of fibers along with cellular configuration of parenchyma ground, the hollow vessels within bamboo culm affected the crack propagation too, by crack deflection or crack-tip energy dissipation. It is expected that the tortuous crack propagation mode exhibited in the present study could be applicable to other cellular natural materials as well.

  17. Carcinogenic metal compounds: recent insight into molecular and cellular mechanisms

    Energy Technology Data Exchange (ETDEWEB)

    Beyersmann, Detmar [University of Bremen (Germany). Biochemistry, Department of Biology and Chemistry; Hartwig, Andrea [Technical University of Berlin (Germany). Institute of Food Technology and Food Chemistry

    2008-08-15

    Mechanisms of carcinogenicity are discussed for metals and their compounds, classified as carcinogenic to humans or considered to be carcinogenic to humans: arsenic, antimony, beryllium, cadmium, chromium, cobalt, lead, nickel and vanadium. Physicochemical properties govern uptake, intracellular distribution and binding of metal compounds. Interactions with proteins (e.g., with zinc finger structures) appear to be more relevant for metal carcinogenicity than binding to DNA. In general, metal genotoxicity is caused by indirect mechanisms. In spite of diverse physicochemical properties of metal compounds, three predominant mechanisms emerge: (1) interference with cellular redox regulation and induction of oxidative stress, which may cause oxidative DNA damage or trigger signaling cascades leading to stimulation of cell growth; (2) inhibition of major DNA repair systems resulting in genomic instability and accumulation of critical mutations; (3) deregulation of cell proliferation by induction of signaling pathways or inactivation of growth controls such as tumor suppressor genes. In addition, specific metal compounds exhibit unique mechanisms such as interruption of cell-cell adhesion by cadmium, direct DNA binding of trivalent chromium, and interaction of vanadate with phosphate binding sites of protein phosphatases. (orig.)

  18. Relevance of Dynamic Clustering to Biological Networks

    CERN Document Server

    Kaneko, K

    1993-01-01

    Abstract Network of nonlinear dynamical elements often show clustering of synchronization by chaotic instability. Relevance of the clustering to ecological, immune, neural, and cellular networks is discussed, with the emphasis of partially ordered states with chaotic itinerancy. First, clustering with bit structures in a hypercubic lattice is studied. Spontaneous formation and destruction of relevant bits are found, which give self-organizing, and chaotic genetic algorithms. When spontaneous changes of effective couplings are introduced, chaotic itinerancy of clusterings is widely seen through a feedback mechanism, which supports dynamic stability allowing for complexity and diversity, known as homeochaos. Second, synaptic dynamics of couplings is studied in relation with neural dynamics. The clustering structure is formed with a balance between external inputs and internal dynamics. Last, an extension allowing for the growth of the number of elements is given, in connection with cell differentiation. Effecti...

  19. Complexity, dynamic cellular network, and tumorigenesis.

    Science.gov (United States)

    Waliszewski, P

    1997-01-01

    A holistic approach to tumorigenesis is proposed. The main element of the model is the existence of dynamic cellular network. This network comprises a molecular and an energetistic structure of a cell connected through the multidirectional flow of information. The interactions within dynamic cellular network are complex, stochastic, nonlinear, and also involve quantum effects. From this non-reductionist perspective, neither tumorigenesis can be limited to the genetic aspect, nor the initial event must be of molecular nature, nor mutations and epigenetic factors are mutually exclusive, nor a link between cause and effect can be established. Due to complexity, an unstable stationary state of dynamic cellular network rather than a group of unrelated genes determines the phenotype of normal and transformed cells. This implies relativity of tumor suppressor genes and oncogenes. A bifurcation point is defined as an unstable state of dynamic cellular network leading to the other phenotype-stationary state. In particular, the bifurcation point may be determined by a change of expression of a single gene. Then, the gene is called bifurcation point gene. The unstable stationary state facilitates the chaotic dynamics. This may result in a fractal dimension of both normal and tumor tissues. The co-existence of chaotic dynamics and complexity is the essence of cellular processes and shapes differentiation, morphogenesis, and tumorigenesis. In consequence, tumorigenesis is a complex, unpredictable process driven by the interplay between self-organisation and selection.

  20. 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.

  1. Cellular automata: structures

    OpenAIRE

    Ollinger, Nicolas

    2002-01-01

    Jury : François Blanchard (Rapporteur), Marianne Delorme (Directeur), Jarkko Kari (Président), Jacques Mazoyer (Directeur), Dominique Perrin, Géraud Sénizergues (Rapporteur); Cellular automata provide a uniform framework to study an important problem of "complex systems" theory: how and why do system with a easily understandable -- local -- microscopic behavior can generate a more complicated -- global -- macroscopic behavior? Since its introduction in the 40s, a lot of work has been done to ...

  2. Engineering Cellular Metabolism

    DEFF Research Database (Denmark)

    Nielsen, Jens; Keasling, Jay

    2016-01-01

    Metabolic engineering is the science of rewiring the metabolism of cells to enhance production of native metabolites or to endow cells with the ability to produce new products. The potential applications of such efforts are wide ranging, including the generation of fuels, chemicals, foods, feeds...... of metabolic engineering and will discuss how new technologies can enable metabolic engineering to be scaled up to the industrial level, either by cutting off the lines of control for endogenous metabolism or by infiltrating the system with disruptive, heterologous pathways that overcome cellular regulation....

  3. Failover in cellular automata

    CERN Document Server

    Kumar, Shailesh

    2010-01-01

    A cellular automata (CA) configuration is constructed that exhibits emergent failover. The configuration is based on standard Game of Life rules. Gliders and glider-guns form the core messaging structure in the configuration. The blinker is represented as the basic computational unit, and it is shown how it can be recreated in case of a failure. Stateless failover using primary-backup mechanism is demonstrated. The details of the CA components used in the configuration and its working are described, and a simulation of the complete configuration is also presented.

  4. Chronobiology: relevance for tuberculosis.

    Science.gov (United States)

    Santos, Lígia Gabrielle; Pires, Gabriel Natan; Azeredo Bittencourt, Lia Rita; Tufik, Sergio; Andersen, Monica Levy

    2012-07-01

    Despite the knowledge concerning the pathogenesis of tuberculosis, this disease remains one of the most important causes of mortality worldwide. Several risk factors are well-known, such poverty, HIV infection, and poor nutrition, among others. However, some issues that may influence tuberculosis warrant further investigation. In particular, the chronobiological aspects related to tuberculosis have garnered limited attention. In general, the interface between tuberculosis and chronobiology is manifested in four ways: variations in vitamin D bioavailability, winter conditions, associated infections, and circannual oscillations of lymphocytes activity. Moreover, tuberculosis is related to the following chronobiological factors: seasonality, latitude, photoperiod and radiation. Despite the relevance of these topics, the relationship between them has been weakly reviewed. This review aims to synthesize the studies regarding the association between tuberculosis and chronobiology, as well as urge critical discussion and highlight its applicability to health policies for tuberculosis.

  5. WD40 proteins propel cellular networks.

    Science.gov (United States)

    Stirnimann, Christian U; Petsalaki, Evangelia; Russell, Robert B; Müller, Christoph W

    2010-10-01

    Recent findings indicate that WD40 domains play central roles in biological processes by acting as hubs in cellular networks; however, they have been studied less intensely than other common domains, such as the kinase, PDZ or SH3 domains. As suggested by various interactome studies, they are among the most promiscuous interactors. Structural studies suggest that this property stems from their ability, as scaffolds, to interact with diverse proteins, peptides or nucleic acids using multiple surfaces or modes of interaction. A general scaffolding role is supported by the fact that no WD40 domain has been found with intrinsic enzymatic activity despite often being part of large molecular machines. We discuss the WD40 domain distributions in protein networks and structures of WD40-containing assemblies to demonstrate their versatility in mediating critical cellular functions.

  6. pna - assisted cellular migration on patterned surfaces

    OpenAIRE

    2013-01-01

    ABSTRACT - The ability to control the cellular microenvironment, such as cell-substrate and cell-cell interactions at the micro- and nanoscale, is important for advances in several fields such as medicine and immunology, biochemistry, biomaterials, and tissue engineering. In order to undergo fundamental biological processes, most mammalian cells must adhere to the underlying extracellular matrix (ECM), eliciting cell adhesion and migration processes that are critical to embryogenesis, angioge...

  7. Cellular circadian clocks in mood disorders.

    Science.gov (United States)

    McCarthy, Michael J; Welsh, David K

    2012-10-01

    Bipolar disorder (BD) and major depressive disorder (MDD) are heritable neuropsychiatric disorders associated with disrupted circadian rhythms. The hypothesis that circadian clock dysfunction plays a causal role in these disorders has endured for decades but has been difficult to test and remains controversial. In the meantime, the discovery of clock genes and cellular clocks has revolutionized our understanding of circadian timing. Cellular circadian clocks are located in the suprachiasmatic nucleus (SCN), the brain's primary circadian pacemaker, but also throughout the brain and peripheral tissues. In BD and MDD patients, defects have been found in SCN-dependent rhythms of body temperature and melatonin release. However, these are imperfect and indirect indicators of SCN function. Moreover, the SCN may not be particularly relevant to mood regulation, whereas the lateral habenula, ventral tegmentum, and hippocampus, which also contain cellular clocks, have established roles in this regard. Dysfunction in these non-SCN clocks could contribute directly to the pathophysiology of BD/MDD. We hypothesize that circadian clock dysfunction in non-SCN clocks is a trait marker of mood disorders, encoded by pathological genetic variants. Because network features of the SCN render it uniquely resistant to perturbation, previous studies of SCN outputs in mood disorders patients may have failed to detect genetic defects affecting non-SCN clocks, which include not only mood-regulating neurons in the brain but also peripheral cells accessible in human subjects. Therefore, reporters of rhythmic clock gene expression in cells from patients or mouse models could provide a direct assay of the molecular gears of the clock, in cellular clocks that are likely to be more representative than the SCN of mood-regulating neurons in patients. This approach, informed by the new insights and tools of modern chronobiology, will allow a more definitive test of the role of cellular circadian clocks

  8. Cellular image classification

    CERN Document Server

    Xu, Xiang; Lin, Feng

    2017-01-01

    This book introduces new techniques for cellular image feature extraction, pattern recognition and classification. The authors use the antinuclear antibodies (ANAs) in patient serum as the subjects and the Indirect Immunofluorescence (IIF) technique as the imaging protocol to illustrate the applications of the described methods. Throughout the book, the authors provide evaluations for the proposed methods on two publicly available human epithelial (HEp-2) cell datasets: ICPR2012 dataset from the ICPR'12 HEp-2 cell classification contest and ICIP2013 training dataset from the ICIP'13 Competition on cells classification by fluorescent image analysis. First, the reading of imaging results is significantly influenced by one’s qualification and reading systems, causing high intra- and inter-laboratory variance. The authors present a low-order LP21 fiber mode for optical single cell manipulation and imaging staining patterns of HEp-2 cells. A focused four-lobed mode distribution is stable and effective in optical...

  9. Engineering Cellular Metabolism.

    Science.gov (United States)

    Nielsen, Jens; Keasling, Jay D

    2016-03-10

    Metabolic engineering is the science of rewiring the metabolism of cells to enhance production of native metabolites or to endow cells with the ability to produce new products. The potential applications of such efforts are wide ranging, including the generation of fuels, chemicals, foods, feeds, and pharmaceuticals. However, making cells into efficient factories is challenging because cells have evolved robust metabolic networks with hard-wired, tightly regulated lines of communication between molecular pathways that resist efforts to divert resources. Here, we will review the current status and challenges of metabolic engineering and will discuss how new technologies can enable metabolic engineering to be scaled up to the industrial level, either by cutting off the lines of control for endogenous metabolism or by infiltrating the system with disruptive, heterologous pathways that overcome cellular regulation.

  10. Mitochondrial and cellular mechanisms for managing lipid excess

    Directory of Open Access Journals (Sweden)

    Miguel A Aon

    2014-07-01

    Full Text Available Current scientific debates center on the impact of lipids and mitochondrial function on diverse aspects of human health, nutrition and disease, among them the association of lipotoxicity with the onset of insulin resistance in skeletal muscle, and with heart dysfunction in obesity and diabetes. Mitochondria play a fundamental role in aging and in prevalent acute or chronic diseases. Lipids are main mitochondrial fuels however these molecules can also behave as uncouplers and inhibitors of oxidative phosphorylation. Knowledge about the functional composition of these contradictory effects and their impact on mitochondrial-cellular energetics/redox status is incomplete.Cells store fatty acids (FAs as triacylglycerol and package them into cytoplasmic lipid droplets (LDs. New emerging data shows the LD as a highly dynamic storage pool of FAs that can be used for energy reserve. Lipid excess packaging into LDs can be seen as an adaptive response to fulfilling energy supply without hindering mitochondrial or cellular redox status and keeping low concentration of lipotoxic intermediates.Herein we review the mechanisms of action and utilization of lipids by mitochondria reported in liver, heart and skeletal muscle under relevant physiological situations, e.g. exercise. We report on perilipins, a family of proteins that associate with LDs in response to loading of cells with lipids. Evidence showing that in addition to physical contact, mitochondria and LDs exhibit metabolic interactions is presented and discussed. A hypothetical model of channeled lipid utilization by mitochondria is proposed. Direct delivery and channeled processing of lipids in mitochondria could represent a reliable and efficient way to maintain ROS within levels compatible with signaling while ensuring robust and reliable energy supply.

  11. Connecting Photosynthesis and Cellular Respiration: Preservice Teachers' Conceptions

    Science.gov (United States)

    Brown, Mary H.; Schwartz, Renee S.

    2009-01-01

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

  12. Empirical multiscale networks of cellular regulation.

    Directory of Open Access Journals (Sweden)

    Benjamin de Bivort

    2007-10-01

    Full Text Available Grouping genes by similarity of expression across multiple cellular conditions enables the identification of cellular modules. The known functions of genes enable the characterization of the aggregate biological functions of these modules. In this paper, we use a high-throughput approach to identify the effective mutual regulatory interactions between modules composed of mouse genes from the Alliance for Cell Signaling (AfCS murine B-lymphocyte database which tracks the response of approximately 15,000 genes following chemokine perturbation. This analysis reveals principles of cellular organization that we discuss along four conceptual axes. (1 Regulatory implications: the derived collection of influences between any two modules quantifies intuitive as well as unexpected regulatory interactions. (2 Behavior across scales: trends across global networks of varying resolution (composed of various numbers of modules reveal principles of assembly of high-level behaviors from smaller components. (3 Temporal behavior: tracking the mutual module influences over different time intervals provides features of regulation dynamics such as duration, persistence, and periodicity. (4 Gene Ontology correspondence: the association of modules to known biological roles of individual genes describes the organization of functions within coexpressed modules of various sizes. We present key specific results in each of these four areas, as well as derive general principles of cellular organization. At the coarsest scale, the entire transcriptional network contains five divisions: two divisions devoted to ATP production/biosynthesis and DNA replication that activate all other divisions, an "extracellular interaction" division that represses all other divisions, and two divisions (proliferation/differentiation and membrane infrastructure that activate and repress other divisions in specific ways consistent with cell cycle control.

  13. Topology of the interactions pattern in pharmaceutically relevant polymorphs of methylxanthines (caffeine, theobromine, and theophiline): combined experimental (¹H-¹⁴N nuclear quadrupole double resonance) and computational (DFT and Hirshfeld-based) study.

    Science.gov (United States)

    Latosińska, Jolanta Natalia; Latosińska, Magdalena; Olejniczak, Grzegorz A; Seliger, Janez; Žagar, Veselko

    2014-09-22

    Three anhydrous methylxanthines: caffeine (1,3,7-trimethylxanthine; 1,3,7-trimethyl-1H-purine-2,6-(3H,7H)-dione) and its two metabolites theophylline (1,3-dimethylxanthine; 1,3-dimethyl-7H-purine-2,6-dione) and theobromine (3,7-dimethyl-xanthine; 3,7-dimethyl-7H-purine-2,6-dione), which reveal multifaceted therapeutic potential, have been studied experimentally in solid state by (1)H-(14)N NMR-NQR (nuclear magnetic resonance-nuclear quadrupole resonance) double resonance (NQDR). For each compound the complete NQR spectrum consisting of 12 lines was recorded. The multiplicity of NQR lines indicates the presence of a stable β form of anhydrous caffeine at 233 K and stable form II of anhydrous theobromine at 213 K. The assignment of signals detected in NQR experiment to particular nitrogen atoms was made on the basis of quantum chemistry calculations performed for monomer, cluster, and solid at the DFT/GGA/BLYP/DPD level. The shifts due to crystal packing interactions were evaluated, and the multiplets detected by NQR were assigned to N(9) in theobromine and N(1) and N(9) in caffeine. The ordering theobromine > theophylline > caffeine site and theophylline theobromine theobromine) to π···π stacking (caffeine). Substantial differences in the intermolecular interactions in stable forms of methylxanthines differing in methylation (site or number) were analyzed within the Hirshfeld surface-based approach. The analysis of local environment of the nitrogen nucleus permitted drawing some conclusions on the nature of the interactions required for effective processes of recognition and binding of a given methylxanthine to A1-A(2A) receptor (target for caffeine in the brain). Although the interactions responsible for linking neighboring methylxanthines molecules in crystals and methylxanthines with targets in the human organism can differ significantly, the knowledge of the topology of interactions provides reliable preliminary information about the nature of this binding.

  14. 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…

  15. Communication and interaction with the society inside of a construction process of waste disposal - relevant aspects; Comunicacao e interacao com a sociedade dentro de um processo de construcao de repositorio de rejeitos - aspectos relevantes. Projeto CIS

    Energy Technology Data Exchange (ETDEWEB)

    Almeida, Ivan Pedro Salati de

    2010-07-01

    The CIS Project was established in order to analyze aspects related to the process of communication and interaction with society in the construction of a waste disposal and to propose measures that can improve the performance of organs responsible of this undertaking. This document is the first product of the discussion of a multidisciplinary group consisting of representatives from CNEN - Brazilian Nuclear Energy Commission, INB - Brazilian Nuclear Industries, ELETRONUCLEAR and CTMSP - Navy Technology Center. This document aims to provide a data base to the responsible about radioactive waste disposals decision. Therefore tries to illustrate and to characterize the situation related to the subject Communication and Interaction with Society, based on works about the subject and examples of national or other countries

  16. Examining Different Regions of Relevance: From Highly Relevant to Not Relevant.

    Science.gov (United States)

    Spink, Amanda; Greisdorf, Howard; Bateman, Judy

    1998-01-01

    Proposes a useful concept of relevance as a relationship and an effect on the movement of a user through the iterative stages of their information seeking process, and that users' relevance judgments can be plotted on a Three-Dimensional Spatial Model of Relevance Level, Degree and Time. Discusses implications for the development of information…

  17. Cellular neurothekeoma with melanocytosis.

    Science.gov (United States)

    Wu, Ren-Chin; Hsieh, Yi-Yueh; Chang, Yi-Chin; Kuo, Tseng-Tong

    2008-02-01

    Cellular neurothekeoma (CNT) is a benign dermal tumor mainly affecting the head and neck and the upper extremities. It is characterized histologically by interconnecting fascicles of plump spindle or epithelioid cells with ample cytoplasm infiltrating in the reticular dermis. The histogenesis of CNT has been controversial, although it is generally regarded as an immature counterpart of classic/myxoid neurothekeoma, a tumor with nerve sheath differentiation. Two rare cases of CNT containing melanin-laden cells were described. Immunohistochemical study with NKI/C3, vimentin, epithelial membrane antigen, smooth muscle antigen, CD34, factor XIIIa, collagen type IV, S100 protein and HMB-45 was performed. Both cases showed typical growth pattern of CNT with interconnecting fascicles of epithelioid cells infiltrating in collagenous stroma. One of the nodules contained areas exhibiting atypical cytological features. Melanin-laden epithelioid or dendritic cells were diffusely scattered throughout one nodule, and focally present in the peripheral portion of the other nodule. Both nodules were strongly immunoreactive to NKI/C3 and vimentin, but negative to all the other markers employed. CNT harboring melanin-laden cells may pose diagnostic problems because of their close resemblance to nevomelanocytic lesions and other dermal mesenchymal tumors. These peculiar cases may also provide further clues to the histogenesis of CNT.

  18. Mechanobiology and the microcirculation: cellular, nuclear and fluid mechanics.

    Science.gov (United States)

    Dahl, Kris Noel; Kalinowski, Agnieszka; Pekkan, Kerem

    2010-04-01

    Endothelial cells are stimulated by shear stress throughout the vasculature and respond with changes in gene expression and by morphological reorganization. Mechanical sensors of the cell are varied and include cell surface sensors that activate intracellular chemical signaling pathways. Here, possible mechanical sensors of the cell including reorganization of the cytoskeleton and the nucleus are discussed in relation to shear flow. A mutation in the nuclear structural protein lamin A, related to Hutchinson-Gilford progeria syndrome, is reviewed specifically as the mutation results in altered nuclear structure and stiffer nuclei; animal models also suggest significantly altered vascular structure. Nuclear and cellular deformation of endothelial cells in response to shear stress provides partial understanding of possible mechanical regulation in the microcirculation. Increasing sophistication of fluid flow simulations inside the vessel is also an emerging area relevant to the microcirculation as visualization in situ is difficult. This integrated approach to study--including medicine, molecular and cell biology, biophysics and engineering--provides a unique understanding of multi-scale interactions in the microcirculation.

  19. Relevance of Viroporin Ion Channel Activity on Viral Replication and Pathogenesis.

    Science.gov (United States)

    Nieto-Torres, Jose L; Verdiá-Báguena, Carmina; Castaño-Rodriguez, Carlos; Aguilella, Vicente M; Enjuanes, Luis

    2015-07-03

    Modification of host-cell ionic content is a significant issue for viruses, as several viral proteins displaying ion channel activity, named viroporins, have been identified. Viroporins interact with different cellular membranes and self-assemble forming ion conductive pores. In general, these channels display mild ion selectivity, and, eventually, membrane lipids play key structural and functional roles in the pore. Viroporins stimulate virus production through different mechanisms, and ion channel conductivity has been proved particularly relevant in several cases. Key stages of the viral cycle such as virus uncoating, transport and maturation are ion-influenced processes in many viral species. Besides boosting virus propagation, viroporins have also been associated with pathogenesis. Linking pathogenesis either to the ion conductivity or to other functions of viroporins has been elusive for a long time. This article summarizes novel pathways leading to disease stimulated by viroporin ion conduction, such as inflammasome driven immunopathology.

  20. Relevance of Viroporin Ion Channel Activity on Viral Replication and Pathogenesis

    Directory of Open Access Journals (Sweden)

    Jose L. Nieto-Torres

    2015-07-01

    Full Text Available Modification of host-cell ionic content is a significant issue for viruses, as several viral proteins displaying ion channel activity, named viroporins, have been identified. Viroporins interact with different cellular membranes and self-assemble forming ion conductive pores. In general, these channels display mild ion selectivity, and, eventually, membrane lipids play key structural and functional roles in the pore. Viroporins stimulate virus production through different mechanisms, and ion channel conductivity has been proved particularly relevant in several cases. Key stages of the viral cycle such as virus uncoating, transport and maturation are ion-influenced processes in many viral species. Besides boosting virus propagation, viroporins have also been associated with pathogenesis. Linking pathogenesis either to the ion conductivity or to other functions of viroporins has been elusive for a long time. This article summarizes novel pathways leading to disease stimulated by viroporin ion conduction, such as inflammasome driven immunopathology.

  1. Proteomic dissection of biological pathways/processes through profiling protein-protein interaction networks

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Cellular functions, either under the normal or pathological conditions or under different stresses, are the results of the coordinated action of multiple proteins interacting in macromolecular complexes or assemblies. The precise determination of the specific composition of protein complexes, especially using scalable and high-throughput methods, represents a systematic approach toward revealing particular cellular biological functions. In this regard, the direct profiling protein-protein interactions (PPIs) represent an efficient way to dissect functional pathways for revealing novel protein functions. In this review, we illustrate the technological evolution for the large-scale and precise identification of PPIs toward higher physiologically relevant accuracy. These techniques aim at improving the efficiency of complex pull-down, the signal specificity and accuracy in distinguishing specific PPIs, and the accuracy of identifying physiological relevant PPIs. A newly developed streamline proteomic approach for mapping the binary relationship of PPIs in a protein complex is introduced.

  2. Quantum features of natural cellular automata

    Science.gov (United States)

    Elze, Hans-Thomas

    2016-03-01

    Cellular automata can show well known features of quantum mechanics, such as a linear rule according to which they evolve and which resembles a discretized version of the Schrödinger equation. This includes corresponding conservation laws. The class of “natural” Hamiltonian cellular automata is based exclusively on integer-valued variables and couplings and their dynamics derives from an Action Principle. They can be mapped reversibly to continuum models by applying Sampling Theory. Thus, “deformed” quantum mechanical models with a finite discreteness scale l are obtained, which for l → 0 reproduce familiar continuum results. We have recently demonstrated that such automata can form “multipartite” systems consistently with the tensor product structures of nonrelativistic many-body quantum mechanics, while interacting and maintaining the linear evolution. Consequently, the Superposition Principle fully applies for such primitive discrete deterministic automata and their composites and can produce the essential quantum effects of interference and entanglement.

  3. Designing beauty the art of cellular automata

    CERN Document Server

    Martínez, Genaro

    2016-01-01

    This fascinating, colourful book offers in-depth insights and first-hand working experiences in the production of art works, using simple computational models with rich morphological behaviour, at the edge of mathematics, computer science, physics and biology. It organically combines ground breaking scientific discoveries in the theory of computation and complex systems with artistic representations of the research results. In this appealing book mathematicians, computer scientists, physicists, and engineers brought together marvelous and esoteric patterns generated by cellular automata, which are arrays of simple machines with complex behavior. Configurations produced by cellular automata uncover mechanics of dynamic patterns formation, their propagation and interaction in natural systems: heart pacemaker, bacterial membrane proteins, chemical rectors, water permeation in soil, compressed gas, cell division, population dynamics, reaction-diffusion media and self-organisation. The book inspires artists to tak...

  4. Quantum features of natural cellular automata

    CERN Document Server

    Elze, Hans-Thomas

    2016-01-01

    Cellular automata can show well known features of quantum mechanics, such as a linear rule according to which they evolve and which resembles a discretized version of the Schroedinger equation. This includes corresponding conservation laws. The class of "natural" Hamiltonian cellular automata is based exclusively on integer-valued variables and couplings and their dynamics derives from an Action Principle. They can be mapped reversibly to continuum models by applying Sampling Theory. Thus, "deformed" quantum mechanical models with a finite discreteness scale $l$ are obtained, which for $l\\rightarrow 0$ reproduce familiar continuum results. We have recently demonstrated that such automata can form "multipartite" systems consistently with the tensor product structures of nonrelativistic many-body quantum mechanics, while interacting and maintaining the linear evolution. Consequently, the Superposition Principle fully applies for such primitive discrete deterministic automata and their composites and can produce...

  5. Construction of drug-polymer thermodynamic phase diagrams using Flory-Huggins interaction theory: identifying the relevance of temperature and drug weight fraction to phase separation within solid dispersions.

    Science.gov (United States)

    Tian, Yiwei; Booth, Jonathan; Meehan, Elizabeth; Jones, David S; Li, Shu; Andrews, Gavin P

    2013-01-07

    Amorphous drug-polymer solid dispersions have the potential to enhance the dissolution performance and thus bioavailability of BCS class II drug compounds. The principle drawback of this approach is the limited physical stability of amorphous drug within the dispersion. Accurate determination of the solubility and miscibility of drug in the polymer matrix is the key to the successful design and development of such systems. In this paper, we propose a novel method, based on Flory-Huggins theory, to predict and compare the solubility and miscibility of drug in polymeric systems. The systems chosen for this study are (1) hydroxypropyl methylcellulose acetate succinate HF grade (HPMCAS-HF)-felodipine (FD) and (2) Soluplus (a graft copolymer of polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol)-FD. Samples containing different drug compositions were mixed, ball milled, and then analyzed by differential scanning calorimetry (DSC). The value of the drug-polymer interaction parameter χ was calculated from the crystalline drug melting depression data and extrapolated to lower temperatures. The interaction parameter χ was also calculated at 25 °C for both systems using the van Krevelen solubility parameter method. The rank order of interaction parameters of the two systems obtained at this temperature was comparable. Diagrams of drug-polymer temperature-composition and free energy of mixing (ΔG(mix)) were constructed for both systems. The maximum crystalline drug solubility and amorphous drug miscibility may be predicted based on the phase diagrams. Hyper-DSC was used to assess the validity of constructed phase diagrams by annealing solid dispersions at specific drug loadings. Three different samples for each polymer were selected to represent different regions within the phase diagram.

  6. User perspectives on relevance criteria

    DEFF Research Database (Denmark)

    Maglaughlin, Kelly L.; Sonnenwald, Diane H.

    2002-01-01

    matter, thought catalyst), full text (e.g., audience, novelty, type, possible content, utility), journal/publisher (e.g., novelty, main focus, perceived quality), and personal (e.g., competition, time requirements). Results further indicate that multiple criteria are used when making relevant, partially...... relevant, and not-relevant judgments, and that most criteria can have either a positive or negative contribution to the relevance of a document. The criteria most frequently mentioned by study participants were content, followed by criteria characterizing the full text document. These findings may have...... implications for relevance feedback in information retrieval systems, suggesting that systems accept and utilize multiple positive and negative relevance criteria from users. Systems designers may want to focus on supporting content criteria followed by full text criteria as these may provide the greatest cost...

  7. Relevance-driven Pragmatic Inferences

    Institute of Scientific and Technical Information of China (English)

    王瑞彪

    2013-01-01

    Relevance theory, an inferential approach to pragmatics, claims that the hearer is expected to pick out the input of op-timal relevance from a mass of alternative inputs produced by the speaker in order to interpret the speaker ’s intentions. The de-gree of the relevance of an input can be assessed in terms of cognitive effects and the processing effort. The input of optimal rele-vance is the one yielding the greatest positive cognitive effect and requiring the least processing effort. This paper attempts to as-sess the degrees of the relevance of a mass of alternative inputs produced by an imaginary speaker from the perspective of her cor-responding hearer in terms of cognitive effects and the processing effort with a view to justifying the feasibility of the principle of relevance in pragmatic inferences.

  8. 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...

  9. SEM++: A particle model of cellular growth, signaling and migration

    Science.gov (United States)

    Milde, Florian; Tauriello, Gerardo; Haberkern, Hannah; Koumoutsakos, Petros

    2014-06-01

    We present a discrete particle method to model biological processes from the sub-cellular to the inter-cellular level. Particles interact through a parametrized force field to model cell mechanical properties, cytoskeleton remodeling, growth and proliferation as well as signaling between cells. We discuss the guiding design principles for the selection of the force field and the validation of the particle model using experimental data. The proposed method is integrated into a multiscale particle framework for the simulation of biological systems.

  10. Minimal model for complex dynamics in cellular processes.

    Science.gov (United States)

    Suguna, C; Chowdhury, K K; Sinha, S

    1999-11-01

    Cellular functions are controlled and coordinated by the complex circuitry of biochemical pathways regulated by genetic and metabolic feedback processes. This paper aims to show, with the help of a minimal model of a regulated biochemical pathway, that the common nonlinearities and control structures present in biomolecular interactions are capable of eliciting a variety of functional dynamics, such as homeostasis, periodic, complex, and chaotic oscillations, including transients, that are observed in various cellular processes.

  11. A high-efficiency cellular extraction system for biological proteomics

    OpenAIRE

    2015-01-01

    Recent developments in quantitative high-resolution mass spectrometry have led to significant improvements in the sensitivity and specificity of biochemical analyses of cellular reactions, protein-protein interactions, and small molecule drug discovery. These approaches depend on cellular proteome extraction that preserves native protein activities. Here, we systematically analyzed mechanical methods of cell lysis and physical protein extraction to identify those that maximize the extraction ...

  12. Free fall and cellular automata

    Directory of Open Access Journals (Sweden)

    Pablo Arrighi

    2016-03-01

    Full Text Available Three reasonable hypotheses lead to the thesis that physical phenomena can be described and simulated with cellular automata. In this work, we attempt to describe the motion of a particle upon which a constant force is applied, with a cellular automaton, in Newtonian physics, in Special Relativity, and in General Relativity. The results are very different for these three theories.

  13. About Strongly Universal Cellular Automata

    Directory of Open Access Journals (Sweden)

    Maurice Margenstern

    2013-09-01

    Full Text Available In this paper, we construct a strongly universal cellular automaton on the line with 11 states and the standard neighbourhood. We embed this construction into several tilings of the hyperbolic plane and of the hyperbolic 3D space giving rise to strongly universal cellular automata with 10 states.

  14. Reactive Programming of Cellular Automata

    OpenAIRE

    Boussinot, Frédéric

    2004-01-01

    Implementation of cellular automata using reactive programming gives a way to code cell behaviors in an abstract and modular way. Multiprocessing also becomes possible. The paper describes the implementation of cellular automata with the reactive programming language LOFT, a thread-based extension of C. Self replicating loops considered in artificial life are coded to show the interest of the approach.

  15. Cellular based cancer vaccines

    DEFF Research Database (Denmark)

    Hansen, Morten; Met, O; Svane, I M;

    2012-01-01

    Cancer vaccines designed to re-calibrate the existing host-tumour interaction, tipping the balance from tumor acceptance towards tumor control holds huge potential to complement traditional cancer therapies. In general, limited success has been achieved with vaccines composed of tumor...... in vitro migration via autocrine receptor-mediated endocytosis of CCR7. In the current review, we discuss optimal design of DC maturation focused on pre-clinical as well as clinical results from standard and polarized dendritic cell based cancer vaccines....

  16. Interaction Analysis through Proteomic Phage Display

    Directory of Open Access Journals (Sweden)

    Gustav N. Sundell

    2014-01-01

    Full Text Available Phage display is a powerful technique for profiling specificities of peptide binding domains. The method is suited for the identification of high-affinity ligands with inhibitor potential when using highly diverse combinatorial peptide phage libraries. Such experiments further provide consensus motifs for genome-wide scanning of ligands of potential biological relevance. A complementary but considerably less explored approach is to display expression products of genomic DNA, cDNA, open reading frames (ORFs, or oligonucleotide libraries designed to encode defined regions of a target proteome on phage particles. One of the main applications of such proteomic libraries has been the elucidation of antibody epitopes. This review is focused on the use of proteomic phage display to uncover protein-protein interactions of potential relevance for cellular function. The method is particularly suited for the discovery of interactions between peptide binding domains and their targets. We discuss the largely unexplored potential of this method in the discovery of domain-motif interactions of potential biological relevance.

  17. 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,...

  18. Interactions of glutathione transferases with 4-hydroxynonenal.

    Science.gov (United States)

    Balogh, Larissa M; Atkins, William M

    2011-05-01

    Electrophilic products of lipid peroxidation are important contributors to the progression of several pathological states. The prototypical α,β-unsaturated aldehyde, 4-hydroxynonenal (HNE), triggers cellular events associated with oxidative stress, which can be curtailed by the glutathione-dependent elimination of HNE. The glutathione transferases (GSTs) are a major determinate of the intracellular concentration of HNE and can influence susceptibility to toxic effects, particularly when HNE and GST levels are altered in disease states. In this article, we provide a brief summary of the cellular effects of HNE, followed by a review of its GST-catalyzed detoxification, with an emphasis on the structural attributes that play an important role in the interactions with alpha-class GSTs. Some of the key determining characteristics that impart high alkenal activity reside in the unique C-terminal interactions of the GSTA4-4 enzyme. Studies encompassing both kinetic and structural analyses of related isoforms will be highlighted, with additional attention to stereochemical aspects that demonstrate the capacity of GSTA4-4 to detoxify both enantiomers of the biologically relevant racemic mixture while generating a select set of diastereomeric products with subsequent implications. A summary of the literature that examines the interplay between GSTs and HNE in model systems relevant to oxidative stress will also be discussed to demonstrate the magnitude of importance of GSTs in the overall detoxification scheme.

  19. Cellular peptidyl-prolyl cis/trans isomerase Pin1 facilitates replication of feline coronavirus.

    Science.gov (United States)

    Tanaka, Yoshikazu; Amano, Arisa; Morisaki, Masateru; Sato, Yuka; Sasaki, Takashi

    2016-02-01

    Although feline coronavirus (FCoV) causes feline infectious peritonitis (FIP), which is a fatal infectious disease, there are no effective therapeutic medicines or vaccines. Previously, in vitro studies have shown that cyclosporin (CsA) and FK506 inhibit virus replication in diverse coronaviruses. CsA and FK506 are targets of clinically relevant immunosuppressive drugs and bind to cellular cyclophilins (Cyps) or FK506 binding proteins (FKBPs), respectively. Both Cyp and FKBP have peptidyl-prolyl cis-trans isomerase (PPIase) activity. However, protein interacting with NIMA (Pin1), a member of the parvulin subfamily of PPIases that differs from Cyps and FKBPs, is essential for various signaling pathways. Here we demonstrated that genetic silencing or knockout of Pin1 resulted in decreased FCoV replication in vitro. Dipentamethylene thiuram monosulfide, a specific inhibitor of Pin1, inhibited FCoV replication. These data indicate that Pin1 modulates FCoV propagation.

  20. Physics of Cellular Movements

    Science.gov (United States)

    Sackmann, Erich; Keber, Felix; Heinrich, Doris

    2010-04-01

    The survival of cells depends on perpetual active motions, including (a) bending excitations of the soft cell envelopes, (b) the bidirectional transport of materials and organelles between the cell center and the periphery, and (c) the ongoing restructuring of the intracellular macromolecular scaffolds mediating global cell changes associated with cell adhesion locomotion and phagocytosis. Central questions addressed are the following: How can this bustling motion of extremely complex soft structures be characterized and measured? What are the major driving forces? Further topics include (a) the active dynamic control of global shape changes by the interactive coupling of the aster-like soft scaffold of microtubules and the network of actin filaments associated with the cell envelope (the actin cortex) and (b) the generation of propulsion forces by solitary actin gelation waves propagating within the actin cortex.

  1. Protein source and choice of anticoagulant decisively affect nanoparticle protein corona and cellular uptake

    Science.gov (United States)

    Schöttler, S.; Klein, Katja; Landfester, K.; Mailänder, V.

    2016-03-01

    Protein adsorption on nanoparticles has been a focus of the field of nanocarrier research in the past few years and more and more papers are dealing with increasingly detailed lists of proteins adsorbed to a plethora of nanocarriers. While there is an urgent need to understand the influence of this protein corona on nanocarriers' interactions with cells the strong impact of the protein source on corona formation and the consequence for interaction with different cell types are factors that are regularly neglected, but should be taken into account for a meaningful analysis. In this study, the importance of the choice of protein source used for in vitro protein corona analysis is concisely investigated. Major and decisive differences in cellular uptake of a polystyrene nanoparticle incubated in fetal bovine serum, human serum, human citrate and heparin plasma are reported. Furthermore, the protein compositions are determined for coronas formed in the respective incubation media. A strong influence of heparin, which is used as an anticoagulant for plasma generation, on cell interaction is demonstrated. While heparin enhances the uptake into macrophages, it prevents internalization into HeLa cells. Taken together we can give the recommendation that human plasma anticoagulated with citrate seems to give the most relevant results for in vitro studies of nanoparticle uptake.Protein adsorption on nanoparticles has been a focus of the field of nanocarrier research in the past few years and more and more papers are dealing with increasingly detailed lists of proteins adsorbed to a plethora of nanocarriers. While there is an urgent need to understand the influence of this protein corona on nanocarriers' interactions with cells the strong impact of the protein source on corona formation and the consequence for interaction with different cell types are factors that are regularly neglected, but should be taken into account for a meaningful analysis. In this study, the importance

  2. "Gastric cytoprotection" is still relevant.

    Science.gov (United States)

    Szabo, Sandor

    2014-12-01

    rapid vascular changes (e.g. increased VP and blood flow), followed by cellular events (e.g. infiltration by acute and chronic inflammatory cells). Thus, PG and histamine, by increasing VP create a perivascular edema that dilutes and delays toxic agents reaching the subepithelial capillaries. Otherwise, damaging chemicals may induce severe early vascular injury resulting in blood flow stasis, hypoxia, and necrosis of surrounding epithelial and mesenchymal cells. In this complex response, increased mucus and/or bicarbonate secretion seem to cause luminal dilution of gastrotoxic chemicals that is further reinforced by a perivascular, histodilutional component. This mechanistic explanation would encompass the protective actions of diverse agents as PG, small doses of histamine, motility stimulants, and dilute irritants (i.e. "adaptive cytoprotection"). Thus, although markedly increased VP is pathologic, slight increase in VP seems to be protective, that is, a key element in the complex pathophysiologic response during acute gastroprotection. Over the years, "gastroprotection" was also applied to accelerated healing of chronic gastroduodenal ulcers without reduction of acid secretion. The likely main mechanism here is the binding of angiogenic growth factors (e.g. basic fibroblast growth factor, vascular endothelial growth factor) to the heparin-like structures of sucralfate and sofalcone. Thus, despite intensive research of the last 30 years, gastroprotection is incompletely understood, and we are still far away from effectively treating Helicobacter pylori-negative ulcers and preventing nonsteroidal anti-inflammatory drugs-caused erosions and ulcers in the upper and lower gastrointestinal tract; hence "gastric cytoprotection" research is still relevant.

  3. Particularidades relevantes da interação humano-animal para o bem-estar e produtividade de vacas leiteiras Particularities of the human-animal interactions relevant to the welfare and productivity of dairy cows

    Directory of Open Access Journals (Sweden)

    Luciana Aparecida Honorato

    2012-02-01

    Full Text Available Mudanças na qualidade da relação entre os animais e as pessoas podem influenciar substancialmente na produtividade e no bem-estar dos animais e, potencialmente, dos humanos envolvidos na atividade leiteira. Importantes alterações no sentido da melhoria dessas relações podem ser obtidas através de programas de treinamento, ou outras formas de extensão. Para que isso tenha efetividade, é necessário conhecer como interagem os aspectos dessa relação, que incluem além dos animais e os homens, o ambiente em que eles se inserem. A maioria dos estudos publicados confirma o modelo de retroalimentação positiva de atitudes e comportamentos humanos e comportamento dos animais. Porém, esses estudos têm sido desenvolvidos em países da Europa ou na Austrália, na maioria das vezes, sob condições de criação intensiva confinada e, geralmente, com o intuito de indicar um perfil ideal de empregado para trabalhar com os animais. Nesta revisão, mostra-se que o sistema de criação pode exercer uma forte interferência nesse processo e conclui-se sugerindo o desenvolvimento de estudos voltados a compreender as relações entre humanos e animais em diferentes sistemas de criação, enfocando as diversas realidades do nosso país. Esses estudos devem procurar entender de que modo características como o manejo alimentar e sanitário empregado, a qualidade das instalações, a genética, o tamanho e a composição dos rebanhos, e as peculiaridades culturais regionais influenciam na qualidade dessas relações.Changes in the quality of interactions between animals and humans have a profound influence on the productivity and welfare of animals and, potentially, of humans involved in the dairy activity. Important alterations in these interactions can be obtained through training programs, or other forms of extension. To do so effectively, it is necessary to understand how interact the several aspects of this relationship, which includes besides the

  4. Is transmission electron microscopy (TEM) a promising approach for qualitative and quantitative investigations of polymyxin B and miconazole interactions with cellular and subcellular structures of Staphylococcus pseudintermedius, Escherichia coli, Pseudomonas aeruginosa and Malassezia pachydermatis?

    Science.gov (United States)

    Voget, Michael; Lorenz, Dorothea; Lieber-Tenorio, Elisabeth; Hauck, Ruediger; Meyer, Michael; Cieslicki, Michael

    2015-12-31

    Antimicrobial therapy using a combination of polymyxin B and miconazole is effective against the main bacterial pathogens associated with otitis externa in dogs, and a synergistic effect of both drugs has been shown previously. The objective of the present investigation was to visualize ultrastructural changes after exposure of Escherichia coli, Pseudomonas aeruginosa, Staphylococcus pseudintermedius and Malassezia pachydermatis to polymyxin B and miconazole by transmission electron microscopic (TEM). For this, cultures of E. coli, P. aeruginosa, S. pseudintermedius and M. pachydermatis were exposed to polymyxin B and miconazole, alone or in combination for 24 h. Ultrastructural changes were observed most frequently in the cell envelope of the four microorganisms. Exposure to polymyxin B seemed to cause more damage than miconazole within the range of concentrations applied. Treatment resulted in changes of the cell size: in E. coli, cell size increased significantly after treatment with either compound alone; in P. aeruginosa, cell size decreased significantly after treatment with polymyxin B and with miconazole; exposure of S. pseudintermedius to miconazole caused a decrease in cell size; in M. pachydermatis, cell size increased significantly after treatment with polymyxin B.; in E.coli, S. pseudintermedius and M. pachydermatis, cell size changed highly significant, in P. aeruginosa significantly after exposure to the combination of both compounds. In conclusion, by using a different approach than previous investigations, this study confirmed a clear combinatory effect of polymyxin B and miconazole against the tested microorganisms involved in canine otitis externa. It is the first time that visualization technologies were applied to compare the effect of single drugs to their combinatory effects on cellular and subcellular entities of selected bacterial and yeast species.

  5. Cellular regulation of the dopamine transporter

    DEFF Research Database (Denmark)

    Eriksen, Jacob

    2010-01-01

    The dopamine transporter (DAT) mediates reuptake of dopamine from the synaptic cleft and is a target for widely abused psychostimulants such as cocaine and amphetamine. Nonetheless, little is known about the cellular distribution and trafficking of natively expressed DAT. DAT and its trafficking...... in heterologous cells and in cultured DA neurons. DAT has been shown to be regulated by the dopamine D2 receptor (D2R), the primary target foranti-psychotics, through a direct interaction. D2R is among other places expressed as an autoreceptor in DA neurons. Transient over-expression of DAT with D2R in HEK293...

  6. Different Candida parapsilosis clinical isolates and lipase deficient strain trigger an altered cellular immune response

    Directory of Open Access Journals (Sweden)

    Renata eToth

    2015-10-01

    Full Text Available Numerous human diseases can be associated with fungal infections either as potential causative agents or as a result of changed immune status due to a primary disease. Fungal infections caused by Candida species can vary from mild to severe dependent upon the site of infection, length of exposure and past medical history. Patients with impaired immune status are at increased risk for chronic fungal infections. Recent epidemiologic studies have revealed the increasing incidence of candidiasis caused by non-albicans species such as C. parapsilosis. Due to its increasing relevance we chose two distinct C. parapsilosis strains, to describe the cellular innate immune response towards this species. In the first section of our study we compared the interaction of CLIB 214 and GA1 cells with murine and human macrophages. Both strains are commonly used to investigate C. parapsilosis virulence properties. CLIB 214 is a rapidly pseudohyphae-forming strain and GA1 is an isolate that mainly exists in a yeast form. Our results showed, that the phagocyte response was similar in terms of overall uptake, however differences were observed in macrophage migration and engulfment of fungal cells. As C. parapsilosis releases extracellular lipases in order to promote host invasion we further investigated the role of these secreted components during the distinct stages of the phagocytic process. Using a secreted lipase deficient mutant strain and the parental strain GA1 individually and simultaneously, we confirmed that fungal secreted lipases influence the fungi’s virulence by detecting altered innate cellular responses.In this study we report that two isolates of a single species can trigger markedly distinct host responses and that lipase secretion plays a role on the cellular level of host pathogen interactions.

  7. Pathologic Cellular Events in Smoking-Related Pancreatitis

    Energy Technology Data Exchange (ETDEWEB)

    Thrower, Edwin [Department of Internal Medicine, Section of Digestive Diseases, Yale University School of Medicine, New Haven, CT 06520 (United States); Veterans Affairs Connecticut Healthcare, West Haven, CT 06516 (United States)

    2015-04-29

    Pancreatitis, a debilitating inflammatory disorder, results from pancreatic injury. Alcohol abuse is the foremost cause, although cigarette smoking has recently surfaced as a distinct risk factor. The mechanisms by which cigarette smoke and its toxins initiate pathological cellular events leading to pancreatitis, have not been clearly defined. Although cigarette smoke is composed of more than 4000 compounds, it is mainly nicotine and the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), which have been extensively studied with respect to pancreatic diseases. This review summarizes these research findings and highlights cellular pathways which may be of relevance in initiation and progression of smoking-related pancreatitis.

  8. A Real Space Cellular Automaton Laboratory

    Science.gov (United States)

    Rozier, O.; Narteau, C.

    2013-12-01

    Investigations in geomorphology may benefit from computer modelling approaches that rely entirely on self-organization principles. In the vast majority of numerical models, instead, points in space are characterised by a variety of physical variables (e.g. sediment transport rate, velocity, temperature) recalculated over time according to some predetermined set of laws. However, there is not always a satisfactory theoretical framework from which we can quantify the overall dynamics of the system. For these reasons, we prefer to concentrate on interaction patterns using a basic cellular automaton modelling framework, the Real Space Cellular Automaton Laboratory (ReSCAL), a powerful and versatile generator of 3D stochastic models. The objective of this software suite released under a GNU license is to develop interdisciplinary research collaboration to investigate the dynamics of complex systems. The models in ReSCAL are essentially constructed from a small number of discrete states distributed on a cellular grid. An elementary cell is a real-space representation of the physical environment and pairs of nearest neighbour cells are called doublets. Each individual physical process is associated with a set of doublet transitions and characteristic transition rates. Using a modular approach, we can simulate and combine a wide range of physical, chemical and/or anthropological processes. Here, we present different ingredients of ReSCAL leading to applications in geomorphology: dune morphodynamics and landscape evolution. We also discuss how ReSCAL can be applied and developed across many disciplines in natural and human sciences.

  9. Coordination of autophagy with other cellular activities

    Institute of Scientific and Technical Information of China (English)

    Yan WANG; Zheng-hong QIN

    2013-01-01

    The cell biological phenomenon of autophagy has attracted increasing attention in recent years,partly as a consequence of the discovery of key components of its cellular machinery.Autophagy plays a crucial role in a myriad of cellular functions.Autophagy has its own regulatory mechanisms,but this process is not isolated.Autophagy is coordinated with other cellular activities to maintain cell homeostasis.Autophagy is critical for a range of human physiological processes.The multifunctional roles of autophagy are explained by its ability to interact with several key components of various cell pathways.In this review,we focus on the coordination between autophagy and other physiological processes,including the ubiquitin-proteasome system (UPS),energy homeostasis,aging,programmed cell death,the immune responses,microbial invasion and inflammation.The insights gained from investigating autophagic networks should increase our understanding of their roles in human diseases and their potential as targets for therapeutic intervention.

  10. Stress testing at the cellular and molecular level to unravel cellular dysfunction and growth factor signal transduction defects: what Molecular Cell Biology can learn from Cardiology.

    Science.gov (United States)

    Waltenberger, Johannes

    2007-11-01

    Clinical medicine has been revolutionized by the impact of cellular and molecular biology in the past 30 years. This article focuses on a novel approach, whereby the clinically proven and important concept of patient or organ stress testing is being applied to cellular models, thereby developing and validating novel quantitative molecular and cellular stress tests. One example is monocyte chemotaxis analysis, whereby circulating monocytes freshly isolated from peripheral blood are being tested for their migratory responsiveness towards relevant biological stimuli such as growth factors or chemokines. These stimuli are relevant for recruiting monocytes to sites of local inflammation such as during wound healing or arteriogenesis, i.e. growth of collateral arteries. Initial clinical studies to validate "ligand-induced monocyte chemotaxis" indicate that this parameter is impaired in the presence of various cardiovascular risk factors including diabetes mellitus, hypercholesterolemia or smoking. In addition, there is proof of concept that impaired monocyte chemotaxis is reversible as shown for anti-oxidants in smokers. Moreover, the parameter "ligand-induced monocyte chemotaxis" is of great relevance for basic science (including Molecular Cell Biology) as unravelling the underlying molecular mechanisms of cellular dysfunction will certainly stimulate our understanding of the molecular basis of cellular function. This article highlights the concept of stress testing in modern medicine. Cellular stress testing is introduced as a novel and intriguing approach, which was developed as bedside-to-bench. Future prospective clinical trials will have to validate the predictive value of cellular stress testing.

  11. A Course in Cellular Bioengineering.

    Science.gov (United States)

    Lauffenburger, Douglas A.

    1989-01-01

    Gives an overview of a course in chemical engineering entitled "Cellular Bioengineering," dealing with how chemical engineering principles can be applied to molecular cell biology. Topics used are listed and some key references are discussed. Listed are 85 references. (YP)

  12. 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

  13. Energy Landscape of Cellular Networks

    Science.gov (United States)

    Wang, Jin

    2008-03-01

    Cellular Networks are in general quite robust and perform their biological functions against the environmental perturbations. Progresses have been made from experimental global screenings, topological and engineering studies. However, there are so far few studies of why the network should be robust and perform biological functions from global physical perspectives. In this work, we will explore the global properties of the network from physical perspectives. The aim of this work is to develop a conceptual framework and quantitative physical methods to study the global nature of the cellular network. The main conclusion of this presentation is that we uncovered the underlying energy landscape for several small cellular networks such as MAPK signal transduction network and gene regulatory networks, from the experimentally measured or inferred inherent chemical reaction rates. The underlying dynamics of these networks can show bi-stable as well as oscillatory behavior. The global shapes of the energy landscapes of the underlying cellular networks we have studied are robust against perturbations of the kinetic rates and environmental disturbances through noise. We derived a quantitative criterion for robustness of the network function from the underlying landscape. It provides a natural explanation of the robustness and stability of the network for performing biological functions. We believe the robust landscape is a global universal property for cellular networks. We believe the robust landscape is a quantitative realization of Darwinian principle of natural selection at the cellular network level. It may provide a novel algorithm for optimizing the network connections, which is crucial for the cellular network design and synthetic biology. Our approach is general and can be applied to other cellular networks.

  14. Cellular antioxidant activity of common vegetables.

    Science.gov (United States)

    Song, Wei; Derito, Christopher M; Liu, M Keshu; He, Xiangjiu; Dong, Mei; Liu, Rui Hai

    2010-06-01

    The measurement of antioxidant activity using biologically relevant assays is important to screen fruits, vegetables, natural products, and dietary supplements for potential health benefits. The cellular antioxidant activity (CAA) assay quantifies antioxidant activity using a cell culture model and was developed to meet the need for a more biologically representative method than the popular chemistry antioxidant capacity measures. The objective of the study was to determine the CAA, total phenolic contents, and oxygen radical absorbance capacity (ORAC) values of 27 vegetables commonly consumed in the United States. Beets, broccoli, and red pepper had the highest CAA values, whereas cucumber had the lowest. CAA values were significantly correlated to total phenolic content. Potatoes were found to be the largest contributors of vegetable phenolics and CAA to the American diet. Increased fruit and vegetable consumption is an effective strategy to increase antioxidant intake and decrease oxidative stress and may lead to reduced risk of developing chronic diseases, such as cancer and cardiovascular disease.

  15. X-ray Spectroscopic Characterization of Co(IV) and Metal-Metal Interactions in Co4O4: Electronic Structure Contributions to the Formation of High-Valent States Relevant to the Oxygen Evolution Reaction.

    Science.gov (United States)

    Hadt, Ryan G; Hayes, Dugan; Brodsky, Casey N; Ullman, Andrew M; Casa, Diego M; Upton, Mary H; Nocera, Daniel G; Chen, Lin X

    2016-08-31

    The formation of high-valent states is a key factor in making highly active transition-metal-based catalysts of the oxygen evolution reaction (OER). These high oxidation states will be strongly influenced by the local geometric and electronic structures of the metal ion, which are difficult to study due to spectroscopically active and complex backgrounds, short lifetimes, and limited concentrations. Here, we use a wide range of complementary X-ray spectroscopies coupled to DFT calculations to study Co(III)4O4 cubanes and their first oxidized derivatives, which provide insight into the high-valent Co(IV) centers responsible for the activity of molecular and heterogeneous OER catalysts. The combination of X-ray absorption and 1s3p resonant inelastic X-ray scattering (Kβ RIXS) allows Co(IV) to be isolated and studied against a spectroscopically active Co(III) background. Co K- and L-edge X-ray absorption data allow for a detailed characterization of the 3d-manifold of effectively localized Co(IV) centers and provide a direct handle on the t2g-based redox-active molecular orbital. Kβ RIXS is also shown to provide a powerful probe of Co(IV), and specific spectral features are sensitive to the degree of oxo-mediated metal-metal coupling across Co4O4. Guided by the data, calculations show that electron-hole delocalization can actually oppose Co(IV) formation. Computational extension of Co4O4 to CoM3O4 structures (M = redox-inactive metal) defines electronic structure contributions to Co(IV) formation. Redox activity is shown to be linearly related to covalency, and M(III) oxo inductive effects on Co(IV) oxo bonding can tune the covalency of high-valent sites over a large range and thereby tune E(0) over hundreds of millivolts. Additionally, redox-inactive metal substitution can also switch the ground state and modify metal-metal and antibonding interactions across the cluster.

  16. Mathematical Modeling of Cellular Metabolism.

    Science.gov (United States)

    Berndt, Nikolaus; Holzhütter, Hermann-Georg

    2016-01-01

    Cellular metabolism basically consists of the conversion of chemical compounds taken up from the extracellular environment into energy (conserved in energy-rich bonds of organic phosphates) and a wide array of organic molecules serving as catalysts (enzymes), information carriers (nucleic acids), and building blocks for cellular structures such as membranes or ribosomes. Metabolic modeling aims at the construction of mathematical representations of the cellular metabolism that can be used to calculate the concentration of cellular molecules and the rates of their mutual chemical interconversion in response to varying external conditions as, for example, hormonal stimuli or supply of essential nutrients. Based on such calculations, it is possible to quantify complex cellular functions as cellular growth, detoxification of drugs and xenobiotic compounds or synthesis of exported molecules. Depending on the specific questions to metabolism addressed, the methodological expertise of the researcher, and available experimental information, different conceptual frameworks have been established, allowing the usage of computational methods to condense experimental information from various layers of organization into (self-) consistent models. Here, we briefly outline the main conceptual frameworks that are currently exploited in metabolism research.

  17. Quantitative investigation of cellular growth in directional solidification by phase-field simulation.

    Science.gov (United States)

    Wang, Zhijun; Wang, Jincheng; Li, Junjie; Yang, Gencang; Zhou, Yaohe

    2011-10-01

    Using a quantitative phase-field model, a systematic investigation of cellular growth in directional solidification is carried out with emphasis on the selection of cellular tip undercooling, tip radius, and cellular spacing. Previous analytical models of cellular growth are evaluated according to the phase-field simulation results. The results show that cellular tip undercooling and tip radius not only depend on the pulling velocity and thermal gradient, but also depend on the cellular interaction related to the cellular spacing. The cellular interaction results in a finite stable range of cellular spacing. The lower limit is determined by the submerging mechanism while the upper limit comes from the tip splitting instability corresponding to the absence of the cellular growth solution, both of which can be obtained from phase-field simulation. Further discussions on the phase-field results also present an analytical method to predict the lower limit. Phase-field simulations on cell elimination between cells with equal spacing validate the finite range of cellular spacing and give deep insight into the cellular doublon and oscillatory instability between cell elimination and tip splitting.

  18. Modeling In Vitro Cellular Responses to Silver Nanoparticles

    Directory of Open Access Journals (Sweden)

    Dwaipayan Mukherjee

    2014-01-01

    Full Text Available Engineered nanoparticles (NPs have been widely demonstrated to induce toxic effects to various cell types. In vitro cell exposure systems have high potential for reliable, high throughput screening of nanoparticle toxicity, allowing focusing on particular pathways while excluding unwanted effects due to other cells or tissue dosimetry. The work presented here involves a detailed biologically based computational model of cellular interactions with NPs; it utilizes measurements performed in human cell culture systems in vitro, to develop a mechanistic mathematical model that can support analysis and prediction of in vivo effects of NPs. The model considers basic cellular mechanisms including proliferation, apoptosis, and production of cytokines in response to NPs. This new model is implemented for macrophages and parameterized using in vitro measurements of changes in cellular viability and mRNA levels of cytokines: TNF, IL-1b, IL-6, IL-8, and IL-10. The model includes in vitro cellular dosimetry due to nanoparticle transport and transformation. Furthermore, the model developed here optimizes the essential cellular parameters based on in vitro measurements, and provides a “stepping stone” for the development of more advanced in vivo models that will incorporate additional cellular and NP interactions.

  19. Combinatorial approaches to evaluate nanodiamond uptake and induced cellular fate.

    Science.gov (United States)

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

    2016-02-26

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

  20. Combinatorial approaches to evaluate nanodiamond uptake and induced cellular fate

    Science.gov (United States)

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

    2016-02-01

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

  1. Particles and Patterns in Cellular Automata

    Energy Technology Data Exchange (ETDEWEB)

    Jen, E.; Das, R.; Beasley, C.E.

    1999-06-03

    This is the final report of a three-year, Laboratory Directed Research and Development (LDRD) project at Los Alamos National Laboratory (LANL). Our objective has been to develop tools for studying particle interactions in a class of dynamical systems characterized by discreteness, determinism, local interaction, and an inherently parallel form of evolution. These systems can be described by cellular automata (CA) and the behavior we studied has improved our understanding of the nature of patterns generated by CAs, their ability to perform global computations, and their relationship to continuous dynamical systems. We have also developed a rule-table mathematics that enables one to custom-design CA rule tables to generate patterns of specified types, or to perform specified computational tasks.

  2. Relevance theory: pragmatics and cognition.

    Science.gov (United States)

    Wearing, Catherine J

    2015-01-01

    Relevance Theory is a cognitively oriented theory of pragmatics, i.e., a theory of language use. It builds on the seminal work of H.P. Grice(1) to develop a pragmatic theory which is at once philosophically sensitive and empirically plausible (in both psychological and evolutionary terms). This entry reviews the central commitments and chief contributions of Relevance Theory, including its Gricean commitment to the centrality of intention-reading and inference in communication; the cognitively grounded notion of relevance which provides the mechanism for explaining pragmatic interpretation as an intention-driven, inferential process; and several key applications of the theory (lexical pragmatics, metaphor and irony, procedural meaning). Relevance Theory is an important contribution to our understanding of the pragmatics of communication.

  3. Clinical relevance in anesthesia journals

    DEFF Research Database (Denmark)

    Lauritsen, Jakob; Møller, Ann M

    2006-01-01

    The purpose of this review is to present the latest knowledge and research on the definition and distribution of clinically relevant articles in anesthesia journals. It will also discuss the importance of the chosen methodology and outcome of articles.......The purpose of this review is to present the latest knowledge and research on the definition and distribution of clinically relevant articles in anesthesia journals. It will also discuss the importance of the chosen methodology and outcome of articles....

  4. Evaluation of arene ruthenium(II) N-heterocyclic carbene complexes as organometallics interacting with thiol and selenol containing biomolecules.

    Science.gov (United States)

    Oehninger, Luciano; Stefanopoulou, Maria; Alborzinia, Hamed; Schur, Julia; Ludewig, Stephanie; Namikawa, Kazuhiko; Muñoz-Castro, Alvaro; Köster, Reinhard W; Baumann, Knut; Wölfl, Stefan; Sheldrick, William S; Ott, Ingo

    2013-02-07

    Metal complexes with N-heterocyclic carbene (NHC) ligands have been widely used in catalytic chemistry and are now increasingly considered for the development of new chemical tools and metal based drugs. Ruthenium complexes of the type (p-cymene)(NHC)RuCl(2) interacted with biologically relevant thiols and selenols, which resulted in the inhibition of enzymes such as thioredoxin reductase or cathepsin B. Pronounced antiproliferative effects could be obtained provided that an appropriate cellular uptake was achieved. Inhibition of tumor cell growth was accompanied by a perturbation of metabolic parameters such as cellular respiration.

  5. Mechanisms of cellular invasion by intracellular parasites.

    Science.gov (United States)

    Walker, Dawn M; Oghumu, Steve; Gupta, Gaurav; McGwire, Bradford S; Drew, Mark E; Satoskar, Abhay R

    2014-04-01

    Numerous disease-causing parasites must invade host cells in order to prosper. Collectively, such pathogens are responsible for a staggering amount of human sickness and death throughout the world. Leishmaniasis, Chagas disease, toxoplasmosis, and malaria are neglected diseases and therefore are linked to socio-economical and geographical factors, affecting well-over half the world's population. Such obligate intracellular parasites have co-evolved with humans to establish a complexity of specific molecular parasite-host cell interactions, forming the basis of the parasite's cellular tropism. They make use of such interactions to invade host cells as a means to migrate through various tissues, to evade the host immune system, and to undergo intracellular replication. These cellular migration and invasion events are absolutely essential for the completion of the lifecycles of these parasites and lead to their for disease pathogenesis. This review is an overview of the molecular mechanisms of protozoan parasite invasion of host cells and discussion of therapeutic strategies, which could be developed by targeting these invasion pathways. Specifically, we focus on four species of protozoan parasites Leishmania, Trypanosoma cruzi, Plasmodium, and Toxoplasma, which are responsible for significant morbidity and mortality.

  6. Hierarchical Cellular Structures in High-Capacity Cellular Communication Systems

    CERN Document Server

    Jain, R K; Agrawal, N K

    2011-01-01

    In the prevailing cellular environment, it is important to provide the resources for the fluctuating traffic demand exactly in the place and at the time where and when they are needed. In this paper, we explored the ability of hierarchical cellular structures with inter layer reuse to increase the capacity of mobile communication network by applying total frequency hopping (T-FH) and adaptive frequency allocation (AFA) as a strategy to reuse the macro and micro cell resources without frequency planning in indoor pico cells [11]. The practical aspects for designing macro- micro cellular overlays in the existing big urban areas are also explained [4]. Femto cells are inducted in macro / micro / pico cells hierarchical structure to achieve the required QoS cost effectively.

  7. Two HAP2-GCS1 homologs responsible for gamete interactions in the cellular slime mold with multiple mating types: Implication for common mechanisms of sexual reproduction shared by plants and protozoa and for male-female differentiation.

    Science.gov (United States)

    Okamoto, Marina; Yamada, Lixy; Fujisaki, Yukie; Bloomfield, Gareth; Yoshida, Kentaro; Kuwayama, Hidekazu; Sawada, Hitoshi; Mori, Toshiyuki; Urushihara, Hideko

    2016-07-01

    Fertilization is a central event in sexual reproduction, and understanding its molecular mechanisms has both basic and applicative biological importance. Recent studies have uncovered the molecules that mediate this process in a variety of organisms, making it intriguing to consider conservation and evolution of the mechanisms of sexual reproduction across phyla. The social amoeba Dictyostelium discoideum undergoes sexual maturation and forms gametes under dark and humid conditions. It exhibits three mating types, type-I, -II, and -III, for the heterothallic mating system. Based on proteome analyses of the gamete membranes, we detected expression of two homologs of the plant fertilization protein HAP2-GCS1. When their coding genes were disrupted in type-I and type-II strains, sexual potency was completely lost, whereas disruption in the type-III strain did not affect mating behavior, suggesting that the latter acts as female in complex organisms. Our results demonstrate the highly conserved function of HAP2-GCS1 in gamete interactions and suggest the presence of additional allo-recognition mechanisms in D. discoideum gametes.

  8. Sulfation patterns determine cellular internalization of heparin-like polysaccharides

    OpenAIRE

    Raman, Karthik; Mencio, Caitlin; Desai, Umesh R.; Kuberan, Balagurunathan

    2013-01-01

    Heparin is a highly sulfated polysaccharide which serves biologically relevant roles as an anticoagulant and anti-cancer agent. While it is well known that modification of heparin’s sulfation pattern can drastically influence its ability to bind growth factors and other extracellular molecules, very little is known about the cellular uptake of heparin and the role sulfation patterns serve in affecting its internalization. In this study, we chemically synthesized several fluorescently-labeled ...

  9. Clinically relevant characterization of lung adenocarcinoma subtypes based on cellular pathways: an international validation study.

    Directory of Open Access Journals (Sweden)

    Christopher M Bryant

    Full Text Available Lung adenocarcinoma (AD represents a predominant type of lung cancer demonstrating significant morphologic and molecular heterogeneity. We sought to understand this heterogeneity by utilizing gene expression analyses of 432 AD samples and examining associations between 27 known cancer-related pathways and the AD subtype, clinical characteristics and patient survival. Unsupervised clustering of AD and gene expression enrichment analysis reveals that cell proliferation is the most important pathway separating tumors into subgroups. Further, AD with increased cell proliferation demonstrate significantly poorer outcome and an increased solid AD subtype component. Additionally, we find that tumors with any solid component have decreased survival as compared to tumors without a solid component. These results lead to the potential to use a relatively simple pathological examination of a tumor in order to determine its aggressiveness and the patient's prognosis. Additional results suggest the ability to use a similar approach to determine a patient's sensitivity to targeted treatment. We then demonstrated the consistency of these findings using two independent AD cohorts from Asia (N = 87 and Europe (N = 89 using the identical analytic procedures.

  10. The relevance of cellular to clinical electrophysiology in classifying antiarrhythmic actions.

    Science.gov (United States)

    Vaughan Williams, E M

    1992-01-01

    The division of class I antiarrhythmic agents (sodium-channel blockers) into Ia, Ib, and Ic subgroups was based on clinical observations. Lidocaine, mexiletine, and tocainide (Ib) did not alter the QRS or H-V interval in sinus rhythm, but prolonged effective refractory period (ERP) in spite of some shortening of the J-T interval. Encainide, flecainide, and lorcainide (Ic) widened the QRS and prolonged H-V in sinus rhythm and at low concentration, but had little effect on the ERP or J-T. These clinical findings could be explained by fast onset/offset kinetics of Ib drugs, that when used in high concentrations, blocked most sodium channels during the action potential plateau; therefore, at the beginning of diastole, insufficient drug-free channels were available to support conduction, and the ERP was prolonged. Rapid dissociation of the drugs after repolarization insured that by the end of diastole most channels were again drug free, so that the QRS and H-V were normal. The Ic compounds were more potent, but of slow onset, so that a steady-state block of Na channels was not achieved until after many beats. Offset was also slow, so that a proportion of channels was persistently unavailable, Na current was reduced, and conduction slowed, causing widening of the QRS and lengthening of H-V. Because the remaining drug-free channels were normal, they recovered rapidly from inactivation, and the ERP was not prolonged. By clinical criteria, moricizine also must be classed as Ic, and its offset/onset kinetics are much slower than those of Ib drugs.(ABSTRACT TRUNCATED AT 250 WORDS)

  11. Discovery of a New Cellular Motion and Its Relevance to Breast Cancer and Involution

    Science.gov (United States)

    2014-02-01

    tissue- polarity; however, the fundamental biophysical processes whi h a single cell must undergo multiple rounds of mitosis to assemble into...several rounds of mitosis to assemble into a polarized and functional tissue are not well understood. Even less understood is what

  12. The Relevance of Coding Gene Polymorphysms of Cytokines and Cellular Receptors in Sepsis

    Directory of Open Access Journals (Sweden)

    Georgescu Anca Meda

    2017-02-01

    Full Text Available Sepsis is an injurious systemic host response to infection, which can often lead to septic shock and death. Recently, the immune-pathogenesis and genomics of sepsis have become a research topic focusing on the establishment of diagnostic and prognostic biomarkers. As yet, none have been identified as having the necessary specificity to be used independently of other factors in this respect. However the accumulation of current evidence regarding genetic variations, especially the single nucleotide polymorphisms (SNPs of cytokines and other innate immunity determinants, partially explains the susceptibility and individual differences of patients with regard to the evolution of sepsis. This article outlines the role of genetic variation of some serum proteins which have the potential to be used as biomarker values in evaluating sepsis susceptibility and the progression of the condition.

  13. Classifying cellular automata using grossone

    Science.gov (United States)

    D'Alotto, Louis

    2016-10-01

    This paper proposes an application of the Infinite Unit Axiom and grossone, introduced by Yaroslav Sergeyev (see [7] - [12]), to the development and classification of one and two-dimensional cellular automata. By the application of grossone, new and more precise nonarchimedean metrics on the space of definition for one and two-dimensional cellular automata are established. These new metrics allow us to do computations with infinitesimals. Hence configurations in the domain space of cellular automata can be infinitesimally close (but not equal). That is, they can agree at infinitely many places. Using the new metrics, open disks are defined and the number of points in each disk computed. The forward dynamics of a cellular automaton map are also studied by defined sets. It is also shown that using the Infinite Unit Axiom, the number of configurations that follow a given configuration, under the forward iterations of cellular automaton maps, can now be computed and hence a classification scheme developed based on this computation.

  14. Prognosis of Different Cellular Generations

    Directory of Open Access Journals (Sweden)

    Preetish Ranjan

    2013-04-01

    Full Text Available Technological advancement in mobile telephony from 1G to 3G, 4G and 5G has a very axiomatic fact that made an entire world a global village. The cellular system employs a different design approach and technology that most commercial radio and television system use. In the cellular system, the service area is divided into cells and a transmitter is designed to serve an individual cell. The system seeks to make efficient use of available channels by using low-power transmitters to allow frequency reuse at a smaller distance. Maximizing the number of times each channel can be reused in a given geographical area is the key to an efficient cellular system design. During the past three decades, the world has seen significant changes in telecommunications industry. There have been some remarkable aspects to the rapid growth in wireless communications, as seen by the large expansion in mobile systems. This paper focuses on “Past, Present & Future of Cellular Telephony” and some light has been thrown upon the technologies of the cellular systems, namely 1G, 2G, 2.5G, 3G and future generations like 4G and 5G systems as well.

  15. Pharmacokinetics interactions of monoclonal antibodies.

    Science.gov (United States)

    Ferri, Nicola; Bellosta, Stefano; Baldessin, Ludovico; Boccia, Donatella; Racagni, Giorgi; Corsini, Alberto

    2016-09-01

    The clearance of therapeutic monoclonal antibodies (mAbs) typically does not involve cytochrome P450 (CYP450)-mediated metabolism or interaction with cell membrane transporters, therefore the pharmacokinetics interactions of mAbs and small molecule drugs are limited. However, a drug may affect the clearance of mAbs through the modulation of immune response (e.g., methotrexate reduces the clearance of infliximab, adalimumab, and golimumab, possibly due to methotrexate's inhibitory effect on the formation of antibodies against the mAbs). In addition, mAbs that are cytokine modulators may modify the metabolism of drugs through their effects on P450 enzymes expression. For example, cytokine modulators such as tocilizumab (anti-IL-6 receptor antibody) may reverse the "inhibitory" effect of IL-6 on CYP substrates, resulting in a "normalization" of CYP activities. Finally, a drug may alter the clearance of mAbs by either increasing or reducing the levels of expression of targets of mAbs on the cell surface. For instance, statins and fibrates induce PCSK9 expression and therefore increase cellular uptake and clearance of alirocumab and evolocumab, anti-PCSK9 antibodies. In the present review, we will provide an overview on the pharmacokinetics properties of mAbs as related to the most relevant examples of mAbs-small molecule drug interaction.

  16. Biological Effects of Electromagnetic Fields on Cellular Growth

    Science.gov (United States)

    Eftekhari, Beheshte; Wilson, James; Masood, Samina

    2012-10-01

    The interaction of organisms with environmental magnetic fields at the cellular level is well documented, yet not fully understood. We review the existing experimental results to understand the physics behind the effects of ambient magnetic fields on the growth, metabolism, and proliferation of in vitro cell cultures. Emphasis is placed on identifying the underlying physical principles responsible for alterations to cell structure and behavior.

  17. Modeling diffusion of innovations with probabilistic cellular automata

    CERN Document Server

    Boccara, N; Boccara, Nino; Fuks, Henryk

    1997-01-01

    We present a family of one-dimensional cellular automata modeling the diffusion of an innovation in a population. Starting from simple deterministic rules, we construct models parameterized by the interaction range and exhibiting a second-order phase transition. We show that the number of individuals who eventually keep adopting the innovation strongly depends on connectivity between individuals.

  18. Cellular models for Parkinson's disease.

    Science.gov (United States)

    Falkenburger, Björn H; Saridaki, Theodora; Dinter, Elisabeth

    2016-10-01

    Developing new therapeutic strategies for Parkinson's disease requires cellular models. Current models reproduce the two most salient changes found in the brains of patients with Parkinson's disease: The degeneration of dopaminergic neurons and the existence of protein aggregates consisting mainly of α-synuclein. Cultured cells offer many advantages over studying Parkinson's disease directly in patients or in animal models. At the same time, the choice of a specific cellular model entails the requirement to focus on one aspect of the disease while ignoring others. This article is intended for researchers planning to use cellular models for their studies. It describes for commonly used cell types the aspects of Parkinson's disease they model along with technical advantages and disadvantages. It might also be helpful for researchers from other fields consulting literature on cellular models of Parkinson's disease. Important models for the study of dopaminergic neuron degeneration include Lund human mesencephalic cells and primary neurons, and a case is made for the use of non-dopaminergic cells to model pathogenesis of non-motor symptoms of Parkinson's disease. With regard to α-synuclein aggregates, this article describes strategies to induce and measure aggregates with a focus on fluorescent techniques. Cellular models reproduce the two most salient changes of Parkinson's disease, the degeneration of dopaminergic neurons and the existence of α-synuclein aggregates. This article is intended for researchers planning to use cellular models for their studies. It describes for commonly used cell types and treatments the aspects of Parkinson's disease they model along with technical advantages and disadvantages. Furthermore, this article describes strategies to induce and measure aggregates with a focus on fluorescent techniques. This article is part of a special issue on Parkinson disease.

  19. Cellular basis of Alzheimer's disease.

    Science.gov (United States)

    Bali, Jitin; Halima, Saoussen Ben; Felmy, Boas; Goodger, Zoe; Zurbriggen, Sebastian; Rajendran, Lawrence

    2010-12-01

    Alzheimer's disease (AD) is the most common form of neurodegenerative disease. A characteristic feature of the disease is the presence of amyloid-β (Aβ) which either in its soluble oligomeric form or in the plaque-associated form is causally linked to neurodegeneration. Aβ peptide is liberated from the membrane-spanning -amyloid precursor protein by sequential proteolytic processing employing β- and γ-secretases. All these proteins involved in the production of Aβ peptide are membrane associated and hence, membrane trafficking and cellular compartmentalization play important roles. In this review, we summarize the key cellular events that lead to the progression of AD.

  20. Pathologically Relevant Prelamin A Interactions with Transcription Factors.

    Science.gov (United States)

    Infante, Arantza; Rodríguez, Clara I

    2016-01-01

    LMNA-linked laminopathies are a group of rare human diseases caused by mutations in LMNA or by disrupted posttranslational processing of its largest encoded isoform, prelamin A. The accumulation of mutated or immature forms of farnesylated prelamin A, named progerin or prelamin A, respectively, dominantly disrupts nuclear lamina structure with toxic effects in cells. One hypothesis is that aberrant lamin filament networks disrupt or "trap" proteins such as transcription factors, thereby interfering with their normal activity. Since laminopathies mainly affect tissues of mesenchymal origin, we tested this hypothesis by generating an experimental model of laminopathy by inducing prelamin A accumulation in human mesenchymal stem cells (hMSCs). We provide detailed protocols for inducing and detecting prelamin A accumulation in hMSCs, and describe the bioinformatic analysis and in vitro assays of transcription factors potentially affected by prelamin A accumulation.

  1. Clinical relevance of sirolimus drug interactions in transplant patients.

    Science.gov (United States)

    Sádaba, B; Campanero, M A; Quetglas, E G; Azanza, J R

    2004-12-01

    Sirolimus, a new immunosuppressant drug; is metabolized by cytochrome P450 3A4 (CYP3A4) and is a substrate of the P-glycoprotein drug efflux pump. The CYP3A4/P-glycoprotein system is mainly localized in the liver and intestine. It is responsible for the severe first pass metabolism of sirolimus with a low bioavailability. Drugs like voriconazole, itraconazole, fluconazole, and erytrhomycin may decrease the metabolic activity of this enzymatic system. This report documents in five patients that coadministration of these antimicrobials with sirolimus increases the blood concentrations of the immunosuppressant. The dose-normalized trough blood concentration showed a mean increase of sevenfold with the coadministration of these drugs. It is essential to monitor the blood sirolimus concentrations and to adjust the sirolimus doses before and after coadministration of these drugs.

  2. The Relevance of Social Interactions on Housing Satisfaction

    Science.gov (United States)

    Vera-Toscano, Esperanza; Ateca-Amestoy, Victoria

    2008-01-01

    For most individuals, housing is the largest consumption and investment item of their lifetime and, as a result, housing satisfaction is an important component of their quality of life. The purpose of this paper then is to investigate the determinants of individual housing satisfaction as a particular domain of satisfaction with life as a whole,…

  3. Surface interactions with electromagnetic spectrum relevant to solar thermal propulsion

    Science.gov (United States)

    Bonometti, Joseph Alexander John

    1997-11-01

    Elements of solar thermal rocket propulsion systems were experimentally examined to quantify the most significant physical parameters related to concentrating and capturing solar energy. A detailed examination of the sun's electromagnetic flux impingement upon a solar concentrator, redirection to a secondary reflector or refractor optic and absorption in an opaque cavity surface are presented. Research performed includes the analysis and design of a unique high temperature solar laboratory at the University of Alabama in Huntsville, its construction and subsequent operation. The entire facility was a prerequisite to conducting this experimental research and is the result of an initial two-year research effort. Four primary elements were experimentally examined and their relationship to the solar heating profile analyzed to optimize it for use in a solar thermal upper stage. The first was the comparison of concentrator types to define the incident energy profile with the conclusion that their type or quality was insignificant to the thermal heating profile in an absorber cavity. Rigid, thin-film and Fresnel concentrators were experimentally assessed. The second element was the evaluation of the absorber geometry's length-to-diameter ratio of a cylindrical cavity and included the addition of a secondary optic. The secondary optic was recognized as a requirement in the solar thermal rocket and could either improve the flux distribution on the cavity wall using a refractor with extractor rod, or hinder it as in using a parabolic reflector. The third was direct measurement of absorber material properties at elevated temperatures. Reflectivity, absorptivity and emissivity were determined for rhenium at 1000 Kelvin. The reflectivity measurements included both diffuse and specular reflection components and sample coupons of rhenium and niobium were shown to decrease in reflectivity when heated to temperatures approaching 1200 degrees Kelvin. The methodology was unique in that solar energy was utilized to both heat the sample and produce a direct reflectance measurement at temperature while encompassing all applicable wavelengths. The final element was to explore an innovative surface tailoring concept to enhance the energy distribution within an absorber cavity. Cavity surface tailoring of a tungsten absorber was demonstrated to be a viable concept which can be employed in continuous thrust or pulse/storage engine concepts. Experimental heating profiles were analyzed and regression models developed to describe the cavity surface temperatures.

  4. Interactions between macro- and micro-circulation: are they relevant?

    Science.gov (United States)

    Rizzoni, Damiano; De Ciuceis, Carolina; Salvetti, Massimo; Paini, Anna; Rossini, Claudia; Agabiti-Rosei, Claudia; Muiesan, Maria Lorenza

    2015-06-01

    Macrovasculature, microvasculature, and the heart are the main determinants of the structure and function of the circulatory system. Due to viscoelastic properties of large arteries, the pulsatile pressure and flow that result from intermittent ventricular ejection are smoothed out, so that microvasculature mediates steadily the delivery of nutrients and oxygen to tissues. The disruption of this function, which occurs when microvascular structure develops, mainly in response to hypertension, leads to end-organ damage. Microvascular structure is not only the site of vascular resistance but probably also the origin of most of the wave reflections generating increased central systolic blood pressure in the elderly. Many data of the literature suggest that hypertension-related damage to the micro and macrovascular system may be corrected by pharmacological agents. Among them, β-blocking agents and diuretics have a negligible effect on microvascular structure, while renin-angiotensin system antagonists and calcium entry blockers have favorable actions, improving large artery mechanics and possibly reducing central wave reflections. Central pulse pressure, indicative of changes in large conduit arteries is an independent determinant of vascular remodelling in small resistance arteries and might represent a main target of antihypertensive treatment.

  5. Volcanic ash melting under conditions relevant to ash turbine interactions.

    Science.gov (United States)

    Song, Wenjia; Lavallée, Yan; Hess, Kai-Uwe; Kueppers, Ulrich; Cimarelli, Corrado; Dingwell, Donald B

    2016-03-02

    The ingestion of volcanic ash by jet engines is widely recognized as a potentially fatal hazard for aircraft operation. The high temperatures (1,200-2,000 °C) typical of jet engines exacerbate the impact of ash by provoking its melting and sticking to turbine parts. Estimation of this potential hazard is complicated by the fact that chemical composition, which affects the temperature at which volcanic ash becomes liquid, can vary widely amongst volcanoes. Here, based on experiments, we parameterize ash behaviour and develop a model to predict melting and sticking conditions for its global compositional range. The results of our experiments confirm that the common use of sand or dust proxy is wholly inadequate for the prediction of the behaviour of volcanic ash, leading to overestimates of sticking temperature and thus severe underestimates of the thermal hazard. Our model can be used to assess the deposition probability of volcanic ash in jet engines.

  6. Regularization in Matrix Relevance Learning

    NARCIS (Netherlands)

    Schneider, Petra; Bunte, Kerstin; Stiekema, Han; Hammer, Barbara; Villmann, Thomas; Biehl, Michael

    2010-01-01

    A In this paper, we present a regularization technique to extend recently proposed matrix learning schemes in learning vector quantization (LVQ). These learning algorithms extend the concept of adaptive distance measures in LVQ to the use of relevance matrices. In general, metric learning can displa

  7. On Cellular MIMO Channel Capacity

    Science.gov (United States)

    Adachi, Koichi; Adachi, Fumiyuki; Nakagawa, Masao

    To increase the transmission rate without bandwidth expansion, the multiple-input multiple-output (MIMO) technique has recently been attracting much attention. The MIMO channel capacity in a cellular system is affected by the interference from neighboring co-channel cells. In this paper, we introduce the cellular channel capacity and evaluate its outage capacity, taking into account the frequency-reuse factor, path loss exponent, standard deviation of shadowing loss, and transmission power of a base station (BS). Furthermore, we compare the cellular MIMO downlink channel capacity with those of other multi-antenna transmission techniques such as single-input multiple-output (SIMO) and space-time block coded multiple-input single-output (STBC-MISO). We show that the optimum frequency-reuse factor F that maximizes 10%-outage capacity is 3 and both 50%- and 90%-outage capacities is 1 irrespective of the type of multi-antenna transmission technique, where q%-outage capacity is defined as the channel capacity that gives an outage probability of q%. We also show that the cellular MIMO channel capacity is always higher than those of SIMO and STBC-MISO.

  8. Cellular uptake of metallated cobalamins

    DEFF Research Database (Denmark)

    Tran, MQT; Stürup, Stefan; Lambert, Ian H.;

    2016-01-01

    Cellular uptake of vitamin B12-cisplatin conjugates was estimated via detection of their metal constituents (Co, Pt, and Re) by inductively coupled plasma mass spectrometry (ICP-MS). Vitamin B12 (cyano-cob(iii)alamin) and aquo-cob(iii)alamin [Cbl-OH2](+), which differ in the β-axial ligands (CN(-...

  9. EXTRACELLULAR VESICLES: CLASSIFICATION, FUNCTIONS AND CLINICAL RELEVANCE

    Directory of Open Access Journals (Sweden)

    A. V. Oberemko

    2014-12-01

    Full Text Available This review presents a generalized definition of vesicles as bilayer extracellular organelles of all celular forms of life: not only eu-, but also prokaryotic. The structure and composition of extracellular vesicles, history of research, nomenclature, their impact on life processes in health and disease are discussed. Moreover, vesicles may be useful as clinical instruments for biomarkers, and they are promising as biotechnological drug. However, many questions in this area are still unresolved and need to be addressed in the future. The most interesting from the point of view of practical health care represents a direction to study the effect of exosomes and microvesicles in the development and progression of a particular disease, the possibility of adjusting the pathological process by means of extracellular vesicles of a particular type, acting as an active ingredient. Relevant is the further elucidation of the role and importance of exosomes to the surrounding cells, tissues and organs at the molecular level, the prospects for the use of non-cellular vesicles as biomarkers of disease.

  10. Relevance of extracellular DNA in rhizosphere

    Science.gov (United States)

    Pietramellara, Giacomo; Ascher, Judith; Baraniya, Divyashri; Arfaioli, Paola; Ceccherini, Maria Teresa; Hawes, Martha

    2013-04-01

    One of the most promising areas for future development is the manipulation of the rhizosphere to produce sustainable and efficient agriculture production systems. Using Omics approaches, to define the distinctive features of eDNA systems and structures, will facilitate progress in rhizo-enforcement and biocontrol studies. The relevance of these studies results clear when we consider the plethora of ecological functions in which eDNA is involved. This fraction can be actively extruded by living cells or discharged during cellular lysis and may exert a key role in the stability and variability of the soil bacterial genome, resulting also a source of nitrogen and phosphorus for plants due to the root's capacity to directly uptake short DNA fragments. The adhesive properties of the DNA molecule confer to eDNA the capacity to inhibit or kill pathogenic bacteria by cation limitation induction, and to facilitate formation of biofilm and extracellular traps (ETs), that may protect microorganisms inhabiting biofilm and plant roots against pathogens and allelopathic substances. The ETs are actively extruded by root border cells when they are dispersed in the rhizosphere, conferring to plants the capacity to extend an endogenous pathogen defence system outside the organism. Moreover, eDNA could be involved in rhizoremediation in heavy metal polluted soil acting as a bioflotation reagent.

  11. Food-drug interactions

    DEFF Research Database (Denmark)

    Schmidt, Lars E; Dalhoff, Kim

    2002-01-01

    Interactions between food and drugs may inadvertently reduce or increase the drug effect. The majority of clinically relevant food-drug interactions are caused by food-induced changes in the bioavailability of the drug. Since the bioavailability and clinical effect of most drugs are correlated......, the bioavailability is an important pharmacokinetic effect parameter. However, in order to evaluate the clinical relevance of a food-drug interaction, the impact of food intake on the clinical effect of the drug has to be quantified as well. As a result of quality review in healthcare systems, healthcare providers...... are increasingly required to develop methods for identifying and preventing adverse food-drug interactions. In this review of original literature, we have tried to provide both pharmacokinetic and clinical effect parameters of clinically relevant food-drug interactions. The most important interactions are those...

  12. Filovirus tropism: Cellular molecules for viral entry

    Directory of Open Access Journals (Sweden)

    Ayato eTakada

    2012-02-01

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

  13. Cellular receptors for plasminogen activators recent advances.

    Science.gov (United States)

    Ellis, V

    1997-10-01

    The generation of the broad-specificity protease plasmin by the plasminogen activators urokinase-type plasminogen activator (uPA) and tissue-type plasminogen activator (tPA) is implicated in a variety of pathophysiological processes, including vascular fibrin dissolution, extracellular matrix degradation and remodeling, and cell migration. A mechanism for the regulation of plasmin generation is through binding of the plasminogen activators to specific cellular receptors: uPA to the glycolipid-anchored membrane protein urokinase-type plasminogen activator receptor (uPAR) and tPA to a number of putative binding sites. The uPA-uPAR complex can interact with a variety of ligands, including plasminogen, vitronectin, and integrins, indicating a multifunctional role for uPAR, regulating not only efficient and spatially restricted plasmin generation but also having the potential to modulate cell adhesion and signal transduction. The cellular binding of tPA, although less well characterized, also has the capacity to regulate plasmin generation and to play a significant role in vessel-wall biology. (Trends Cardiovasc Med 1997;7:227-234). © 1997, Elsevier Science Inc.

  14. Cellular automaton rules conserving the number of active sites

    CERN Document Server

    Boccara, N; Boccara, Nino; Fuks, Henryk

    1997-01-01

    This paper shows how to determine all the unidimensional two-state cellular automaton rules of a given number of inputs which conserve the number of active sites. These rules have to satisfy a necessary and sufficient condition. If the active sites are viewed as cells occupied by identical particles, these cellular automaton rules represent evolution operators of systems of identical interacting particles whose total number is conserved. Some of these rules, which allow motion in both directions, mimic ensembles of one-dimensional pseudo-random walkers. The corresponding stochastic processes are, however, not Gaussian.

  15. A cellular automaton evacuation model based on mobile robot's behaviors

    Institute of Scientific and Technical Information of China (English)

    WENG WenGuo; YUAN HongYong; FAN WeiCheng

    2007-01-01

    The research of evacuation in some emergencies, e.g. fire, is of great benefit to reducing the injuries of persons. In this paper, a cellular automaton evacuation model based on mobile robot's behaviors is presented. Each person is treated as an intelligent mobile robot, and motor schemas, including move-to-goal, avoid-obstacle, swirl-obstacle and nervous-motion, drive persons to interact with their environment. The motor schemas are combined with cellular automaton theory, and an evacuation model is built. Evacuation simulation of persons with different move velocities shows that the presented model can predict accurately the evacuation phenomena in some emergencies.

  16. Cellular Automata Models for Diffusion of Innovations

    CERN Document Server

    Fuks, H; Fuks, Henryk; Boccara, Nino

    1997-01-01

    We propose a probabilistic cellular automata model for the spread of innovations, rumors, news, etc. in a social system. The local rule used in the model is outertotalistic, and the range of interaction can vary. When the range R of the rule increases, the takeover time for innovation increases and converges toward its mean-field value, which is almost inversely proportional to R when R is large. Exact solutions for R=1 and $R=\\infty$ (mean-field) are presented, as well as simulation results for other values of R. The average local density is found to converge to a certain stationary value, which allows us to obtain a semi-phenomenological solution valid in the vicinity of the fixed point n=1 (for large t).

  17. The LAILAPS search engine: relevance ranking in life science databases.

    Science.gov (United States)

    Lange, Matthias; Spies, Karl; Bargsten, Joachim; Haberhauer, Gregor; Klapperstück, Matthias; Leps, Michael; Weinel, Christian; Wünschiers, Röbbe; Weissbach, Mandy; Stein, Jens; Scholz, Uwe

    2010-01-15

    Search engines and retrieval systems are popular tools at a life science desktop. The manual inspection of hundreds of database entries, that reflect a life science concept or fact, is a time intensive daily work. Hereby, not the number of query results matters, but the relevance does. In this paper, we present the LAILAPS search engine for life science databases. The concept is to combine a novel feature model for relevance ranking, a machine learning approach to model user relevance profiles, ranking improvement by user feedback tracking and an intuitive and slim web user interface, that estimates relevance rank by tracking user interactions. Queries are formulated as simple keyword lists and will be expanded by synonyms. Supporting a flexible text index and a simple data import format, LAILAPS can easily be used both as search engine for comprehensive integrated life science databases and for small in-house project databases. With a set of features, extracted from each database hit in combination with user relevance preferences, a neural network predicts user specific relevance scores. Using expert knowledge as training data for a predefined neural network or using users own relevance training sets, a reliable relevance ranking of database hits has been implemented. In this paper, we present the LAILAPS system, the concepts, benchmarks and use cases. LAILAPS is public available for SWISSPROT data at http://lailaps.ipk-gatersleben.de.

  18. Statistical physical models of cellular motility

    Science.gov (United States)

    Banigan, Edward J.

    Cellular motility is required for a wide range of biological behaviors and functions, and the topic poses a number of interesting physical questions. In this work, we construct and analyze models of various aspects of cellular motility using tools and ideas from statistical physics. We begin with a Brownian dynamics model for actin-polymerization-driven motility, which is responsible for cell crawling and "rocketing" motility of pathogens. Within this model, we explore the robustness of self-diffusiophoresis, which is a general mechanism of motility. Using this mechanism, an object such as a cell catalyzes a reaction that generates a steady-state concentration gradient that propels the object in a particular direction. We then apply these ideas to a model for depolymerization-driven motility during bacterial chromosome segregation. We find that depolymerization and protein-protein binding interactions alone are sufficient to robustly pull a chromosome, even against large loads. Next, we investigate how forces and kinetics interact during eukaryotic mitosis with a many-microtubule model. Microtubules exert forces on chromosomes, but since individual microtubules grow and shrink in a force-dependent way, these forces lead to bistable collective microtubule dynamics, which provides a mechanism for chromosome oscillations and microtubule-based tension sensing. Finally, we explore kinematic aspects of cell motility in the context of the immune system. We develop quantitative methods for analyzing cell migration statistics collected during imaging experiments. We find that during chronic infection in the brain, T cells run and pause stochastically, following the statistics of a generalized Levy walk. These statistics may contribute to immune function by mimicking an evolutionarily conserved efficient search strategy. Additionally, we find that naive T cells migrating in lymph nodes also obey non-Gaussian statistics. Altogether, our work demonstrates how physical

  19. Brief Review on the Relevance Theory

    Institute of Scientific and Technical Information of China (English)

    龚腾龙; 阿勒腾

    2015-01-01

    Relevance theory has had an impact on the study in various disciplines including linguistics,literature and so on. This paper gives a brief review of the relevance theory and two principles of relevance.

  20. Reversibly assembled cellular composite materials.

    Science.gov (United States)

    Cheung, Kenneth C; Gershenfeld, Neil

    2013-09-13

    We introduce composite materials made by reversibly assembling a three-dimensional lattice of mass-produced carbon fiber-reinforced polymer composite parts with integrated mechanical interlocking connections. The resulting cellular composite materials can respond as an elastic solid with an extremely large measured modulus for an ultralight material (12.3 megapascals at a density of 7.2 milligrams per cubic centimeter). These materials offer a hierarchical decomposition in modeling, with bulk properties that can be predicted from component measurements and deformation modes that can be determined by the placement of part types. Because site locations are locally constrained, structures can be produced in a relative assembly process that merges desirable features of fiber composites, cellular materials, and additive manufacturing.

  1. Socially Relevant Knowledge Based Telemedicine

    Science.gov (United States)

    2011-10-01

    managing patient’s airway and interpreting electrocardiograms. Life threatening situations as cardiac arrests are announced as a code blue...while performing time-critical procedure. The lack of verbal interaction, physical cues (like facial expressions, eye movement, movement etc.), and...Nov 6-10, 2004, Chicago, Illinois, USA. [5] Ducheneaut, N., Moore, R. J., The Social Side of Gaming: A Study of Interaction Patterns in a Massively

  2. Cellular interactions on hierarchical poly(ε-caprolactone) nanowire micropatterns.

    Science.gov (United States)

    Du, Ke; Gan, Zhihua

    2012-09-26

    A double template method to fabricate poly(ε-caprolactone) (PCL) hierarchical patterned nanowires with highly ordered nano- and microscaled topography was developed in this study. The topography of PCL film with a patterned nanowire surface can be easily and well controlled by changing the template and melting time of PCL film on the templates. The surface morphology, water contact angle, protein adsorption, and cell growth behavior on the PCL films with different surface structures were well studied. The results revealed that the PCL nanowire arrays and the hierarchical patterned nanowires showed higher capability of protein adsorption and better cell growth than the PCL film with smooth surface. Typically, the PCL surface with hierarchical nanowire patterns was most favorable for cell attachment and proliferation. The present study was innovative at fabrication of polymer substrates with hierarchical architecture of nanowires inside microscaled islands to gain insight into the cell response to this unique topography and to develop a new method of constructing the bionic surface for tissue engineering applications.

  3. Plasmin-Cellular Interactions in Breast Cancer Invasion and Metastasis.

    Science.gov (United States)

    1997-10-01

    Heymann Nephritis autoantigen (gp330) binds plas- minogen (Kanalas and Makker , 1991). The present study was undertaken to identify major plas- minogen...Nat. Acad. Sei. USA 76,353-357. Kanalas, J. J. and Makker , S. P. (1991). Identification of the rat Heymann nephritis autoantigen (GP330) as a

  4. Glycosylation regulates prestin cellular activity.

    Science.gov (United States)

    Rajagopalan, Lavanya; Organ-Darling, Louise E; Liu, Haiying; Davidson, Amy L; Raphael, Robert M; Brownell, William E; Pereira, Fred A

    2010-03-01

    Glycosylation is a common post-translational modification of proteins and is implicated in a variety of cellular functions including protein folding, degradation, sorting and trafficking, and membrane protein recycling. The membrane protein prestin is an essential component of the membrane-based motor driving electromotility changes (electromotility) in the outer hair cell (OHC), a central process in auditory transduction. Prestin was earlier identified to possess two N-glycosylation sites (N163, N166) that, when mutated, marginally affect prestin nonlinear capacitance (NLC) function in cultured cells. Here, we show that the double mutant prestin(NN163/166AA) is not glycosylated and shows the expected NLC properties in the untreated and cholesterol-depleted HEK 293 cell model. In addition, unlike WT prestin that readily forms oligomers, prestin(NN163/166AA) is enriched as monomers and more mobile in the plasma membrane, suggesting that oligomerization of prestin is dependent on glycosylation but is not essential for the generation of NLC in HEK 293 cells. However, in the presence of increased membrane cholesterol, unlike the hyperpolarizing shift in NLC seen with WT prestin, cells expressing prestin(NN163/166AA) exhibit a linear capacitance function. In an attempt to explain this finding, we discovered that both WT prestin and prestin(NN163/166AA) participate in cholesterol-dependent cellular trafficking. In contrast to WT prestin, prestin(NN163/166AA) shows a significant cholesterol-dependent decrease in cell-surface expression, which may explain the loss of NLC function. Based on our observations, we conclude that glycosylation regulates self-association and cellular trafficking of prestin(NN163/166AA). These observations are the first to implicate a regulatory role for cellular trafficking and sorting in prestin function. We speculate that the cholesterol regulation of prestin occurs through localization to and internalization from membrane microdomains by

  5. Stochastic Nature in Cellular Processes

    Institute of Scientific and Technical Information of China (English)

    刘波; 刘圣君; 王祺; 晏世伟; 耿轶钊; SAKATA Fumihiko; GAO Xing-Fa

    2011-01-01

    The importance of stochasticity in cellular processes is increasingly recognized in both theoretical and experimental studies. General features of stochasticity in gene regulation and expression are briefly reviewed in this article, which include the main experimental phenomena, classification, quantization and regulation of noises. The correlation and transmission of noise in cascade networks are analyzed further and the stochastic simulation methods that can capture effects of intrinsic and extrinsic noise are described.

  6. Cellular fiber–reinforced concrete

    OpenAIRE

    Isachenko S.; Kodzoev M.

    2016-01-01

    Methods disperse reinforcement of concrete matrix using polypropylene, glass, basalt and metal fibers allows to make the construction of complex configuration, solve the problem of frost products. Dispersed reinforcement reduces the overall weight of the structures. The fiber replaces the secondary reinforcement, reducing the volume of use of structural steel reinforcement. Cellular Fiber concretes are characterized by high-performance properties, especially increased bending strength and...

  7. Identification of Nonstationary Cellular Automata

    Institute of Scientific and Technical Information of China (English)

    AndrewI.Adamatzky

    1992-01-01

    The principal feature of nonstationary cellular automata(NCA) is that a local transitiol rule of each cell is changed at each time step depending on neighborhood configuration at previous time step.The identification problem for NCA is extraction of local transition rules and the establishment of mechanism for changing these rules using sequence of NCA configurations.We present serial and parallel algorithms for identification of NCA.

  8. The insect cellular immune response

    Institute of Scientific and Technical Information of China (English)

    Michael R. Strand

    2008-01-01

    The innate immune system of insects is divided into humoral defenses that include the production of soluble effector molecules and cellular defenses like phagocytosis and encapsulation that are mediated by hemocytes. This review summarizes current understanding of the cellular immune response. Insects produce several terminally differentiated types of hemocytes that are distinguished by morphology, molecular and antigenic markers, and function. The differentiated hemocytes that circulate in larval or nymphal stage insects arise from two sources: progenitor cells produced during embryogenesis and mesodermally derived hematopoietic organs. Regulation of hematopoiesis and hemocyte differentiation also involves several different signaling pathways. Phagocytosis and encapsulation require that hemocytes first recognize a given target as foreign followed by activation of downstream signaling and effector responses. A number of humoral and cellular receptors have been identified that recognize different microbes and multicellular parasites. In turn, activation of these receptors stimulates a number of signaling pathways that regulate different hemocyte functions. Recent studies also identify hemocytes as important sources of a number of humoral effector molecules required for killing different foreign invaders.

  9. Progress of cellular dedifferentiation research

    Institute of Scientific and Technical Information of China (English)

    LIU Hu-xian; HU Da-hai; JIA Chi-yu; FU Xiao-bing

    2006-01-01

    Differentiation, the stepwise specialization of cells, and transdifferentiation, the apparent switching of one cell type into another, capture much of the stem cell spotlight. But dedifferentiation, the developmental reversal of a cell before it reinvents itself, is an important process too. In multicellular organisms, cellular dedifferentiation is the major process underlying totipotency, regeneration and formation of new stem cell lineages. In humans,dedifferentiation is often associated with carcinogenesis.The study of cellular dedifferentiation in animals,particularly early events related to cell fate-switch and determination, is limited by the lack of a suitable,convenient experimental system. The classic example of dedifferentiation is limb and tail regeneration in urodele amphibians, such as salamanders. Recently, several investigators have shown that certain mammalian cell types can be induced to dedifferentiate to progenitor cells when stimulated with the appropriate signals or materials. These discoveries open the possibility that researchers might enhance the endogenous regenerative capacity of mammals by inducing cellular dedifferentiation in vivo.

  10. Acute, regional inflammatory response after traumatic brain injury: Implications for cellular therapy

    OpenAIRE

    Harting, Matthew T.; jimenez, fernando; Adams, Sasha D.; Mercer, David W.; Cox, Charles S.

    2008-01-01

    While cellular therapy has shown promise in the management of traumatic brain injury (TBI), microenvironment interactions between the intracerebral milieu and therapeutic stem cells are poorly understood. We sought to characterize the acute, regional inflammatory response after TBI.

  11. Inferring Biologically Relevant Models: Nested Canalyzing Functions

    CERN Document Server

    Hinkelmann, Franziska

    2010-01-01

    Inferring dynamic biochemical networks is one of the main challenges in systems biology. Given experimental data, the objective is to identify the rules of interaction among the different entities of the network. However, the number of possible models fitting the available data is huge and identifying a biologically relevant model is of great interest. Nested canalyzing functions, where variables in a given order dominate the function, have recently been proposed as a framework for modeling gene regulatory networks. Previously we described this class of functions as an algebraic toric variety. In this paper, we present an algorithm that identifies all nested canalyzing models that fit the given data. We demonstrate our methods using a well-known Boolean model of the cell cycle in budding yeast.

  12. Cellular identity at the single-cell level.

    Science.gov (United States)

    Coskun, Ahmet F; Eser, Umut; Islam, Saiful

    2016-10-20

    A single cell creates surprising heterogeneity in a multicellular organism. While every organismal cell shares almost an identical genome, molecular interactions in cells alter the use of DNA sequences to modulate the gene of interest for specialization of cellular functions. Each cell gains a unique identity through molecular coding across the DNA, RNA, and protein conversions. On the other hand, loss of cellular identity leads to critical diseases such as cancer. Most cell identity dissection studies are based on bulk molecular assays that mask differences in individual cells. To probe cell-to-cell variability in a population, we discuss single cell approaches to decode the genetic, epigenetic, transcriptional, and translational mechanisms for cell identity formation. In combination with molecular instructions, the physical principles behind cell identity determination are examined. Deciphering and reprogramming cellular types impact biology and medicine.

  13. 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

  14. Mammalian prions and their wider relevance in neurodegenerative diseases.

    Science.gov (United States)

    Collinge, John

    2016-11-10

    Prions are notorious protein-only infectious agents that cause invariably fatal brain diseases following silent incubation periods that can span a lifetime. These diseases can arise spontaneously, through infection or be inherited. Remarkably, prions are composed of self-propagating assemblies of a misfolded cellular protein that encode information, generate neurotoxicity and evolve and adapt in vivo. Although parallels have been drawn with Alzheimer's disease and other neurodegenerative conditions involving the deposition of assemblies of misfolded proteins in the brain, insights are now being provided into the usefulness and limitations of prion analogies and their aetiological and therapeutic relevance.

  15. The role of actin networks in cellular mechanosensing

    Science.gov (United States)

    Azatov, Mikheil

    Physical processes play an important role in many biological phenomena, such as wound healing, organ development, and tumor metastasis. During these processes, cells constantly interact with and adapt to their environment by exerting forces to mechanically probe the features of their surroundings and generating appropriate biochemical responses. The mechanisms underlying how cells sense the physical properties of their environment are not well understood. In this thesis, I present my studies to investigate cellular responses to the stiffness and topography of the environment. In order to sense the physical properties of their environment, cells dynamically reorganize the structure of their actin cytoskeleton, a dynamic network of biopolymers, altering the shape and spatial distribution of protein assemblies. Several observations suggest that proteins that crosslink actin filaments may play an important role in cellular mechanosensitivity. Palladin is an actin-crosslinking protein that is found in the lamellar actin network, stress fibers and focal adhesions, cellular structures that are critical for mechanosensing of the physical environment. By virtue of its close interactions with these structures in the cell, palladin may play an important role in cell mechanics. However, the role of actin crosslinkers in general, and palladin in particular, in cellular force generation and mechanosensing is not well known. I have investigated the role of palladin in regulating the plasticity of the actin cytoskeleton and cellular force generation in response to alterations in substrate stiffness. I have shown that the expression levels of palladin modulate the forces exerted by cells and their ability to sense substrate stiffness. Perturbation experiments also suggest that palladin levels in cells altered myosin motor activity. These results suggest that the actin crosslinkers, such as palladin, and myosin motors coordinate for optimal cell function and to prevent aberrant

  16. Relevance as Process: Judgements in the Context of Scholarly Research

    Science.gov (United States)

    Anderson, Theresa Dirndorfer

    2005-01-01

    Introduction: This paper discusses how exploring the research process in-depth and over time contributes to a fuller understanding of interactions with various representations of information. Method. A longitudinal ethnographic study explored decisions made by two informants involved in scholarly research. Relevance assessment and information…

  17. Myoblast fusion: Experimental systems and cellular mechanisms.

    Science.gov (United States)

    Schejter, Eyal D

    2016-12-01

    Fusion of myoblasts gives rise to the large, multi-nucleated muscle fibers that power and support organism motion and form. The mechanisms underlying this prominent form of cell-cell fusion have been investigated by a variety of experimental approaches, in several model systems. The purpose of this review is to describe and discuss recent progress in the field, as well as point out issues currently unresolved and worthy of further investigation. Following a description of several new experimental settings employed in the study of myoblast fusion, a series of topics relevant to the current understanding of the process are presented. These pertain to elements of three major cellular machineries- cell-adhesion, the actin-based cytoskeleton and membrane-associated elements- all of which play key roles in mediating myoblast fusion. Among the issues raised are the diversity of functions ascribed to different adhesion proteins (e.g. external cell apposition and internal recruitment of cytoskeleton regulators); functional significance of fusion-associated actin structures; and discussion of alternative mechanisms employing single or multiple fusion pore formation as the basis for muscle cell fusion.

  18. Situating relevance: exploring individual relevance assessments in context

    Directory of Open Access Journals (Sweden)

    Theresa Dirndorfer Anderson

    2001-01-01

    Full Text Available This paper discusses some of the challenges encountered whilst researching and writing a thesis that explores individual understandings of relevance and topic. It is based upon a discussion paper and presentation prepared as part of the Doctoral Workshop held during the ISIC 2000 Conference in Borås, Sweden. The focus of this paper is the doing of qualitative research. To provide a framework for this discussion, the key assumptions that have shaped the author's thesis are presented in the first section of this paper. The paper then focuses on some of the dilemmas of qualitative research encountered during the research and writing of this thesis, giving particular attention to the notion of context and the writing of qualitative research. Forthcoming results from the thesis are mentioned in the closing section. A Thesis Summary is also provided at the end of this paper.

  19. Numerical simulation of Mach reflection of cellular detonations

    Science.gov (United States)

    Li, J.; Lee, J. H. S.

    2016-09-01

    The Mach reflection of cellular detonation waves on a wedge is investigated numerically in an attempt to elucidate the effect of cellular instabilities on Mach reflection, the dependence of self-similarity on the thickness of a detonation wave, and the initial development of the Mach stem near the wedge apex. A two-step chain-branching reaction model is used to give a thermally neutral induction zone followed by a chemical reaction zone for the detonation wave. A sufficiently large distance of travel of the Mach stem is computed to observe the asymptotic behavior in the far field. Depending on the scale at which the Mach reflection process occurs, it is found that the Mach reflection of a cellular detonation behaves essentially in the same way as a planar ZND detonation wave. The cellular instabilities, however, cause the triple-point trajectory to fluctuate. The fluctuations are due to interactions of the triple point of the Mach stem with the transverse waves of cellular instabilities. In the vicinity of the wedge apex, the Mach reflection is found to be self-similar and corresponds to that of a shock wave of the same strength, since the Mach stem is highly overdriven initially. In the far field, the triple-point trajectory approaches a straight line, indicating that the Mach reflection becomes self-similar asymptotically. The distance of the approach to self-similarity is found to decrease rapidly with decreasing thickness of the detonation front.

  20. Arrayed cellular environments for stem cells and regenerative medicine.

    Science.gov (United States)

    Titmarsh, Drew M; Chen, Huaying; Wolvetang, Ernst J; Cooper-White, Justin J

    2013-02-01

    The behavior and composition of both multipotent and pluripotent stem cell populations are exquisitely controlled by a complex, spatiotemporally variable interplay of physico-chemical, extracellular matrix, cell-cell interaction, and soluble factor cues that collectively define the stem cell niche. The push for stem cell-based regenerative medicine models and therapies has fuelled demands for increasingly accurate cellular environmental control and enhanced experimental throughput, driving an evolution of cell culture platforms away from conventional culture formats toward integrated systems. Arrayed cellular environments typically provide a set of discrete experimental elements with variation of one or several classes of stimuli across elements of the array. These are based on high-content/high-throughput detection, small sample volumes, and multiplexing of environments to increase experimental parameter space, and can be used to address a range of biological processes at the cell population, single-cell, or subcellular level. Arrayed cellular environments have the capability to provide an unprecedented understanding of the molecular and cellular events that underlie expansion and specification of stem cell and therapeutic cell populations, and thus generate successful regenerative medicine outcomes. This review focuses on recent key developments of arrayed cellular environments and their contribution and potential in stem cells and regenerative medicine.

  1. A sub-cellular viscoelastic model for cell population mechanics.

    Directory of Open Access Journals (Sweden)

    Yousef Jamali

    Full Text Available Understanding the biomechanical properties and the effect of biomechanical force on epithelial cells is key to understanding how epithelial cells form uniquely shaped structures in two or three-dimensional space. Nevertheless, with the limitations and challenges posed by biological experiments at this scale, it becomes advantageous to use mathematical and 'in silico' (computational models as an alternate solution. This paper introduces a single-cell-based model representing the cross section of a typical tissue. Each cell in this model is an individual unit containing several sub-cellular elements, such as the elastic plasma membrane, enclosed viscoelastic elements that play the role of cytoskeleton, and the viscoelastic elements of the cell nucleus. The cell membrane is divided into segments where each segment (or point incorporates the cell's interaction and communication with other cells and its environment. The model is capable of simulating how cells cooperate and contribute to the overall structure and function of a particular tissue; it mimics many aspects of cellular behavior such as cell growth, division, apoptosis and polarization. The model allows for investigation of the biomechanical properties of cells, cell-cell interactions, effect of environment on cellular clusters, and how individual cells work together and contribute to the structure and function of a particular tissue. To evaluate the current approach in modeling different topologies of growing tissues in distinct biochemical conditions of the surrounding media, we model several key cellular phenomena, namely monolayer cell culture, effects of adhesion intensity, growth of epithelial cell through interaction with extra-cellular matrix (ECM, effects of a gap in the ECM, tensegrity and tissue morphogenesis and formation of hollow epithelial acini. The proposed computational model enables one to isolate the effects of biomechanical properties of individual cells and the

  2. Multi-cellular logistics of collective cell migration.

    Directory of Open Access Journals (Sweden)

    Masataka Yamao

    Full Text Available During development, the formation of biological networks (such as organs and neuronal networks is controlled by multicellular transportation phenomena based on cell migration. In multi-cellular systems, cellular locomotion is restricted by physical interactions with other cells in a crowded space, similar to passengers pushing others out of their way on a packed train. The motion of individual cells is intrinsically stochastic and may be viewed as a type of random walk. However, this walk takes place in a noisy environment because the cell interacts with its randomly moving neighbors. Despite this randomness and complexity, development is highly orchestrated and precisely regulated, following genetic (and even epigenetic blueprints. Although individual cell migration has long been studied, the manner in which stochasticity affects multi-cellular transportation within the precisely controlled process of development remains largely unknown. To explore the general principles underlying multicellular migration, we focus on the migration of neural crest cells, which migrate collectively and form streams. We introduce a mechanical model of multi-cellular migration. Simulations based on the model show that the migration mode depends on the relative strengths of the noise from migratory and non-migratory cells. Strong noise from migratory cells and weak noise from surrounding cells causes "collective migration," whereas strong noise from non-migratory cells causes "dispersive migration." Moreover, our theoretical analyses reveal that migratory cells attract each other over long distances, even without direct mechanical contacts. This effective interaction depends on the stochasticity of the migratory and non-migratory cells. On the basis of these findings, we propose that stochastic behavior at the single-cell level works effectively and precisely to achieve collective migration in multi-cellular systems.

  3. Cellular effector mechanisms against Plasmodium liver stages.

    Science.gov (United States)

    Frevert, Ute; Nardin, Elizabeth

    2008-10-01

    Advances in our understanding of the molecular and cell biology of the malaria parasite have led to new vaccine development efforts resulting in a pipeline of over 40 candidates undergoing clinical phase I-III trials. Vaccine-induced CD4+ and CD8+ T cells specific for pre-erythrocytic stage antigens have been found to express cytolytic and multi-cytokine effector functions that support a key role for these T cells within the hepatic environment. However, little is known of the cellular interactions that occur during the effector phase in which the intracellular hepatic stage of the parasite is targeted and destroyed. This review focuses on cell biological aspects of the interaction between malaria-specific effector cells and the various antigen-presenting cells that are known to exist within the liver, including hepatocytes, dendritic cells, Kupffer cells, stellate cells and sinusoidal endothelia. Considering the unique immune properties of the liver, it is conceivable that these different hepatic antigen-presenting cells fulfil distinct but complementary roles during the effector phase against Plasmodium liver stages.

  4. The Need for Culturally Relevant Dance Education

    Science.gov (United States)

    McCarthy-Brown, Nyama

    2009-01-01

    There is a need for culturally relevant teaching in dance education. Many dance teachers have heard the buzz words "culturally relevant teaching methods." Yet these dance educators acknowledge that the "dance culture" is not always synonymous with "culturally relevant." This paper examines the issue of culturally relevant teaching methods in dance…

  5. HCVpro: Hepatitis C virus protein interaction database

    KAUST Repository

    Kwofie, Samuel K.

    2011-12-01

    It is essential to catalog characterized hepatitis C virus (HCV) protein-protein interaction (PPI) data and the associated plethora of vital functional information to augment the search for therapies, vaccines and diagnostic biomarkers. In furtherance of these goals, we have developed the hepatitis C virus protein interaction database (HCVpro) by integrating manually verified hepatitis C virus-virus and virus-human protein interactions curated from literature and databases. HCVpro is a comprehensive and integrated HCV-specific knowledgebase housing consolidated information on PPIs, functional genomics and molecular data obtained from a variety of virus databases (VirHostNet, VirusMint, HCVdb and euHCVdb), and from BIND and other relevant biology repositories. HCVpro is further populated with information on hepatocellular carcinoma (HCC) related genes that are mapped onto their encoded cellular proteins. Incorporated proteins have been mapped onto Gene Ontologies, canonical pathways, Online Mendelian Inheritance in Man (OMIM) and extensively cross-referenced to other essential annotations. The database is enriched with exhaustive reviews on structure and functions of HCV proteins, current state of drug and vaccine development and links to recommended journal articles. Users can query the database using specific protein identifiers (IDs), chromosomal locations of a gene, interaction detection methods, indexed PubMed sources as well as HCVpro, BIND and VirusMint IDs. The use of HCVpro is free and the resource can be accessed via http://apps.sanbi.ac.za/hcvpro/ or http://cbrc.kaust.edu.sa/hcvpro/. © 2011 Elsevier B.V.

  6. Active elastic thin shell theory for cellular deformations

    Science.gov (United States)

    Berthoumieux, Hélène; Maître, Jean-Léon; Heisenberg, Carl-Philipp; Paluch, Ewa K.; Jülicher, Frank; Salbreux, Guillaume

    2014-06-01

    We derive the equations for a thin, axisymmetric elastic shell subjected to an internal active stress giving rise to active tension and moments within the shell. We discuss the stability of a cylindrical elastic shell and its response to a localized change in internal active stress. This description is relevant to describe the cellular actomyosin cortex, a thin shell at the cell surface behaving elastically at a short timescale and subjected to active internal forces arising from myosin molecular motor activity. We show that the recent observations of cell deformation following detachment of adherent cells (Maître J-L et al 2012 Science 338 253-6) are well accounted for by this mechanical description. The actin cortex elastic and bending moduli can be obtained from a quantitative analysis of cell shapes observed in these experiments. Our approach thus provides a non-invasive, imaging-based method for the extraction of cellular physical parameters.

  7. Cellular immune responses to HIV

    Science.gov (United States)

    McMichael, Andrew J.; Rowland-Jones, Sarah L.

    2001-04-01

    The cellular immune response to the human immunodeficiency virus, mediated by T lymphocytes, seems strong but fails to control the infection completely. In most virus infections, T cells either eliminate the virus or suppress it indefinitely as a harmless, persisting infection. But the human immunodeficiency virus undermines this control by infecting key immune cells, thereby impairing the response of both the infected CD4+ T cells and the uninfected CD8+ T cells. The failure of the latter to function efficiently facilitates the escape of virus from immune control and the collapse of the whole immune system.

  8. 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 rat...... pancreatic alpha-cells and somatotrophs. We found a pharmacological dissociation between the actions on KATP channels and exocytosis and suggest that compounds that, unlike repaglinide, have direct stimulatory effects on exocytosis in somatotrophs and alpha- and beta-cells, such as sulphonylureas...

  9. Game of Life Cellular Automata

    CERN Document Server

    Adamatzky, Andrew

    2010-01-01

    In the late 1960s, British mathematician John Conway invented a virtual mathematical machine that operates on a two-dimensional array of square cell. Each cell takes two states, live and dead. The cells' states are updated simultaneously and in discrete time. A dead cell comes to life if it has exactly three live neighbours. A live cell remains alive if two or three of its neighbours are alive, otherwise the cell dies. Conway's Game of Life became the most programmed solitary game and the most known cellular automaton. The book brings together results of forty years of study into computational

  10. Cellular automata a parallel model

    CERN Document Server

    Mazoyer, J

    1999-01-01

    Cellular automata can be viewed both as computational models and modelling systems of real processes. This volume emphasises the first aspect. In articles written by leading researchers, sophisticated massive parallel algorithms (firing squad, life, Fischer's primes recognition) are treated. Their computational power and the specific complexity classes they determine are surveyed, while some recent results in relation to chaos from a new dynamic systems point of view are also presented. Audience: This book will be of interest to specialists of theoretical computer science and the parallelism challenge.

  11. ING proteins in cellular senescence.

    Science.gov (United States)

    Menéndez, Camino; Abad, María; Gómez-Cabello, Daniel; Moreno, Alberto; Palmero, Ignacio

    2009-05-01

    Cellular senescence is an effective anti-tumor barrier that acts by restraining the uncontrolled proliferation of cells carrying potentially oncogenic alterations. ING proteins are putative tumor suppressor proteins functionally linked to the p53 pathway and to chromatin regulation. ING proteins exert their tumor-protective action through different types of responses. Here, we review the evidence on the participation of ING proteins, mainly ING1 and ING2, in the implementation of the senescent response. The currently available data support an important role of ING proteins as regulators of senescence, in connection with the p53 pathway and chromatin organization.

  12. Cellular Analogs of Operant Behavior.

    Science.gov (United States)

    1992-07-31

    ing of single units can be demonstrated, does such a cellular subset of neighboring pyramidal cells and interneurons as well as process contribute...excite dopamine neurons by -hyperpolarization of local interneurons . J. Neurosci. 12:483-488; 1992. Kosterlitz, H. W. Biosynthesis of morphine in the...II 197 1 1 ocation preltereite iindiis- HOIdlod VA. artdo \\M I . \\.ill I ’’’’i i R i l’)89) ( pioid mediationl lserilI1 reintoree-Cd bK amlphetcamine

  13. 5G Ultra-Dense Cellular Networks

    OpenAIRE

    Ge, Xiaohu; Tu, Song; Mao, Guoqiang; Wang, Cheng-xiang; Han, Tao

    2015-01-01

    Traditional ultra-dense wireless networks are recommended as a complement for cellular networks and are deployed in partial areas, such as hotspot and indoor scenarios. Based on the massive multiple-input multi-output (MIMO) antennas and the millimeter wavecommunication technologies, the 5G ultra-dense cellular network is proposed to deploy in overall cellular scenarios. Moreover, a distribution network architecture is presented for 5G ultra-dense cellular networks. Furthermore, the backhaul ...

  14. Using cellular network diagrams to interpret large-scale datasets: past progress and future challenges

    Science.gov (United States)

    Karp, Peter D.; Latendresse, Mario; Paley, Suzanne

    2011-03-01

    Cellular networks are graphs of molecular interactions within the cell. Thanks to the confluence of genome sequencing and bioinformatics, scientists are now able to reconstruct cellular network models for more than 1,000 organisms. A variety of bioinformatics tools have been developed to support the visualization and navigation of cellular network data. Another important application is the use of cellular network diagrams to visualize and interpret large-scale datasets, such as gene-expression data. We present the Cellular Overview, a network visualization tool developed at SRI International (SRI) to support visualization, navigation, and interpretation of large-scale datasets on metabolic networks. Different variations of the diagram have been generated algorithmically for more than 1,000 organisms. We discuss the graphical design of the diagram and its interactive capabilities.

  15. Traction Stresses and Translational Distortion of the Nucleus During Fibroblast Migration on a Physiologically Relevant ECM Mimic

    Science.gov (United States)

    Pan, Zhi; Ghosh, Kaustabh; Liu, Yajie; Clark, Richard A.F.; Rafailovich, Miriam H.

    2009-01-01

    Cellular traction forces, resulting in cell-substrate physical interactions, are generated by actin-myosin complexes and transmitted to the extracellular matrix through focal adhesions. These processes are highly dynamic under physiological conditions and modulate cell migration. To better understand the precise dynamics of cell migration, we measured the spatiotemporal redistribution of cellular traction stresses (force per area) during fibroblast migration at a submicron level and correlated it with nuclear translocation, an indicator of cell migration, on a physiologically relevant extracellular matrix mimic. We found that nuclear translocation occurred in pulses whose magnitude was larger on the low ligand density surfaces than on the high ligand density surfaces. Large nuclear translocations only occurred on low ligand density surfaces when the rear traction stresses completely relocated to a posterior nuclear location, whereas such relocation took much longer time on high ligand density surfaces, probably due to the greater magnitude of traction stresses. Nuclear distortion was also observed as the traction stresses redistributed. Our results suggest that the reinforcement of the traction stresses around the nucleus as well as the relaxation of nuclear deformation are critical steps during fibroblast migration, serving as a speed regulator, which must be considered in any dynamic molecular reconstruction model of tissue cell migration. A traction gradient foreshortening model was proposed to explain how the relocation of rear traction stresses leads to pulsed fibroblast migration. PMID:19450499

  16. Melanoma screening with cellular phones.

    Directory of Open Access Journals (Sweden)

    Cesare Massone

    Full Text Available BACKGROUND: Mobile teledermatology has recently been shown to be suitable for teledermatology despite limitations in image definition in preliminary studies. The unique aspect of mobile teledermatology is that this system represents a filtering or triage system, allowing a sensitive approach for the management of patients with emergent skin diseases. METHODOLOGY/PRINCIPAL FINDINGS: In this study we investigated the feasibility of teleconsultation using a new generation of cellular phones in pigmented skin lesions. 18 patients were selected consecutively in the Pigmented Skin Lesions Clinic of the Department of Dermatology, Medical University of Graz, Graz (Austria. Clinical and dermoscopic images were acquired using a Sony Ericsson with a built-in two-megapixel camera. Two teleconsultants reviewed the images on a specific web application (http://www.dermahandy.net/default.asp where images had been uploaded in JPEG format. Compared to the face-to-face diagnoses, the two teleconsultants obtained a score of correct telediagnoses of 89% and of 91.5% reporting the clinical and dermoscopic images, respectively. CONCLUSIONS/SIGNIFICANCE: The present work is the first study performing mobile teledermoscopy using cellular phones. Mobile teledermatology has the potential to become an easy applicable tool for everyone and a new approach for enhanced self-monitoring for skin cancer screening in the spirit of the eHealth program of the European Commission Information for Society and Media.

  17. Cellular functions of the microprocessor.

    Science.gov (United States)

    Macias, Sara; Cordiner, Ross A; Cáceres, Javier F

    2013-08-01

    The microprocessor is a complex comprising the RNase III enzyme Drosha and the double-stranded RNA-binding protein DGCR8 (DiGeorge syndrome critical region 8 gene) that catalyses the nuclear step of miRNA (microRNA) biogenesis. DGCR8 recognizes the RNA substrate, whereas Drosha functions as an endonuclease. Recent global analyses of microprocessor and Dicer proteins have suggested novel functions for these components independent of their role in miRNA biogenesis. A HITS-CLIP (high-throughput sequencing of RNA isolated by cross-linking immunoprecipitation) experiment designed to identify novel substrates of the microprocessor revealed that this complex binds and regulates a large variety of cellular RNAs. The microprocessor-mediated cleavage of several classes of RNAs not only regulates transcript levels, but also modulates alternative splicing events, independently of miRNA function. Importantly, DGCR8 can also associate with other nucleases, suggesting the existence of alternative DGCR8 complexes that may regulate the fate of a subset of cellular RNAs. The aim of the present review is to provide an overview of the diverse functional roles of the microprocessor.

  18. Cellular automata modelling of SEIRS

    Institute of Scientific and Technical Information of China (English)

    Liu Quan-Xing; Jin Zhen

    2005-01-01

    In this paper the SEIRS epidemic spread is analysed, and a two-dimensional probability cellular automata model for SEIRS is presented. Each cellular automation cell represents a part of the population that may be found in one of five states of individuals: susceptible, exposed (or latency), infected, immunized (or recovered) and death. Here studied are the effects of two cases on the epidemic spread. i.e. the effects of non-segregation and segregation on the latency and the infected of population. The conclusion is reached that the epidemic will persist in the case of non-segregation but it will decrease in the case of segregation. The proposed model can serve as a basis for the development of algorithms to simulate real epidemics based on real data. Last we find the density series of the exposed and the infected will fluctuate near a positive equilibrium point, when the constant for the immunized is less than its corresponding constant τ0. Our theoretical results are verified by numerical simulations.

  19. Ancient "Observatories" - A Relevant Concept?

    Science.gov (United States)

    Belmonte, Juan Antonio

    It is quite common, when reading popular books on astronomy, to see a place referred to as "the oldest observatory in the world". In addition, numerous books on archaeoastronomy, of various levels of quality, frequently refer to the existence of "prehistoric" or "ancient" observatories when describing or citing monuments that were certainly not built with the primary purpose of observing the skies. Internet sources are also guilty of this practice. In this chapter, the different meanings of the word observatory will be analyzed, looking at how their significances can be easily confused or even interchanged. The proclaimed "ancient observatories" are a typical result of this situation. Finally, the relevance of the concept of the ancient observatory will be evaluated.

  20. A quantum relativistic battle of the sexes cellular automaton

    Science.gov (United States)

    Alonso-Sanz, Ramón; Situ, Haozhen

    2017-02-01

    The effect of variable entangling on the dynamics of a spatial quantum relativistic formulation of the iterated battle of the sexes game is studied in this work. The game is played in the cellular automata manner, i.e., with local and synchronous interaction. The game is assessed in fair and unfair contests. Despite the full range of quantum parameters initially accessible, they promptly converge into fairly stable configurations, that often show rich spatial structures in simulations with no negligible entanglement.

  1. Variable entangling in a quantum prisoner's dilemma cellular automaton

    Science.gov (United States)

    Alonso-Sanz, Ramón

    2015-01-01

    The effect of variable entangling on the dynamics of a spatial quantum formulation of the iterated prisoner's dilemma game is studied in this work. The game is played in the cellular automata manner, i.e., with local and synchronous interaction. The effect of spatial structure is assessed when allowing the players to adopt quantum and classical strategies, both in the two- and three-parameter strategy spaces.

  2. Protein-protein interactions

    DEFF Research Database (Denmark)

    Byron, Olwyn; Vestergaard, Bente

    2015-01-01

    Responsive formation of protein:protein interaction (PPI) upon diverse stimuli is a fundament of cellular function. As a consequence, PPIs are complex, adaptive entities, and exist in structurally heterogeneous interplays defined by the energetic states of the free and complexed protomers......, are reported. The aim is to depict how the elucidation of the interplay of structures requires the interplay of methods....

  3. Panels of chemically-modified heparin polysaccharides and natural heparan sulfate saccharides both exhibit differences in binding to Slit and Robo, as well as variation between protein binding and cellular activity.

    Science.gov (United States)

    Ahmed, Yassir A; Yates, Edwin A; Moss, Diana J; Loeven, Markus A; Hussain, Sadaf-Ahmahni; Hohenester, Erhard; Turnbull, Jeremy E; Powell, Andrew K

    2016-10-20

    Heparin/heparan sulfate (HS) glycosaminoglycans are required for Slit-Robo cellular responses. Evidence exists for interactions between each combination of Slit, Robo and heparin/HS and for formation of a ternary complex. Heparin/HS are complex mixtures displaying extensive structural diversity. The relevance of this diversity has been studied to a limited extent using a few select chemically-modified heparins as models of HS diversity. Here we extend these studies by parallel screening of structurally diverse panels of eight chemically-modified heparin polysaccharides and numerous natural HS oligosaccharide chromatographic fractions for binding to both Drosophila Slit and Robo N-terminal domains and for activation of a chick retina axon response to the Slit fragment. Both the polysaccharides and oligosaccharide fractions displayed variability in binding and cellular activity that could not be attributed solely to increasing sulfation, extending evidence for the importance of structural diversity to natural HS as well as model modified heparins. They also displayed differences in their interactions with Slit compared to Robo, with Robo preferring compounds with higher sulfation. Furthermore, the patterns of cellular activity across compounds were different to those for binding to each protein, suggesting that biological outcomes are selectively determined in a subtle manner that does not simply reflect the sum of the separate interactions of heparin/HS with Slit and Robo.

  4. Physiologically relevant organs on chips.

    Science.gov (United States)

    Yum, Kyungsuk; Hong, Soon Gweon; Healy, Kevin E; Lee, Luke P

    2014-01-01

    Recent advances in integrating microengineering and tissue engineering have generated promising microengineered physiological models for experimental medicine and pharmaceutical research. Here we review the recent development of microengineered physiological systems, or also known as "ogans-on-chips", that reconstitute the physiologically critical features of specific human tissues and organs and their interactions. This technology uses microengineering approaches to construct organ-specific microenvironments, reconstituting tissue structures, tissue-tissue interactions and interfaces, and dynamic mechanical and biochemical stimuli found in specific organs, to direct cells to assemble into functional tissues. We first discuss microengineering approaches to reproduce the key elements of physiologically important, dynamic mechanical microenvironments, biochemical microenvironments, and microarchitectures of specific tissues and organs in microfluidic cell culture systems. This is followed by examples of microengineered individual organ models that incorporate the key elements of physiological microenvironments into single microfluidic cell culture systems to reproduce organ-level functions. Finally, microengineered multiple organ systems that simulate multiple organ interactions to better represent human physiology, including human responses to drugs, is covered in this review. This emerging organs-on-chips technology has the potential to become an alternative to 2D and 3D cell culture and animal models for experimental medicine, human disease modeling, drug development, and toxicology.

  5. Soft Interaction in Liposome Nanocarriers for Therapeutic Drug Delivery

    Directory of Open Access Journals (Sweden)

    Domenico Lombardo

    2016-06-01

    Full Text Available The development of smart nanocarriers for the delivery of therapeutic drugs has experienced considerable expansion in recent decades, with the development of new medicines devoted to cancer treatment. In this respect a wide range of strategies can be developed by employing liposome nanocarriers with desired physico-chemical properties that, by exploiting a combination of a number of suitable soft interactions, can facilitate the transit through the biological barriers from the point of administration up to the site of drug action. As a result, the materials engineer has generated through the bottom up approach a variety of supramolecular nanocarriers for the encapsulation and controlled delivery of therapeutics which have revealed beneficial developments for stabilizing drug compounds, overcoming impediments to cellular and tissue uptake, and improving biodistribution of therapeutic compounds to target sites. Herein we present recent advances in liposome drug delivery by analyzing the main structural features of liposome nanocarriers which strongly influence their interaction in solution. More specifically, we will focus on the analysis of the relevant soft interactions involved in drug delivery processes which are responsible of main behaviour of soft nanocarriers in complex physiological fluids. Investigation of the interaction between liposomes at the molecular level can be considered an important platform for the modeling of the molecular recognition processes occurring between cells. Some relevant strategies to overcome the biological barriers during the drug delivery of the nanocarriers are presented which outline the main structure-properties relationships as well as their advantages (and drawbacks in therapeutic and biomedical applications.

  6. A cellular automata evacuation model considering friction and repulsion

    Institute of Scientific and Technical Information of China (English)

    SONG Weiguo; YU Yanfei; FAN Weicheng; Zhang Heping

    2005-01-01

    There exist interactions among pedestrians and between pedestrian and environment in evacuation. These interactions include attraction, repulsion and friction that play key roles in human evacuation behaviors, speed and efficiency. Most former evacuation models focus on the attraction force, while repulsion and friction are not well modeled. As a kind of multi-particle self-driven model, the social force model introduced in recent years can represent those three forces but with low simulation efficiency because it is a continuous model with complex rules. Discrete models such as the cellular automata model and the lattice gas model have simple rules and high simulation efficiency, but are not quite suitable for interactions' simulation. In this paper, a new cellular automata model based on traditional models is introduced in which repulsion and friction are modeled quantitatively. It is indicated that the model can simulate some basic behaviors, e.g.arching and the "faster-is-slower" phenomenon, in evacuation as multi-particle self-driven models, but with high efficiency as the normal cellular automata model and the lattice gas model.

  7. Cellular uptake of metallated cobalamins

    DEFF Research Database (Denmark)

    Tran, Mai Thanh Quynh; Stürup, Stefan; Lambert, Ian Henry

    2016-01-01

    Cellular uptake of vitamin B12-cisplatin conjugates was estimated via detection of their metal constituents (Co, Pt, and Re) by inductively coupled plasma mass spectrometry (ICP-MS). Vitamin B12 (cyano-cob(iii)alamin) and aquo-cob(iii)alamin [Cbl-OH2](+), which differ in the β-axial ligands (CN...... including [Cbl-OH2](+), [{Co}-CN-{cis-PtCl(NH3)2}](+), [{Re}-{Co}-CN-{cis-PtCl(NH3)2}](+), and [{Co}-CN-{trans-Pt(Cyt)(NH3)2}](2+) (Cyt = cytarabin) was high compared to neutral B12, which implied the existence of an additional internalization pathway for charged B12 vitamin analogs. The affinities...

  8. Discrete geodesics and cellular automata

    CERN Document Server

    Arrighi, Pablo

    2015-01-01

    This paper proposes a dynamical notion of discrete geodesics, understood as straightest trajectories in discretized curved spacetime. The notion is generic, as it is formulated in terms of a general deviation function, but readily specializes to metric spaces such as discretized pseudo-riemannian manifolds. It is effective: an algorithm for computing these geodesics naturally follows, which allows numerical validation---as shown by computing the perihelion shift of a Mercury-like planet. It is consistent, in the continuum limit, with the standard notion of timelike geodesics in a pseudo-riemannian manifold. Whether the algorithm fits within the framework of cellular automata is discussed at length. KEYWORDS: Discrete connection, parallel transport, general relativity, Regge calculus.

  9. Thermomechanical characterisation of cellular rubber

    Science.gov (United States)

    Seibert, H.; Scheffer, T.; Diebels, S.

    2016-09-01

    This contribution discusses an experimental possibility to characterise a cellular rubber in terms of the influence of multiaxiality, rate dependency under environmental temperature and its behaviour under hydrostatic pressure. In this context, a mixed open and closed cell rubber based on an ethylene propylene diene monomer is investigated exemplarily. The present article intends to give a general idea of the characterisation method and the considerable effects of this special type of material. The main focus lies on the experimental procedure and the used testing devices in combination with the analysis methods such as true three-dimensional digital image correlation. The structural compressibility is taken into account by an approach for a material model using the Theory of Porous Media with additional temperature dependence.

  10. Cellular compartmentalization of secondary metabolism

    Directory of Open Access Journals (Sweden)

    H. Corby eKistler

    2015-02-01

    Full Text Available Fungal secondary metabolism is often considered apart from the essential housekeeping functions of the cell. However, there are clear links between fundamental cellular metabolism and the biochemical pathways leading to secondary metabolite synthesis. Besides utilizing key biochemical precursors shared with the most essential processes of the cell (e.g. amino acids, acetyl CoA, NADPH, enzymes for secondary metabolite synthesis are compartmentalized at conserved subcellular sites that position pathway enzymes to use these common biochemical precursors. Co-compartmentalization of secondary metabolism pathway enzymes also may function to channel precursors, promote pathway efficiency and sequester pathway intermediates and products from the rest of the cell. In this review we discuss the compartmentalization of three well-studied fungal secondary metabolite biosynthetic pathways for penicillin G, aflatoxin and deoxynivalenol, and summarize evidence used to infer subcellular localization. We also discuss how these metabolites potentially are trafficked within the cell and may be exported.

  11. Fundamental Limits to Cellular Sensing

    Science.gov (United States)

    ten Wolde, Pieter Rein; Becker, Nils B.; Ouldridge, Thomas E.; Mugler, Andrew

    2016-03-01

    In recent years experiments have demonstrated that living cells can measure low chemical concentrations with high precision, and much progress has been made in understanding what sets the fundamental limit to the precision of chemical sensing. Chemical concentration measurements start with the binding of ligand molecules to receptor proteins, which is an inherently noisy process, especially at low concentrations. The signaling networks that transmit the information on the ligand concentration from the receptors into the cell have to filter this receptor input noise as much as possible. These networks, however, are also intrinsically stochastic in nature, which means that they will also add noise to the transmitted signal. In this review, we will first discuss how the diffusive transport and binding of ligand to the receptor sets the receptor correlation time, which is the timescale over which fluctuations in the state of the receptor, arising from the stochastic receptor-ligand binding, decay. We then describe how downstream signaling pathways integrate these receptor-state fluctuations, and how the number of receptors, the receptor correlation time, and the effective integration time set by the downstream network, together impose a fundamental limit on the precision of sensing. We then discuss how cells can remove the receptor input noise while simultaneously suppressing the intrinsic noise in the signaling network. We describe why this mechanism of time integration requires three classes (groups) of resources—receptors and their integration time, readout molecules, energy—and how each resource class sets a fundamental sensing limit. We also briefly discuss the scheme of maximum-likelihood estimation, the role of receptor cooperativity, and how cellular copy protocols differ from canonical copy protocols typically considered in the computational literature, explaining why cellular sensing systems can never reach the Landauer limit on the optimal trade

  12. Cell adaptation to a physiologically relevant ECM mimic with different viscoelastic properties

    Science.gov (United States)

    Ghosh, Kaustabh; Pan, Zhi; Guan, E; Ge, Shouren; Liu, Yajie; Nakamura, Toshio; Ren, Xiang-Dong; Rafailovich, Miriam; Clark, Richard A.F.

    2009-01-01

    To successfully induce tissue repair or regeneration in vivo, bioengineered constructs must possess both optimal bioactivity and mechanical strength. This is because cell interaction with the extracellular matrix (ECM) produces two different but concurrent signaling mechanisms: ligation-induced signaling, which depends on ECM biological stimuli, and traction-induced signaling, which depends on ECM mechanical stimuli. In this report, we provide a fundamental understanding of how alterations in mechanical stimuli alone, produced by varying the viscoelastic properties of our bioengineered construct, modulate phenotypic behavior at the whole-cell level. Using a physiologically-relevant ECM mimic composed of hyaluronan and fibronectin, we found that adult human dermal fibroblasts modify their mechanical response in order to match substrate stiffness. More specifically, the cells on stiffer substrates had higher modulus and a more stretched and organized actin cytoskeleton (and vice versa), which translated into larger traction forces exerted on the substrate. This modulation of cellular mechanics had contrasting effects on migration and proliferation, where cells migrated faster on softer substrates while proliferating preferentially on the stiffer ones. These findings implicate substrate rigidity as a critical design parameter in the development of bioengineered constructs aimed at eliciting maximal cell and tissue function. PMID:17049594

  13. Vygotsky's Crisis: Argument, context, relevance.

    Science.gov (United States)

    Hyman, Ludmila

    2012-06-01

    Vygotsky's The Historical Significance of the Crisis in Psychology (1926-1927) is an important text in the history and philosophy of psychology that has only become available to scholars in 1982 in Russian, and in 1997 in English. The goal of this paper is to introduce Vygotsky's conception of psychology to a wider audience. I argue that Vygotsky's argument about the "crisis" in psychology and its resolution can be fully understood only in the context of his social and political thinking. Vygotsky shared the enthusiasm, widespread among Russian leftist intelligentsia in the 1920s, that Soviet society had launched an unprecedented social experiment: The socialist revolution opened the way for establishing social conditions that would let the individual flourish. For Vygotsky, this meant that "a new man" of the future would become "the first and only species in biology that would create itself." He envisioned psychology as a science that would serve this humanist teleology. I propose that The Crisis is relevant today insofar as it helps us define a fundamental problem: How can we systematically account for the development of knowledge in psychology? I evaluate how Vygotsky addresses this problem as a historian of the crisis.

  14. GO-2D: identifying 2-dimensional cellular-localized functional modules in Gene Ontology

    Directory of Open Access Journals (Sweden)

    Yang Da

    2007-01-01

    Full Text Available Abstract Background Rapid progress in high-throughput biotechnologies (e.g. microarrays and exponential accumulation of gene functional knowledge make it promising for systematic understanding of complex human diseases at functional modules level. Based on Gene Ontology, a large number of automatic tools have been developed for the functional analysis and biological interpretation of the high-throughput microarray data. Results Different from the existing tools such as Onto-Express and FatiGO, we develop a tool named GO-2D for identifying 2-dimensional functional modules based on combined GO categories. For example, it refines biological process categories by sorting their genes into different cellular component categories, and then extracts those combined categories enriched with the interesting genes (e.g., the differentially expressed genes for identifying the cellular-localized functional modules. Applications of GO-2D to the analyses of two human cancer datasets show that very specific disease-relevant processes can be identified by using cellular location information. Conclusion For studying complex human diseases, GO-2D can extract functionally compact and detailed modules such as the cellular-localized ones, characterizing disease-relevant modules in terms of both biological processes and cellular locations. The application results clearly demonstrate that 2-dimensional approach complementary to current 1-dimensional approach is powerful for finding modules highly relevant to diseases.

  15. Mushroom Lectins: Specificity, Structure and Bioactivity Relevant to Human Disease

    Directory of Open Access Journals (Sweden)

    Mohamed Ali Abol Hassan

    2015-04-01

    Full Text Available Lectins are non-immunoglobulin proteins that bind diverse sugar structures with a high degree of selectivity. Lectins play crucial role in various biological processes such as cellular signaling, scavenging of glycoproteins from the circulatory system, cell–cell interactions in the immune system, differentiation and protein targeting to cellular compartments, as well as in host defence mechanisms, inflammation, and cancer. Among all the sources of lectins, plants have been most extensively studied. However, more recently fungal lectins have attracted considerable attention due to their antitumor, antiproliferative and immunomodulatory activities. Given that only 10% of mushroom species are known and have been taxonomically classified, mushrooms represent an enormous unexplored source of potentially useful and novel lectins. In this review we provide an up-to-date summary on the biochemical, molecular and structural properties of mushroom lectins, as well as their versatile applications specifically focusing on mushroom lectin bioactivity.

  16. Does relevance matter in academic policy research?

    DEFF Research Database (Denmark)

    Dredge, Dianne

    2015-01-01

    A reflection on whether relevance matters in tourism policy research. A debate among tourism scholars.......A reflection on whether relevance matters in tourism policy research. A debate among tourism scholars....

  17. Science and the struggle for relevance

    NARCIS (Netherlands)

    Hessels, L.K.

    2010-01-01

    This thesis deals with struggles for relevance of university researchers, their efforts to make their work correspond with ruling standards of relevance and to influence these standards. Its general research question is: How to understand changes in the struggle for relevance of Dutch academic resea

  18. Relevance Measures Using Geographic Scopes and Types

    NARCIS (Netherlands)

    Andogah, Geoffrey; Bouma, Gosse; Peters, C; Jikoun,; Mandl, T; Muller, H; Oard, DW; Penas, A; Petras,; Santos, D

    2008-01-01

    This paper proposes two kinds of relevance measures to rank documents by geographic restriction: scope-based and type-based. The non-geographic and geographic relevance scores are combined using a weighted harmonic mean. The proposed relevance measures and weighting schemes are evaluated on GeoCLEF

  19. The Development of Relevance in Information Retrieval

    Directory of Open Access Journals (Sweden)

    Mu-hsuan Huang

    1997-12-01

    Full Text Available This article attempts to investigate the notion of relevance in information retrieval. It discusses various definitions for relevance from historical viewpoints and the characteristics of relevance judgments. Also, it introduces empirical results of important related researches.[Article content in Chinese

  20. The Personal Relevance of the Social Studies.

    Science.gov (United States)

    VanSickle, Ronald L.

    1990-01-01

    Conceptualizes a personal-relevance framework derived from Ronald L. VanSickle's five areas of life integrated with four general motivating goals from Abraham Maslow's hierarchy of needs and Richard and Patricia Schmuck's social motivation theory. Illustrates ways to apply the personal relevance framework to make social studies more relevant to…