Age differences in how consumers behave following exposure to DTC advertising.

PubMed

DeLorme, Denise E; Huh, Jisu; Reid, Leonard N

2006-01-01

This study was conducted to provide additional evidence on how consumers behave following direct-to-consumer (DTC) advertising exposure and to determine if there are differences in ad-prompted acts (drug inquiry and drug requests) between different age groups (i.e., older, mature, and younger adults). The results suggest that younger, mature, and older consumers are all moved to act by DTC drug ads, but that each age group behaves in different ways. Somewhat surprisingly, age was not predictive of ad-prompted behavior. DTC advertising was no more effective at moving older consumers to behave than their younger counterparts. These results suggest that age does not matter that much when it comes to the "moving power" of prescription drug advertising, even though research indicates that older consumers are more vulnerable to the persuasive effects of communication.

Neuronal Representation of Social Information in the Medial Amygdala of Awake Behaving Mice.

PubMed

Li, Ying; Mathis, Alexander; Grewe, Benjamin F; Osterhout, Jessica A; Ahanonu, Biafra; Schnitzer, Mark J; Murthy, Venkatesh N; Dulac, Catherine

2017-11-16

The medial amygdala (MeA) plays a critical role in processing species- and sex-specific signals that trigger social and defensive behaviors. However, the principles by which this deep brain structure encodes social information is poorly understood. We used a miniature microscope to image the Ca 2+ dynamics of large neural ensembles in awake behaving mice and tracked the responses of MeA neurons over several months. These recordings revealed spatially intermingled subsets of MeA neurons with distinct temporal dynamics. The encoding of social information in the MeA differed between males and females and relied on information from both individual cells and neuronal populations. By performing long-term Ca 2+ imaging across different social contexts, we found that sexual experience triggers lasting and sex-specific changes in MeA activity, which, in males, involve signaling by oxytocin. These findings reveal basic principles underlying the brain's representation of social information and its modulation by intrinsic and extrinsic factors. Copyright © 2017 Elsevier Inc. All rights reserved.

A Babcock-Leighton Solar Dynamo Model with Multi-cellular Meridional Circulation in Advection- and Diffusion-dominated Regimes

NASA Astrophysics Data System (ADS)

Belucz, Bernadett; Dikpati, Mausumi; Forgács-Dajka, Emese

2015-06-01

Babcock-Leighton type-solar dynamo models with single-celled meridional circulation are successful in reproducing many solar cycle features. Recent observations and theoretical models of meridional circulation do not indicate a single-celled flow pattern. We examine the role of complex multi-cellular circulation patterns in a Babcock-Leighton solar dynamo in advection- and diffusion-dominated regimes. We show from simulations that the presence of a weak, second, high-latitude reverse cell speeds up the cycle and slightly enhances the poleward branch in the butterfly diagram, whereas the presence of a second cell in depth reverses the tilt of the butterfly wing to an antisolar type. A butterfly diagram constructed from the middle of convection zone yields a solar-like pattern, but this may be difficult to realize in the Sun because of magnetic buoyancy effects. Each of the above cases behaves similarly in higher and lower magnetic diffusivity regimes. However, our dynamo with a meridional circulation containing four cells in latitude behaves distinctly differently in the two regimes, producing solar-like butterfly diagrams with fast cycles in the higher diffusivity regime, and complex branches in butterfly diagrams in the lower diffusivity regime. We also find that dynamo solutions for a four-celled pattern, two in radius and two in latitude, prefer to quickly relax to quadrupolar parity if the bottom flow speed is strong enough, of similar order of magnitude as the surface flow speed.

A BABCOCK–LEIGHTON SOLAR DYNAMO MODEL WITH MULTI-CELLULAR MERIDIONAL CIRCULATION IN ADVECTION- AND DIFFUSION-DOMINATED REGIMES

DOE Office of Scientific and Technical Information (OSTI.GOV)

Belucz, Bernadett; Forgács-Dajka, Emese; Dikpati, Mausumi, E-mail: bbelucz@astro.elte.hu, E-mail: dikpati@ucar.edu

Babcock–Leighton type-solar dynamo models with single-celled meridional circulation are successful in reproducing many solar cycle features. Recent observations and theoretical models of meridional circulation do not indicate a single-celled flow pattern. We examine the role of complex multi-cellular circulation patterns in a Babcock–Leighton solar dynamo in advection- and diffusion-dominated regimes. We show from simulations that the presence of a weak, second, high-latitude reverse cell speeds up the cycle and slightly enhances the poleward branch in the butterfly diagram, whereas the presence of a second cell in depth reverses the tilt of the butterfly wing to an antisolar type. A butterflymore » diagram constructed from the middle of convection zone yields a solar-like pattern, but this may be difficult to realize in the Sun because of magnetic buoyancy effects. Each of the above cases behaves similarly in higher and lower magnetic diffusivity regimes. However, our dynamo with a meridional circulation containing four cells in latitude behaves distinctly differently in the two regimes, producing solar-like butterfly diagrams with fast cycles in the higher diffusivity regime, and complex branches in butterfly diagrams in the lower diffusivity regime. We also find that dynamo solutions for a four-celled pattern, two in radius and two in latitude, prefer to quickly relax to quadrupolar parity if the bottom flow speed is strong enough, of similar order of magnitude as the surface flow speed.« less

In vitro comparison of human fibroblasts from intact and ruptured ACL for use in tissue engineering.

PubMed

Brune, T; Borel, A; Gilbert, T W; Franceschi, J P; Badylak, S F; Sommer, P

2007-12-17

The present study compares fibroblasts extracted from intact and ruptured human anterior cruciate ligaments (ACL) for creation of a tissue engineered ACL-construct, made of porcine small intestinal submucosal extracellular matrix (SIS-ECM) seeded with these ACL cells. The comparison is based on histological, immunohistochemical and RT-PCR analyses. Differences were observed between cells in a ruptured ACL (rACL) and cells in an intact ACL (iACL), particularly with regard to the expression of integrin subunits and smooth muscle actin (SMA). Despite these differences in the cell source, both cell populations behaved similarly when seeded on an SIS-ECM scaffold, with similar cell morphology, connective tissue organization and composition, SMA and integrin expression. This study shows the usefulness of naturally occurring scaffolds such as SIS-ECM for the study of cell behaviour in vitro, and illustrates the possibility to use autologous cells extracted from ruptured ACL biopsies as a source for tissue engineered ACL constructs.

Action Potential Waveform Variability Limits Multi-Unit Separation in Freely Behaving Rats

PubMed Central

Stratton, Peter; Cheung, Allen; Wiles, Janet; Kiyatkin, Eugene; Sah, Pankaj; Windels, François

2012-01-01

Extracellular multi-unit recording is a widely used technique to study spontaneous and evoked neuronal activity in awake behaving animals. These recordings are done using either single-wire or mulitwire electrodes such as tetrodes. In this study we have tested the ability of single-wire electrodes to discriminate activity from multiple neurons under conditions of varying noise and neuronal cell density. Using extracellular single-unit recording, coupled with iontophoresis to drive cell activity across a wide dynamic range, we studied spike waveform variability, and explored systematic differences in single-unit spike waveform within and between brain regions as well as the influence of signal-to-noise ratio (SNR) on the similarity of spike waveforms. We also modelled spike misclassification for a range of cell densities based on neuronal recordings obtained at different SNRs. Modelling predictions were confirmed by classifying spike waveforms from multiple cells with various SNRs using a leading commercial spike-sorting system. Our results show that for single-wire recordings, multiple units can only be reliably distinguished under conditions of high recording SNR (≥4) and low neuronal density (≈20,000/ mm3). Physiological and behavioural changes, as well as technical limitations typical of awake animal preparations, reduce the accuracy of single-channel spike classification, resulting in serious classification errors. For SNR <4, the probability of misclassifying spikes approaches 100% in many cases. Our results suggest that in studies where the SNR is low or neuronal density is high, separation of distinct units needs to be evaluated with great caution. PMID:22719894

Persistence, period and precision of autonomous cellular oscillators from the zebrafish segmentation clock

PubMed Central

Webb, Alexis B; Lengyel, Iván M; Jörg, David J; Valentin, Guillaume; Jülicher, Frank; Morelli, Luis G; Oates, Andrew C

2016-01-01

In vertebrate development, the sequential and rhythmic segmentation of the body axis is regulated by a “segmentation clock”. This clock is comprised of a population of coordinated oscillating cells that together produce rhythmic gene expression patterns in the embryo. Whether individual cells autonomously maintain oscillations, or whether oscillations depend on signals from neighboring cells is unknown. Using a transgenic zebrafish reporter line for the cyclic transcription factor Her1, we recorded single tailbud cells in vitro. We demonstrate that individual cells can behave as autonomous cellular oscillators. We described the observed variability in cell behavior using a theory of generic oscillators with correlated noise. Single cells have longer periods and lower precision than the tissue, highlighting the role of collective processes in the segmentation clock. Our work reveals a population of cells from the zebrafish segmentation clock that behave as self-sustained, autonomous oscillators with distinctive noisy dynamics. DOI: http://dx.doi.org/10.7554/eLife.08438.001 PMID:26880542

Longevity of U cells of differentiated yeast colonies grown on respiratory medium depends on active glycolysis.

PubMed

Čáp, Michal; Váchová, Libuše; Palková, Zdena

2015-01-01

Colonies of Saccharomyces cerevisiae laboratory strains pass through specific developmental phases when growing on solid respiratory medium. During entry into the so-called alkali phase, in which ammonia signaling is initiated, 2 prominent cell types are formed within the colonies: U cells in upper colony regions, which have a longevity phenotype and activate the expression of a large number of metabolic genes, and L cells in lower regions, which die more quickly and exhibit a starvation phenotype. Here, we performed a detailed analysis of the activities of enzymes of central carbon metabolism in lysates of both cell types and determined several fermentation end products, showing that previously reported expression differences are reflected in the different enzymatic capabilities of each cell type. Hence, U cells, despite being grown on respiratory medium, behave as fermenting cells, whereas L cells rely on respiratory metabolism and possess active gluconeogenesis. Using a spectrum of different inhibitors, we showed that glycolysis is essential for the formation, and particularly, the survival of U cells. We also showed that β-1,3-glucans that are released from the cell walls of L cells are the most likely source of carbohydrates for U cells.

Ophiobolin A, a sesterpenoid fungal phytotoxin, displays different mechanisms of cell death in mammalian cells depending upon the cancer cell origin.

PubMed

Morrison, Rachel; Lodge, Tiffany; Evidente, Antonio; Kiss, Robert; Townley, Helen

2017-03-01

Herein we have undertaken a systematic analysis of the effects of the fungal derivative ophiobolin A (OphA) on eight cancer cell lines from different tissue types. The LD50 for each cell line was determined and the change in cell size determined. Flow cytometric analysis and western blotting were used to assess the cell death markers for early apoptosis, late apoptosis and necrosis, and the involvement of the caspase signalling pathway. Alterations in calcium levels and reactive oxygen species were assessed due to their integral involvement in intracellular signalling. Subsequently, the endoplasmic reticulum (ER) and mitochondrial responses were investigated more closely. The extent of ER swelling, and the upregulation of proteins involved in the unfolded protein responses (UPR) were seen to vary according to cell line. The mitochondria were also shown to behave differently in response to the OphA in the different cell lines in terms of the change in membrane potential, the total area of mitochondria in the cell and the number of mitochondrial bifurcations. The data obtained in the present study indicate that the cancer cell lines tested are unable to successfully activate the ER stress/UPR responses, and that the mitochondria appear to be a central player in OphA-induced cancer cell death.

Pericytes of Multiple Organs Do Not Behave as Mesenchymal Stem Cells In Vivo.

PubMed

Guimarães-Camboa, Nuno; Cattaneo, Paola; Sun, Yunfu; Moore-Morris, Thomas; Gu, Yusu; Dalton, Nancy D; Rockenstein, Edward; Masliah, Eliezer; Peterson, Kirk L; Stallcup, William B; Chen, Ju; Evans, Sylvia M

2017-03-02

Pericytes are widely believed to function as mesenchymal stem cells (MSCs), multipotent tissue-resident progenitors with great potential for regenerative medicine. Cultured pericytes isolated from distinct tissues can differentiate into multiple cell types in vitro or following transplantation in vivo. However, the cell fate plasticity of endogenous pericytes in vivo remains unclear. Here, we show that the transcription factor Tbx18 selectively marks pericytes and vascular smooth muscle cells in multiple organs of adult mouse. Fluorescence-activated cell sorting (FACS)-purified Tbx18-expressing cells behaved as MSCs in vitro. However, lineage-tracing experiments using an inducible Tbx18-CreERT2 line revealed that pericytes and vascular smooth muscle cells maintained their identity in aging and diverse pathological settings and did not significantly contribute to other cell lineages. These results challenge the current view of endogenous pericytes as multipotent tissue-resident progenitors and suggest that the plasticity observed in vitro or following transplantation in vivo arises from artificial cell manipulations ex vivo. Copyright © 2016 Elsevier Inc. All rights reserved.

From elasticity to inelasticity in cancer cell mechanics: A loss of scale-invariance

NASA Astrophysics Data System (ADS)

Laperrousaz, B.; Drillon, G.; Berguiga, L.; Nicolini, F.; Audit, B.; Satta, V. Maguer; Arneodo, A.; Argoul, F.

2016-08-01

Soft materials such as polymer gels, synthetic biomaterials and living biological tissues are generally classified as viscoelastic or viscoplastic materials, because they behave neither as pure elastic solids, nor as pure viscous fluids. When stressed beyond their linear viscoelastic regime, cross-linked biopolymer gels can behave nonlinearly (inelastically) up to failure. In living cells, this type of behavior is more frequent because their cytoskeleton is basically made of cross-linked biopolymer chains with very different structural and flexibility properties. These networks have high sensitivity to stress and great propensity to local failure. But in contrast to synthetic passive gels, they can "afford" these failures because they have ATP driven reparation mechanisms which often allow the recovery of the original texture. A cell pressed in between two plates for a long period of time may recover its original shape if the culture medium brings all the nutrients for keeping it alive. When the failure events are too frequent or too strong, the reparation mechanisms may abort, leading to an irreversible loss of mechanical homeostasis and paving the way for chronic diseases such as cancer. To illustrate this discussion, we consider a model of immature cell transformation during cancer progression, the chronic myelogenous leukemia (CML), where the formation of the BCR-ABL oncogene results from a single chromosomal translocation t(9; 22). Within the assumption that the cell response to stress is scale invariant, we show that the power-law exponent that characterizes their mechanosensitivity can be retrieved from AFM force indentation curves. Comparing control and BCR-ABL transduced cells, we observe that in the later case, one month after transduction, a small percentage the cancer cells no longer follows the control cell power law, as an indication of disruption of the initial cytoskeleton network structure.

In vitro Method to Observe E-selectin-mediated Interactions Between Prostate Circulating Tumor Cells Derived From Patients and Human Endothelial Cells

PubMed Central

Gakhar, Gunjan; Bander, Neil H.; Nanus, David M.

2014-01-01

Metastasis is a process in which tumor cells shed from the primary tumor intravasate blood vascular and lymphatic system, thereby, gaining access to extravasate and form a secondary niche. The extravasation of tumor cells from the blood vascular system can be studied using endothelial cells (ECs) and tumor cells obtained from different cell lines. Initial studies were conducted using static conditions but it has been well documented that ECs behave differently under physiological flow conditions. Therefore, different flow chamber assemblies are currently being used to studying cancer cell interactions with ECs. Current flow chamber assemblies offer reproducible results using either different cell lines or fluid at different shear stress conditions. However, to observe and study interactions with rare cells such as circulating tumor cells (CTCs), certain changes are required to be made to the conventional flow chamber assembly. CTCs are a rare cell population among millions of blood cells. Consequently, it is difficult to obtain a pure population of CTCs. Contamination of CTCs with different types of cells normally found in the circulation is inevitable using present enrichment or depletion techniques. In the present report, we describe a unique method to fluorescently label circulating prostate cancer cells and study their interactions with ECs in a self-assembled flow chamber system. This technique can be further applied to observe interactions between prostate CTCs and any protein of interest. PMID:24894373

Effect of Hypergravity on Carbonanhydrase Reactivity in inner Ear Ioncytes of developing Cichlid Fish

NASA Astrophysics Data System (ADS)

Beier, M.; Anken, R.; Rahmann, H.

It has been shown earlier that hypergravity slows down inner ear otolith growth in developing fish. Otolith growth in terms of mineralisation mainly depends on the enzyme carboanhydrase (CAH), which is responsible for the provision of the pH- value necessary for calcium carbonate deposition and thus also is presumed to play a prominent role in Ménière's disease (a sensory - motor disorder inducing vertigo and kinetosis). Larval siblings of cichlid fish (Oreochromis mossambicus) were subjected to hypergravity (3g; 6 hours) during development and separated into normally and kinetotically swimming individuals following the transfer to 1g (i.e., stopping the centrifuge; kinetotically behaving fish performed spinning movements). Subsequently, CAH was histochemically demonstrated in inner ear ionocytes (cells involved in the endolymphatic ion exchange) and enzyme reactivity was determined densitometrically. The results showed that CAH-reactivity was significantly increased in normally behaving hyper-g specimens as compared to controls kept at 1g, whereas no difference in enzyme reactivity was evident between the controls and kinetotically behaving fish. On the background of earlier studies, according to which (1) hypergravity induces a decrease of otolith growth and (2) the otolithic calcium incorporation (visualized using the calcium -tracer alizarin complexone) of kinetotically swimming hyper - g fish was lower as compared to normally behaving hyper - g animals, the present study strongly supports the concept that an increase in CAH-reactivity may result in a decrease of otolithic calcium deposition. The mechanism regulating CAH-activity hitherto remains to be determined. Acknowledgement: This work was financially supported by the German Aerospace Center (DLR) (FKZ: 50 WB 9997).

Dual Roles for Spike Signaling in Cortical Neural Populations

PubMed Central

Ballard, Dana H.; Jehee, Janneke F. M.

2011-01-01

A prominent feature of signaling in cortical neurons is that of randomness in the action potential. The output of a typical pyramidal cell can be well fit with a Poisson model, and variations in the Poisson rate repeatedly have been shown to be correlated with stimuli. However while the rate provides a very useful characterization of neural spike data, it may not be the most fundamental description of the signaling code. Recent data showing γ frequency range multi-cell action potential correlations, together with spike timing dependent plasticity, are spurring a re-examination of the classical model, since precise timing codes imply that the generation of spikes is essentially deterministic. Could the observed Poisson randomness and timing determinism reflect two separate modes of communication, or do they somehow derive from a single process? We investigate in a timing-based model whether the apparent incompatibility between these probabilistic and deterministic observations may be resolved by examining how spikes could be used in the underlying neural circuits. The crucial component of this model draws on dual roles for spike signaling. In learning receptive fields from ensembles of inputs, spikes need to behave probabilistically, whereas for fast signaling of individual stimuli, the spikes need to behave deterministically. Our simulations show that this combination is possible if deterministic signals using γ latency coding are probabilistically routed through different members of a cortical cell population at different times. This model exhibits standard features characteristic of Poisson models such as orientation tuning and exponential interval histograms. In addition, it makes testable predictions that follow from the γ latency coding. PMID:21687798

Sublethal Total Body Irradiation Leads to Early Cerebellar Damage and Oxidative Stress

DTIC Science & Technology

2010-01-01

mice: protective effect of alpha - lipoic acid . Behav Brain Res 2007b; 177(1): 7-14. [8] Manda K, Ueno M, Anzai K. Melatonin mitigates oxidative...Memory impairment, oxidative damage and apoptosis induced by space radiation: ameliorative potential of alpha - lipoic acid . Behav Brain Res 2008b...1977; 171(1): 39-50. [6] Manda K, Ueno M, Moritake T, Anzai K. - Lipoic acid attenuates x-irradiation-induced oxidative stress in mice. Cell Biol

Two-Photon Functional Imaging of the Auditory Cortex in Behaving Mice: From Neural Networks to Single Spines.

PubMed

Li, Ruijie; Wang, Meng; Yao, Jiwei; Liang, Shanshan; Liao, Xiang; Yang, Mengke; Zhang, Jianxiong; Yan, Junan; Jia, Hongbo; Chen, Xiaowei; Li, Xingyi

2018-01-01

In vivo two-photon Ca 2+ imaging is a powerful tool for recording neuronal activities during perceptual tasks and has been increasingly applied to behaving animals for acute or chronic experiments. However, the auditory cortex is not easily accessible to imaging because of the abundant temporal muscles, arteries around the ears and their lateral locations. Here, we report a protocol for two-photon Ca 2+ imaging in the auditory cortex of head-fixed behaving mice. By using a custom-made head fixation apparatus and a head-rotated fixation procedure, we achieved two-photon imaging and in combination with targeted cell-attached recordings of auditory cortical neurons in behaving mice. Using synthetic Ca 2+ indicators, we recorded the Ca 2+ transients at multiple scales, including neuronal populations, single neurons, dendrites and single spines, in auditory cortex during behavior. Furthermore, using genetically encoded Ca 2+ indicators (GECIs), we monitored the neuronal dynamics over days throughout the process of associative learning. Therefore, we achieved two-photon functional imaging at multiple scales in auditory cortex of behaving mice, which extends the tool box for investigating the neural basis of audition-related behaviors.

Two-Photon Functional Imaging of the Auditory Cortex in Behaving Mice: From Neural Networks to Single Spines

PubMed Central

Li, Ruijie; Wang, Meng; Yao, Jiwei; Liang, Shanshan; Liao, Xiang; Yang, Mengke; Zhang, Jianxiong; Yan, Junan; Jia, Hongbo; Chen, Xiaowei; Li, Xingyi

2018-01-01

In vivo two-photon Ca2+ imaging is a powerful tool for recording neuronal activities during perceptual tasks and has been increasingly applied to behaving animals for acute or chronic experiments. However, the auditory cortex is not easily accessible to imaging because of the abundant temporal muscles, arteries around the ears and their lateral locations. Here, we report a protocol for two-photon Ca2+ imaging in the auditory cortex of head-fixed behaving mice. By using a custom-made head fixation apparatus and a head-rotated fixation procedure, we achieved two-photon imaging and in combination with targeted cell-attached recordings of auditory cortical neurons in behaving mice. Using synthetic Ca2+ indicators, we recorded the Ca2+ transients at multiple scales, including neuronal populations, single neurons, dendrites and single spines, in auditory cortex during behavior. Furthermore, using genetically encoded Ca2+ indicators (GECIs), we monitored the neuronal dynamics over days throughout the process of associative learning. Therefore, we achieved two-photon functional imaging at multiple scales in auditory cortex of behaving mice, which extends the tool box for investigating the neural basis of audition-related behaviors. PMID:29740289

Ophiobolin A, a sesterpenoid fungal phytotoxin, displays different mechanisms of cell death in mammalian cells depending upon the cancer cell origin

PubMed Central

Morrison, Rachel; Lodge, Tiffany; Evidente, Antonio; Kiss, Robert; Townley, Helen

2017-01-01

Herein we have undertaken a systematic analysis of the effects of the fungal derivative ophiobolin A (OphA) on eight cancer cell lines from different tissue types. The LD50 for each cell line was determined and the change in cell size determined. Flow cytometric analysis and western blotting were used to assess the cell death markers for early apoptosis, late apoptosis and necrosis, and the involvement of the caspase signalling pathway. Alterations in calcium levels and reactive oxygen species were assessed due to their integral involvement in intracellular signalling. Subsequently, the endoplasmic reticulum (ER) and mitochondrial responses were investigated more closely. The extent of ER swelling, and the upregulation of proteins involved in the unfolded protein responses (UPR) were seen to vary according to cell line. The mitochondria were also shown to behave differently in response to the OphA in the different cell lines in terms of the change in membrane potential, the total area of mitochondria in the cell and the number of mitochondrial bifurcations. The data obtained in the present study indicate that the cancer cell lines tested are unable to successfully activate the ER stress/UPR responses, and that the mitochondria appear to be a central player in OphA-induced cancer cell death. PMID:28112374

The relevance of ice crystal formation for the cryopreservation of tissues and organs.

PubMed

Pegg, David E

2010-07-01

This paper discusses the role of ice crystal formation in causing or contributing to the difficulties that have been encountered in attempts to develop effective methods for the cryopreservation of some tissues and all organs. It is shown that extracellular ice can be severely damaging but also that cells in situ in tissues can behave quite differently from similar cells in a suspension with respect to intracellular freezing. It is concluded that techniques that avoid the formation of ice altogether are most likely to yield effective methods for the cryopreservation of recalcitrant tissues and vascularised organs. Copyright 2010 Elsevier Inc. All rights reserved.

Multiscale biomechanics of brain tumours favours cancer invasion by cell softening and tissue stiffening

NASA Astrophysics Data System (ADS)

Kas, Josef; Fritsch, Anatol; Grosser, Steffen; Friebe, Sabrina; Reiss-Zimmermann, Martin; Müller, Wolf; Hoffmann, Karl-Titus; Sack, Ingolf

Cancer progression needs two contradictory mechanical prerequisites. For metastasis individual cancer cells or small clusters have to flow through the microenvironment by overcoming the yield stress exerted by the surrounding. On the other hand a tumour has to behave as a solid to permit cell proliferation and spreading of the tumour mass against its surrounding. We determine that the high mechanical adaptability of cancer cells and the scale controlled viscoelastic properties of tissues reconcile both conflicting properties, fluid and solid, simultaneously in brain tumours. We resolve why different techniques that assess cell and tissue mechanics have produced apparently conflicting results by our finding that tumours generate different viscoelastic behaviours on different length scales, which are in concert optimal for tumour spreading and metastasis. Single cancer cells become very soft in their elastic behavior which promotes cell unjamming. On the level of direct cell-to-cell interactions cells feel their micro-environment as rigid elastic substrate that stimulates cancer on the molecular level. All over a tumour has predominately a stiff elastic character in terms of viscoelastic behaviour caused by a solid backbone. Simultaneously, the tumour mass is characterized by a large local variability in the storage and loss modulus that is caused by areas of a more fluid nature.

Random-access scanning microscopy for 3D imaging in awake behaving animals

PubMed Central

Nadella, K. M. Naga Srinivas; Roš, Hana; Baragli, Chiara; Griffiths, Victoria A.; Konstantinou, George; Koimtzis, Theo; Evans, Geoffrey J.; Kirkby, Paul A.; Silver, R. Angus

2018-01-01

Understanding how neural circuits process information requires rapid measurements from identified neurons distributed in 3D space. Here we describe an acousto-optic lens two-photon microscope that performs high-speed focussing and line-scanning within a volume spanning hundreds of micrometres. We demonstrate its random access functionality by selectively imaging cerebellar interneurons sparsely distributed in 3D and by simultaneously recording from the soma, proximal and distal dendrites of neocortical pyramidal cells in behaving mice. PMID:27749836

S1P dependent inter organ trafficking of group 2 innate lymphoid cells suppots host defense

USDA-ARS?s Scientific Manuscript database

Innate lymphoid cells (ILCs) are considered to be the innate counterparts of adaptive T lymphocytes and play important roles in host defense, tissue repair, metabolic homeostasis, and inflammatory diseases. ILCs are generally thought of as tissue-resident cells, but whether ILCs strictly behave in a...

Cellular uptake and trafficking of polydiacetylene micelles

NASA Astrophysics Data System (ADS)

Gravel, Edmond; Thézé, Benoit; Jacques, Isabelle; Anilkumar, Parambath; Gombert, Karine; Ducongé, Frédéric; Doris, Eric

2013-02-01

Polydiacetylene (PDA) micelles coated with either carboxylate-, ammonium-, or methoxy-polyethyleneglycol (PEG) chains were assembled and loaded with a fluorescent dye (DiO). Their interaction with MCF-7 human breast tumor cells was investigated by epi-fluorescence microscopy and fluorescence-activated cell sorting (FACS) to determine their internalization pathway and intracellular fate. It was found that the ionic character of the micelles influenced their internalization kinetics through a caveolae-mediated pathway and that all micelle types behaved somewhat similarly inside cells.Polydiacetylene (PDA) micelles coated with either carboxylate-, ammonium-, or methoxy-polyethyleneglycol (PEG) chains were assembled and loaded with a fluorescent dye (DiO). Their interaction with MCF-7 human breast tumor cells was investigated by epi-fluorescence microscopy and fluorescence-activated cell sorting (FACS) to determine their internalization pathway and intracellular fate. It was found that the ionic character of the micelles influenced their internalization kinetics through a caveolae-mediated pathway and that all micelle types behaved somewhat similarly inside cells. Electronic supplementary information (ESI) available: Detailed synthetic procedures and supplementary figures. See DOI: 10.1039/c2nr34149b

A contrastive study of three graphite anodes in the piperidinium based electrolytes for lithium ion batteries

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jiang, Xiao-Tao; Wang, Chen-Yi; Gao, Kun, E-mail: gaokun0451@163.com

Graphical abstract: The fitting results of R{sub sei} and R{sub ct} of three graphite/Li cells. Besides three graphite/Li cells show the similar R{sub sei}, the NG198/Li cell demonstrates a higher R{sub ct} value in all test temperatures. Especially, the R{sub ct} at 333 K is even up to 355.8 Ω cm{sup 2}. Obviously, the narrow distribution of edge plane for NG198 caused this result, and then greatly restricts its cell capacity. By contrast, CMB with bigger specific surface area and more Li{sup +} insertion points shows lower resistance at room temperature, which should help to improve its capacity. - Highlights:more » • SEI film is closely related to graphite structures and formation temperature. • The graphite with bigger surface area and more Li{sup +} insertion points behaves better. • The graphite with narrow edge plane is uncompetitive for ionic liquid electrolyte. - Abstract: The electrochemical behaviors of natural graphite (NG198), artificial graphite (AG360) and carbon microbeads (CMB) in an ionic liquid based electrolyte are investigated by cyclic voltammetry (CV). The surface and structure of three graphite materials are characterized by scanning electron microscope (SEM) and X-ray diffraction (XRD) before and after cycling. It is found that solid electrolyte interface (SEI) is closely related to graphite structure. Benefiting from larger specific surface area and more dispersed Li{sup +} insertion points, CMB shows a better Li{sup +} insertion/de-insertion behavior than NG198 and AG360. Furthermore, electrochemical impedance spectra (EIS) prove that the SEI of different graphite electrodes has different intrinsic resistance and Li{sup +} penetrability. By comparison, CMB behaves better cell performances than AG360, while the narrow edge plane makes NG198 uncompetitive as a potential anode for the ionic liquids (ILs)-type Li-ion battery.« less

Fluorescent dye technique as an alternative to gfp-labeled plasmid for visualization of Escherichia coli O157:H7 cells on romaine lettuce leaves following sanitizer treatment

USDA-ARS?s Scientific Manuscript database

The task of imaging Escherichia coli O157:H7 cells on artificially inoculated produce often requires genetic modification of the cells through the introduction of gfp-labeled plasmid. However, these modified cells do not behave as the parent cells and the auto fluorescence of lettuce leaves interfe...

Experimental Investigation of Shear Driven Liquid Films for Film Cooling Applications in Liquid Rocket Engines

DTIC Science & Technology

2012-12-01

6 1.1.1 Differences Between Hot-Fire at Subcritical Conditions and Cold Flow ........10 1.1.2 Differences at Supercritical Conditions...cooling. 1.1.2 Differences at Supercritical Conditions Liquid film cooling is expected to behave even more differently at supercritical conditions...phase will behave more like the mixing of two gases of dissimilar densities. Once enough heat is imparted into the supercritical fuel film, it

Cancer cell migration within 3D layer-by-layer microfabricated photocrosslinked PEG scaffolds with tunable stiffness.

PubMed

Soman, Pranav; Kelber, Jonathan A; Lee, Jin Woo; Wright, Tracy N; Vecchio, Kenneth S; Klemke, Richard L; Chen, Shaochen

2012-10-01

Our current understanding of 3-dimensional (3D) cell migration is primarily based on results from fibrous scaffolds with randomly organized internal architecture. Manipulations that change the stiffness of these 3D scaffolds often alter other matrix parameters that can modulate cell motility independently or synergistically, making observations less predictive of how cells behave when migrating in 3D. In order to decouple microstructural influences and stiffness effects, we have designed and fabricated 3D polyethylene glycol (PEG) scaffolds that permit orthogonal tuning of both elastic moduli and microstructure. Scaffolds with log-pile architectures were used to compare the 3D migration properties of normal breast epithelial cells (HMLE) and Twist-transformed cells (HMLET). Our results indicate that the nature of cell migration is significantly impacted by the ability of cells to migrate in the third dimension. 2D ECM-coated PEG substrates revealed no statistically significant difference in cell migration between HMLE and HMLET cells among substrates of different stiffness. However, when cells were allowed to move along the third dimension, substantial differences were observed for cell displacement, velocity and path straightness parameters. Furthermore, these differences were sensitive to both substrate stiffness and the presence of the Twist oncogene. Importantly, these 3D modes of migration provide insight into the potential for oncogene-transformed cells to migrate within and colonize tissues of varying stiffness. Copyright © 2012 Elsevier Ltd. All rights reserved.

Patient-specific modeling and analysis of dynamic behavior of individual sickle red blood cells under hypoxic conditions

NASA Astrophysics Data System (ADS)

Li, Xuejin; Du, E.; Li, Zhen; Tang, Yu-Hang; Lu, Lu; Dao, Ming; Karniadakis, George

2015-11-01

Sickle cell anemia is an inherited blood disorder exhibiting heterogeneous morphology and abnormal dynamics under hypoxic conditions. We developed a time-dependent cell model that is able to simulate the dynamic processes of repeated sickling and unsickling of red blood cells (RBCs) under physiological conditions. By using the kinetic cell model with parameters derived from patient-specific data, we present a mesoscopic computational study of the dynamic behavior of individual sickle RBCs flowing in a microfluidic channel with multiple microgates. We investigate how individual sickle RBCs behave differently from healthy ones in channel flow, and analyze the alteration of cellular behavior and response to single-cell capillary obstruction induced by cell rheologic rigidification and morphological change due to cell sickling under hypoxic conditions. We also simulate the flow dynamics of sickle RBCs treated with hydroxyurea (HU) and quantify the relative enhancement of hemodynamic performance of HU. This work was supported by the National Institutes of Health (NIH) Grant U01HL114476.

Pore-level numerical analysis of the infrared surface temperature of metallic foam

NASA Astrophysics Data System (ADS)

Li, Yang; Xia, Xin-Lin; Sun, Chuang; Tan, He-Ping; Wang, Jing

2017-10-01

Open-cell metallic foams are increasingly used in various thermal systems. The temperature distributions are significant for the comprehensive understanding of these foam-based engineering applications. This study aims to numerically investigate the modeling of the infrared surface temperature (IRST) of open-cell metallic foam measured by an infrared camera placed above the sample. Two typical approaches based on Backward Monte Carlo simulation are developed to estimate the IRSTs: the first one, discrete-scale approach (DSA), uses a realistic discrete representation of the foam structure obtained from a computed tomography reconstruction while the second one, continuous-scale approach (CSA), assumes that the foam sample behaves like a continuous homogeneous semi-transparent medium. The radiative properties employed in CSA are directly determined by a ray-tracing process inside the discrete foam representation. The IRSTs for different material properties (material emissivity, specularity parameter) are computed by the two approaches. The results show that local IRSTs can vary according to the local compositions of the foam surface (void and solid). The temperature difference between void and solid areas is gradually attenuated with increasing material emissivity. In addition, the annular void space near to the foam surface behaves like a black cavity for thermal radiation, which is ensued by copious neighboring skeletons. For most of the cases studied, the mean IRSTs computed by the DSA and CSA are close to each other, except when the material emissivity is highly weakened and the sample temperature is extremely high.

The influence of cell interactions and tissue mass on differentiation of sea urchin mesomeres.

PubMed

Khaner, O; Wilt, F

1990-07-01

The developmental potential of different blastomeres of the sea urchin embryo was re-examined. We have employed a new method to isolate substantial numbers of different kinds of blastomeres from 16-cell-stage embryos, and we have used newly available molecular markers to analyze possible vegetal differentiation. We have found that, while isolated mesomere pairs behave according to the classical expectations and develop into ectodermal vesicles, there is a clear effect of reaggregating two or more mesomere pairs. They survive better in long-term culture and, after prolonged periods, they display an astonishing ability to express vegetal differentiation. We also combined mesomeres with stained micromeres or macromeres from the vegetal hemisphere. Although induction of guts and spicules was observed, there was little if any effect of varying the ratio of different blastomeres on the kinds of differentiation obtained.

D'Arcy Thompson's 'on Growth and form': From soap bubbles to tissue self-organization.

PubMed

Heisenberg, Carl-Philipp

2017-06-01

Tissues are thought to behave like fluids with a given surface tension. Differences in tissue surface tension (TST) have been proposed to trigger cell sorting and tissue envelopment. D'Arcy Thompson in his seminal book 'On Growth and Form' has introduced this concept of differential TST as a key physical mechanism dictating tissue formation and organization within the developing organism. Over the past century, many studies have picked up the concept of differential TST and analyzed the role and cell biological basis of TST in development, underlining the importance and influence of this concept in developmental biology. Copyright © 2017 Elsevier B.V. All rights reserved.

Self-Enhancing in Perceptions of Behaving Unethically.

ERIC Educational Resources Information Center

Manley, Gregory G.; Russell, Craig J.; Buckley, M. Ronald

2001-01-01

Presented with ethics scenarios, the majority of 43 accounting and 43 marketing majors perceived themselves less likely to behave unethically than others would. Marketing majors showed significantly higher levels of self-enhancement bias, a difference that decreased as perceived risk increased. (SK)

Correlations and Functional Connections in a Population of Grid Cells

PubMed Central

Roudi, Yasser

2015-01-01

We study the statistics of spike trains of simultaneously recorded grid cells in freely behaving rats. We evaluate pairwise correlations between these cells and, using a maximum entropy kinetic pairwise model (kinetic Ising model), study their functional connectivity. Even when we account for the covariations in firing rates due to overlapping fields, both the pairwise correlations and functional connections decay as a function of the shortest distance between the vertices of the spatial firing pattern of pairs of grid cells, i.e. their phase difference. They take positive values between cells with nearby phases and approach zero or negative values for larger phase differences. We find similar results also when, in addition to correlations due to overlapping fields, we account for correlations due to theta oscillations and head directional inputs. The inferred connections between neurons in the same module and those from different modules can be both negative and positive, with a mean close to zero, but with the strongest inferred connections found between cells of the same module. Taken together, our results suggest that grid cells in the same module do indeed form a local network of interconnected neurons with a functional connectivity that supports a role for attractor dynamics in the generation of grid pattern. PMID:25714908

On-line and real-time diagnosis method for proton membrane fuel cell (PEMFC) stack by the superposition principle

NASA Astrophysics Data System (ADS)

Lee, Young-Hyun; Kim, Jonghyeon; Yoo, Seungyeol

2016-09-01

The critical cell voltage drop in a stack can be followed by stack defect. A method of detecting defective cell is the cell voltage monitoring. The other methods are based on the nonlinear frequency response. In this paper, the superposition principle for the diagnosis of PEMFC stack is introduced. If critical cell voltage drops exist, the stack behaves as a nonlinear system. This nonlinearity can explicitly appear in the ohmic overpotential region of a voltage-current curve. To detect the critical cell voltage drop, a stack is excited by two input direct test-currents which have smaller amplitude than an operating stack current and have an equal distance value from the operating current. If the difference between one voltage excited by a test current and the voltage excited by a load current is not equal to the difference between the other voltage response and the voltage excited by the load current, the stack system acts as a nonlinear system. This means that there is a critical cell voltage drop. The deviation from the value zero of the difference reflects the grade of the system nonlinearity. A simulation model for the stack diagnosis is developed based on the SPP, and experimentally validated.

Cholesteric microlenses and micromirrors in the beetle cuticle and in synthetic oligomer films: a comparative study

NASA Astrophysics Data System (ADS)

Agez, Gonzague; Bayon, Chloé; Mitov, Michel

2017-02-01

The polygonal texture in cholesteric liquid crystals consist in an array of contiguous polygonal cells. The optical response and the structure of polygonal texture are investigated in the cuticle of beetle Chrysina gloriosa and in synthetic oligomer films. In the insect carapace, the polygons are concave and behave as spherical micro-mirrors whereas they are convex and behave as diverging microlenses in synthetic films. The characteristics of light focusing (spot, donut or continuum background) are highly tunable with the wavelength and the polarization of the incident light.

Embryonic origin of adult stem cells required for tissue homeostasis and regeneration

PubMed Central

Davies, Erin L; Lei, Kai; Seidel, Christopher W; Kroesen, Amanda E; McKinney, Sean A; Guo, Longhua; Robb, Sofia MC; Ross, Eric J; Gotting, Kirsten; Alvarado, Alejandro Sánchez

2017-01-01

Planarian neoblasts are pluripotent, adult somatic stem cells and lineage-primed progenitors that are required for the production and maintenance of all differentiated cell types, including the germline. Neoblasts, originally defined as undifferentiated cells residing in the adult parenchyma, are frequently compared to embryonic stem cells yet their developmental origin remains obscure. We investigated the provenance of neoblasts during Schmidtea mediterranea embryogenesis, and report that neoblasts arise from an anarchic, cycling piwi-1+ population wholly responsible for production of all temporary and definitive organs during embryogenesis. Early embryonic piwi-1+ cells are molecularly and functionally distinct from neoblasts: they express unique cohorts of early embryo enriched transcripts and behave differently than neoblasts in cell transplantation assays. Neoblast lineages arise as organogenesis begins and are required for construction of all major organ systems during embryogenesis. These subpopulations are continuously generated during adulthood, where they act as agents of tissue homeostasis and regeneration. DOI: http://dx.doi.org/10.7554/eLife.21052.001 PMID:28072387

History of Fuel Cell R&D at Fort Belvoir, Virginia

DTIC Science & Technology

2008-04-01

PEMFC but BOP is reduced. In many respects it behaves like a PAFC. MOLTEN CARBONATE FUEL CELL (MCFC) The MCFC operates at high temperature...clean up as required by the PEMFC . It can utilize air cooling without concern electrolyte control which greatly eases BOP issues. The PAFC is highly

Terrestrial Microgravity Model and Threshold Gravity Simulation sing Magnetic Levitation

NASA Technical Reports Server (NTRS)

Ramachandran, N.

2005-01-01

What is the threshold gravity (minimum gravity level) required for the nominal functioning of the human system? What dosage is required? Do human cell lines behave differently in microgravity in response to an external stimulus? The critical need for such a gravity simulator is emphasized by recent experiments on human epithelial cells and lymphocytes on the Space Shuttle clearly showing that cell growth and function are markedly different from those observed terrestrially. Those differences are also dramatic between cells grown in space and those in Rotating Wall Vessels (RWV), or NASA bioreactor often used to simulate microgravity, indicating that although morphological growth patterns (three dimensional growth) can be successiblly simulated using RWVs, cell function performance is not reproduced - a critical difference. If cell function is dramatically affected by gravity off-loading, then cell response to stimuli such as radiation, stress, etc. can be very different from terrestrial cell lines. Yet, we have no good gravity simulator for use in study of these phenomena. This represents a profound shortcoming for countermeasures research. We postulate that we can use magnetic levitation of cells and tissue, through the use of strong magnetic fields and field gradients, as a terrestrial microgravity model to study human cells. Specific objectives of the research are: 1. To develop a tried, tested and benchmarked terrestrial microgravity model for cell culture studies; 2. Gravity threshold determination; 3. Dosage (magnitude and duration) of g-level required for nominal functioning of cells; 4. Comparisons of magnetic levitation model to other models such as RWV, hind limb suspension, etc. and 5. Cellular response to reduced gravity levels of Moon and Mars.

Acid, basic, and neutral peptidases present different profiles in chromophobe renal cell carcinoma and in oncocytoma.

PubMed

Blanco, Lorena; Larrinaga, Gorka; Pérez, Itxaro; López, José I; Gil, Javier; Agirregoitia, Ekaitz; Varona, Adolfo

2008-04-01

Renal cell carcinomas (RCCs) are neoplasias with high prevalence and mortality. We previously reported that several peptidases may be involved in the pathophysiology of clear cell renal cell carcinoma (CCRCC). Now, to gain insight into the reasons that lead the various RCC types to behave very differently with regard to aggressiveness and response to anticancer treatments, we analyzed subsets of chromophobe renal cell carcinoma (ChRCC), and renal oncocytoma (RO), a benign tumor; as well as different grades and stages of CCRCCs. Particulate APN, APB, and APA activities were decreased in both ChRCC and RO (tumor vs. nontumor tissues). Interestingly, activities were downregulated in a tumor-type specific way and the intensities of the decreases were stronger in the benign tumor than in the malignant type. Moreover, when two key histopathological parameters for tumor prognosis (high vs. low stage and grade) were analyzed, increases of activity were also observed in several of these cell surface peptidases (APN, APB). Some soluble activities (APB, Asp-AP) were also downregulated in the RCCs. With respect to genetic expression, PSA and APN were in a positive correlation related to their activities in both ChRCC and RO; but not APB, Asp-AP, APA, and PGI. These results may suggest an involvement of several peptidases in the pathophysiology of renal cancer, since they presented different patterns of activity and expression in tumors with different behaviors.

Cross-stream distribution of red blood cells in sickle-cell disease

NASA Astrophysics Data System (ADS)

Zhang, Xiao; Lam, Wilbur; Graham, Michael

2017-11-01

Experiments revealed that in blood flow, red blood cells (RBCs) tend to migrate away from the vessel walls, leaving a cell-free layer near the walls, while leukocytes and platelets tend to marginate towards the vessel walls. This segregation behavior of different cellular components in blood flow can be driven by their differences in stiffness and shape. An alteration of this segregation behavior may explain endothelial dysfunction and pain crisis associated with sickle-cell disease (SCD). It is hypothesized that the sickle RBCs, which are considerably stiffer than the healthy RBCs, may marginate towards the vessel walls and exert repeated damage to the endothelial cells. Direct simulations are performed to study the flowing suspensions of deformable biconcave discoids and stiff sickles representing healthy and sickle cells, respectively. It is observed that the sickles exhibit a strong margination towards the walls. The biconcave discoids in flowing suspensions undergo a so-called tank-treading motion, while the sickles behave as rigid bodies and undergo a tumbling motion. The margination behavior and tumbling motion of the sickles may help substantiate the aforementioned hypothesis of the mechanism for the SCD complications and shed some light on the design of novel therapies.

Behavior of restriction–modification systems as selfish mobile elements and their impact on genome evolution

PubMed Central

Kobayashi, Ichizo

2001-01-01

Restriction–modification (RM) systems are composed of genes that encode a restriction enzyme and a modification methylase. RM systems sometimes behave as discrete units of life, like viruses and transposons. RM complexes attack invading DNA that has not been properly modified and thus may serve as a tool of defense for bacterial cells. However, any threat to their maintenance, such as a challenge by a competing genetic element (an incompatible plasmid or an allelic homologous stretch of DNA, for example) can lead to cell death through restriction breakage in the genome. This post-segregational or post-disturbance cell killing may provide the RM complexes (and any DNA linked with them) with a competitive advantage. There is evidence that they have undergone extensive horizontal transfer between genomes, as inferred from their sequence homology, codon usage bias and GC content difference. They are often linked with mobile genetic elements such as plasmids, viruses, transposons and integrons. The comparison of closely related bacterial genomes also suggests that, at times, RM genes themselves behave as mobile elements and cause genome rearrangements. Indeed some bacterial genomes that survived post-disturbance attack by an RM gene complex in the laboratory have experienced genome rearrangements. The avoidance of some restriction sites by bacterial genomes may result from selection by past restriction attacks. Both bacteriophages and bacteria also appear to use homologous recombination to cope with the selfish behavior of RM systems. RM systems compete with each other in several ways. One is competition for recognition sequences in post-segregational killing. Another is super-infection exclusion, that is, the killing of the cell carrying an RM system when it is infected with another RM system of the same regulatory specificity but of a different sequence specificity. The capacity of RM systems to act as selfish, mobile genetic elements may underlie the structure and function of RM enzymes. PMID:11557807

Behavior of restriction-modification systems as selfish mobile elements and their impact on genome evolution.

PubMed

Kobayashi, I

2001-09-15

Restriction-modification (RM) systems are composed of genes that encode a restriction enzyme and a modification methylase. RM systems sometimes behave as discrete units of life, like viruses and transposons. RM complexes attack invading DNA that has not been properly modified and thus may serve as a tool of defense for bacterial cells. However, any threat to their maintenance, such as a challenge by a competing genetic element (an incompatible plasmid or an allelic homologous stretch of DNA, for example) can lead to cell death through restriction breakage in the genome. This post-segregational or post-disturbance cell killing may provide the RM complexes (and any DNA linked with them) with a competitive advantage. There is evidence that they have undergone extensive horizontal transfer between genomes, as inferred from their sequence homology, codon usage bias and GC content difference. They are often linked with mobile genetic elements such as plasmids, viruses, transposons and integrons. The comparison of closely related bacterial genomes also suggests that, at times, RM genes themselves behave as mobile elements and cause genome rearrangements. Indeed some bacterial genomes that survived post-disturbance attack by an RM gene complex in the laboratory have experienced genome rearrangements. The avoidance of some restriction sites by bacterial genomes may result from selection by past restriction attacks. Both bacteriophages and bacteria also appear to use homologous recombination to cope with the selfish behavior of RM systems. RM systems compete with each other in several ways. One is competition for recognition sequences in post-segregational killing. Another is super-infection exclusion, that is, the killing of the cell carrying an RM system when it is infected with another RM system of the same regulatory specificity but of a different sequence specificity. The capacity of RM systems to act as selfish, mobile genetic elements may underlie the structure and function of RM enzymes.

Laser beam coupling into nerve fiber myelin allows one to assess its structural membrane properties

NASA Astrophysics Data System (ADS)

Kutuzov, Nikolay P.; Brazhe, Alexey R.; Lyaskovskiy, Vladimir L.; Maksimov, Georgy V.

2015-05-01

We show that myelin, the insulation wrap of nerve fibers, can couple laser light, thus behaving as a single-cell optical device. The effect was employed to map distinct myelin regions based on the coupling efficiency. Raman spectra acquisition allowed us to simultaneously understand the underlying microscopic differences in the membrane lipid ordering degree. The described method potentially provides new capabilities in myelin-associated disease studies and can be used as a handy tool for myelin structure investigation in combination with other methods.

Mechanical behavior in living cells consistent with the tensegrity model

NASA Technical Reports Server (NTRS)

Wang, N.; Naruse, K.; Stamenovic, D.; Fredberg, J. J.; Mijailovich, S. M.; Tolic-Norrelykke, I. M.; Polte, T.; Mannix, R.; Ingber, D. E.

2001-01-01

Alternative models of cell mechanics depict the living cell as a simple mechanical continuum, porous filament gel, tensed cortical membrane, or tensegrity network that maintains a stabilizing prestress through incorporation of discrete structural elements that bear compression. Real-time microscopic analysis of cells containing GFP-labeled microtubules and associated mitochondria revealed that living cells behave like discrete structures composed of an interconnected network of actin microfilaments and microtubules when mechanical stresses are applied to cell surface integrin receptors. Quantitation of cell tractional forces and cellular prestress by using traction force microscopy confirmed that microtubules bear compression and are responsible for a significant portion of the cytoskeletal prestress that determines cell shape stability under conditions in which myosin light chain phosphorylation and intracellular calcium remained unchanged. Quantitative measurements of both static and dynamic mechanical behaviors in cells also were consistent with specific a priori predictions of the tensegrity model. These findings suggest that tensegrity represents a unified model of cell mechanics that may help to explain how mechanical behaviors emerge through collective interactions among different cytoskeletal filaments and extracellular adhesions in living cells.

The Yin and Yang of Innate Lymphoid Cells in Cancer.

PubMed

Carrega, Paolo; Campana, Stefania; Bonaccorsi, Irene; Ferlazzo, Guido

2016-11-01

The recent appreciation of novel subsets of innate lymphoid cells (ILCs) as important regulators of tissue homeostasis, inflammation and repair, raise questions regarding the presence and role of these cells in cancer tissues. In addition to natural killer and fetal lymphoid tissue inducer (LTi) cells, the ILC family comprises non-cytolytic, cytokine-producing cells that are classified into ILC1, ILC2 and ILC3 based on phenotypic and functional characteristics. Differently from natural killer cells, which are the prototypical members of ILC1 and whose role in tumors is better established, the involvement of other ILC subsets in cancer progression or resistance is still fuzzy and in several instances controversial, since current studies indicate both context-dependent beneficial or pathogenic effects. Here, we review the current knowledge regarding the involvement of these novel ILC subsets in the context of tumor immunology, highlighting how ILC subsets might behave either as friends or foes. Copyright © 2016 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

Effector and central memory T helper 2 cells respond differently to peptide immunotherapy

PubMed Central

Mackenzie, Karen J.; Nowakowska, Dominika J.; Leech, Melanie D.; McFarlane, Amanda J.; Wilson, Claire; Fitch, Paul M.; O’Connor, Richard A.; Howie, Sarah E. M.; Schwarze, Jürgen; Anderton, Stephen M.

2014-01-01

Peptide immunotherapy (PIT) offers realistic prospects for the treatment of allergic diseases, including allergic asthma. Much is understood of the behavior of naive T cells in response to PIT. However, treatment of patients with ongoing allergic disease requires detailed understanding of the responses of allergen-experienced T cells. CD62L expression by allergen-experienced T cells corresponds to effector/effector memory (CD62Llo) and central memory (CD62Lhi) subsets, which vary with allergen exposure (e.g., during, or out with, pollen season). The efficacy of PIT on different T helper 2 (Th2) cell memory populations is unknown. We developed a murine model of PIT in allergic airway inflammation (AAI) driven by adoptively transferred, traceable ovalbumin-experienced Th2 cells. PIT effectively suppressed AAI driven by unfractionated Th2 cells. Selective transfer of CD62Lhi and CD62Llo Th2 cells revealed that these two populations behaved differently from one another and from previously characterized (early deletional) responses of naive CD4+ T cells to PIT. Most notably, allergen-reactive CD62Llo Th2 cells were long-lived within the lung after PIT, before allergen challenge, in contrast to CD62Lhi Th2 cells. Despite this, PIT was most potent against CD62Llo Th2 cells in protecting from AAI, impairing their ability to produce Th2 cytokines, whereas this capacity was heightened in PIT-treated CD62Lhi Th2 cells. We conclude that Th2 cells do not undergo an early deletional form of tolerance after PIT. Moreover, memory Th2 subsets respond differently to PIT. These findings have implications for the clinical translation of PIT in different allergic scenarios. PMID:24516158

Large-Scale Fluorescence Calcium-Imaging Methods for Studies of Long-Term Memory in Behaving Mammals

PubMed Central

Jercog, Pablo; Rogerson, Thomas; Schnitzer, Mark J.

2016-01-01

During long-term memory formation, cellular and molecular processes reshape how individual neurons respond to specific patterns of synaptic input. It remains poorly understood how such changes impact information processing across networks of mammalian neurons. To observe how networks encode, store, and retrieve information, neuroscientists must track the dynamics of large ensembles of individual cells in behaving animals, over timescales commensurate with long-term memory. Fluorescence Ca2+-imaging techniques can monitor hundreds of neurons in behaving mice, opening exciting avenues for studies of learning and memory at the network level. Genetically encoded Ca2+ indicators allow neurons to be targeted by genetic type or connectivity. Chronic animal preparations permit repeated imaging of neural Ca2+ dynamics over multiple weeks. Together, these capabilities should enable unprecedented analyses of how ensemble neural codes evolve throughout memory processing and provide new insights into how memories are organized in the brain. PMID:27048190

A theoretical and computational framework for mechanics of the cortex

NASA Astrophysics Data System (ADS)

Torres-SáNchez, Alejandro; Arroyo, Marino

The cell cortex is a thin network of actin filaments lying beneath the cell surface of animal cells. Myosin motors exert contractile forces in this network leading to active stresses, which play a key role in processes such as cytokinesis or cell migration. Thus, understanding the mechanics of the cortex is fundamental to understand the mechanics of animal cells. Due to the dynamic remodeling of the actin network, the cortex behaves as a viscoelastic fluid. Furthermore, due to the difference between its thickness (tens of nanometers) and its dimensions (tens of microns), the cortex can be regarded a surface. Thus, we can model the cortex as a viscoelastic fluid, confined to a surface, that generates active stresses. Interestingly, geometric confinement results in the coupling between shape generation and material flows. In this work we present a theoretical framework to model the mechanics of the cortex that couples elasticity, hydrodynamics and force generation. We complement our theoretical description with a computational setting to simulate the resulting non-linear equations. We use this methodology to understand different processes such as asymmetric cell division or experimental probing of the rheology of the cortex We acknowledge the support of the Europen Research Council through Grant ERC CoG-681434.

Cell lineage patterns in the shoot meristem of the sunflower embryo in the dry seed

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jegla, D.E.; Sussex, I.M.

1989-01-01

We mapped the fate of cells in the shoot meristem of the dry-seed embryo of sunflower, Helianthus annuus L. cv. Peredovic, using irradiation-induced somatic sectors. We analyzed 249 chlorophyll-deficient or glabrous (hairless) sectors generated in 236 plants. Most sectors observed in the inflorescence extended into vegetative nodes. Thus cell lineages that ultimately gave rise to reproductive structures also contributed to vegetative structures. No single sector extended the entire length of the shoot. Thus the shoot is not derived from one or a few apical initials. Rather, the position, vertical extent, and width of the sectors at different levels of themore » shoot suggest that the shoot is derived from three to four circumferential populations of cells in each of three cell layers of the embryo meristem. Sectors had no common boundaries even in plants with two or three independent sectors, but varied in extent and overlapped along the length of the shoot. Thus individual cells in a single circumferential population behaved independently to contribute lineages of different vertical extents to the growing shoot. The predicted number of circumferential populations of cells as well as the apparent cell number in each population was consistent with the actual number of cells in the embryo meristem observed in histological sections.« less

Disentangling Random Motion and Flow in a Complex Medium

PubMed Central

Koslover, Elena F.; Chan, Caleb K.; Theriot, Julie A.

2016-01-01

We describe a technique for deconvolving the stochastic motion of particles from large-scale fluid flow in a dynamic environment such as that found in living cells. The method leverages the separation of timescales to subtract out the persistent component of motion from single-particle trajectories. The mean-squared displacement of the resulting trajectories is rescaled so as to enable robust extraction of the diffusion coefficient and subdiffusive scaling exponent of the stochastic motion. We demonstrate the applicability of the method for characterizing both diffusive and fractional Brownian motion overlaid by flow and analytically calculate the accuracy of the method in different parameter regimes. This technique is employed to analyze the motion of lysosomes in motile neutrophil-like cells, showing that the cytoplasm of these cells behaves as a viscous fluid at the timescales examined. PMID:26840734

Chromatid repulsion associated with Roberts/SC phocomelia syndrome is reduced in malignant cells and not expressed in interspecies somatic-cell hybrids.

PubMed Central

Krassikoff, N E; Cowan, J M; Parry, D M; Francke, U

1986-01-01

Different cell types from a female patient with Roberts/SC phocomelia syndrome were evaluated quantitatively for the presence of repulsion of heterochromatin and satellite regions of mitotic chromosomes. Whereas EBV-transformed lymphoblasts from an established cell line revealed these phenomena at frequencies equal to those in PHA-stimulated lymphocytes and cultured skin fibroblasts, aneuploid cells from a metastatic melanoma displayed them at 50% lower frequency. Cocultivation of the patient's fibroblasts with either an immortal Chinese hamster cell line or with a human male fibroblast strain carrying a t(4;6)(p14;q21) translocation showed that the phenomenon was not corrected or induced by a diffusible factor or by cell-to-cell contact. In each experiment, only the patient's metaphase spreads revealed chromatid repulsion. In fusion hybrids between the patient's fibroblasts and an established Chinese hamster cell line, the human chromosomes behaved perfectly normally, suggesting that the gene product which is missing or mutant in Roberts/SC phocomelia syndrome is supplied by the Chinese hamster genome. Images Fig. 1 Fig. 2 Fig. 3 PMID:3788975

The longest telomeres: a general signature of adult stem cell compartments

PubMed Central

Flores, Ignacio; Canela, Andres; Vera, Elsa; Tejera, Agueda; Cotsarelis, George; Blasco, María A.

2008-01-01

Identification of adult stem cells and their location (niches) is of great relevance for regenerative medicine. However, stem cell niches are still poorly defined in most adult tissues. Here, we show that the longest telomeres are a general feature of adult stem cell compartments. Using confocal telomere quantitative fluorescence in situ hybridization (telomapping), we find gradients of telomere length within tissues, with the longest telomeres mapping to the known stem cell compartments. In mouse hair follicles, we show that cells with the longest telomeres map to the known stem cell compartments, colocalize with stem cell markers, and behave as stem cells upon treatment with mitogenic stimuli. Using K15-EGFP reporter mice, which mark hair follicle stem cells, we show that GFP-positive cells have the longest telomeres. The stem cell compartments in small intestine, testis, cornea, and brain of the mouse are also enriched in cells with the longest telomeres. This constitutes the description of a novel general property of adult stem cell compartments. Finally, we make the novel finding that telomeres shorten with age in different mouse stem cell compartments, which parallels a decline in stem cell functionality, suggesting that telomere loss may contribute to stem cell dysfunction with age. PMID:18283121

Four Novel Splice-Switch Reporter Cell Lines: Distinct Impact of Oligonucleotide Chemistry and Delivery Vector on Biological Activity.

PubMed

Rocha, Cristina S J; Lundin, Karin E; Behlke, Mark A; Zain, Rula; El Andaloussi, Samir; Smith, C I Edvard

2016-12-01

New advances in oligonucleotide (ON) chemistry emerge continuously, and over the last few years, several aspects of ON delivery have been improved. However, clear knowledge regarding how certain chemistries behave alone, or in combination with various delivery vectors, is limited. Moreover, characterization is frequently limited to a single reporter cell line and, when different cell types are studied, experiments are commonly not carried out under similar conditions, hampering comparative analysis. To address this, we have developed a small "tissue" library of new, stable, pLuc/705 splice-switching reporter cell lines (named HuH7_705, U-2 OS_705, C2C12_705, and Neuro-2a_705). Our data show that, indeed, the cell type used in activity screenings influences the efficiency of ONs of different chemistry (phosphorothioate with locked nucleic acid or 2'-O-methyl with or without N,N-diethyl-4-(4-nitronaphthalen-1-ylazo)-phenylamine). Likewise, the delivery method, Lipofectamine ® 2000, PepFect14 nanoparticles, or "naked" uptake, also demonstrates cell-type-dependent outcomes. Taken together, these cell lines can potentially become useful tools for future in vitro evaluation of new nucleic acid-based oligomers as well as delivery compounds for splice-switching approaches and cell-specific therapies.

Terrestrial Microgravity Model and Threshold Gravity Simulation using Magnetic Levitation

NASA Technical Reports Server (NTRS)

Ramachandran, N.

2005-01-01

What is the threshold gravity (minimum gravity level) required for the nominal functioning of the human system? What dosage is required? Do human cell lines behave differently in microgravity in response to an external stimulus? The critical need for such a gravity simulator is emphasized by recent experiments on human epithelial cells and lymphocytes on the Space Shuttle clearly showing that cell growth and function are markedly different from those observed terrestrially. Those differences are also dramatic between cells grown in space and those in Rotating Wall Vessels (RWV), or NASA bioreactor often used to simulate microgravity, indicating that although morphological growth patterns (three dimensional growth) can be successfully simulated using RWVs, cell function performance is not reproduced - a critical difference. If cell function is dramatically affected by gravity off-loading, then cell response to stimuli such as radiation, stress, etc. can be very different from terrestrial cell lines. Yet, we have no good gravity simulator for use in study of these phenomena. This represents a profound shortcoming for countermeasures research. We postulate that we can use magnetic levitation of cells and tissue, through the use of strong magnetic fields and field gradients, as a terrestrial microgravity model to study human cells. Specific objectives of the research are: 1. To develop a tried, tested and benchmarked terrestrial microgravity model for cell culture studies; 2. Gravity threshold determination; 3. Dosage (magnitude and duration) of g-level required for nominal functioning of cells; 4. Comparisons of magnetic levitation model to other models such as RWV, hind limb suspension, etc. and 5. Cellular response to reduced gravity levels of Moon and Mars. The paper will discuss experiments md modeling work to date in support of this project.

Threshold Gravity Determination and Artificial Gravity Studies Using Magnetic Levitation

NASA Technical Reports Server (NTRS)

Ramachandran, N.; Leslie, F.

2005-01-01

What is the threshold gravity (minimum gravity level) required for the nominal functioning of the human system? What dosage is required (magnitude and duration)? Do human cell lines behave differently in microgravity in response to an external stimulus? The critical need for a variable gravity simulator is emphasized by recent experiments on human epithelial cells and lymphocytes on the Space Shuttle clearly showing that cell growth and function are markedly different from those observed terrestrially. Those differences are also dramatic between cells grown in space and those in Rotating Wall Vessels (RWV), or NASA bioreactor often used to simulate microgravity, indicating that although morphological growth patterns (three dimensional growth) can be successfully simulated using RWVs, cell function performance is not reproduced - a critical difference. If cell function is dramatically affected by gravity off-loading, then cell response to stimuli such as radiation, stress, etc. can be very different from terrestrial cell lines. Yet, we have no good gravity simulator for use in study of these phenomena. This represents a profound shortcoming for countermeasures research. We postulate that we can use magnetic levitation of cells and tissue, through the use of strong magnetic fields and field gradients, as a terrestrial microgravity model to study human cells. Specific objectives of the research are: 1. To develop a tried, tested and benchmarked terrestrial microgravity model for cell culture studies; 2. Gravity threshold determination; 3. Dosage (magnitude and duration) of g-level required for nominal functioning of cells; 4. Comparisons of magnetic levitation model to other models such as RWV, hind limb suspension, etc. and 5. Cellular response to reduced gravity levels of Moon and Mars.

Multiwavelength micromirrors in the cuticle of scarab beetle Chrysina gloriosa.

PubMed

Agez, Gonzague; Bayon, Chloé; Mitov, Michel

2017-01-15

Beetles from the genus Chrysina show vivid reflections from bright green to metallic silver-gold as a consequence of the cholesteric liquid crystal organization of chitin molecules. Particularly, the cuticle of Chrysina gloriosa exhibits green and silver stripes. By combining confocal microscopy and spectrophotometry, scanning electron microscopy and numerical simulations, the relationship between the reflectance and the structural parameters for both stripes at the micro- and nanoscales are established. Over the visible and near IR spectra, polygonal cells in tessellated green stripes behave as multiwavelength selective micro-mirrors and the silver stripes as specular broadband mirrors. Thermoregulation, conspecifics or intra-species communication, or camouflage against predators are discussed as possible functions. As a prerequisite to bio-inspired artificial replicas, the physical characteristics of the polygonal texture in Chrysina gloriosa cuticle are compared to their equivalents in synthetic cholesteric oligomers and their fundamental differences are ascertained. It is shown that the cuticle has concave cells whereas the artificial films have convex cells, contrary to expectation and assumption in the literature. The present results may provide inspiration for fabricating multiwavelength selective micromirrors or spatial wavelength-specific light modulators. Many insects own a tessellated carapace with bumps, pits or indentations. Little is known on the physical properties of these geometric variations and biological functions are unknown or still debated. We show that the polygonal cells in scarab beetle Chrysina gloriosa behave as multiwavelength selective micromirrors over the visible and infrared spectra, with a variety of spatial patterns. In the context of biomimetic materials, we demonstrate that the carapace has concave cells whereas the artificial films have convex cells, contrary to expectation in the literature. Thermoregulation, communication or camouflage are discussed as advanced functions. Results may provide inspiration for fabricating spatial wavelength-specific light modulators and optical packet switching in routing technologies. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Mechanisms underlying the organizer formation in Bufo arenarum embryos.

PubMed

Manes, M E; Nieto, O L

1989-06-01

In the early gastrula of Bufo arenarum the prospective mesoderm was previously identified as a marginal belt of grey cells. To analyze their differentiation capacity explants of these cells were cultured within ectodermal vesicles, in isolation and in combination with vegetal components. When cultured in isolation, dorsal and ventral fragments from the deep marginal zone behaved differently. Whilst ventral explants produced blood cells, dorsal explants failed to differentiate, remaining as masses of yolk-laden cells. On the other hand, both cultures were drastically modified when associated with superficial cells from the blastoporal zone, which caused the following effects: a) Promotion of differentiation in dorsal marginal explants, able now to produce notochordal and somitic structures, in addition to mesenchymatic cells. b) Promotion of dorsalization in ventral marginal explants, which changed their expected destiny developing axial components, similar to those furnished by "activated" dorso marginal explants. On the contrary, combined cultures of animal and vegetal pieces were unable to generate mesodermal structures. These studies suggest that the axial mesoderm, identified as the "organizer", develops from a marginal substrate of genuine mesodermal cells through a dorsalizing inductive stimulus originated in superficial periblastoporal cells.

Live-cell imaging to measure BAX recruitment kinetics to mitochondria during apoptosis

PubMed Central

Maes, Margaret E.; Schlamp, Cassandra L.

2017-01-01

The pro-apoptotic BCL2 gene family member, BAX, plays a pivotal role in the intrinsic apoptotic pathway. Under cellular stress, BAX recruitment to the mitochondria occurs when activated BAX forms dimers, then oligomers, to initiate mitochondria outer membrane permeabilization (MOMP), a process critical for apoptotic progression. The activation and recruitment of BAX to form oligomers has been studied for two decades using fusion proteins with a fluorescent reporter attached in-frame to the BAX N-terminus. We applied high-speed live cell imaging to monitor the recruitment of BAX fusion proteins in dying cells. Data from time-lapse imaging was validated against the activity of endogenous BAX in cells, and analyzed using sigmoid mathematical functions to obtain detail of the kinetic parameters of the recruitment process at individual mitochondrial foci. BAX fusion proteins behave like endogenous BAX during apoptosis. Kinetic studies show that fusion protein recruitment is also minimally affected in cells lacking endogenous BAK or BAX genes, but that the kinetics are moderately, but significantly, different with different fluorescent tags in the fusion constructs. In experiments testing BAX recruitment in 3 different cell lines, our results show that regardless of cell type, once activated, BAX recruitment initiates simultaneously within a cell, but exhibits varying rates of recruitment at individual mitochondrial foci. Very early during BAX recruitment, pro-apoptotic molecules are released in the process of MOMP, but different molecules are released at different times and rates relative to the time of BAX recruitment initiation. These results provide a method for BAX kinetic analysis in living cells and yield greater detail of multiple characteristics of BAX-induced MOMP in living cells that were initially observed in cell free studies. PMID:28880942

Live-cell imaging to measure BAX recruitment kinetics to mitochondria during apoptosis.

PubMed

Maes, Margaret E; Schlamp, Cassandra L; Nickells, Robert W

2017-01-01

The pro-apoptotic BCL2 gene family member, BAX, plays a pivotal role in the intrinsic apoptotic pathway. Under cellular stress, BAX recruitment to the mitochondria occurs when activated BAX forms dimers, then oligomers, to initiate mitochondria outer membrane permeabilization (MOMP), a process critical for apoptotic progression. The activation and recruitment of BAX to form oligomers has been studied for two decades using fusion proteins with a fluorescent reporter attached in-frame to the BAX N-terminus. We applied high-speed live cell imaging to monitor the recruitment of BAX fusion proteins in dying cells. Data from time-lapse imaging was validated against the activity of endogenous BAX in cells, and analyzed using sigmoid mathematical functions to obtain detail of the kinetic parameters of the recruitment process at individual mitochondrial foci. BAX fusion proteins behave like endogenous BAX during apoptosis. Kinetic studies show that fusion protein recruitment is also minimally affected in cells lacking endogenous BAK or BAX genes, but that the kinetics are moderately, but significantly, different with different fluorescent tags in the fusion constructs. In experiments testing BAX recruitment in 3 different cell lines, our results show that regardless of cell type, once activated, BAX recruitment initiates simultaneously within a cell, but exhibits varying rates of recruitment at individual mitochondrial foci. Very early during BAX recruitment, pro-apoptotic molecules are released in the process of MOMP, but different molecules are released at different times and rates relative to the time of BAX recruitment initiation. These results provide a method for BAX kinetic analysis in living cells and yield greater detail of multiple characteristics of BAX-induced MOMP in living cells that were initially observed in cell free studies.

Ethical Practice: A Study of Chilean School Leaders

ERIC Educational Resources Information Center

Cuellar, Carolina; Giles, David L.

2012-01-01

Purpose: This article seeks to report on a research inquiry that explored the educational praxis of ethical school leaders in Chile. Behaving ethically is an imperative for school leaders. Being an ethical educational leader is something different. It is not only about behaving according to standards, but also rather involves an ethical way of…

Effects of trypsin and low Ca2+ on zonulae adhaerentes between chick retinal pigment epithelial cells in organ culture.

PubMed

Sandig, M; Hergott, G J; Kalnins, V I

1990-01-01

The junctional complexes in chick retinal pigment epithelial (RPE) cells in situ contain unusually large zonulae adhaerentes (ZAs) composed of subunits termed zonula adhaerens complexes (ZACs). To determine whether the properties of the ZAs differ between RPE cells which contain ZACs, and MDCK cells which lack ZACs, we investigated the effects of treatment with trypsin and/or low Ca2+ by transmission electron microscopy and staining for F-actin. Treatment of RPE cells for 1 h with trypsin alone has no apparent effect on the morphology of the ZA in either MDCK or RPE cells. In contrast to the ZAs in MDCK cells, which split after 3 min in low Ca2+, the ZAs in chick RPE cells stay intact even after 2 h, although the intermembrane discs, i.e., the extracellular components of the ZACs, are no longer visible. After 30 min of treatment with trypsin and low Ca2+, the ZAs split in both cell types. The CMBs start to contract, translocate toward the cell interior, and eventually disappear. This process continues even when the RPE cells are returned to normal medium. New ZAs, composed of ZACs, form between RPE cells 3 h after return to normal medium. These findings suggest that the ZACs in the ZAs of RPE cells are not directly responsible for the increase in resistance to low Ca2+. They also show that the ZA-junctions in RPE cells are not only structurally different from those previously examined, but also behave differently in response to experimental manipulation.

Pycnogenol (PYC) induces apoptosis in human fibrosarcoma (HFS) cells under metal-mediated oxidative stress.

PubMed

Park, Yeon Sun; Kim, Young Gon

2011-01-01

Pycnogenol (PYC), polyphenolic compounds with antioxidant activity, acted as a prooxidant. PYC caused oxidative stress in human fibrosarcoma cells (HFS) when administered following pretreatment with iron chloride. The generated reactive oxygen species (ROS) caused the formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in DNA and resulted in more apoptosis in HFS cells than in the human fibroblastoma (HFB) cells. DNA damage and cellular viability at different PYC concentrations were closely consistent with cell growth, high performance liquid chromatography (HPLC), Enzyme Linked Immunosorbent Assay (ELISA) and assays of two major antioxidant enzymes, superoxide dismutase (SOD) and catalase. Although the presence of PYC induced total SOD and catalase activities under oxidative stress in dose dependent fashion, more apoptotic cells were induced in HFS cells with increased [8-OHdG] than in HFB cells. The results suggest that PYC selectively induced cell death in HFS cells. This further confirmed that PYC-induced apoptosis is mediated primarily through the activation of caspase-3 apoptotic marker in HFS cells but not in HFB cells. We conclude that PYC would behave as either antioxidant or prooxidant dependant upon the cellular types.

Cells containing aragonite crystals mediate responses to gravity in Trichoplax adhaerens (Placozoa), an animal lacking neurons and synapses.

PubMed

Mayorova, Tatiana D; Smith, Carolyn L; Hammar, Katherine; Winters, Christine A; Pivovarova, Natalia B; Aronova, Maria A; Leapman, Richard D; Reese, Thomas S

2018-01-01

Trichoplax adhaerens has only six cell types. The function as well as the structure of crystal cells, the least numerous cell type, presented an enigma. Crystal cells are arrayed around the perimeter of the animal and each contains a birefringent crystal. Crystal cells resemble lithocytes in other animals so we looked for evidence they are gravity sensors. Confocal microscopy showed that their cup-shaped nuclei are oriented toward the edge of the animal, and that the crystal shifts downward under the influence of gravity. Some animals spontaneously lack crystal cells and these animals behaved differently upon being tilted vertically than animals with a typical number of crystal cells. EM revealed crystal cell contacts with fiber cells and epithelial cells but these contacts lacked features of synapses. EM spectroscopic analyses showed that crystals consist of the aragonite form of calcium carbonate. We thus provide behavioral evidence that Trichoplax are able to sense gravity, and that crystal cells are likely to be their gravity receptors. Moreover, because placozoans are thought to have evolved during Ediacaran or Cryogenian eras associated with aragonite seas, and their crystals are made of aragonite, they may have acquired gravity sensors during this early era.

Stimulus selectivity and response latency in putative inhibitory and excitatory neurons of the primate inferior temporal cortex

PubMed Central

Mruczek, Ryan E. B.

2012-01-01

The cerebral cortex is composed of many distinct classes of neurons. Numerous studies have demonstrated corresponding differences in neuronal properties across cell types, but these comparisons have largely been limited to conditions outside of awake, behaving animals. Thus the functional role of the various cell types is not well understood. Here, we investigate differences in the functional properties of two widespread and broad classes of cells in inferior temporal cortex of macaque monkeys: inhibitory interneurons and excitatory projection cells. Cells were classified as putative inhibitory or putative excitatory neurons on the basis of their extracellular waveform characteristics (e.g., spike duration). Consistent with previous intracellular recordings in cortical slices, putative inhibitory neurons had higher spontaneous firing rates and higher stimulus-evoked firing rates than putative excitatory neurons. Additionally, putative excitatory neurons were more susceptible to spike waveform adaptation following very short interspike intervals. Finally, we compared two functional properties of each neuron's stimulus-evoked response: stimulus selectivity and response latency. First, putative excitatory neurons showed stronger stimulus selectivity compared with putative inhibitory neurons. Second, putative inhibitory neurons had shorter response latencies compared with putative excitatory neurons. Selectivity differences were maintained and latency differences were enhanced during a visual search task emulating more natural viewing conditions. Our results suggest that short-latency inhibitory responses are likely to sculpt visual processing in excitatory neurons, yielding a sparser visual representation. PMID:22933717

Control of internal and external short circuits in lithium batteries using a composite thermal switch

NASA Technical Reports Server (NTRS)

Mcdonald, Robert C.; Pickett, Jerome; Goebel, Franz

1991-01-01

A composite material has been developed, consisting of a blend of metal and fluorocarbon particles, which behaves as an electronic conductor at room temperature and which abruptly becomes an insulator at a predetermined temperature. This switching behavior results from the difference in thermal expansion coefficients between the conductive and non-conductive portions of the composite. This material was applied as a thin film between the carbon cathode in Li/SOCl2 cells, and the metallic cathode current collector. Using test articles incorporating this feature it was shown that lithium cells externally heated or internally heated during a short circuit lost rate capability and the ability to overheat well below the melting point of lithium (180 C). Thus, during an internal or external cell short circuit, the potential for thermal runaway involving reactions of molten lithium is avoided.

High saturation solar light beam induced current scanning of solar cells.

PubMed

Vorster, F J; van Dyk, E E

2007-01-01

The response of the electrical parameters of photovoltaic cells under concentrated solar irradiance has been the subject of many studies performed in recent times. The high saturation conditions typically found in solar cells that are subjected to highly concentrated solar radiation may cause electrically active cell features to behave differently than under monochromatic laser illumination, normally used in light beam induced current (LBIC) investigations. A high concentration solar LBIC (S-LBIC) measurement system has been developed to perform localized cell characterization. The responses of silicon solar cells that were measured qualitatively include externally biased induced cell current at specific cell voltages, I(V), open circuit voltage, V(oc), and the average rate of change of the cell bias with the induced current, DeltaV/DeltaI(V), close to the zero bias region. These images show the relative scale of the parameters of a cell up to the penetration depth of the solar beam and can be obtained with relative ease, qualifying important electrical response features of the solar cell. The S-LBIC maps were also compared with maps that were similarly obtained using a high intensity He-Ne laser beam probe. This article reports on the techniques employed and initial results obtained.

Defining Tumor Cell and Immune Cell Behavior in Vivo during Pulmonary Metastasis of Breast Cancer

DTIC Science & Technology

2015-09-01

cancer cell extravasation , establishment and growth. PLoS One 4, e6562, doi:10.1371/journal.pone.0006562 (2009). 2 Qian, B. Z. et al. CCL2...cytoplast­ingesting cells behaved with respect to extravasation . We used i.v. injection of labelled anti­CD45 antibody15 to localize ZsGreen+ populations relative...to the vasculature at 4 and 24 h after injection. Consistent with previous data3, non­alveolar macrophages extravasated over this time period (Fig

Septic disruption of lactiferous ducts with heterogeneous carcinoma of the breast in a lactating woman.

PubMed

Naim, Mohammed; John, Vanesa T; Gaur, Kavita; Anees, Afzal

2010-08-06

This report documents the diagnostic histopathological features of heterogeneous breast carcinoma following sepsis and disruption of the lactiferous ducts in a lactating woman and discusses the pathogenesis. Sections from the nipple revealed disrupted collecting lactiferous ducts presenting with intraduct precarcinoma and carcinoma of the epidermoid type, and attached reparative sprouts lined by lactiferous cells. Breast lobules showed generalised benign adenotic change with various foci of carcinoma microscopically identifiable as intraduct primitive lactiferal ectodermal carcinoma, lactating carcinoma, primitive neuroendocrine carcinoma and myoepithelioid granulomatous carcinoma. The findings led to the conclusion that the lactiferous ducts are susceptible to sepsis and disruption, which may predispose a patient to breast carcinoma. The pattern of carcinoma suggested that lactiferous epithelial cells behaved colonially, with different metaplastic changes, precarcinoma and carcinoma.

Multiple Approaches to the Investigation of Cell Assembly in Memory Research-Present and Future.

PubMed

Sakurai, Yoshio; Osako, Yuma; Tanisumi, Yuta; Ishihara, Eriko; Hirokawa, Junya; Manabe, Hiroyuki

2018-01-01

In this review article we focus on research methodologies for detecting the actual activity of cell assemblies, which are populations of functionally connected neurons that encode information in the brain. We introduce and discuss traditional and novel experimental methods and those currently in development and briefly discuss their advantages and disadvantages for the detection of cell-assembly activity. First, we introduce the electrophysiological method, i.e., multineuronal recording, and review former and recent examples of studies showing models of dynamic coding by cell assemblies in behaving rodents and monkeys. We also discuss how the firing correlation of two neurons reflects the firing synchrony among the numerous surrounding neurons that constitute cell assemblies. Second, we review the recent outstanding studies that used the novel method of optogenetics to show causal relationships between cell-assembly activity and behavioral change. Third, we review the most recently developed method of live-cell imaging, which facilitates the simultaneous observation of firings of a large number of neurons in behaving rodents. Currently, all these available methods have both advantages and disadvantages, and no single measurement method can directly and precisely detect the actual activity of cell assemblies. The best strategy is to combine the available methods and utilize each of their advantages with the technique of operant conditioning of multiple-task behaviors in animals and, if necessary, with brain-machine interface technology to verify the accuracy of neural information detected as cell-assembly activity.

Shape Matters: Intravital Microscopy Reveals Surprising Geometrical Dependence for Nanoparticles in Tumor Models of Extravasation

PubMed Central

Smith, Bryan Ronain; Kempen, Paul; Bouley, Donna; Xu, Alexander; Liu, Zhuang; Melosh, Nicholas; Dai, Hongjie; Sinclair, Robert; Gambhir, Sanjiv Sam

2012-01-01

Delivery is one of the most critical obstacles confronting nanoparticle use in cancer diagnosis and therapy. For most oncological applications, nanoparticles must extravasate in order to reach tumor cells and perform their designated task. However, little understanding exists regarding the effect of nanoparticle shape on extravasation. Herein we use real-time intravital microscopic imaging to meticulously examine how two different nanoparticles behave across three different murine tumor models. The study quantitatively demonstrates that high-aspect ratio single-walled carbon nanotubes (SWNTs) display extravasational behavior surprisingly different from, and counterintuitive to, spherical nanoparticles although the nanoparticles have similar surface coatings, area, and charge. This work quantitatively indicates that nanoscale extravasational competence is highly dependent on nanoparticle geometry and is heterogeneous. PMID:22650417

Comparison of effects on macrophage cultures of glass fibre, glass powder, and chrysotile asbestos

PubMed Central

Beck, E. G.; Holt, P. F.; Manojlović, N.

1972-01-01

Beck, E. G., Holt, P. F., and Manojlović, N. (1972).Brit. J. industr. Med.,29, 280-286. Comparison of effects on macrophage cultures of glass fibre, glass powder, and chrysotile asbestos. The effects on macrophage cultures of glass fibre, glass powder, and chrysotile asbestos are compared. Glass fibre behaves like chrysotile in producing an increase in cell membrane permeability in cultured macrophages. This is demonstrable by the increase in lactic dehydrogenase activity in the supernatant fluid. The metabolism, measured by lactate production, is not reduced as it is when quartz is phagocytosed. Glass powder behaves like the inert dust corundum, producing little change in the number of cells stained by erythrosin B and a small increase in lactate dehydrogenase activity, both being in the range of the control. There is an increase in lactate production as a result of higher metabolism due to phagocytosis. Dusts may produce two basic effects, namely a toxic effect and change in cell membrane permeability. A non-specific effect on the cell membrane due to the slow and sometimes incomplete process of ingestion of long fibres is probably a function of the morphology, particularly the length of the fibres. A primary specific effect induced by some dusts immediately follows contact with the cell membrane. Images PMID:4339803

Is autophagy the key mechanism by which the sphingolipid rheostat controls the cell fate decision?

PubMed

Lavieu, Gregory; Scarlatti, Francesca; Sala, Giusy; Levade, Thierry; Ghidoni, Riccardo; Botti, Joëlle; Codogno, Patrice

2007-01-01

Sphingolipids are major constituents of biological membrane and some of them behave as second messengers involved in the cell fate decision. Ceramide and sphingosine 1-phosphate (S1P) constitute a rheostat system in which ceramide promotes cell death and S1P increases cell survival. We have shown that both sphingolipids are able to trigger autophagy with opposing outcomes on cell survival. Here we discuss and speculate on the diverging functions of the autophagic pathways induced by ceramide and S1P, respectively.

In vitro biology of fibropapilloma-associated turtle herpesvirus and host cells in Hawaiian green turtles (Chelonia mydas)

USGS Publications Warehouse

Work, Thierry M.; Dagenais, Julie; Balazs, George H.; Schumacher, Joanne; Lewis, Teresa D.; Leong, Jo-Ann C.; Casey, Rufina N.; Casey, James W.

2009-01-01

Fibropapillomatosis (FP) of green turtles has a global distribution and causes debilitating tumours of the skin and internal organs in several species of marine turtles. FP is associated with a presently non-cultivable alphaherpesvirus Chelonid fibropapilloma-associated herpesvirus (CFPHV). Our aims were to employ quantitative PCR targeted to pol DNA of CFPHV to determine (i) if DNA sequesters by tumour size and/or cell type, (ii) whether subculturing of cells is a viable strategy for isolating CFPHV and (iii) whether CFPHV can be induced to a lytic growth cycle in vitro using chemical modulators of replication (CMRs), temperature variation or co-cultivation. Additional objectives included determining whether non-tumour and tumour cells behave differently in vitro and confirming the phenotype of cultured cells using cell-type-specific antigens. CFPHV pol DNA was preferentially concentrated in dermal fibroblasts of skin tumours and the amount of viral DNA per cell was independent of tumour size. Copy number of CFPHV pol DNA per cell rapidly decreased with cell doubling of tumour-derived fibroblasts in culture. Attempts to induce viral replication in known CFPHV-DNA-positive cells using temperature or CMR failed. No significant differences were seen in in vitro morphology or growth characteristics of fibroblasts from tumour cells and paired normal skin, nor from CFPHV pol-DNA-positive intestinal tumour cells. Tumour cells were confirmed as fibroblasts or keratinocytes by positive staining with anti-vimentin and anti-pancytokeratin antibodies, respectively. CFPHV continues to be refractory to in vitro cultivation.

The restriction-modification genes of Escherichia coli K-12 may not be selfish: they do not resist loss and are readily replaced by alleles conferring different specificities.

PubMed

O'Neill, M; Chen, A; Murray, N E

1997-12-23

Type II restriction and modification (R-M) genes have been described as selfish because they have been shown to impose selection for the maintenance of the plasmid that encodes them. In our experiments, the type I R-M system EcoKI does not behave in the same way. The genes specifying EcoKI are, however, normally residents of the chromosome and therefore our analyses were extended to monitor the deletion of chromosomal genes rather than loss of plasmid vector. If EcoKI were to behave in the same way as the plasmid-encoded type II R-M systems, the loss of the relevant chromosomal genes by mutation or recombination should lead to cell death because the cell would become deficient in modification enzyme and the bacterial chromosome would be vulnerable to the restriction endonuclease. Our data contradict this prediction; they reveal that functional type I R-M genes in the chromosome are readily replaced by mutant alleles and by alleles encoding a type I R-M system of different specificity. The acquisition of allelic genes conferring a new sequence specificity, but not the loss of the resident genes, is dependent on the product of an unlinked gene, one predicted [Prakash-Cheng, A., Chung, S. S. & Ryu, J. (1993) Mol. Gen. Genet. 241, 491-496] to be relevant to control of expression of the genes that encode EcoKI. Our evidence suggests that not all R-M systems are evolving as "selfish" units; rather, the diversity and distribution of the family of type I enzymes we have investigated require an alternative selective pressure.

Optogenetic activation of septal cholinergic neurons suppresses sharp wave ripples and enhances theta oscillations in the hippocampus.

PubMed

Vandecasteele, Marie; Varga, Viktor; Berényi, Antal; Papp, Edit; Barthó, Péter; Venance, Laurent; Freund, Tamás F; Buzsáki, György

2014-09-16

Theta oscillations in the limbic system depend on the integrity of the medial septum. The different populations of medial septal neurons (cholinergic and GABAergic) are assumed to affect different aspects of theta oscillations. Using optogenetic stimulation of cholinergic neurons in ChAT-Cre mice, we investigated their effects on hippocampal local field potentials in both anesthetized and behaving mice. Cholinergic stimulation completely blocked sharp wave ripples and strongly suppressed the power of both slow oscillations (0.5-2 Hz in anesthetized, 0.5-4 Hz in behaving animals) and supratheta (6-10 Hz in anesthetized, 10-25 Hz in behaving animals) bands. The same stimulation robustly increased both the power and coherence of theta oscillations (2-6 Hz) in urethane-anesthetized mice. In behaving mice, cholinergic stimulation was less effective in the theta (4-10 Hz) band yet it also increased the ratio of theta/slow oscillation and theta coherence. The effects on gamma oscillations largely mirrored those of theta. These findings show that medial septal cholinergic activation can both enhance theta rhythm and suppress peri-theta frequency bands, allowing theta oscillations to dominate.

Temperature-Related Divergence in Experimental Populations of DROSOPHILA MELANOGASTER. I. Genetic and Developmental Basis of Wing Size and Shape Variation

PubMed Central

Cavicchi, Sandro; Guerra, Daniela; Giorgi, Gianfranco; Pezzoli, Cristina

1985-01-01

The effects of environmental temperature on wing size and shape of Drosophila melanogaster were analyzed in populations derived from an Oregon laboratory strain kept at three temperatures (18°, 25°, 28°) for 4 yr. Temperature-directed selection was identified for both wing size and shape. The length of the four longitudinal veins, used as a test for wing size variations in the different populations, appears to be affected by both genetic and maternal influences. Vein expression appears to be dependent upon developmental pattern of the wing: veins belonging to the same compartment are coordinated in their expression and relative position, whereas veins belonging to different compartments are not. Both wing and cell areas show genetic divergence, particularly in the posterior compartment. Cell number seems to compensate for cell size variations. Such compensation is carried out both at the level of single organisms and at the level of population as a whole. The two compartments behave as individual units of selection. PMID:17246257

Expanding and characterizing esophageal epithelial cells obtained from children with eosinophilic esophagitis.

PubMed

Sayej, Wael N; Foster, Christopher; Jensen, Todd; Chatfield, Sydney; Finck, Christine

2018-06-12

The role of epithelial cells in eosinophilic esophagitis (EoE) is not well understood. In this study, our aim was to isolate, culture, and expand esophageal epithelial cells obtained from patients with or without EoE and characterize differences observed over time in culture. Biopsies were obtained at the time of endoscopy from children with EoE or suspected to have EoE. We established patient-derived esophageal epithelial cell (PDEEC) lines utilizing conditional reprogramming methods. We determined integrin profiles, gene expression, MHC class II expression, and reactivity to antigen stimulation. The PDEECs were found to maintain their phenotype over several passages. There were differences in integrin profiles and gene expression levels in EoE-Active compared to normal controls and EoE-Remission patients. Once stimulated with antigens, PDEECs express MHC class II molecules on their surface, and when co-cultured with autologous T-cells, there is increased IL-6 and TNF-α secretion in EoE-Active patients vs. controls. We are able to isolate, culture, and expand esophageal epithelial cells from pediatric patients with and without EoE. Once stimulated with antigens, these cells express MHC class II molecules and behave as non-professional antigen-presenting cells. This method will help us in developing an ex vivo, individualized, patient-specific model for diagnostic testing for causative antigens.

CROSS-DISCIPLINARY PHYSICS AND RELATED AREAS OF SCIENCE AND TECHNOLOGY: Influence of the total gas flow rate on high rate growth microcrystalline silicon films and solar cells

NASA Astrophysics Data System (ADS)

Han, Xiao-Yan; Hou, Guo-Fu; Zhang, Xiao-Dan; Wei, Chang-Chun; Li, Gui-Jun; Zhang, De-Kun; Chen, Xin-Liang; Sun, Jian; Zhang, Jian-Jun; Zhao, Ying; Geng, Xin-Hua

2009-08-01

This paper reports that high-rate-deposition of microcrystalline silicon solar cells was performed by very-high-frequency plasma-enhanced chemical vapor deposition. These solar cells, whose intrinsic μc-Si:H layers were prepared by using a different total gas flow rate (Ftotal), behave much differently in performance, although their intrinsic layers have similar crystalline volume fraction, opto-electronic properties and a deposition rate of ~ 1.0 nm/s. The influence of Ftotal on the micro-structural properties was analyzed by Raman and Fourier transformed infrared measurements. The results showed that the vertical uniformity and the compact degree of μc-Si:H thin films were improved with increasing Ftotal. The variation of the microstructure was regarded as the main reason for the difference of the J-V parameters. Combined with optical emission spectroscopy, we found that the gas temperature plays an important role in determining the microstructure of thin films. With Ftotal of 300 sccm, a conversion efficiency of 8.11% has been obtained for the intrinsic layer deposited at 8.5 Å/s (1 Å = 0.1 nm).

Primary cutaneous perivascular epithelioid cell tumor (PEComa): Five new cases and review of the literature.

PubMed

Stuart, Lauren N; Tipton, Russell G; DeWall, Michael R; Parker, Douglas C; Stelton, Christina D; Morrison, Annie O; Coleman, Landon W; Fosko, Scott W; Vidal, Claudia I; Yadira Hurley, Maria; Deeken, Amy H; Gardner, Jerad M

2017-08-01

PEComas represent a family of uncommon mesenchymal tumors composed of "perivascular epithelioid cells" with a distinct immunophenotype that typically shows both myogenic and melanocytic differentiation. The PEComa family includes angiomyolipoma (AML), clear cell "sugar" tumor of the lung and extra pulmonary sites, lymphangioleiomyomatosis and clear cell myomelanocytic tumor of the falciform ligament/ligamentum teres. Very rarely, PEComas may arise in the skin. Primary cutaneous PEComas typically display a dermal proliferation of epithelioid cells with pale, clear, or granular pink cytoplasm arranged in nests and trabecula with an intervening arborizing network of delicate capillaries. Primary cutaneous PEComas have a lower frequency of myogenic marker expression than their deep soft tissue and visceral counterparts. They also often express strong diffuse CD10, leading to potential confusion with metastatic renal cell carcinoma. Most cases behave indolently. We report 5 additional cases of this rare entity. All showed classic histologic features and expression of either HMB-45 and/or Melan-A/MART-1. Four cases were tested for myogenic markers (2 were positive & 2 were negative). Three cases were tested for CD10 (all 3 were positive). All of our cases with clinical follow-up behaved indolently. Table 1 provides a summary of findings for all 5 cases in our series. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Fabrication of hierarchical micro-nanotopographies for cell attachment studies.

PubMed

López-Bosque, M J; Tejeda-Montes, E; Cazorla, M; Linacero, J; Atienza, Y; Smith, K H; Lladó, A; Colombelli, J; Engel, E; Mata, A

2013-06-28

We report on the development of micro/nanofabrication processes to create hierarchical surface topographies that expand from 50 nm to microns in size on different materials. Three different approaches (named FIB1, FIB2, and EBL) that combine a variety of techniques such as photolithography, reactive ion etching, focused ion beam lithography, electron beam lithography, and soft lithography were developed, each one providing different advantages and disadvantages. The EBL approach was employed to fabricate substrates comprising channels with features between 200 nm and 10 μm in size on polymethylmethacrylate (PMMA), which were then used to investigate the independent or competitive effects of micro- and nanotopographies on cell adhesion and morphology. Rat mesenchymal stem cells (rMSCs) were cultured on four different substrates including 10 μm wide and 500 nm deep channels separated by 10 μm distances (MICRO), 200 nm wide and 100 nm deep nanochannels separated by 200 nm distances (NANO), their combination in parallel (PARAL), and in a perpendicular direction (PERP). Rat MSCs behaved differently on all tested substrates with a high degree of alignment (as measured by both number of aligned cells and average angle) on both NANO and MICRO. Furthermore, cells exhibited the highest level of alignment on PARAL, suggesting a synergetic effect of the two scales of topographies. On the other hand, cells on PERP exhibited the lowest alignment and a consistent change in morphology over time that seemed to be the result of interactions with both micro- and nanochannels positioned in the perpendicular direction, also suggesting a competitive effect of the topographies.

Atomic force microscopy as a tool for the investigation of living cells.

PubMed

Morkvėnaitė-Vilkončienė, Inga; Ramanavičienė, Almira; Ramanavičius, Arūnas

2013-01-01

Atomic force microscopy is a valuable and useful tool for the imaging and investigation of living cells in their natural environment at high resolution. Procedures applied to living cell preparation before measurements should be adapted individually for different kinds of cells and for the desired measurement technique. Different ways of cell immobilization, such as chemical fixation on the surface, entrapment in the pores of a membrane, or growing them directly on glass cover slips or on plastic substrates, result in the distortion or appearance of artifacts in atomic force microscopy images. Cell fixation allows the multiple use of samples and storage for a prolonged period; it also increases the resolution of imaging. Different atomic force microscopy modes are used for the imaging and analysis of living cells. The contact mode is the best for cell imaging because of high resolution, but it is usually based on the following: (i) image formation at low interaction force, (ii) low scanning speed, and (iii) usage of "soft," low resolution cantilevers. The tapping mode allows a cell to behave like a very solid material, and destructive shear forces are minimized, but imaging in liquid is difficult. The force spectroscopy mode is used for measuring the mechanical properties of cells; however, obtained results strongly depend on the cell fixation method. In this paper, the application of 3 atomic force microscopy modes including (i) contact, (ii) tapping, and (iii) force spectroscopy for the investigation of cells is described. The possibilities of cell preparation for the measurements, imaging, and determination of mechanical properties of cells are provided. The applicability of atomic force microscopy to diagnostics and other biomedical purposes is discussed.

Operating principles of Notch-Delta-Jagged module of cell-cell communication

NASA Astrophysics Data System (ADS)

Jolly, Mohit Kumar; Boareto, Marcelo; Lu, Mingyang; Onuchic, Jose' N.; Clementi, Cecilia; Ben-Jacob, Eshel

2015-05-01

Notch pathway is an evolutionarily conserved cell-cell communication mechanism governing cell-fate during development and tumor progression. It is activated when Notch receptor of one cell binds to either of its ligand—Delta or Jagged—of another cell. Notch-Delta (ND) signaling forms a two-way switch, and two cells interacting via ND signaling adopt different fates—Sender (high ligand, low receptor) and Receiver (low ligand, high receptor). Notch-Delta-Jagged signaling (NDJ) behaves as a three-way switch and enables an additional fate—hybrid Sender/Receiver (S/R) (medium ligand, medium receptor). Here, by extending our framework of NDJ signaling for a two-cell system, we show that higher production rate of Jagged, but not that of Delta, expands the range of parameters for which both cells attain the hybrid S/R state. Conversely, glycosyltransferase Fringe and cis-inhibition reduces this range of conditions, and reduces the relative stability of the hybrid S/R state, thereby promoting cell-fate divergence and consequently lateral inhibition-based patterns. Lastly, soluble Jagged drives the cells to attain the hybrid S/R state, and soluble Delta drives them to be Receivers. We also discuss the critical role of hybrid S/R state in promoting cancer metastasis by enabling collective cell migration and expanding cancer stem cell (CSC) population.

Safety testing of lithium cells

NASA Astrophysics Data System (ADS)

Bene, J.

1981-03-01

The testing consisted of a forced discharge to zero volts constant current under isothermal conditions. The temperature range was -40 to 65 C. Short circuit tests, drop tests, and puncture tests were run to determine how a cell might behave if it developed a leak. Once the sulfur dioxide is exhausted, a lithium acetontirile reaction occurs. An excess of sulfur dioxide must be maintained in order to avoid chemical explosions.

Safety testing of lithium cells

NASA Technical Reports Server (NTRS)

Bene, J.

1981-01-01

The testing consisted of a forced discharge to zero volts constant current under isothermal conditions. The temperature range was -40 to 65 C. Short circuit tests, drop tests, and puncture tests were run to determine how a cell might behave if it developed a leak. Once the sulfur dioxide is exhausted, a lithium acetontirile reaction occurs. An excess of sulfur dioxide must be maintained in order to avoid chemical explosions.

Cytocompatibility of amorphous hydrogenated carbon nitride films deposited by CH4/N2 dielectric barrier discharge plasmas with respect to cell lines

NASA Astrophysics Data System (ADS)

Majumdar, Abhijit; Schröder, Karsten; Hippler, Rainer

2008-10-01

Special amorphous hydrogenated carbon nitride (a-H-CNx) films have been prepared on glass substrates for the investigation of adhesion and proliferation of different mammalian cell lines. CH4/N2 dielectric barrier discharge plasmas were applied to deposit a-H-CNx coatings at half of the atmospheric pressure. Film quality was modified by varying the CH4:N2 ratio and deposition duration. Chemical composition was determined by x-ray photoelectron spectroscopy and Fourier transformed infrared spectroscopy. The N/C ratio was in the range of 0.20-0.55. A very small surface roughness was verified by atomic force microscopy. Human embryonic kidney (HEK) and rat adrenal pheochromocytoma (PC12) cells were cultivated on the a-H-CNx films to investigate the cytocompatibility of these surfaces. The microscopic images show that both kinds of cells lines were unable to survive. The cells did not adhere to the surfaces, and most of the cells died after certain time spans. Increased amounts of nitrogen in the film induce an accelerated cell death. It is concluded, that the deposited CNx film behaves cytotoxic to HEK and PC12 cell lines.

Distinct metabolic responses of an ovarian cancer stem cell line.

PubMed

Vermeersch, Kathleen A; Wang, Lijuan; McDonald, John F; Styczynski, Mark P

2014-12-18

Cancer metabolism is emerging as an important focus area in cancer research. However, the in vitro cell culture conditions under which much cellular metabolism research is performed differ drastically from in vivo tumor conditions, which are characterized by variations in the levels of oxygen, nutrients like glucose, and other molecules like chemotherapeutics. Moreover, it is important to know how the diverse cell types in a tumor, including cancer stem cells that are believed to be a major cause of cancer recurrence, respond to these variations. Here, in vitro environmental perturbations designed to mimic different aspects of the in vivo environment were used to characterize how an ovarian cancer cell line and its derived, isogenic cancer stem cells metabolically respond to environmental cues. Mass spectrometry was used to profile metabolite levels in response to in vitro environmental perturbations. Docetaxel, the chemotherapeutic used for this experiment, caused significant metabolic changes in amino acid and carbohydrate metabolism in ovarian cancer cells, but had virtually no metabolic effect on isogenic ovarian cancer stem cells. Glucose deprivation, hypoxia, and the combination thereof altered ovarian cancer cell and cancer stem cell metabolism to varying extents for the two cell types. Hypoxia had a much larger effect on ovarian cancer cell metabolism, while glucose deprivation had a greater effect on ovarian cancer stem cell metabolism. Core metabolites and pathways affected by these perturbations were identified, along with pathways that were unique to cell types or perturbations. The metabolic responses of an ovarian cancer cell line and its derived isogenic cancer stem cells differ greatly under most conditions, suggesting that these two cell types may behave quite differently in an in vivo tumor microenvironment. While cancer metabolism and cancer stem cells are each promising potential therapeutic targets, such varied behaviors in vivo would need to be considered in the design and early testing of such treatments.

National survey of distracted and drowsy driving attitudes and behaviors : 2002. Volume 1, Findings

DOT National Transportation Integrated Search

2003-04-01

This report represents the findings on distracted driving (including cell phone use) and drowsy driving. The data come from a pair of studies undertaken by the National Highway Traffic Safety Administration (NHTSA) to better understand drivers' behav...

Difference, Explanation, Certainty and Terror: A View from a Londoner about the Formation of Children's Spirituality as Relational Consciousness

ERIC Educational Resources Information Center

Johnson, Helen

2006-01-01

The manner in which we relate and behave towards one another can be analysed in political and social terms. Significantly, in the examination of children's spirituality, the concept of relational consciousness has revealed how early we become aware of people and phenomena beyond ourselves. But our desire to relate and behave reasonably towards…

Anticancer Agents: Does a Phosphonium Behave Like a Gold(I) Phosphine Complex? Let a "Smart" Probe Answer!

PubMed

Ali, Moussa; Dondaine, Lucile; Adolle, Anais; Sampaio, Carla; Chotard, Florian; Richard, Philippe; Denat, Franck; Bettaieb, Ali; Le Gendre, Pierre; Laurens, Véronique; Goze, Christine; Paul, Catherine; Bodio, Ewen

2015-06-11

Gold phosphine complexes, such as auranofin, have been recognized for decades as antirheumatic agents. Clinical trials are now underway to validate their use in anticancer or anti-HIV treatments. However, their mechanisms of action remain unclear. A challenging question is whether the gold phosphine complex is a prodrug that is administered in an inactive precursor form or rather that the gold atom remains attached to the phosphine ligand during treatment. In this study, we present two novel gold complexes, which we compared to auranofin and to their phosphonium analogue. The chosen ligand is a phosphine-based smart probe, whose strong fluorescence depends on the presence of the gold atom. The in vitro biological action of the gold complexes and the phosphonium derivative were investigated, and a preliminary in vivo study in healthy zebrafish larvae allowed us to evaluate gold complex biodistribution and toxicity. The different analyses carried out showed that these gold complexes were stable and behaved differently from phosphonium and auranofin, both in vitro and in vivo. Two-photon microscopy experiments demonstrated that the cellular targets of these gold complexes are not the same as those of the phosphonium analogue. Moreover, despite similar IC50 values in some cancer cell lines, gold complexes displayed a low toxicity in vivo, in contrast to the phosphonium salt. They are therefore suitable for future in vivo investigations.

Cells containing aragonite crystals mediate responses to gravity in Trichoplax adhaerens (Placozoa), an animal lacking neurons and synapses

PubMed Central

Smith, Carolyn L.; Hammar, Katherine; Winters, Christine A.; Pivovarova, Natalia B.; Aronova, Maria A.; Leapman, Richard D.; Reese, Thomas S.

2018-01-01

Trichoplax adhaerens has only six cell types. The function as well as the structure of crystal cells, the least numerous cell type, presented an enigma. Crystal cells are arrayed around the perimeter of the animal and each contains a birefringent crystal. Crystal cells resemble lithocytes in other animals so we looked for evidence they are gravity sensors. Confocal microscopy showed that their cup-shaped nuclei are oriented toward the edge of the animal, and that the crystal shifts downward under the influence of gravity. Some animals spontaneously lack crystal cells and these animals behaved differently upon being tilted vertically than animals with a typical number of crystal cells. EM revealed crystal cell contacts with fiber cells and epithelial cells but these contacts lacked features of synapses. EM spectroscopic analyses showed that crystals consist of the aragonite form of calcium carbonate. We thus provide behavioral evidence that Trichoplax are able to sense gravity, and that crystal cells are likely to be their gravity receptors. Moreover, because placozoans are thought to have evolved during Ediacaran or Cryogenian eras associated with aragonite seas, and their crystals are made of aragonite, they may have acquired gravity sensors during this early era. PMID:29342202

Granulosa cells of the cumulus oophorus are different from mural granulosa cells in their response to gonadotrophins and IGF-I.

PubMed

Khamsi, F; Roberge, S

2001-09-01

There are two types of granulosa cells: those which surround the oocyte are cumulus cells (CC) and those which surround the antrum are mural granulosa cells (MGC). These cells are under the influence of several hormones and growth factors, the most important of which are gonadotrophins and IGF-I. In this article, we report novel observations on the differences between these two types of granulosa cells and their interaction with gonadotrophins and IGF-I. We were able to conduct physiological studies on the role of IGF-I by using an analogue of IGF-I which does not bind to IGF-I-binding proteins (LR3-IGF-I). Immature rats received saline, equine chorionic gonadotrophin (eCG), LR3-IGF-I or eCG plus LR3-IGF-I by infusion using a pump from 24-29 days of age. The rats were killed and the ovaries removed. Surface follicles were punctured and MGC and oocyte cumulus complexes were removed. These were cultured in saline (control) and in three different doses of FSH. Cell replication was assessed by 3H-thymidine incorporation and differentiation was evaluated by the measurement of progesterone secretion. It was noted that CC replicated ten times more than MGC. Similarly, progesterone secretion by CC was six times more than by MGC. In vivo exposure to gonadotrophins (eCG) positively influenced in vitro treatment with FSH in both cell types. This phenomenon was observed in both cell replication and progesterone secretion. The IGF-I analogue had a positive effect on cell replication of MGC but a negative effect on the cell replication of CC. With respect to progesterone secretion, the IGF-I analogue had a negative effect on CC but a positive effect on MGC. In conclusion, CC behaved differently from MGC in response to gonadotrophins and the IGF-I analogue. IGF-I and FSH acted additively, synergistically or antagonistically in different circumstances.

Quantitative analysis of circadian single cell oscillations in response to temperature

PubMed Central

Kramer, Achim; Herzel, Hanspeter

2018-01-01

Body temperature rhythms synchronize circadian oscillations in different tissues, depending on the degree of cellular coupling: the responsiveness to temperature is higher when single circadian oscillators are uncoupled. So far, the role of coupling in temperature responsiveness has only been studied in organotypic tissue slices of the central circadian pacemaker, because it has been assumed that peripheral target organs behave like uncoupled multicellular oscillators. Since recent studies indicate that some peripheral tissues may exhibit cellular coupling as well, we asked whether peripheral network dynamics also influence temperature responsiveness. Using a novel technique for long-term, high-resolution bioluminescence imaging of primary cultured cells, exposed to repeated temperature cycles, we were able to quantitatively measure period, phase, and amplitude of central (suprachiasmatic nuclei neuron dispersals) and peripheral (mouse ear fibroblasts) single cell oscillations in response to temperature. Employing temperature cycles of different lengths, and different cell densities, we found that some circadian characteristics appear cell-autonomous, e.g. period responses, while others seem to depend on the quality/degree of cellular communication, e.g. phase relationships, robustness of the oscillation, and amplitude. Overall, our findings indicate a strong dependence on the cell’s ability for intercellular communication, which is not only true for neuronal pacemakers, but, importantly, also for cells in peripheral tissues. Hence, they stress the importance of comparative studies that evaluate the degree of coupling in a given tissue, before it may be used effectively as a target for meaningful circadian manipulation. PMID:29293562

Magnetization reversal process in (Sm, Dy, Gd) (Co, Fe, Cu, Zr)z magnets with different cellular structures

NASA Astrophysics Data System (ADS)

Liu, Lei; Liu, Zhuang; Zhang, Xin; Feng, Yanping; Wang, Chunxiao; Sun, Yingli; Lee, Don; Yan, Aru; Wu, Qiong

2017-05-01

Magnetization reversal mechanism is found to vary with cellular structures by a comparative study of the magnetization processes of three (Sm, Dy, Gd) (Co, Fe, Cu, Zr)z magnets with different cellular structures. Analysis of domain walls, initial magnetization curves and recoil loops indicates that the morphology of cellular structure has a significant effect on the magnetization process, besides the obvious connection to the difference of domain energy density between cell boundary phase (CBP) and main phase. The magnetization of Sample 2 (with a moderate cell size and uniformly continuous CBPs) behaves as a strong coherence domain-wall pinning effect to the domain wall and lead to a highest coercivity in the magnet. The magnetization of Sample 1 (with thin and discontinuous CBPs) shows an inconsistent pinning effect to the domain wall while that of Sample 3 (with thick and aggregate CBPs) exhibits a two-phase separation magnetization. Both the two cases lead to lower coercivities. A simplified model is given as well to describe the relationships among cellular structure and magnetization behavior.

A comparative study of behavioral and psychological symptoms of dementia in patients with Alzheimer's disease and vascular dementia referred to psychogeriatric services in Korea and the U.K.

PubMed

Shah, Ajit; Ellanchenny, Nalini; Suh, Guk-Hee

2005-06-01

There is a paucity of cross-cultural studies of behavioral and psychological symptoms of dementia (BPSD). BPSD were examined in consecutive series of referrals to a psychogeriatric service in Korea and the U.K. using the Behavioral Pathology in Alzheimer's Disease (BEHAVE-AD) rating scale and the Cornell Scale for Depression in Dementia (CSDD). Results were analyzed separately for Alzheimer's disease and vascular dementia. Koreans in both diagnostic groups had lower Mini-mental State Examination (MMSE) scores and higher BEHAVE-AD total and subscale scores for most subscales. In both countries, for both diagnostic groups, the total BEHAVE-AD score and several subscale scores were negatively correlated with the MMSE scores. Logistic regression analysis for Alzheimer's disease revealed that BEHAVE-AD total and most subscale scores independently predicted the country of origin in addition to the MMSE scores predicting the same. These differences in BPSD are most likely explained by the lower MMSE scores in the Korean sample. However, genuine differences in BPSD between the two countries can only be critically examined in a cross-cultural population-based epidemiological study for both diagnostic categories using validated instruments to measure BPSD and controlling for the influence of MMSE score.

Plasma BDNF levels are correlated with aggressiveness in patients with amnestic mild cognitive impairment or Alzheimer disease.

PubMed

Nagata, Tomoyuki; Kobayashi, Nobuyuki; Shinagawa, Shunichiro; Yamada, Hisashi; Kondo, Kazuhiro; Nakayama, Kazuhiko

2014-04-01

In the present study, we examined whether neuropsychiatric symptoms were correlated with plasma brain-derived neurotrophic factor (BDNF) levels as a state marker or were associated with the BDNF polymorphism Val66Met in patients with amnestic mild cognitive impairment (A-MCI) or Alzheimer disease (AD). One hundred and seventy-six outpatients with AD (n = 129) or A-MCI (n = 47) were selected and their plasma BDNF concentrations measured. Next, we investigated the correlation between the plasma BDNF level and the Behavioral Pathology in Alzheimer Disease (Behave-AD) subscale scores, which reflect neuropsychiatric symptoms. We also compared the plasma BDNF level and the Behave-AD subscale scores among the BDNF Val66Met genotypic groups. Among the seven Behave-AD subscale scores, aggressiveness was positively correlated with the plasma BDNF level (ρ = 0.237, P < 0.005), but did not differ significantly among the three BDNF Val66Met genotypic groups. The Behave-AD total and other subscale scores did not differ significantly among the BDNF Val66Met genotypic groups and were not associated with the plasma BDNF level. Moreover, the plasma BDNF level did not differ significantly among the three BDNF Val66Met genotypic groups or between patients with A-MCI and those with AD. The plasma BDNF level was robustly correlated with aggressiveness, implying that the plasma BDNF level might be useful as a behavioral state marker in patients with AD or A-MCI.

Interaction of phospholipid vesicles with cells. Endocytosis and fusion as alternate mechanisms for the uptake of lipid-soluble and water-soluble molecules

PubMed Central

1975-01-01

Depending on their phospholipid composition, liposomes are endocytosed by, or fuse with, the plasma membrane, of Acanthamoeba castellanii. Unilamellar egg lecithin vesicles are endocytosed by amoeba at 28 degrees C with equal uptake of the phospholipid bilayer and the contents of the internal aqueous space of the vesicles. Uptake is inhibited almost completely by incubation at 4 degrees C or in the presence of dinitrophenol. After uptake at 28 degrees C, the vesicle phospholipid can be visualized by electron microscope autoradiography within cytoplasmic vacuoles. In contrast, uptake of unilamellar dipalmitoyl lecithin vesicles and multilamellar dipalmitoyl lecithin liposomes is only partially inhibited at 4 degrees C, by dinitrophenol and by prior fixation of the amoebae with glutaraldehyde, each of which inhibits pinocytosis. Vesicle contents are taken up only about 40% as well as the phospholipid bilayer. Electron micrographs are compatible with the interpretation that dipalmitoyl lecithin vesicles fuse with the amoeba plasma membrane, adding their phospholipid to the cell surface, while their contents enter the cell cytoplasm. Dimyristoyl lecithin vesicles behave like egg lecithin vesicles while distearoyl lecithin vesicles behave like dipalmitoyl lecithin vesicles. PMID:1174130

Tetrahydrohyperforin and Octahydrohyperforin Are Two New Potent Inhibitors of Angiogenesis

PubMed Central

Martínez-Poveda, Beatriz; Verotta, Luisella; Bombardelli, Ezio; Quesada, Ana R.; Medina, Miguel Ángel

2010-01-01

Background We have previously shown that hyperforin, a phloroglucinol derivative found in St. John's wort, behaves as a potent anti-angiogenic compound. To identify the reactive group(s) mainly involved in this anti-angiogenic effect, we have investigated the anti-angiogenic properties of a series of stable derivatives obtained by oxidative modification of the natural product. In addition, in the present work we have studied the role of the four carbonyl groups present in hyperforin by investigating the potential of some other chemically stable derivatives. Methodology/Principal Findings The experimental procedures included the analysis of the effects of treatment of endothelial cells with these compounds in cell growth, cell viability, cell migration and zymographic assays, as well as the tube formation assay on Matrigel. Our study with hyperforin and eight derivatives shows that the enolized β-dicarbonyl system contained in the structure of hyperforin has a dominant role in its antiangiogenic activity. On the other hand, two of the tested hyperforin derivatives, namely, tetrahydrohyperforin and octahydrohyperforin, behave as potent inhibitors of angiogenesis. Additional characterization of these compounds included a cell specificity study of their effects on cell growth, as well as the in vivo Matrigel plug assay. Conclusions/Significance These observations could be useful for the rational design and chemical synthesis of more effective hyperforin derivatives as anti-angiogenic drugs. Altogether, the results indicate that octahydrohyperforin is a more specific and slightly more potent antiangiogenic compound than hyperforin. PMID:20224821

Membraneless organelles can melt nucleic acid duplexes and act as biomolecular filters

NASA Astrophysics Data System (ADS)

Nott, Timothy J.; Craggs, Timothy D.; Baldwin, Andrew J.

2016-06-01

Membraneless organelles are cellular compartments made from drops of liquid protein inside a cell. These compartments assemble via the phase separation of disordered regions of proteins in response to changes in the cellular environment and the cell cycle. Here we demonstrate that the solvent environment within the interior of these cellular bodies behaves more like an organic solvent than like water. One of the most-stable biological structures known, the DNA double helix, can be melted once inside the liquid droplet, and simultaneously structures formed from regulatory single-stranded nucleic acids are stabilized. Moreover, proteins are shown to have a wide range of absorption or exclusion from these bodies, and can act as importers for otherwise-excluded nucleic acids, which suggests the existence of a protein-mediated trafficking system. A common strategy in organic chemistry is to utilize different solvents to influence the behaviour of molecules and reactions. These results reveal that cells have also evolved this capability by exploiting the interiors of membraneless organelles.

Coaction of intercellular adhesion and cortical tension specifies tissue surface tension

PubMed Central

Manning, M. Lisa; Foty, Ramsey A.; Steinberg, Malcolm S.; Schoetz, Eva-Maria

2010-01-01

In the course of animal morphogenesis, large-scale cell movements occur, which involve the rearrangement, mutual spreading, and compartmentalization of cell populations in specific configurations. Morphogenetic cell rearrangements such as cell sorting and mutual tissue spreading have been compared with the behaviors of immiscible liquids, which they closely resemble. Based on this similarity, it has been proposed that tissues behave as liquids and possess a characteristic surface tension, which arises as a collective, macroscopic property of groups of mobile, cohering cells. But how are tissue surface tensions generated? Different theories have been proposed to explain how mesoscopic cell properties such as cell–cell adhesion and contractility of cell interfaces may underlie tissue surface tensions. Although recent work suggests that both may be contributors, an explicit model for the dependence of tissue surface tension on these mesoscopic parameters has been missing. Here we show explicitly that the ratio of adhesion to cortical tension determines tissue surface tension. Our minimal model successfully explains the available experimental data and makes predictions, based on the feedback between mechanical energy and geometry, about the shapes of aggregate surface cells, which we verify experimentally. This model indicates that there is a crossover from adhesion dominated to cortical-tension dominated behavior as a function of the ratio between these two quantities. PMID:20616053

Behavior of Xeno-Transplanted Undifferentiated Human Induced Pluripotent Stem Cells Is Impacted by Microenvironment Without Evidence of Tumors.

PubMed

Martínez-Cerdeño, Veronica; Barrilleaux, Bonnie L; McDonough, Ashley; Ariza, Jeanelle; Yuen, Benjamin T K; Somanath, Priyanka; Le, Catherine T; Steward, Craig; Horton-Sparks, Kayla; Knoepfler, Paul S

2017-10-01

Human pluripotent stem cells (hPSC) have great clinical potential through the use of their differentiated progeny, a population in which there is some concern over risks of tumorigenicity or other unwanted cellular behavior due to residual hPSC. Preclinical studies using human stem cells are most often performed within a xenotransplant context. In this study, we sought to measure how undifferentiated hPSC behave following xenotransplant. We directly transplanted undifferentiated human induced pluripotent stem cells (hIPSC) and human embryonic stem cells (hESC) into the adult mouse brain ventricle and analyzed their fates. No tumors or precancerous lesions were present at more than one year after transplantation. This result differed with the tumorigenic capacity we observed after allotransplantation of mouse ESC into the mouse brain. A substantial population of cellular derivatives of undifferentiated hESC and hIPSC engrafted, survived, and migrated within the mouse brain parenchyma. Within brain structures, transplanted cell distribution followed a very specific pattern, suggesting the existence of distinct microenvironments that offer different degrees of permissibility for engraftment. Most of the transplanted hESC and hIPSC that developed into brain cells were NeuN+ neuronal cells, and no astrocytes were detected. Substantial cell and nuclear fusion occurred between host and transplanted cells, a phenomenon influenced by microenvironment. Overall, hIPSC appear to be largely functionally equivalent to hESC in vivo. Altogether, these data bring new insights into the behavior of stem cells without prior differentiation following xenotransplantation into the adult brain.

Subpopulation-proteomics in prokaryotic populations.

PubMed

Jahn, Michael; Seifert, Jana; von Bergen, Martin; Schmid, Andreas; Bühler, Bruno; Müller, Susann

2013-02-01

Clonal microbial cells do not behave in an identical manner and form subpopulations during cultivation. Besides varying micro-environmental conditions, cell inherent features like cell cycle dependent localization and concentration of regulatory proteins as well as epigenetic properties are well accepted mechanisms creating cell heterogeneity. Another suspected reason is molecular noise on the transcriptional and translational level. A promising tool to unravel reasons for cell heterogeneity is the combination of cell sorting and subpopulation proteomics. This review summarizes recent developments in prokaryotic single-cell analytics and provides a workflow for selection of single cells, low cell number mass spectrometry, and proteomics evaluation. This approach is useful for understanding the dependency of individual cell decisions on inherent protein profiles. Copyright © 2012 Elsevier Ltd. All rights reserved.

The Effects of Low Level Prenatal Carbon Monoxide on Neocortical Development

DTIC Science & Technology

2010-06-02

amount of NO available, which may have formed free radicals damaging the tissue and resulting in cell death. Treatment with a synthetic cGMP also failed...Watkinson B (36- and 48-month neurobehavioral follow-up of children prenatally exposed to marijuana , cigarettes, and alcohol. J Dev Behav Pediatr

Dynamics of passive and active particles in the cell nucleus.

PubMed

Hameed, Feroz M; Rao, Madan; Shivashankar, G V

2012-01-01

Inspite of being embedded in a dense meshwork of nuclear chromatin, gene loci and large nuclear components are highly dynamic at 37°C. To understand this apparent unfettered movement in an overdense environment, we study the dynamics of a passive micron size bead in live cell nuclei at two different temperatures (25 and 37°C) with and without external force. In the absence of a force, the beads are caged over large time scales. On application of a threshold uniaxial force (about 10(2) pN), the passive beads appear to hop between cages; this large scale movement is absent upon ATP-depletion, inhibition of chromatin remodeling enzymes and RNAi of lamin B1 proteins. Our results suggest that the nucleus behaves like an active solid with a finite yield stress when probed at a micron scale. Spatial analysis of histone fluorescence anisotropy (a measure of local chromatin compaction, defined as the volume fraction of tightly bound chromatin) shows that the bead movement correlates with regions of low chromatin compaction. This suggests that the physical mechanism of the observed yielding is the active opening of free-volume in the nuclear solid via chromatin remodeling. Enriched transcription sites at 25°C also show caging in the absence of the applied force and directed movement beyond a yield stress, in striking contrast with the large scale movement of transcription loci at 37°C in the absence of a force. This suggests that at physiological temperatures, the loci behave as active particles which remodel the nuclear mesh and reduce the local yield stress.

A Molecular Genetic Basis Explaining Altered Bacterial Behavior in Space

PubMed Central

Prasad, Nripesh; Levy, Shawn E.; Stodieck, Louis; Jones, Angela; Shrestha, Shristi; Klaus, David

2016-01-01

Bacteria behave differently in space, as indicated by reports of reduced lag phase, higher final cell counts, enhanced biofilm formation, increased virulence, and reduced susceptibility to antibiotics. These phenomena are theorized, at least in part, to result from reduced mass transport in the local extracellular environment, where movement of molecules consumed and excreted by the cell is limited to diffusion in the absence of gravity-dependent convection. However, to date neither empirical nor computational approaches have been able to provide sufficient evidence to confirm this explanation. Molecular genetic analysis findings, conducted as part of a recent spaceflight investigation, support the proposed model. This investigation indicated an overexpression of genes associated with starvation, the search for alternative energy sources, increased metabolism, enhanced acetate production, and other systematic responses to acidity—all of which can be associated with reduced extracellular mass transport. PMID:27806055

Origin of Complexity in Multicellular Organisms

NASA Astrophysics Data System (ADS)

Furusawa, Chikara; Kaneko, Kunihiko

2000-06-01

Through extensive studies of dynamical system modeling cellular growth and reproduction, we find evidence that complexity arises in multicellular organisms naturally through evolution. Without any elaborate control mechanism, these systems can exhibit complex pattern formation with spontaneous cell differentiation. Such systems employ a ``cooperative'' use of resources and maintain a larger growth speed than simple cell systems, which exist in a homogeneous state and behave ``selfishly.'' The relevance of the diversity of chemicals and reaction dynamics to the growth of a multicellular organism is demonstrated. Chaotic biochemical dynamics are found to provide the multipotency of stem cells.

Progressive mechanical indentation of large-format Li-ion cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Hsin; Kumar, Abhishek; Simunovic, Srdjan

We used large format Li-ion cells to study the mechanical responses of single cells of thickness 6.5 mm and stacks of three cells under compressive loading. We carried out various sequences of increasing depth indentations using a 1.0 inch (25.4 mm) diameter steel ball with steel plate as a rigid support surface. The indentation depths were between 0.025 and 0.250 with main indentation increments tests of 0.025 steps. Increment steps of 0.100 and 0.005 were used to pinpoint the onset of internal-short that occurred between 0.245 and 0.250 . The indented cells were disassembled and inspected for internal damage. Loadmore » vs. time curves were compared with the developed computer models. Separator thinning leading to the short circuit was simulated using both isotropic and anisotropic mechanical properties. This study show that separators behave differently when tested as a single layer vs. a stack in a typical pouch cell. The collective responses of the multiple layers must be taken into account in failure analysis. A model that resolves the details of the individual internal cell components was able to simulate the internal deformation of the large format cells and the onset of failure assumed to coincide with the onset of internal short circuit.« less

Progressive mechanical indentation of large-format Li-ion cells

NASA Astrophysics Data System (ADS)

Wang, Hsin; Kumar, Abhishek; Simunovic, Srdjan; Allu, Srikanth; Kalnaus, Sergiy; Turner, John A.; Helmers, Jacob C.; Rules, Evan T.; Winchester, Clinton S.; Gorney, Philip

2017-02-01

Large format Li-ion cells were used to study the mechanical responses of single cells of thickness 6.5 mm and stacks of three cells under compressive loading. Various sequences of increasing depth indentations were carried out using a 1.0 inch (25.4 mm) diameter steel ball with steel plate as a rigid support surface. The indentation depths were between 0.025″ and 0.250″ with main indentation increments tests of 0.025″ steps. Increment steps of 0.100″ and 0.005″ were used to pinpoint the onset of internal-short that occurred between 0.245″ and 0.250″. The indented cells were disassembled and inspected for internal damage. Load vs. time curves were compared with the developed computer models. Separator thinning leading to the short circuit was simulated using both isotropic and anisotropic mechanical properties. Our study show that separators behave differently when tested as a single layer vs. a stack in a typical pouch cell. The collective responses of the multiple layers must be taken into account in failure analysis. A model that resolves the details of the individual internal cell components was able to simulate the internal deformation of the large format cells and the onset of failure assumed to coincide with the onset of internal short circuit.

Progressive mechanical indentation of large-format Li-ion cells

DOE PAGES

Wang, Hsin; Kumar, Abhishek; Simunovic, Srdjan; ...

2016-12-07

We used large format Li-ion cells to study the mechanical responses of single cells of thickness 6.5 mm and stacks of three cells under compressive loading. We carried out various sequences of increasing depth indentations using a 1.0 inch (25.4 mm) diameter steel ball with steel plate as a rigid support surface. The indentation depths were between 0.025 and 0.250 with main indentation increments tests of 0.025 steps. Increment steps of 0.100 and 0.005 were used to pinpoint the onset of internal-short that occurred between 0.245 and 0.250 . The indented cells were disassembled and inspected for internal damage. Loadmore » vs. time curves were compared with the developed computer models. Separator thinning leading to the short circuit was simulated using both isotropic and anisotropic mechanical properties. This study show that separators behave differently when tested as a single layer vs. a stack in a typical pouch cell. The collective responses of the multiple layers must be taken into account in failure analysis. A model that resolves the details of the individual internal cell components was able to simulate the internal deformation of the large format cells and the onset of failure assumed to coincide with the onset of internal short circuit.« less

Determination of the asphaltene and carboxylic acid content of a heavy oil using a microfluidic device.

PubMed

Bowden, Stephen A; Wilson, Rab; Parnell, John; Cooper, Jonathan M

2009-03-21

Heavy oil utilisation is set to increase over the coming decades as reserves of conventional oil decline. Heavy oil differs from conventional oil in containing relatively large quantities of asphaltene and carboxylic acids. The proportions of these compounds greatly influence how oil behaves during production and its utilisation as a fuel or feedstock. We report the development of a microfluidic technique, based on a H-cell, that can extract the carboxylic acid components of an oil and assess its asphaltene content. Ultimately this technology could yield a field-deployable device capable of performing measurements that facilitate improved resource management at the point of resource-extraction.

CCR4 frameshift mutation identifies a distinct group of adult T cell leukaemia/lymphoma with poor prognosis.

PubMed

Yoshida, Noriaki; Miyoshi, Hiroaki; Kato, Takeharu; Sakata-Yanagimoto, Mamiko; Niino, Daisuke; Taniguchi, Hiroaki; Moriuchi, Yukiyoshi; Miyahara, Masaharu; Kurita, Daisuke; Sasaki, Yuya; Shimono, Joji; Kawamoto, Keisuke; Utsunomiya, Atae; Imaizumi, Yoshitaka; Seto, Masao; Ohshima, Koichi

2016-04-01

Adult T cell leukaemia/lymphoma (ATLL) is an intractable T cell neoplasm caused by human T cell leukaemia virus type 1. Next-generation sequencing-based comprehensive mutation studies have revealed recurrent somatic CCR4 mutations in ATLL, although clinicopathological findings associated with CCR4 mutations remain to be delineated. In the current study, 184 cases of peripheral T cell lymphoma, including 113 cases of ATLL, were subjected to CCR4 mutation analysis. This sequence analysis identified mutations in 27% (30/113) of cases of ATLL and 9% (4/44) of cases of peripheral T cell lymphoma not otherwise specified. Identified mutations included nonsense (NS) and frameshift (FS) mutations. No significant differences in clinicopathological findings were observed between ATLL cases stratified by presence of CCR4 mutation. All ATLL cases with CCR4 mutations exhibited cell-surface CCR4 positivity. Semi-quantitative CCR4 protein analysis of immunohistochemical sections revealed higher CCR4 expression in cases with NS mutations of CCR4 than in cases with wild-type (WT) CCR4. Furthermore, among ATLL cases, FS mutation was significantly associated with a poor prognosis, compared with NS mutation and WT CCR4. These results suggest that CCR4 mutation is an important determinant of the clinical course in ATLL cases, and that NS and FS mutations of CCR4 behave differently with respect to ATLL pathophysiology. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Effects of Discrete Charge Clustering in Simulations of Charged Interfaces.

PubMed

Grime, John M A; Khan, Malek O

2010-10-12

A system of counterions between charged surfaces is investigated, with the surfaces represented by uniform charged planes and three different arrangements of discrete surface charges - an equispaced grid and two different clustered arrangements. The behaviors of a series of systems with identical net surface charge density are examined, with particular emphasis placed on the long ranged corrections via the method of "charged slabs" and the effects of the simulation cell size. Marked differences are observed in counterion distributions and the osmotic pressure dependent on the particular representation of the charged surfaces; the uniformly charged surfaces and equispaced grids of discrete charge behave in a broadly similar manner, but the clustered systems display a pronounced decrease in osmotic pressure as the simulation size is increased. The influence of the long ranged correction is shown to be minimal for all but the very smallest of system sizes.

Treatment with selective estrogen receptor modulators regulates myelin specific T-cells and suppresses experimental autoimmune encephalomyelitis.

PubMed

Bebo, Bruce F; Dehghani, Babak; Foster, Scott; Kurniawan, Astrid; Lopez, Francisco J; Sherman, Larry S

2009-05-01

Steroidal estrogens can regulate inflammatory immune responses and may be involved in the suppression of multiple sclerosis (MS) during pregnancy. However, the risks and side effects associated with steroidal estrogens may limit their usefulness for long-term MS therapy. Selective estrogen receptor modulators (SERMs) could provide an alternative therapeutic strategy, because they behave as estrogen agonists in some tissues, but are either inert or behave like estrogen antagonists in other tissues. In this study, we investigated the ability of two commercially available SERMs (tamoxifen and raloxifene) to regulate myelin specific immunity and experimental autoimmune encephalomyelitis (EAE) in mice. Both tamoxifen and raloxifene suppressed myelin antigen specific T-cell proliferation. However, tamoxifen was more effective in this regard. Tamoxifen treatment reduced the induction of major histocompatibility complex II by lipopolysaccharide stimulated dendritic cells and decreased their ability to activate myelin specific T-cells. At lower doses, tamoxifen was found to increase the levels of Th2 transcription factors and induce a Th2 bias in cultures of myelin-specific splenocytes. EAE symptoms and the degree of demyelination were less severe in mice treated with tamoxifen than in control mice. These findings support the notion that tamoxifen or related SERMs are potential agents that could be used in the treatment of inflammatory autoimmune disorders that affect the central nervous system.

Full utilization of semi-Dirac cones in photonics

NASA Astrophysics Data System (ADS)

Yasa, Utku G.; Turduev, Mirbek; Giden, Ibrahim H.; Kurt, Hamza

2018-05-01

In this study, realization and applications of anisotropic zero-refractive-index materials are proposed by exposing the unit cells of photonic crystals that exhibit Dirac-like cone dispersion to rotational symmetry reduction. Accidental degeneracy of two Bloch modes in the Brillouin zone center of two-dimensional C2-symmetric photonic crystals gives rise to the semi-Dirac cone dispersion. The proposed C2-symmetric photonic crystals behave as epsilon-and-mu-near-zero materials (ɛeff≈ 0 , μeff≈ 0 ) along one propagation direction, but behave as epsilon-near-zero material (ɛeff≈ 0 , μeff≠ 0 ) for the perpendicular direction at semi-Dirac frequency. By extracting the effective medium parameters of the proposed C4- and C2-symmetric periodic media that exhibit Dirac-like and semi-Dirac cone dispersions, intrinsic differences between isotropic and anisotropic materials are investigated. Furthermore, advantages of utilizing semi-Dirac cone materials instead of Dirac-like cone materials in photonic applications are demonstrated in both frequency and time domains. By using anisotropic transmission behavior of the semi-Dirac materials, photonic application concepts such as beam deflectors, beam splitters, and light focusing are proposed. Furthermore, to the best of our knowledge, semi-Dirac cone dispersion is also experimentally demonstrated for the first time by including negative, zero, and positive refraction states of the given material.

Energy independent uptake and release of polystyrene nanoparticles in primary mammalian cell cultures.

PubMed

Fiorentino, Ilaria; Gualtieri, Roberto; Barbato, Vincenza; Mollo, Valentina; Braun, Sabrina; Angrisani, Alberto; Turano, Mimmo; Furia, Maria; Netti, Paolo A; Guarnieri, Daniela; Fusco, Sabato; Talevi, Riccardo

2015-01-15

Nanoparticle (NPs) delivery systems in vivo promises to overcome many obstacles associated with the administration of drugs, vaccines, plasmid DNA and RNA materials, making the study of their cellular uptake a central issue in nanomedicine. The uptake of NPs may be influenced by the cell culture stage and the NPs physical-chemical properties. So far, controversial data on NPs uptake have been derived owing to the heterogeneity of NPs and the general use of immortalized cancer cell lines that often behave differently from each other and from primary mammalian cell cultures. Main aims of the present study were to investigate the uptake, endocytosis pathways, intracellular fate and release of well standardized model particles, i.e. fluorescent 44 nm polystyrene NPs (PS-NPs), on two primary mammalian cell cultures, i.e. bovine oviductal epithelial cells (BOEC) and human colon fibroblasts (HCF) by confocal microscopy and spectrofluorimetric analysis. Different drugs and conditions that inhibit specific internalization routes were used to understand the mechanisms that mediate PS-NP uptake. Our data showed that PS-NPs are rapidly internalized by both cell types 1) with similar saturation kinetics; 2) through ATP-independent processes, and 3) quickly released in the culture medium. Our results suggest that PS-NPs are able to rapidly cross the cell membrane through passive translocation during both uptake and release, and emphasize the need to carefully design NPs for drug delivery, to ensure their selective uptake and to optimize their retainment in the targeted cells. Copyright © 2014 Elsevier Inc. All rights reserved.

Sub-apoptotic dosages of pro-oxidant vitamin cocktails sensitize human melanoma cells to NK cell lysis.

PubMed

Tremante, Elisa; Santarelli, Lory; Lo Monaco, Elisa; Sampaoli, Camilla; Ingegnere, Tiziano; Guerrieri, Roberto; Tomasetti, Marco; Giacomini, Patrizio

2015-10-13

Alpha-tocopheryl succinate (αTOS), vitamin K3 (VK3) and vitamin C (ascorbic acid, AA) were previously shown to synergistically promote different death pathways in carcinoma cells, depending on their concentrations and combinations. Similar effects were observed herein in melanoma cells, although αTOS behaved as an antagonist. Interestingly, suboptimal cell death-inducing concentrations (1.5 μM αTOS/20 μM AA/0.2 μM VK3) effectively up-regulated activating Natural Killer (NK) cell ligands, including MICA (the stress-signaling ligand of the NKG2D receptor), and/or the ligands of at least one of the natural cytotoxicity receptors (NKp30, NKp44 and NKp46) in 5/6 melanoma cell lines. Only an isolated MICA down-regulation was seen. HLA class I, HLA class II, ULBP1, ULBP2, ULBP3, Nectin-2, and PVR displayed little, if any, change in expression. Ligand up-regulation resulted in improved lysis by polyclonal NK cells armed with the corresponding activating receptors. These results provide the first evidence for concerted induction of cell death by cell-autonomous and extrinsic (immune) mechanisms. Alarming the immune system much below the cell damage threshold may have evolved as a sensitive readout of neoplastic transformation and oxidative stress. Cocktails of vitamin analogues at slightly supra-physiological dosages may find application as mild complements of melanoma treatment, and in chemoprevention.

Sub-apoptotic dosages of pro-oxidant vitamin cocktails sensitize human melanoma cells to NK cell lysis

PubMed Central

Tremante, Elisa; Santarelli, Lory; Monaco, Elisa Lo; Sampaoli, Camilla; Ingegnere, Tiziano; Guerrieri, Roberto

2015-01-01

Alpha-tochopheryl succinate (αTOS), vitamin K3 (VK3) and vitamin C (ascorbic acid, AA) were previously shown to synergistically promote different death pathways in carcinoma cells, depending on their concentrations and combinations. Similar effects were observed herein in melanoma cells, although αTOS behaved as an antagonist. Interestingly, suboptimal cell death-inducing concentrations (1.5 μM αTOS/20 μM AA/0.2 μM VK3) effectively up-regulated activating Natural Killer (NK) cell ligands, including MICA (the stress-signaling ligand of the NKG2D receptor), and/or the ligands of at least one of the natural cytotoxicity receptors (NKp30, NKp44 and NKp46) in 5/6 melanoma cell lines. Only an isolated MICA down-regulation was seen. HLA class I, HLA class II, ULBP1, ULBP2, ULBP3, Nectin-2, and PVR displayed little, if any, change in expression. Ligand up-regulation resulted in improved lysis by polyclonal NK cells armed with the corresponding activating receptors. These results provide the first evidence for concerted induction of cell death by cell-autonomous and extrinsic (immune) mechanisms. Alarming the immune system much below the cell damage threshold may have evolved as a sensitive readout of neoplastic transformation and oxidative stress. Cocktails of vitamin analogues at slightly supra-physiological dosages may find application as mild complements of melanoma treatment, and in chemoprevention. PMID:26427039

Intraorganellar acidification by V-ATPases: a target in cell proliferation and cancer therapy.

PubMed

Hernández, Agustín; Serrano, Gloria; Herrera-Palau, Rosana; Pérez-Castiñeira, José R; Serrano, Aurelio

2010-06-01

Vacuolar-type ATPases are multicomponent proton pumps involved in the acidification of single membrane intracellular compartments such as endosomes and lysosomes. They couple the hydrolysis of ATP to the translocation of one to two protons across the membrane. Acidification of the lumen of single membrane organelles is a necessary factor for the correct traffic of membranes and cargo to and from the different internal compartments of a cell. Also, V-ATPases are involved in regulation of pH at the cytosol and, possibly, extracellular milieu. The inhibition of V-ATPases has been shown to induce apoptosis and cell cycle arrest in tumour cells and, therefore, chemicals that behave as inhibitors of this kind of proton pumps have been proposed as putative treatment agents against cancer and many have been patented as such. The compounds filed in patents fall into five major types: plecomacrolides, benzolactone enamides, archazolids, chondropsins and indoles. All these have proved to be apoptosis inducers in cell culture and many to be able to reduce xenograft tumor growth in murine models. The present review will summarize their general structure, origin and mechanisms of action and put them in relation to the patents registered so far for the treatment of cancer.

Graded Positive Feedback in Elasmobranch Ampullae of Lorenzini

NASA Astrophysics Data System (ADS)

Kalmijn, Ad. J.

2003-05-01

The acute electrical sensitivity of marine sharks and rays is the greatest known in the Animal Kingdom. I investigate the possibility that the underlying biophysical principles are the very same as those encountered in the central nervous system of animal and man. The elasmobranch ampullae of Lorenzini detect the weak electric fields originating from the oceanic environment, whereas the nerve cells of the brain detect the electric fields arising, well, from the central nervous system. In responding to electrical signals, the cell membranes of excitable cells behave in different regions of the cell as negative or positive conductors. The negative and positive conductances in series, loaded by the cell's electrolytic environment, constitute a positive feedback circuit. The result may be of an all-or-none nature, as in peripheral nerve conduction, or of a graded nature, as in central processing. In this respect, the operation of the elasmobranch ampullae of Lorenzini is more akin to the graded, integrative processes of higher brain centers than to the conduction of nerve action potentials. Hence, the positive-feedback ampullary circuit promises to help elucidate the functioning of the central nervous system as profoundly as the squid giant axon has served to reveal the process of nervous conduction.

Hospital doctors behave differently, and only by respecting the fundamentals of professional organizations will managers be able to create common goals with professionals.

PubMed

Van Dijck, H

2014-08-01

Hospital doctors behave differently from other hospital workers. The general and specific characteristics of the doctors' behavior are described. As professionals, doctors want to make autonomous decisions and more specifically, they negotiate differently. The best description of their negotiation style is one that features multi-actor, multi-issue characteristics. They behave as actors in a network in never-ending rounds of negotiations with variable issues up for discussion: one time you lose, the next you win. A doctor's career starts with a long residency period in which he or she absorbs professional habits. His or her knowledge and way of organizing are implicit. It is hard for him or her to explicitly describe what he or she is doing. This makes it difficult for managers to discuss quality issues with doctors. Dealing with disruptive behavior is not easy either. The difficult tasks of the chief medical officer, who acts as a go-between, are highlighted. Only when managers respect the fundamentals of the professional organization will they be able to create common goals with the professionals. Common goals bring about better care in hospitals.

Engineering mesenchymal stem cell spheroids by incorporation of mechanoregulator microparticles.

PubMed

Abbasi, Fatemeh; Ghanian, Mohammad Hossein; Baharvand, Hossein; Vahidi, Bahman; Eslaminejad, Mohamadreza Baghaban

2018-05-03

Mechanical forces throughout human mesenchymal stem cell (hMSC) spheroids (mesenspheres) play a predominant role in determining cellular functions of cell growth, proliferation, and differentiation through mechanotransductional mechanisms. Here, we introduce microparticle (MP) incorporation as a mechanical intervention method to alter tensional homeostasis of the mesensphere and explore MSC differentiation in response to MP stiffness. The microparticulate mechanoregulators with different elastic modulus (34 kPa, 0.6 MPa, and 2.2 MPa) were prepared by controlled crosslinking cell-sized microdroplets of polydimethylsiloxane (PDMS). Preparation of MP-MSC composite spheroids enabled us to study the possible effects of MPs through experimental and computational assays. Our results showed that MP incorporation selectively primed MSCs toward osteogenesis, yet hindered adipogenesis. Interestingly, this behavior depended on MP mechanics, as the spheroids that contained MPs with intermediate stiffness behaved similar to control MP-free mesenspheres with more tendencies toward chondrogenesis. However, by using the soft or stiff MPs, the MP-mesenspheres significantly showed signs of osteogenesis. This could be explained by the complex of forces which acted in the cell spheroid and, totally, provided a homeostasis situation. Incorporation of cell-sized polymer MPs as mechanoregulators of cell spheroids could be utilized as a new engineering toolkit for multicellular organoids in disease modeling and tissue engineering applications. Copyright © 2018 Elsevier Ltd. All rights reserved.

Regression-Based Identification of Behavior-Encoding Neurons During Large-Scale Optical Imaging of Neural Activity at Cellular Resolution

PubMed Central

Miri, Andrew; Daie, Kayvon; Burdine, Rebecca D.; Aksay, Emre

2011-01-01

The advent of methods for optical imaging of large-scale neural activity at cellular resolution in behaving animals presents the problem of identifying behavior-encoding cells within the resulting image time series. Rapid and precise identification of cells with particular neural encoding would facilitate targeted activity measurements and perturbations useful in characterizing the operating principles of neural circuits. Here we report a regression-based approach to semiautomatically identify neurons that is based on the correlation of fluorescence time series with quantitative measurements of behavior. The approach is illustrated with a novel preparation allowing synchronous eye tracking and two-photon laser scanning fluorescence imaging of calcium changes in populations of hindbrain neurons during spontaneous eye movement in the larval zebrafish. Putative velocity-to-position oculomotor integrator neurons were identified that showed a broad spatial distribution and diversity of encoding. Optical identification of integrator neurons was confirmed with targeted loose-patch electrical recording and laser ablation. The general regression-based approach we demonstrate should be widely applicable to calcium imaging time series in behaving animals. PMID:21084686

Hypothesis: solid tumours behave as systemic metabolic dictators.

PubMed

Lee, Yang-Ming; Chang, Wei-Chun; Ma, Wen-Lung

2016-06-01

Current knowledge regarding mechanisms of carcinogenesis in human beings centres around the accumulation of genetic instability, amplified cellular signalling, disturbed cellular energy metabolism and microenvironmental regulation governed by complicated cell-cell interactions. In this article, we provide an alternative view of cancer biology. We propose that cancer behaves as a systemic dictator that interacts with tissues throughout the body to control their metabolism and eventually homeostasis. The mechanism of development of this endocrine organ-like tumour (EOLT) tissue might be the driving force for cancer progression. Here, we review the literature that led to the development of this hypothesis. The EOLT phenotype can be defined as a tumour that alters systemic homeostasis. The literature indicates that the EOLT phenotype is present throughout cancer progression. The feedback mechanism that governs the interaction between tumours and various organs is unknown. We believe that investigating the mechanism of EOLT development may advance the current knowledge of regulation within the tumour macroenvironment and consequently lead to new diagnostic methods and therapy. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Ly6d marks the earliest stage of B-cell specification and identifies the branchpoint between B-cell and T-cell development

PubMed Central

Inlay, Matthew A.; Bhattacharya, Deepta; Sahoo, Debashis; Serwold, Thomas; Seita, Jun; Karsunky, Holger; Plevritis, Sylvia K.; Dill, David L.; Weissman, Irving L.

2009-01-01

Common lymphoid progenitors (CLPs) clonally produce both B- and T-cell lineages, but have little myeloid potential in vivo. However, some studies claim that the upstream lymphoid-primed multipotent progenitor (LMPP) is the thymic seeding population, and suggest that CLPs are primarily B-cell-restricted. To identify surface proteins that distinguish functional CLPs from B-cell progenitors, we used a new computational method of Mining Developmentally Regulated Genes (MiDReG). We identified Ly6d, which divides CLPs into two distinct populations: one that retains full in vivo lymphoid potential and produces more thymocytes at early timepoints than LMPP, and another that behaves essentially as a B-cell progenitor. PMID:19833765

Cytotoxicity of Spent Pot Liner on Allium cepa root tip cells: A comparative analysis in meristematic cell type on toxicity bioassays.

PubMed

Palmieri, Marcel José; Andrade-Vieira, Larissa Fonseca; Campos, José Marcello Salabert; Dos Santos Gedraite, Leonardo; Davide, Lisete Chamma

2016-11-01

Spent Pot Liner (SPL) is a waste generated during the production of aluminum. It is comprised of a mixture of substances most of which, like cyanide, aluminum and fluoride, are toxic. Previous studies indicate the highly toxic nature of SPL. However studies using cells of the differentiation/elongation zone of the root meristem (referred as M2 cells in this study) after a proper recovery period in water were never considered. Using these cells could be useful to further understanding the toxicity mechanisms of SPL. A comparative approach between the effects on M2 cells and meristematic cells of the proximal meristem zone (referred as M1 cells in this study) could lead to understanding how DNA damage caused by SPL behaves on successive generations of cells. Allium cepa cells were exposed to 4 different concentrations of SPL (2.5, 5, 7.5 and 10gL(-1)) mixed with soil and diluted in a CaCl2 0.01M to simulate the ionic forces naturally encountered on the environment. A solution containing only soil diluted on CaCl2 0.01M was used as control. M1 and M2 cells were evaluated separately, taking into account four different parameters: (1) mitotic alterations (MA); (2) presence of condensed nuclei (CN); (3) mitotic index (MI); (4) presence of micronucleus (MCN). Significant differences were observed between M1 and M2 roots tip cells for these four parameters accessed. M1 cells was more prompt to reveal citogenotoxicity through the higher frequency of MA observed. Meanwhile, for M2 cells higher frequencies of MCN and CN was noticed, followed by a reduction of MI. Also, it was possible to detect significant differences between the tested treatments and the control on every case. These results indicate SPL toxic effects carries on to future cells generations. This emphasizes the need to properly manage this waste. Joint evaluation of cells from both M1 and M2 regions was proven valuable for the evaluation of a series of parameters on all toxicity tests. Copyright © 2016. Published by Elsevier Inc.

Beyond the bolus: transgenic tools for investigating the neurophysiology of learning and memory.

PubMed

Lykken, Christine; Kentros, Clifford G

2014-10-01

Understanding the neural mechanisms underlying learning and memory in the entorhinal-hippocampal circuit is a central challenge of systems neuroscience. For more than 40 years, electrophysiological recordings in awake, behaving animals have been used to relate the receptive fields of neurons in this circuit to learning and memory. However, the vast majority of such studies are purely observational, as electrical, surgical, and pharmacological circuit manipulations are both challenging and relatively coarse, being unable to distinguish between specific classes of neurons. Recent advances in molecular genetic tools can overcome many of these limitations, enabling unprecedented control over neural activity in behaving animals. Expression of pharmaco- or optogenetic transgenes in cell-type-specific "driver" lines provides unparalleled anatomical and cell-type specificity, especially when delivered by viral complementation. Pharmacogenetic transgenes are specially designed neurotransmitter receptors exclusively activated by otherwise inactive synthetic ligands and have kinetics similar to traditional pharmacology. Optogenetic transgenes use light to control the membrane potential, and thereby operate at the millisecond timescale. Thus, activation of pharmacogenetic transgenes in specific neuronal cell types while recording from other parts of the circuit allows investigation of the role of those neurons in the steady state, whereas optogenetic transgenes allow one to determine the immediate network response. © 2014 Lykken and Kentros; Published by Cold Spring Harbor Laboratory Press.

In situ electrochemical-electron spin resonance investigations of multi-electron redox reaction for organic radical cathodes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang, Qian; Walter, Eric D.; Cosimbescu, Lelia

2016-02-29

Organic radical batteries (ORBs) bearing robust radical polymers as energy storage species, are emerging promisingly with durable high energy and power characteristics by unique tunable redox properties. Here we report the development and application of in situ electrochemical-electron spin resonance (ESR) methodologies to identify the charge transfer mechanism of Poly(2,2,6,6- tetramethylpiperidinyloxy-4-yl methacrylate) (PTMA) based organic radical composite cathodes in the charge-discharge process of lithium half cells. The in situ experiments allow each electrochemical state to be associated with the chemical state (or environment) of the radical species upon the cell cycling. In situ ESR spectra of the composite cathode demonstratemore » a two-electron redox reaction of PTMA. Moreover, two different local environments of radical species are found in the composite electrode that includes both concentrated and isolated radicals. These two types of radicals show similarities during the redox reaction process while behave quite differently in the non-faradic reaction of ion sorption/desorption on the electrode surface.« less

Do you BEHAVE? - Application of the BehavePlus fire modeling system

Treesearch

Pat Andrews

2010-01-01

The BehavePlus fire modeling system is the successor to BEHAVE, which was first used in the field in 1984. It is public domain software, available for free use on personal computers. Information on user communities and fire management applications can be useful in designing next generation systems. Several sources of information about BehavePlus are summarized to...

Phase transitions and size scaling of membrane-less organelles

PubMed Central

2013-01-01

The coordinated growth of cells and their organelles is a fundamental and poorly understood problem, with implications for processes ranging from embryonic development to oncogenesis. Recent experiments have shed light on the cell size–dependent assembly of membrane-less cytoplasmic and nucleoplasmic structures, including ribonucleoprotein (RNP) granules and other intracellular bodies. Many of these structures behave as condensed liquid-like phases of the cytoplasm/nucleoplasm. The phase transitions that appear to govern their assembly exhibit an intrinsic dependence on cell size, and may explain the size scaling reported for a number of structures. This size scaling could, in turn, play a role in cell growth and size control. PMID:24368804

The quantal theory of how the immune system discriminates between "self and non-self"

PubMed

Smith, Kendall A

2004-12-17

In the past 50 years, immunologists have accumulated an amazing amount of information as to how the immune system functions. However, one of the most fundamental aspects of immunity, how the immune system discriminates between self vs. non-self, still remains an enigma. Any attempt to explain this most intriguing and fundamental characteristic must account for this decision at the level of the whole immune system, but as well, at the level of the individual cells making up the immune system. Moreover, it must provide for a molecular explanation as to how and why the cells behave as they do. The "Quantal Theory", proposed herein, is based upon the "Clonal Selection Theory", first proposed by Sir McFarland Burnet in 1955, in which he explained the remarkable specificity as well as diversity of recognition of everything foreign in the environment. The "Quantal Theory" is built upon Burnet's premise that after antigen selection of cell clones, a proliferative expansion of the selected cells ensues. Furthermore, it is derived from experiments which indicate that the proliferation of antigen-selected cell clones is determined by a quantal, "all-or-none", decision promulgated by a critical number of cellular receptors triggered by the T Cell Growth Factor (TCGF), interleukin 2 (IL2). An extraordinary number of experiments reported especially in the past 20 years, and detailed herein, indicate that the T cell Antigen Receptor (TCR) behaves similarly, and also that there are several critical numbers of triggered TCRs that determine different fates of the T cells. Moreover, the fates of the cells appear ultimately to be determined by the TCR triggering of the IL2 and IL2 receptor (IL2R) genes, which are also expressed in a very quantal fashion. The "Quantal Theory" states that the fundamental decisions of the T cell immune system are dependent upon the cells receiving a critical number of triggered TCRs and IL2Rs and that the cells respond in an all-or-none fashion. The "Quantal Theory" accounts fully for the development of T cells in the thymus, and such fundamental cellular fates as both "positive" and "negative" selection, as well as the decision to differentiate into a "Regulatory T cell" (T-Reg). In the periphery, the "Quantal Theory" accounts for the decision to proliferate or not in response to the presence of an antigen, either non-self or self, or to differentiate into a T-Reg. Since the immune system discriminates between self and non-self antigens by the accumulated number of triggered TCRs and IL2Rs, therapeutic manipulation of the determinants of these quantal decisions should permit new approaches to either enhance or dampen antigen-specific immune responses.

Analysis of type II diabetes mellitus adipose-derived stem cells for tissue engineering applications

PubMed Central

Minteer, Danielle Marie; Young, Matthew T; Lin, Yen-Chih; Over, Patrick J; Rubin, J Peter; Gerlach, Jorg C

2015-01-01

To address the functionality of diabetic adipose-derived stem cells in tissue engineering applications, adipose-derived stem cells isolated from patients with and without type II diabetes mellitus were cultured in bioreactor culture systems. The adipose-derived stem cells were differentiated into adipocytes and maintained as functional adipocytes. The bioreactor system utilizes a hollow fiber–based technology for three-dimensional perfusion of tissues in vitro, creating a model in which long-term culture of adipocytes is feasible, and providing a potential tool useful for drug discovery. Daily metabolic activity of the adipose-derived stem cells was analyzed within the medium recirculating throughout the bioreactor system. At experiment termination, tissues were extracted from bioreactors for immunohistological analyses in addition to gene and protein expression. Type II diabetic adipose-derived stem cells did not exhibit significantly different glucose consumption compared to adipose-derived stem cells from patients without type II diabetes (p > 0.05, N = 3). Expression of mature adipocyte genes was not significantly different between diabetic/non-diabetic groups (p > 0.05, N = 3). Protein expression of adipose tissue grown within all bioreactors was verified by Western blotting.The results from this small-scale study reveal adipose-derived stem cells from patients with type II diabetes when removed from diabetic environments behave metabolically similar to the same cells of non-diabetic patients when cultured in a three-dimensional perfusion bioreactor, suggesting that glucose transport across the adipocyte cell membrane, the hindrance of which being characteristic of type II diabetes, is dependent on environment. The presented observation describes a tissue-engineered tool for long-term cell culture and, following future adjustments to the culture environment and increased sample sizes, potentially for anti-diabetic drug testing. PMID:26090087

The Hpp Rule with Memory and the Density Classification Task

NASA Astrophysics Data System (ADS)

Alonso-Sanz, Ramón

This article considers an extension to the standard framework of cellular automata by implementing memory capability in cells. It is shown that the important block HPP rule behaves as an excellent classifier of the density in the initial configuration when applied to cells endowed with pondered memory of their previous states. If the weighing is made so that the most recent state values are assigning the highest weights, the HPP rule surpasses the performance of the best two-dimensional density classifiers reported in the literature.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, Meiye; Singh, Anup K.

In this study, cell signaling is a dynamic and complex process. A typical signaling pathway may begin with activation of cell surface receptors, leading to activation kinase cascade that culminates in induction of mRNA and non-coding miRNA production in the nucleus, followed by modulation of mRNA expression by miRNAs in the cytosol, and end with production of proteins in response to the signaling pathway. Signaling pathways involve proteins, miRNA, and mRNAs, along with various forms of transient post-translational modifications, and detecting each type of signaling molecule requires categorically different sample preparation methods such as Western blotting for proteins, PCR formore » nucleic acids, and flow cytometry for post-translational modifications. Since we know that cells in populations behave heterogeneously1, especially in the cases of stem cells, cancer, and hematopoiesis, there is need for a new technology that provides capability to detect and quantify multiple categories of signaling molecules in intact single cells to provide a comprehensive view of the cell’s physiological state. In this technical brief, we describe our microfluidic platform with a portfolio of customized molecular assays that can detect nucleic acids, proteins, and post-translational modifications in single intact cells with >95% reduction in reagent requirement in under 8 hours.« less

On the Role of the Pedunculopontine Nucleus and Mesencephalic Reticular Formation in Locomotion in Nonhuman Primates.

PubMed

Goetz, Laurent; Piallat, Brigitte; Bhattacharjee, Manik; Mathieu, Hervé; David, Olivier; Chabardès, Stéphan

2016-05-04

The mesencephalic reticular formation (MRF) is formed by the pedunculopontine and cuneiform nuclei, two neuronal structures thought to be key elements in the supraspinal control of locomotion, muscle tone, waking, and REM sleep. The role of MRF has also been advocated in modulation of state of arousal leading to transition from wakefulness to sleep and it is further considered to be a main player in the pathophysiology of gait disorders seen in Parkinson's disease. However, the existence of a mesencephalic locomotor region and of an arousal center has not yet been demonstrated in primates. Here, we provide the first extensive electrophysiological mapping of the MRF using extracellular recordings at rest and during locomotion in a nonhuman primate (NHP) (Macaca fascicularis) model of bipedal locomotion. We found different neuronal populations that discharged according to a phasic or a tonic mode in response to locomotion, supporting the existence of a locomotor neuronal circuit within these MRF in behaving primates. Altogether, these data constitute the first electrophysiological characterization of a locomotor neuronal system present within the MRF in behaving NHPs under normal conditions, in accordance with several studies done in different experimental animal models. We provide the first extensive electrophysiological mapping of the two major components of the mesencephalic reticular formation (MRF), namely the pedunculopontine and cuneiform nuclei. We exploited a nonhuman primate (NHP) model of bipedal locomotion with extracellular recordings in behaving NHPs at rest and during locomotion. Different MRF neuronal groups were found to respond to locomotion, with phasic or tonic patterns of response. These data constitute the first electrophysiological evidences of a locomotor neuronal system within the MRF in behaving NHPs. Copyright © 2016 the authors 0270-6474/16/364917-13$15.00/0.

Chemical Oxidation of a Redox-Active, Ferrocene-Containing Cationic Lipid: Influence on Interactions with DNA and Characterization in the Context of Cell Transfection

PubMed Central

Aytar, Burcu S.; Muller, John P. E.; Golan, Sharon; Kondo, Yukishige; Talmon, Yeshayahu; Abbott, Nicholas L.; Lynn, David M.

2012-01-01

We report an approach to the chemical oxidation of a ferrocene-containing cationic lipid [bis(11-ferrocenylundecyl)dimethylammonium bromide, BFDMA] that provides redox-based control over the delivery of DNA to cells. We demonstrate that BFDMA can be oxidized rapidly and quantitatively by treatment with Fe(III)sulfate. This chemical approach, while offering practical advantages compared to electrochemical methods used in past studies, was found to yield BFDMA/DNA lipoplexes that behave differently in the context of cell transfection from lipoplexes formed using electrochemically oxidized BFDMA. Specifically, while lipoplexes of the latter do not transfect cells efficiently, lipoplexes of chemically oxidized BFDMA promoted high levels of transgene expression (similar to levels promoted by reduced BFDMA). Characterization by SANS and cryo-TEM revealed lipoplexes of chemically and electrochemically oxidized BFDMA to both have amorphous nanostructures, but these lipoplexes differed significantly in size and zeta potential. Our results suggest that differences in zeta potential arise from the presence of residual Fe2+ and Fe3+ ions in samples of chemically oxidized BFDMA. Addition of the iron chelating agent EDTA to solutions of chemically oxidized BFDMA produced samples functionally similar to electrochemically oxidized BFDMA. These EDTA-treated samples could also be chemically reduced by treatment with ascorbic acid to produce samples of reduced BFDMA that do promote transfection. Our results demonstrate that entirely chemical approaches to oxidation and reduction can be used to achieve redox-based ‘on/off’ control of cell transfection similar to that achieved using electrochemical methods. PMID:22980739

Chaos Quantum-Behaved Cat Swarm Optimization Algorithm and Its Application in the PV MPPT

PubMed Central

2017-01-01

Cat Swarm Optimization (CSO) algorithm was put forward in 2006. Despite a faster convergence speed compared with Particle Swarm Optimization (PSO) algorithm, the application of CSO is greatly limited by the drawback of “premature convergence,” that is, the possibility of trapping in local optimum when dealing with nonlinear optimization problem with a large number of local extreme values. In order to surmount the shortcomings of CSO, Chaos Quantum-behaved Cat Swarm Optimization (CQCSO) algorithm is proposed in this paper. Firstly, Quantum-behaved Cat Swarm Optimization (QCSO) algorithm improves the accuracy of the CSO algorithm, because it is easy to fall into the local optimum in the later stage. Chaos Quantum-behaved Cat Swarm Optimization (CQCSO) algorithm is proposed by introducing tent map for jumping out of local optimum in this paper. Secondly, CQCSO has been applied in the simulation of five different test functions, showing higher accuracy and less time consumption than CSO and QCSO. Finally, photovoltaic MPPT model and experimental platform are established and global maximum power point tracking control strategy is achieved by CQCSO algorithm, the effectiveness and efficiency of which have been verified by both simulation and experiment. PMID:29181020

Chaos Quantum-Behaved Cat Swarm Optimization Algorithm and Its Application in the PV MPPT.

PubMed

Nie, Xiaohua; Wang, Wei; Nie, Haoyao

2017-01-01

Cat Swarm Optimization (CSO) algorithm was put forward in 2006. Despite a faster convergence speed compared with Particle Swarm Optimization (PSO) algorithm, the application of CSO is greatly limited by the drawback of "premature convergence," that is, the possibility of trapping in local optimum when dealing with nonlinear optimization problem with a large number of local extreme values. In order to surmount the shortcomings of CSO, Chaos Quantum-behaved Cat Swarm Optimization (CQCSO) algorithm is proposed in this paper. Firstly, Quantum-behaved Cat Swarm Optimization (QCSO) algorithm improves the accuracy of the CSO algorithm, because it is easy to fall into the local optimum in the later stage. Chaos Quantum-behaved Cat Swarm Optimization (CQCSO) algorithm is proposed by introducing tent map for jumping out of local optimum in this paper. Secondly, CQCSO has been applied in the simulation of five different test functions, showing higher accuracy and less time consumption than CSO and QCSO. Finally, photovoltaic MPPT model and experimental platform are established and global maximum power point tracking control strategy is achieved by CQCSO algorithm, the effectiveness and efficiency of which have been verified by both simulation and experiment.

Optogenetic Modulation and Multi-Electrode Analysis of Cerebellar Networks In Vivo

PubMed Central

Kruse, Wolfgang; Krause, Martin; Aarse, Janna; Mark, Melanie D.; Manahan-Vaughan, Denise; Herlitze, Stefan

2014-01-01

The firing patterns of cerebellar Purkinje cells (PCs), as the sole output of the cerebellar cortex, determine and tune motor behavior. PC firing is modulated by various inputs from different brain regions and by cell-types including granule cells (GCs), climbing fibers and inhibitory interneurons. To understand how signal integration in PCs occurs and how subtle changes in the modulation of PC firing lead to adjustment of motor behaviors, it is important to precisely record PC firing in vivo and to control modulatory pathways in a spatio-temporal manner. Combining optogenetic and multi-electrode approaches, we established a new method to integrate light-guides into a multi-electrode system. With this method we are able to variably position the light-guide in defined regions relative to the recording electrode with micrometer precision. We show that PC firing can be precisely monitored and modulated by light-activation of channelrhodopsin-2 (ChR2) expressed in PCs, GCs and interneurons. Thus, this method is ideally suited to investigate the spatio/temporal modulation of PCs in anesthetized and in behaving mice. PMID:25144735

Two Different Template Replicators Coexisting in the Same Protocell: Stochastic Simulation of an Extended Chemoton Model

PubMed Central

Zachar, István; Fedor, Anna; Szathmáry, Eörs

2011-01-01

The simulation of complex biochemical systems, consisting of intertwined subsystems, is a challenging task in computational biology. The complex biochemical organization of the cell is effectively modeled by the minimal cell model called chemoton, proposed by Gánti. Since the chemoton is a system consisting of a large but fixed number of interacting molecular species, it can effectively be implemented in a process algebra-based language such as the BlenX programming language. The stochastic model behaves comparably to previous continuous deterministic models of the chemoton. Additionally to the well-known chemoton, we also implemented an extended version with two competing template cycles. The new insight from our study is that the coupling of reactions in the chemoton ensures that these templates coexist providing an alternative solution to Eigen's paradox. Our technical innovation involves the introduction of a two-state switch to control cell growth and division, thus providing an example for hybrid methods in BlenX. Further developments to the BlenX language are suggested in the Appendix. PMID:21818258

Two different template replicators coexisting in the same protocell: stochastic simulation of an extended chemoton model.

PubMed

Zachar, István; Fedor, Anna; Szathmáry, Eörs

2011-01-01

The simulation of complex biochemical systems, consisting of intertwined subsystems, is a challenging task in computational biology. The complex biochemical organization of the cell is effectively modeled by the minimal cell model called chemoton, proposed by Gánti. Since the chemoton is a system consisting of a large but fixed number of interacting molecular species, it can effectively be implemented in a process algebra-based language such as the BlenX programming language. The stochastic model behaves comparably to previous continuous deterministic models of the chemoton. Additionally to the well-known chemoton, we also implemented an extended version with two competing template cycles. The new insight from our study is that the coupling of reactions in the chemoton ensures that these templates coexist providing an alternative solution to Eigen's paradox. Our technical innovation involves the introduction of a two-state switch to control cell growth and division, thus providing an example for hybrid methods in BlenX. Further developments to the BlenX language are suggested in the Appendix.

Dermal regulatory T cells display distinct migratory behavior that is modulated during adaptive and innate inflammation.

PubMed

Chow, Zachary; Mueller, Scott N; Deane, James A; Hickey, Michael J

2013-09-15

Regulatory T cells (Tregs) are important in controlling skin inflammation, an effect dependent on their ability to home to this organ. However, little is known regarding their behavior in the skin. In this study, we used multiphoton imaging in Foxp3-GFP mice to examine the behavior of endogenous Tregs in resting and inflamed skin. Although Tregs were readily detectable in the uninflamed dermis, most were nonmotile. Induction of contact sensitivity increased the proportion of motile Tregs, and also induced Treg recruitment. This response was significantly blunted in mice challenged with an irrelevant hapten, or by inhibition of effector cell recruitment, indicating a role for T cell-dependent inflammation in induction of Treg migration. Moreover, induction of Treg migration was inhibited by local injection of a CCR4 antagonist, indicating a role for CCR4 in this response. Exposure of naive mice to hapten also induced an increase in the proportion of migratory Tregs, demonstrating that innate signals can also induce Treg migration. Simultaneous examination of the migration of CD4⁺ effector cells and Tregs in the same region of uninflamed skin demonstrated that effector cells behaved differently, being uniformly highly migratory. These findings indicate that Treg behavior in skin differs from that of CD4⁺ effector cells, in that only a low proportion of Tregs is migratory under resting conditions. However, in response to both adaptive and innate inflammation, the proportion of migratory Tregs increases, raising the possibility that this response is important in multiple forms of skin inflammation.

Small-scale spatial cognition in pigeons.

PubMed

Cheng, Ken; Spetch, Marcia L; Kelly, Debbie M; Bingman, Verner P

2006-05-01

Roberts and Van Veldhuizen's [Roberts, W.A., Van Veldhuizen, N., 1985. Spatial memory in pigeons on the radial maze. J. Exp. Psychol.: Anim. Behav. Proc. 11, 241-260] study on pigeons in the radial maze sparked research on landmark use by pigeons in lab-based tasks as well as variants of the radial-maze task. Pigeons perform well on open-field versions of the radial maze, with feeders scattered on the laboratory floor. Pigeons can also be trained to search precisely for buried food. The search can be based on multiple landmarks, but is sometimes controlled by just one or two landmarks, with the preferred landmarks varying across individuals. Findings are similar in landmark-based searching on a computer monitor and on a lab floor, despite many differences between the two kinds of tasks. A number of general learning principles are found in landmark-based searching, such as cue competition, generalization and peak shift, and selective attention. Pigeons also learn the geometry of the environment in which they are searching. Neurophysiological studies have implicated the hippocampal formation (HF) in avian spatial cognition, with the right hippocampus hypothesized to play a more important role in the spatial recognition of goal locations. Most recently, single-cell recording from the pigeon's hippocampal formation has revealed cells with different properties from the classic 'place' cells of rats, as well as differences in the two sides of the hippocampus.

Three-Dimensional Scaffolds for Tissue Engineering Applications: Role of Porosity and Pore Size

PubMed Central

Loh, Qiu Li

2013-01-01

Tissue engineering applications commonly encompass the use of three-dimensional (3D) scaffolds to provide a suitable microenvironment for the incorporation of cells or growth factors to regenerate damaged tissues or organs. These scaffolds serve to mimic the actual in vivo microenvironment where cells interact and behave according to the mechanical cues obtained from the surrounding 3D environment. Hence, the material properties of the scaffolds are vital in determining cellular response and fate. These 3D scaffolds are generally highly porous with interconnected pore networks to facilitate nutrient and oxygen diffusion and waste removal. This review focuses on the various fabrication techniques (e.g., conventional and rapid prototyping methods) that have been employed to fabricate 3D scaffolds of different pore sizes and porosity. The different pore size and porosity measurement methods will also be discussed. Scaffolds with graded porosity have also been studied for their ability to better represent the actual in vivo situation where cells are exposed to layers of different tissues with varying properties. In addition, the ability of pore size and porosity of scaffolds to direct cellular responses and alter the mechanical properties of scaffolds will be reviewed, followed by a look at nature's own scaffold, the extracellular matrix. Overall, the limitations of current scaffold fabrication approaches for tissue engineering applications and some novel and promising alternatives will be highlighted. PMID:23672709

High temperature mechanical properties of zirconia tapes used for electrolyte supported solid oxide fuel cells

NASA Astrophysics Data System (ADS)

Fleischhauer, Felix; Bermejo, Raul; Danzer, Robert; Mai, Andreas; Graule, Thomas; Kuebler, Jakob

2015-01-01

Solid-Oxide-Fuel-Cell systems are efficient devices to convert the chemical energy stored in fuels into electricity. The functionality of the cell is related to the structural integrity of the ceramic electrolyte, since its failure can lead to drastic performance losses. The mechanical property which is of most interest is the strength distribution at all relevant temperatures and how it is affected with time due to the environment. This study investigates the impact of the temperature on the strength and the fracture toughness of different zirconia electrolytes as well as the change of the elastic constants. 3YSZ and 6ScSZ materials are characterised regarding the influence of sub critical crack growth (SCCG) as one of the main lifetime limiting effects for ceramics at elevated temperatures. In addition, the reliability of different zirconia tapes is assessed with respect to temperature and SCCG. It was found that the strength is only influenced by temperature through the change in fracture toughness. SCCG has a large influence on the strength and the lifetime for intermediate temperature, while its impact becomes limited at temperatures higher than 650 °C. In this context the tetragonal 3YSZ and 6ScSZ behave quite different than the cubic 10Sc1CeSZ, so that at 850 °C it can be regarded as competitive compared to the tetragonal compounds.

Cerebellar granule cells encode the expectation of reward

PubMed Central

Wagner, Mark J; Kim, Tony Hyun; Savall, Joan; Schnitzer, Mark J; Luo, Liqun

2017-01-01

The human brain contains ~60 billion cerebellar granule cells1, which outnumber all other neurons combined. Classical theories posit that a large, diverse population of granule cells allows for highly detailed representations of sensorimotor context, enabling downstream Purkinje cells to sense fine contextual changes2–6. Although evidence suggests a role for cerebellum in cognition7–10, granule cells are known to encode only sensory11–13 and motor14 context. Using two-photon calcium imaging in behaving mice, here we show that granule cells convey information about the expectation of reward. Mice initiated voluntary forelimb movements for delayed water reward. Some granule cells responded preferentially to reward or reward omission, whereas others selectively encoded reward anticipation. Reward responses were not restricted to forelimb movement, as a Pavlovian task evoked similar responses. Compared to predictable rewards, unexpected rewards elicited markedly different granule cell activity despite identical stimuli and licking responses. In both tasks, reward signals were widespread throughout multiple cerebellar lobules. Tracking the same granule cells over several days of learning revealed that cells with reward-anticipating responses emerged from those that responded at the start of learning to reward delivery, whereas reward omission responses grew stronger as learning progressed. The discovery of predictive, non-sensorimotor encoding in granule cells is a major departure from current understanding of these neurons and dramatically enriches contextual information available to postsynaptic Purkinje cells, with important implications for cognitive processing in the cerebellum. PMID:28321129

MicroRNAs in Control of Stem Cells in Normal and Malignant Hematopoiesis

PubMed Central

Roden, Christine; Lu, Jun

2016-01-01

Studies on hematopoietic stem cells (HSCs) and leukemia stem cells (LSCs) have helped to establish the paradigms of normal and cancer stem cell concepts. For both HSCs and LSCs, specific gene expression programs endowed by their epigenome functionally distinguish them from their differentiated progenies. MicroRNAs (miRNAs), as a class of small non-coding RNAs, act to control post-transcriptional gene expression. Research in the past decade has yielded exciting findings elucidating the roles of miRNAs in control of multiple facets of HSC and LSC biology. Here we review recent progresses on the functions of miRNAs in HSC emergence during development, HSC switch from a fetal/neonatal program to an adult program, HSC self-renewal and quiescence, HSC aging, HSC niche, and malignant stem cells. While multiple different miRNAs regulate a diverse array of targets, two common themes emerge in HSC and LSC biology: miRNA mediated regulation of epigenetic machinery and cell signaling pathways. In addition, we propose that miRNAs themselves behave like epigenetic regulators, as they possess key biochemical and biological properties that can provide both stability and alterability to the epigenetic program. Overall, the studies of miRNAs in stem cells in the hematologic contexts not only provide key understandings to post-transcriptional gene regulation mechanisms in HSCs and LSCs, but also will lend key insights for other stem cell fields. PMID:27547713

Mesenchymal stem cells from adipose and bone marrow promote angiogenesis via distinct cytokine and protease expression mechanisms

PubMed Central

Kachgal, Suraj; Putnam, Andrew J.

2012-01-01

Using a fibrin-based angiogenesis model, we have established that there is no canonical mechanism used by ECs to degrade the surrounding extracellular matrix (ECM), but rather the set of proteases used is dependent on the mural cells providing the angiogenic cues. Mesenchymal stem cells (MSCs) originating from different tissues, which are thought to be phenotypically similar, promote angiogenesis through distinct mechanisms. Specifically, adipose-derived stem cells (ASCs) promote utilization of the plasminogen activator-plasmin axis by ECs as the primary means of vessel invasion and elongation in fibrin. Matrix metalloproteinases (MMPs) serve a purpose in regulating capillary diameter and possibly in stabilizing the nascent vessels. These proteolytic mechanisms are more akin to those involved in fibroblast-mediated angiogenesis than to those in bone marrow-derived stem cell (BMSC)-mediated angiogenesis. In addition, expression patterns of angiogenic factors such as urokinase plasminogen activator (uPA), hepatocyte growth factor (HGF), and tumor necrosis factor alpha (TNFα) were similar for ASC and fibroblast-mediated angiogenesis, and in direct contrast to BMSC-mediated angiogenesis. The present study illustrates that the nature of the heterotypic interactions between mural cells and endothelial cells depend on the identity of the mural cell used. Even MSCs which are shown to behave phenotypically similar do not stimulate angiogenesis via the same mechanisms. PMID:21104120

Microfluidic molecular assay platform for the detection of miRNAs, mRNAs, proteins, and posttranslational modifications at single-cell resolution.

PubMed

Wu, Meiye; Singh, Anup K

2014-12-01

Cell signaling is a dynamic and complex process. A typical signaling pathway may begin with activation of cell surface receptors, leading to activation of a kinase cascade that culminates in induction of messenger RNA (mRNA) and noncoding microRNA (miRNA) production in the nucleus, followed by modulation of mRNA expression by miRNAs in the cytosol, and end with production of proteins in response to the signaling pathway. Signaling pathways involve proteins, miRNA, and mRNAs, along with various forms of transient posttranslational modifications, and detecting each type of signaling molecule requires categorically different sample preparation methods such as Western blotting for proteins, PCR for nucleic acids, and flow cytometry for posttranslational modifications. Since we know that cells in populations behave heterogeneously,(1) especially in the cases of stem cells, cancer, and hematopoiesis, there is need for a new technology that provides capability to detect and quantify multiple categories of signaling molecules in intact single cells to provide a comprehensive view of the cell's physiological state. In this Technology Brief, we describe our automated microfluidic platform with a portfolio of customized molecular assays that can detect nucleic acids, proteins, and posttranslational modifications in single intact cells with >95% reduction in reagent requirement in under 8 h. © 2014 Society for Laboratory Automation and Screening.

A Perturbed MicroRNA Expression Pattern Characterizes Embryonic Neural Stem Cells Derived from a Severe Mouse Model of Spinal Muscular Atrophy (SMA)

PubMed Central

Luchetti, Andrea; Ciafrè, Silvia Anna; Murdocca, Michela; Malgieri, Arianna; Masotti, Andrea; Sanchez, Massimo; Farace, Maria Giulia; Novelli, Giuseppe; Sangiuolo, Federica

2015-01-01

Spinal muscular atrophy (SMA) is an inherited neuromuscular disorder and the leading genetic cause of death in infants. Despite the disease-causing gene, survival motor neuron (SMN1), encodes a ubiquitous protein, SMN1 deficiency preferentially affects spinal motor neurons (MNs), leaving the basis of this selective cell damage still unexplained. As neural stem cells (NSCs) are multipotent self-renewing cells that can differentiate into neurons, they represent an in vitro model for elucidating the pathogenetic mechanism of neurodegenerative diseases such as SMA. Here we characterize for the first time neural stem cells (NSCs) derived from embryonic spinal cords of a severe SMNΔ7 SMA mouse model. SMNΔ7 NSCs behave as their wild type (WT) counterparts, when we consider neurosphere formation ability and the expression levels of specific regional and self-renewal markers. However, they show a perturbed cell cycle phase distribution and an increased proliferation rate compared to wild type cells. Moreover, SMNΔ7 NSCs are characterized by the differential expression of a limited number of miRNAs, among which miR-335-5p and miR-100-5p, reduced in SMNΔ7 NSCs compared to WT cells. We suggest that such miRNAs may be related to the proliferation differences characterizing SMNΔ7 NSCs, and may be potentially involved in the molecular mechanisms of SMA. PMID:26258776

A Perturbed MicroRNA Expression Pattern Characterizes Embryonic Neural Stem Cells Derived from a Severe Mouse Model of Spinal Muscular Atrophy (SMA).

PubMed

Luchetti, Andrea; Ciafrè, Silvia Anna; Murdocca, Michela; Malgieri, Arianna; Masotti, Andrea; Sanchez, Massimo; Farace, Maria Giulia; Novelli, Giuseppe; Sangiuolo, Federica

2015-08-06

Spinal muscular atrophy (SMA) is an inherited neuromuscular disorder and the leading genetic cause of death in infants. Despite the disease-causing gene, survival motor neuron (SMN1), encodes a ubiquitous protein, SMN1 deficiency preferentially affects spinal motor neurons (MNs), leaving the basis of this selective cell damage still unexplained. As neural stem cells (NSCs) are multipotent self-renewing cells that can differentiate into neurons, they represent an in vitro model for elucidating the pathogenetic mechanism of neurodegenerative diseases such as SMA. Here we characterize for the first time neural stem cells (NSCs) derived from embryonic spinal cords of a severe SMNΔ7 SMA mouse model. SMNΔ7 NSCs behave as their wild type (WT) counterparts, when we consider neurosphere formation ability and the expression levels of specific regional and self-renewal markers. However, they show a perturbed cell cycle phase distribution and an increased proliferation rate compared to wild type cells. Moreover, SMNΔ7 NSCs are characterized by the differential expression of a limited number of miRNAs, among which miR-335-5p and miR-100-5p, reduced in SMNΔ7 NSCs compared to WT cells. We suggest that such miRNAs may be related to the proliferation differences characterizing SMNΔ7 NSCs, and may be potentially involved in the molecular mechanisms of SMA.

Effect of different professions' clothing on children's height perception.

PubMed

Rashidi, Mahmoud; Keshtkaran, Katayoun; Zabihidan, Sahar; Hosseinchari, Masoud; Pazhoohi, Farid

2012-11-01

Height is a biological factor that can affect how others perceive and behave toward an individual. Height is a biological factor that can affect how others perceive and behave toward an individual. Clothing, as a non-biological factor, can affect these perceptions of height. In this study weClothing, as a non-biological factor, can affect these perceptions of height. In this study we investigated the effect of different professions' clothing on children's perceptions of height. One investigated the effect of different professions' clothing on children's perceptions of height. One hundred and eighty primary school students participated in this study and estimated the height of an actor in the clothing of four different professions which differed in terms of prestige. The results of study showed that the difference between the perceived and actual height was larger when participants estimated the height of socially esteemed professions. Also there was no difference between girls' and boys' estimation of different professions' height. The implications of these findings are discussed.

Stages of Toilet Training: Different Skills, Different Schedules

MedlinePlus

... germs, the potential for mess, the attached cultural stigma, and so on. On the contrary, toddlers and ... in an overemotional way. Instead, calmly ask your child why he is behaving in this way, firmly ...

The Mechanisms for Within-Host Influenza Virus Control Affect Model-Based Assessment and Prediction of Antiviral Treatment

PubMed Central

Cao, Pengxing

2017-01-01

Models of within-host influenza viral dynamics have contributed to an improved understanding of viral dynamics and antiviral effects over the past decade. Existing models can be classified into two broad types based on the mechanism of viral control: models utilising target cell depletion to limit the progress of infection and models which rely on timely activation of innate and adaptive immune responses to control the infection. In this paper, we compare how two exemplar models based on these different mechanisms behave and investigate how the mechanistic difference affects the assessment and prediction of antiviral treatment. We find that the assumed mechanism for viral control strongly influences the predicted outcomes of treatment. Furthermore, we observe that for the target cell-limited model the assumed drug efficacy strongly influences the predicted treatment outcomes. The area under the viral load curve is identified as the most reliable predictor of drug efficacy, and is robust to model selection. Moreover, with support from previous clinical studies, we suggest that the target cell-limited model is more suitable for modelling in vitro assays or infection in some immunocompromised/immunosuppressed patients while the immune response model is preferred for predicting the infection/antiviral effect in immunocompetent animals/patients. PMID:28933757

EGF receptor lysosomal degradation is delayed in the cells stimulated with EGF-Quantum dot bioconjugate but earlier key events of endocytic degradative pathway are similar to that of native EGF

PubMed Central

Leontieva, Ekaterina A.; Kornilova, Elena S.

2017-01-01

Quantum dots (QDs) complexed to ligands recognizing surface receptors undergoing internalization are an attractive tool for live cell imaging of ligand-receptor complexes behavior and for specific tracking of the cells of interest. However, conjugation of quasi-multivalent large QD-particle to monovalent small growth factors like EGF that bound their tyrosine-kinase receptors may affect key endocytic events tightly bound to signaling. Here, by means of confocal microscopy we have addressed the key endocytic events of lysosomal degradative pathway stimulated by native EGF or EGF-QD bioconjugate. We have demonstrated that the decrease in endosome number, increase in mean endosome integrated density and the pattern of EEA1 co-localization with EGF-EGFR complexes at early stages of endocytosis were similar for the both native and QD-conjugated ligands. In both cases enlarged hollow endosomes appeared after wortmannin treatment. This indicates that early endosomal fusions and their maturation proceed similar for both ligands. EGF-QD and native EGF similarly accumulated in juxtanuclear region, and live cell imaging of endosome motion revealed the behavior described elsewhere for microtubule-facilitated motility. Finally, EGF-QD and the receptor were found in lysosomes. However, degradation of receptor part of QD-EGF-EGFR-complex was delayed compared to native EGF, but not inhibited, while QDs fluorescence was detected in lysosomes even after 24 hours. Importantly, in HeLa and A549 cells the both ligands behaved similarly. We conclude that during endocytosis EGF-QD behaves as a neutral marker for degradative pathway up to lysosomal stage and can also be used as a long-term cell marker. PMID:28574831

Tyrosine kinase oncogenes abrogate interleukin-3 dependence of murine myeloid cells through signaling pathways involving c-myc: conditional regulation of c-myc transcription by temperature-sensitive v-abl.

PubMed Central

Cleveland, J L; Dean, M; Rosenberg, N; Wang, J Y; Rapp, U R

1989-01-01

Retroviral expression vectors carrying the tyrosine kinase oncogenes abl, fms, src, and trk abrogate the requirements of murine myeloid FDC-P1 cells for interleukin-3 (IL-3). Factor-independent clones constitutively express c-myc in the absence of IL-3, whereas in parental cultures c-myc transcription requires the presence of the ligand. To directly test the effect of a tyrosine kinase oncogene on c-myc expression, retroviral constructs containing three different temperature-sensitive mutants of v-abl were introduced into myeloid IL-3-dependent FDC-P1 and 32D cells. At the permissive temperature, clones expressing temperature-sensitive abl behaved like wild-type abl-containing cells in their growth properties and expressed c-myc constitutively. Temperature shift experiments demonstrated that both IL-3 abrogation and the regulation of c-myc expression correlated with the presence of functional v-abl. Induction of c-myc expression by reactivation of temperature-sensitive v-abl mimicked c-myc induction by IL-3 in that it did not require protein synthesis and occurred at the level of transcription, with effects on both initiation and a transcription elongation block. However, v-abl-regulated FDC-P1 cell growth differed from IL-3-regulated growth in that c-fos and junB, which are normally induced by IL-3, were not induced by activation of v-abl. Images PMID:2555703

Misfolded rhodopsin mutants display variable aggregation properties.

PubMed

Gragg, Megan; Park, Paul S-H

2018-06-08

The largest class of rhodopsin mutations causing autosomal dominant retinitis pigmentosa (adRP) is mutations that lead to misfolding and aggregation of the receptor. The misfolding mutants have been characterized biochemically, and categorized as either partial or complete misfolding mutants. This classification is incomplete and does not provide sufficient information to fully understand the disease pathogenesis and evaluate therapeutic strategies. A Förster resonance energy transfer (FRET) method was utilized to directly assess the aggregation properties of misfolding rhodopsin mutants within the cell. Partial (P23H and P267L) and complete (G188R, H211P, and P267R) misfolding mutants were characterized to reveal variability in aggregation properties. The complete misfolding mutants all behaved similarly, forming aggregates when expressed alone, minimally interacting with the wild-type receptor when coexpressed, and were unresponsive to treatment with the pharmacological chaperone 9-cis retinal. In contrast, variability was observed between the partial misfolding mutants. In the opsin form, the P23H mutant behaved similarly as the complete misfolding mutants. In contrast, the opsin form of the P267L mutant existed as both aggregates and oligomers when expressed alone and formed mostly oligomers with the wild-type receptor when coexpressed. The partial misfolding mutants both reacted similarly to the pharmacological chaperone 9-cis retinal, displaying improved folding and oligomerization when expressed alone but aggregating with wild-type receptor when coexpressed. The observed differences in aggregation properties and effect of 9-cis retinal predict different outcomes in disease pathophysiology and suggest that retinoid-based chaperones will be ineffective or even detrimental. Copyright © 2018 Elsevier B.V. All rights reserved.

Nonlocal optical effects on the Goos-Hänchen shift at an interface of a composite material of metallic nanoparticles.

PubMed

Huang, J H; Leung, P T

2013-07-01

We present a theoretical study on the nonlocal optical effects on the Goos-Hänchen (GH) shift of reflected light from a composite material of metallic nanoparticles (MNPs). Using different nonlocal effective medium models, it is observed that such effects can be significant for small MNP of sizes down to a few nanometers. For small metallic volume fractions, the composite behaves like dielectric and the nonlocal effects lead to significant different Brewster angles, at which large negative GH shifts take place. For larger volume fractions or shorter wavelengths, the composite behaves more like metals and the nonlocal effects also lead to different Brewster angles but at values close to grazing incidence. These results will have significant implications in the application of different effective medium models for the characterization of these nanometallic composites when the MNPs are down to a few nanometers in size.

Microfluidic molecular assay platform for the detection of miRNAs, mRNAs, proteins, and post-translational modifications at single-cell resolution

DOE PAGES

Wu, Meiye; Singh, Anup K.

2014-07-15

In this study, cell signaling is a dynamic and complex process. A typical signaling pathway may begin with activation of cell surface receptors, leading to activation kinase cascade that culminates in induction of mRNA and non-coding miRNA production in the nucleus, followed by modulation of mRNA expression by miRNAs in the cytosol, and end with production of proteins in response to the signaling pathway. Signaling pathways involve proteins, miRNA, and mRNAs, along with various forms of transient post-translational modifications, and detecting each type of signaling molecule requires categorically different sample preparation methods such as Western blotting for proteins, PCR formore » nucleic acids, and flow cytometry for post-translational modifications. Since we know that cells in populations behave heterogeneously1, especially in the cases of stem cells, cancer, and hematopoiesis, there is need for a new technology that provides capability to detect and quantify multiple categories of signaling molecules in intact single cells to provide a comprehensive view of the cell’s physiological state. In this technical brief, we describe our microfluidic platform with a portfolio of customized molecular assays that can detect nucleic acids, proteins, and post-translational modifications in single intact cells with >95% reduction in reagent requirement in under 8 hours.« less

Identification of novel thiazolo[5,4-d]pyrimidine derivatives as human A1 and A2A adenosine receptor antagonists/inverse agonists.

PubMed

Varano, Flavia; Catarzi, Daniela; Falsini, Matteo; Vincenzi, Fabrizio; Pasquini, Silvia; Varani, Katia; Colotta, Vittoria

2018-07-23

In this study a new set of thiazolo[5,4-d]pyrimidine derivatives was synthesized. These derivatives bear different substituents at positions 2 and 5 of the thiazolopyrimidine core while maintaining a free amino group at position-7. The new compounds were tested for their affinity and potency at human (h) A 1 , A 2A , A 2B and A 3 adenosine receptors expressed in CHO cells. The results reveal that the higher affinity of these new set of thiazolopyrimidines is toward the hA 1 and hA 2A adenosine receptors subtypes and is tuned by the substitution pattern at both the 2 and 5 positions of the thiazolopyrimidine nucleus. Functional studies evidenced that the compounds behaved as dual A 1 /A 2A antagonists/inverse agonists. Compound 3, bearing a 5-((2-methoxyphenyl) methylamino) group and a phenyl moiety at position 2, displayed the highest affinity (hA 1 K i  = 10.2 nM; hA 2A K i  = 4.72 nM) and behaved as a potent A 1 /A 2A antagonist/inverse agonist (hA 1 IC 50  = 13.4 nM; hA 2A IC 50  = 5.34 nM). Copyright © 2018 Elsevier Ltd. All rights reserved.

The C. elegans embryonic fate specification factor EGL-18 (GATA) is reutilized downstream of Wnt signaling to maintain a population of larval progenitor cells.

PubMed

Gorrepati, Lakshmi; Eisenmann, David M

2015-01-01

In metazoans, stem cells in developing and adult tissues can divide asymmetrically to give rise to a daughter that differentiates and a daughter that retains the progenitor fate. Although the short-lived nematode C. elegans does not possess adult somatic stem cells, the lateral hypodermal seam cells behave in a similar manner: they divide once per larval stage to generate an anterior daughter that adopts a non-dividing differentiated fate and a posterior daughter that retains the seam fate and the ability to divide further. Wnt signaling pathway is known to regulate the asymmetry of these divisions and maintain the progenitor cell fate in one daughter, but how activation of the Wnt pathway accomplished this was unknown. We describe here our recent work that identified the GATA transcription factor EGL-18 as a downstream target of Wnt signaling necessary for maintenance of a progenitor population of larval seam cells. EGL-18 was previously shown to act in the initial specification of the seam cells in the embryo. Thus the acquisition of a Wnt-responsive cis-regulatory module allows an embryonic fate specification factor to be reutilized later in life downstream of a different regulator (Wnt signaling) to maintain a progenitor cell population. These results support the use of seam cell development in C. elegans as a simple model system for studying stem and progenitor cell biology.

Buckling analysis of orthotropic protein microtubules under axial and radial compression based on couple stress theory.

PubMed

Beni, Yaghoub Tadi; Zeverdejani, M Karimi; Mehralian, Fahimeh

2017-10-01

Protein microtubules (MTs) are one of the important intercellular components and have a vital role in the stability and strength of the cells. Due to applied external loads, protein microtubules may be involved buckling phenomenon. Due to impact of protein microtubules in cell reactions, it is important to determine their critical buckling load. Considering nature of protein microtubules, various parameters are effective on microtubules buckling. The small size of microtubules and also lack of uniformity of MTs properties in different directions caused the necessity of accuracy in the analysis of these bio-structure. In fact, microtubules must be considered as a size dependent cylinder, which behave as an orthotropic material. Hence, in the present work using first-order shear deformation model (FSDT), the buckling equations of anisotropic MTs are derived based on new modified couple stress theory (NMCST). After solving the stability equations, the influences of various parameters are measured on the MTs critical buckling load. Copyright © 2017 Elsevier Inc. All rights reserved.

Animal studies on Spacelab-3

NASA Technical Reports Server (NTRS)

Schatte, C.; Grindeland, R.; Callahan, P.; Berry, W.; Funk, G.; Lencki, W.

1987-01-01

The flight of two squirrel monkeys and 24 rats on Spacelab-3 was the first mission to provide hands-on maintenance on animals in a laboratory environment. With few exceptions, the animals grew and behaved normally, were free of chronic stress, and differed from ground controls only for gravity dependent parameters. One of the monkeys exhibited symptoms of space sickness similar to those observed in humans, which suggests squirrel monkeys may be good models for studying the space adaptation syndrome. Among the wide variety of parameters measured in the rats, most notable was the dramatic loss of muscle mass and increased fragility of long bones. Other interesting rat findings were those of suppressed interferom production by spleen cells, defective release of growth hormone by somatrophs, possible dissociation of circadian pacemakers, changes in hepatic lipid and carbohydrate metabolism, and hypersensitivity of marrow cells to erythropoietin. These results portend a strong role for animals in identifying and elucidating the physiological and anatomical responses of mammals to microgravity.

Animal studies on Spacelab-3

NASA Technical Reports Server (NTRS)

Schatte, C.; Grindeland, R.; Callahan, P.; Funk, G.; Lencki, W.; Berry, W.

1986-01-01

The flight of two squirrel monkeys and 24 rates on Spacelab-3 was the first mission to provide hand-on maintenance on animals in a laboratory environment. With few exceptions, the animals grew and behaved normally, were free of chronic stress, and differed from ground controls only for gravity-dependent parameters. One of the monkeys exhibited symptoms of space sickness similar to those observed in humans, which suggests squirrel monkeys may be good models for studying the space-adaptation syndrome. Among the wide variety of parameters measured in the rats, most notable was the dramatic loss of muscle mass and increased fragility of long bones. Other interesting rat findings were those of suppressed interferon production by spleen cells, defective release of growth hormone by somatotrophs, possible dissociation of circadian pacemakers, changes in hepatic lipid and carbohydrate metabolism, and hypersensitivity of marrow cells to erythopoietin. These results portend a strong role for animals in identifying and elucidating the physiological and anatomical responses of mammals to microgravity.

Anatomy of the Pythagoras' Tree

ERIC Educational Resources Information Center

Teia, Luis

2016-01-01

The architecture of nature can be seen at play in a tree: no two are alike. The Pythagoras' tree behaves just as a "tree" in that the root plus the same movement repeated over and over again grows from a seed, to a plant, to a tree. In human life, this movement is termed cell division. With triples, this movement is a geometrical and…

Optical Neural Interfaces

PubMed Central

Warden, Melissa R.; Cardin, Jessica A.; Deisseroth, Karl

2014-01-01

Genetically encoded optical actuators and indicators have changed the landscape of neuroscience, enabling targetable control and readout of specific components of intact neural circuits in behaving animals. Here, we review the development of optical neural interfaces, focusing on hardware designed for optical control of neural activity, integrated optical control and electrical readout, and optical readout of population and single-cell neural activity in freely moving mammals. PMID:25014785

Direct observation of hole transfer from semiconducting polymer to carbon nanotubes.

PubMed

Lan, Fei; Li, Guangyong

2013-05-08

Carbon nanotubes have been proven to play significant roles in polymer-based solar cells. However, there is intensive debate on whether carbon nanotube behaves as a donor or acceptor in the semiconducting polymer:carbon nanotube composite. In this paper, we report a direct observation via Kelvin probe force microscopy (KPFM) that single walled carbon nanotubes (SWNTs) behave as hole transporting channels in poly(3-hexylthiophene-2,5-diyl) (P3HT)/SWNT heterojunctions. By comparing the surface potential (SP) change of SWNT in dark and under illumination, we observed that electrons are blocked from SWNT while holes are transferred to SWNT. This observation can be well-explained by our proposed band alignment model of P3HT/SWNT heterojunction. The finding is further verified by hole mobility measurement using the space charge limited current (SCLC) method. SCLC results indicate that the existence of small amount of SWNT (wt 0.5%) promotes device hole mobility to around 15-fold, indicating SWNT act as hole transfer channel. Our finding of hole transporting behavior of SWNT in P3HT/SWNT blend will provide a useful guidance for enhancing the performance of polymer solar cells by carbon nanotubes.

Exogenous adenosine 5'-phosphoramidate behaves as a signal molecule in plants; it augments metabolism of phenylpropanoids and salicylic acid in Arabidopsis thaliana seedlings.

PubMed

Pietrowska-Borek, Małgorzata; Nuc, Katarzyna; Guranowski, Andrzej

2015-09-01

Cells contain various congeners of the canonical nucleotides. Some of these accumulate in cells under stress and may function as signal molecules. Their cellular levels are enzymatically controlled. Previously, we demonstrated a signaling function for diadenosine polyphosphates and cyclic nucleotides in Arabidopsis thaliana and grape, Vitis vinifera. These compounds increased the expression of genes for and the specific activity of enzymes of phenylpropanoid pathways resulting in the accumulation of certain products of these pathways. Here, we show that adenosine 5'-phosphoramidate, whose level can be controlled by HIT-family proteins, induced similar effects. This natural nucleotide, when added to A. thaliana seedlings, activated the genes for phenylalanine:ammonia lyase, 4-coumarate:coenzyme A ligase, cinnamate-4-hydroxylase, chalcone synthase, cinnamoyl-coenzyme A:NADP oxidoreductase and isochorismate synthase, which encode proteins catalyzing key reactions of phenylpropanoid pathways, and caused accumulation of lignins, anthocyanins and salicylic acid. Adenosine 5'-phosphofluoridate, a synthetic congener of adenosine 5'-phosphoramidate, behaved similarly. The results allow us to postulate that adenosine 5'-phosphoramidate should be considered as a novel signaling molecule. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Lattice-based model of ductal carcinoma in situ suggests rules for breast cancer progression to an invasive state.

PubMed

Boghaert, Eline; Radisky, Derek C; Nelson, Celeste M

2014-12-01

Ductal carcinoma in situ (DCIS) is a heterogeneous group of non-invasive lesions of the breast that result from abnormal proliferation of mammary epithelial cells. Pathologists characterize DCIS by four tissue morphologies (micropapillary, cribriform, solid, and comedo), but the underlying mechanisms that distinguish the development and progression of these morphologies are not well understood. Here we explored the conditions leading to the emergence of the different morphologies of DCIS using a two-dimensional multi-cell lattice-based model that incorporates cell proliferation, apoptosis, necrosis, adhesion, and contractility. We found that the relative rates of cell proliferation and apoptosis governed which of the four morphologies emerged. High proliferation and low apoptosis favored the emergence of solid and comedo morphologies. In contrast, low proliferation and high apoptosis led to the micropapillary morphology, whereas high proliferation and high apoptosis led to the cribriform morphology. The natural progression between morphologies cannot be investigated in vivo since lesions are usually surgically removed upon detection; however, our model suggests probable transitions between these morphologies during breast cancer progression. Importantly, cribriform and comedo appear to be the ultimate morphologies of DCIS. Motivated by previous experimental studies demonstrating that tumor cells behave differently depending on where they are located within the mammary duct in vivo or in engineered tissues, we examined the effects of tissue geometry on the progression of DCIS. In agreement with our previous experimental work, we found that cells are more likely to invade from the end of ducts and that this preferential invasion is regulated by cell adhesion and contractility. This model provides additional insight into tumor cell behavior and allows the exploration of phenotypic transitions not easily monitored in vivo.

Rebound spiking in layer II medial entorhinal cortex stellate cells: Possible mechanism of grid cell function

PubMed Central

Shay, Christopher F.; Ferrante, Michele; Chapman, G. William; Hasselmo, Michael E.

2015-01-01

Rebound spiking properties of medial entorhinal cortex (mEC) stellate cells induced by inhibition may underlie their functional properties in awake behaving rats, including the temporal phase separation of distinct grid cells and differences in grid cell firing properties. We investigated rebound spiking properties using whole cell patch recording in entorhinal slices, holding cells near spiking threshold and delivering sinusoidal inputs, superimposed with realistic inhibitory synaptic inputs to test the capacity of cells to selectively respond to specific phases of inhibitory input. Stellate cells showed a specific phase range of hyperpolarizing inputs that elicited spiking, but non-stellate cells did not show phase specificity. In both cell types, the phase range of spiking output occurred between the peak and subsequent descending zero crossing of the sinusoid. The phases of inhibitory inputs that induced spikes shifted earlier as the baseline sinusoid frequency increased, while spiking output shifted to later phases. Increases in magnitude of the inhibitory inputs shifted the spiking output to earlier phases. Pharmacological blockade of h-current abolished the phase selectivity of hyperpolarizing inputs eliciting spikes. A network computational model using cells possessing similar rebound properties as found in vitro produces spatially periodic firing properties resembling grid cell firing when a simulated animal moves along a linear track. These results suggest that the ability of mEC stellate cells to fire rebound spikes in response to a specific range of phases of inhibition could support complex attractor dynamics that provide completion and separation to maintain spiking activity of specific grid cell populations. PMID:26385258

A cellular Potts model for the MMP-dependent and -independent cancer cell migration in matrix microtracks of different dimensions

NASA Astrophysics Data System (ADS)

Scianna, Marco; Preziosi, Luigi

2014-03-01

Cell migration is fundamental in a wide variety of physiological and pathological phenomena, among other in cancer invasion and development. In particular, the migratory/invasive capability of single metastatic cells is fundamental in determining the malignancy of a solid tumor. Specific cell migration phenotypes result for instance from the reciprocal interplay between the biophysical and biochemical properties of both the malignant cells themselves and of the surrounding environment. In particular, the extracellular matrices (ECMs) forming connective tissues can provide both loosely organized zones and densely packed barriers, which may impact cell invasion mode and efficiency. The critical processes involved in cell movement within confined spaces are (i) the proteolytic activity of matrix metalloproteinases (MMPs) and (ii) the deformation of the entire cell body, and in particular of the nucleus. We here present an extended cellular Potts model (CPM) to simulate a bio-engineered matrix system, which tests the active motile behavior of a single cancer cell into narrow channels of different widths. As distinct features of our approach, the cell is modeled as a compartmentalized discrete element, differentiated in the nucleus and in the cytosolic region, while a directional shape-dependent movement is explicitly driven by the evolution of its polarity vector. As outcomes, we find that, in a large track, the tumor cell is not able to maintain a directional movement. On the contrary, a structure of subcellular width behaves as a contact guidance sustaining cell persistent locomotion. In particular, a MMP-deprived cell is able to repolarize and follow the micropattern geometry, while a full MMP activity leads to a secondary track expansion by degrading the matrix structure. Finally, we confirm that cell movement within a subnuclear structure can be achieved either by pericellular proteolysis or by a significant deformation of cell nucleus.

The role of the endothelium in asthma and chronic obstructive pulmonary disease (COPD).

PubMed

Green, Clara E; Turner, Alice M

2017-01-18

COPD and asthma are important chronic inflammatory disorders with a high associated morbidity. Much research has concentrated on the role of inflammatory cells, such as the neutrophil, in these diseases, but relatively little focus has been given to the endothelial tissue, through which inflammatory cells must transmigrate to reach the lung parenchyma and cause damage. There is evidence that there is an abnormal amount of endothelial tissue in COPD and asthma and that this tissue and its' progenitor cells behave in a dysfunctional manner. This article reviews the evidence of the involvement of pulmonary endothelium in COPD and asthma and potential treatment options for this.

Ocular cells and light: harmony or conflict?

PubMed

Jurja, Sanda; Hîncu, Mihaela; Dobrescu, Mihaela Amelia; Golu, Andreea Elena; Bălăşoiu, Andrei Theodor; Coman, Mălina

2014-01-01

Vision is based on the sensitivity of the eye to visible rays of the solar spectrum, which allows the recording and transfer of visual information by photoelectric reaction. Any electromagnetic radiation, if sufficiently intense, may cause damages in living tissues. In a changing environment, the aim of this paper is to point out the impact of light radiation on ocular cells, with its phototoxicity potential on eye tissues. In fact, faced with light and oxygen, the eye behaves like an ephemeral aggregate of unstable molecules, like a temporary crystallization threatened with entropia.

BehavePlus fire modeling system, version 5.0: Variables

Treesearch

Patricia L. Andrews

2009-01-01

This publication has been revised to reflect updates to version 4.0 of the BehavePlus software. It was originally published as the BehavePlus fire modeling system, version 4.0: Variables in July, 2008.The BehavePlus fire modeling system is a computer program based on mathematical models that describe wildland fire behavior and effects and the...

Horizontal Transmission of Cytosolic Sup35 Prions by Extracellular Vesicles.

PubMed

Liu, Shu; Hossinger, André; Hofmann, Julia P; Denner, Philip; Vorberg, Ina M

2016-07-12

Prions are infectious protein particles that replicate by templating their aggregated state onto soluble protein of the same type. Originally identified as the causative agent of transmissible spongiform encephalopathies, prions in yeast (Saccharomyces cerevisiae) are epigenetic elements of inheritance that induce phenotypic changes of their host cells. The prototype yeast prion is the translation termination factor Sup35. Prions composed of Sup35 or its modular prion domain NM are heritable and are transmitted vertically to progeny or horizontally during mating. Interestingly, in mammalian cells, protein aggregates derived from yeast Sup35 NM behave as true infectious entities that employ dissemination strategies similar to those of mammalian prions. While transmission is most efficient when cells are in direct contact, we demonstrate here that cytosolic Sup35 NM prions are also released into the extracellular space in association with nanometer-sized membrane vesicles. Importantly, extracellular vesicles are biologically active and are taken up by recipient cells, where they induce self-sustained Sup35 NM protein aggregation. Thus, in mammalian cells, extracellular vesicles can serve as dissemination vehicles for protein-based epigenetic information transfer. Prions are proteinaceous infectious particles that propagate by templating their quaternary structure onto nascent proteins of the same kind. Prions in yeast act as heritable epigenetic elements that can alter the phenotype when transmitted to daughter cells or during mating. Prion activity is conferred by so-called prion domains often enriched in glutamine and asparagine residues. Interestingly, many mammalian proteins also contain domains with compositional similarity to yeast prion domains. We have recently provided a proof-of-principle demonstration that a yeast prion domain also retains its prion activity in mammalian cells. We demonstrate here that cytosolic prions composed of a yeast prion domain are also packaged into extracellular vesicles that transmit the prion phenotype to bystander cells. Thus, proteins with prion-like domains can behave as proteinaceous information molecules that exploit the cellular vesicle trafficking machinery for intercellular long-distance dissemination. Copyright © 2016 Liu et al.

A novel vibrotactile system for stimulating the glabrous skin of awake freely behaving rats during operant conditioning.

PubMed

Devecioğlu, İsmail; Güçlü, Burak

2015-03-15

Rat skin is innervated by mechanoreceptive fibers similar to those in other mammals. Tactile experiments with behaving rats mostly focus on the vibrissal system which does not exist in humans. The aim of this study was to design and implement a novel vibrotactile system to stimulate the glabrous skin of behaving rats during operant conditioning. A computer-controlled vibrotactile system was developed for various tasks in which the volar surface of unrestrained rats' fore- and hindpaws was stimulated in an operant chamber. The operant chamber was built from off-the-shelf components. A highly accurate electrodynamic shaker with a novel multi-probe design was used for generating mechanical displacements. Twenty-five rats were trained for four sequential tasks: (A) middle-lever (trial start signal) press, (B) side-lever press with an associated visual cue, (C) similar to (B) with the addition of an auditory/tactile stimulus, (D) auditory/tactile detection (yes/no) task. Out of 9 rats which could complete the tactile version of this training schedule, 5 had over 70% accuracy in the tactile version of the detection task. Unlike actuators for stimulating whiskers, this system does not require a particular head/body alignment and can be used with freely behaving animals. The vibrotactile system was found to be effective for conditioning freely behaving rats based on stimuli applied on the glabrous skin. However, detection accuracies were lower compared to those in tasks involving whisker stimulation reported previously, probably due to differences in cortical processing. Copyright © 2015 Elsevier B.V. All rights reserved.

A napthelene-pyrazol conjugate: Al(III) ion-selective blue shifting chemosensor applicable as biomarker in aqueous solution.

PubMed

Mukherjee, Manjira; Pal, Siddhartha; Lohar, Somenath; Sen, Buddhadeb; Sen, Supriti; Banerjee, Samya; Banerjee, Snehasis; Chattopadhyay, Pabitra

2014-10-07

A newly synthesized and crystalographically characterized napthelene–pyrazol conjugate, 1-[(5-phenyl-1H-pyrazole-3-ylimino)-methyl]-naphthalen-2-ol (HL) behaves as an Al(III) ion-selective chemosensor through internal charge transfer (ICT)-chelation-enhanced fluorescence (CHEF) processes in 100 mM HEPES buffer (water–DMSO 5:1, v/v) at biological pH with almost no interference of other competitive ions. This mechanism is readily studied from electronic, fluorimetric and (1)H NMR titration. The probe (HL) behaved as a highly selective fluorescent sensor for Al(III) ions as low as 31.78 nM within a very short response time (15–20 s). The sensor (HL), which has no cytotoxicity, is also efficient in detecting the distribution of Al(III) ions in HeLa cells via image development under fluorescence microscope.

Two-photon calcium imaging in mice navigating a virtual reality environment.

PubMed

Leinweber, Marcus; Zmarz, Pawel; Buchmann, Peter; Argast, Paul; Hübener, Mark; Bonhoeffer, Tobias; Keller, Georg B

2014-02-20

In recent years, two-photon imaging has become an invaluable tool in neuroscience, as it allows for chronic measurement of the activity of genetically identified cells during behavior(1-6). Here we describe methods to perform two-photon imaging in mouse cortex while the animal navigates a virtual reality environment. We focus on the aspects of the experimental procedures that are key to imaging in a behaving animal in a brightly lit virtual environment. The key problems that arise in this experimental setup that we here address are: minimizing brain motion related artifacts, minimizing light leak from the virtual reality projection system, and minimizing laser induced tissue damage. We also provide sample software to control the virtual reality environment and to do pupil tracking. With these procedures and resources it should be possible to convert a conventional two-photon microscope for use in behaving mice.

Motor Behavior Activates Bergmann Glial Networks

PubMed Central

Nimmerjahn, Axel; Mukamel, Eran A.; Schnitzer, Mark J.

2010-01-01

SUMMARY Although it is firmly established neuronal activity is a prime determinant of animal behavior, relationships between astrocytic excitation and animal behavior have remained opaque. Cerebellar Bergmann glia are radial astrocytes that are implicated in motor behavior and exhibit Ca2+-excitation. However, Ca2+-excitation in these cells has not previously been studied in behaving animals. Using two-photon microscopy we found that Bergmann glia exhibit three forms of Ca2+-excitation in awake behaving mice. Two of these are ongoing within the cerebellar vermis. During locomotor performance concerted Ca2+-excitation arises in networks of at least hundreds of Bergmann glia extending across several hundred microns or more. Concerted Ca2+-excitation was abolished by anesthesia or blockade of either neural activity or glutamatergic transmission. Thus, large networks of Bergmann glia can be activated by specific animal behaviors and undergo excitation of sufficient magnitude to potentially initiate macroscopic changes in brain dynamics or blood flow. PMID:19447095

Rational Organization of Lanthanide-Based SMM Dimers into Three-Dimensional Networks.

PubMed

Yi, Xiaohui; Calvez, Guillaume; Daiguebonne, Carole; Guillou, Olivier; Bernot, Kevin

2015-06-01

Optimization of the reaction of [Ln(hfac)3]·2H2O and pyridine-N-oxide (PyNO), which is known to afford double-bridged dimers, leads to triple-bridged dimers of formula [(Ln(hfac)3)2(PyNO)3] (Ln = Gd (1), Dy (2)) from which the Dy derivative (2) behaves as a single-molecule magnet (SMM). The pseudo threefold axis symmetry of this zero-dimensional building block makes possible its extension into a tridimensional network. By changing PyNO for 4,4'-bipyridine N,N'-dioxide (4,4'BipyNO) a tridimensional compound of formula {[Ln(hfac)3]2(4,4'BipyNO)2]} (Ln = Eu (3), Gd (4), and Dy (5)) is then rationally obtained. This covalent three-dimensional (3D) network has a remarkably high cell volume (V = 24 419 A(3)) and is an arrangement of interpenetrated 3D subnetworks whose triple-bridged dimers still behave as SMMs.

Molecular and cellular heterogeneity: the hallmark of glioblastoma.

PubMed

Aum, Diane J; Kim, David H; Beaumont, Thomas L; Leuthardt, Eric C; Dunn, Gavin P; Kim, Albert H

2014-12-01

There has been increasing awareness that glioblastoma, which may seem histopathologically similar across many tumors, actually represents a group of molecularly distinct tumors. Emerging evidence suggests that cells even within the same tumor exhibit wide-ranging molecular diversity. Parallel to the discoveries of molecular heterogeneity among tumors and their individual cells, intense investigation of the cellular biology of glioblastoma has revealed that not all cancer cells within a given tumor behave the same. The identification of a subpopulation of brain tumor cells termed "glioblastoma cancer stem cells" or "tumor-initiating cells" has implications for the management of glioblastoma. This focused review will therefore summarize emerging concepts on the molecular and cellular heterogeneity of glioblastoma and emphasize that we should begin to consider each individual glioblastoma to be an ensemble of molecularly distinct subclones that reflect a spectrum of dynamic cell states.

SERCA directs cell migration and branching across species and germ layers

PubMed Central

Lansdale, Nick; Navarro, Sonia; Truong, Thai V.; Bower, Dan J.; Featherstone, Neil C.; Connell, Marilyn G.; Al Alam, Denise; Frey, Mark R.; Trinh, Le A.; Fernandez, G. Esteban; Warburton, David; Fraser, Scott E.; Bennett, Daimark; Jesudason, Edwin C.

2017-01-01

ABSTRACT Branching morphogenesis underlies organogenesis in vertebrates and invertebrates, yet is incompletely understood. Here, we show that the sarco-endoplasmic reticulum Ca2+ reuptake pump (SERCA) directs budding across germ layers and species. Clonal knockdown demonstrated a cell-autonomous role for SERCA in Drosophila air sac budding. Live imaging of Drosophila tracheogenesis revealed elevated Ca2+ levels in migratory tip cells as they form branches. SERCA blockade abolished this Ca2+ differential, aborting both cell migration and new branching. Activating protein kinase C (PKC) rescued Ca2+ in tip cells and restored cell migration and branching. Likewise, inhibiting SERCA abolished mammalian epithelial budding, PKC activation rescued budding, while morphogens did not. Mesoderm (zebrafish angiogenesis) and ectoderm (Drosophila nervous system) behaved similarly, suggesting a conserved requirement for cell-autonomous Ca2+ signaling, established by SERCA, in iterative budding. PMID:28821490

Measurement and Characterization of Concentrator Solar Cells II

NASA Technical Reports Server (NTRS)

Scheiman, Dave; Sater, Bernard L.; Chubb, Donald; Jenkins, Phillip; Snyder, Dave

2005-01-01

Concentrator solar cells are continuing to get more consideration for use in power systems. This interest is because concentrator systems can have a net lower cost per watt in solar cell materials plus ongoing improvements in sun-tracking technology. Quantitatively measuring the efficiency of solar cells under concentration is difficult. Traditionally, the light concentration on solar cells has been determined by using a ratio of the measured solar cell s short circuit current to that at one sun, this assumes that current changes proportionally with light intensity. This works well with low to moderate (<20 suns) concentration levels on "well-behaved" linear cells but does not apply when cells respond superlinearly, current increases faster than intensity, or sublinearly, current increases more slowly than intensity. This paper continues work on using view factors to determine the concentration level and linearity of the solar cell with mathematical view factor analysis and experimental results [1].

Uncoupling of oxidative phosphorylation and Smac/DIABLO release are not sufficient to account for induction of apoptosis by sulindac sulfide in human colorectal cancer cells.

PubMed

Daouphars, Mikael; Koufany, Meriem; Benani, Alexandre; Marchal, Sophie; Merlin, Jean-Louis; Netter, Patrick; Jouzeau, Jean-Yves

2005-04-01

Non-steroidal anti-inflammatory drugs (NSAIDs) have shown chemopreventive properties in colorectal cancer, involving both cyclooxygenase (COX)-dependent and -independent mechanisms. Apart from their selectivity for COX isoenzymes, NSAIDs differ in their acidic character which supports ability to uncouple oxidative phosphorylation. To assess the possible contribution of uncoupling to their antineoplastic properties, we compared the effect of sulindac sulfide (SS), an acidic NSAID and NS-398, a non-acidic tricyclic, on mitochondrial function and apoptosis in colorectal cancer cell lines (HT29, Caco-2, HCT15 and HCT116). Although cell lines displayed a different COX status, SS and NS-398 caused growth arrest in a dose-related manner. High dose (10(-4)M) of SS but not of NS-398, increased the percentage of subG1 cell population while reducing mitochondrial transmembrane potential (DeltaPsim). Cyclosporin A (CsA, 1 microM) prevented collapse of DeltaPsim induced by 10(-4)M SS but not by 7.5 microM FCCP used as a protonophoric control. SS and FCCP increased the cytosolic release of Smac/DIABLO which was differently affected by CsA pretreatment depending on the uncoupler. Finally, 7.5 microM FCCP failed to induce apoptosis whereas CsA prevented apoptosis induced by SS from 16% in HCT15 to 41% in HCT116. The present study shows that despite the ability of sulindac sulfide to behave as a protonophoric uncoupler, CsA-sensitive opening of mitochondrial permeability transition pore contributes little to its pro-apoptotic effect in colorectal cancer cells.

Mesenchymal Progenitors Residing Close to the Bone Surface Are Functionally Distinct from Those in the Central Bone Marrow

PubMed Central

Siclari, Valerie A.; Zhu, Ji; Akiyama, Kentaro; Liu, Fei; Zhang, Xianrong; Chandra, Abhishek; Nah-Cederquist, Hyun-Duck; Shi, Songtao; Qin, Ling

2013-01-01

Long bone is an anatomically complicated tissue with trabecular-rich metaphyses at two ends and cortical-rich diaphysis at the center. The traditional flushing method only isolates mesenchymal progenitor cells from the central region of long bones and these cells are distant from the bone surface. We propose that mesenchymal progenitors residing in endosteal bone marrow that is close to the sites of bone formation, such as trabecular bone and endosteum, behave differently from those in the central bone marrow. In this report, we separately isolated endosteal bone marrow using a unique enzymatic digestion approach and demonstrated that it contained a much higher frequency of mesenchymal progenitors than the central bone marrow. Endosteal mesenchymal progenitors express traditional mesenchymal stem cell markers and are capable of multi-lineage differentiation. However, we found that mesenchymal progenitors isolated from different anatomical regions of the marrow did exhibit important functional differences. Compared to their central marrow counterparts, endosteal mesenchymal progenitors have superior proliferative ability with reduced expression of cell cycle inhibitors. They showed greater immunosuppressive activity in culture and in a mouse model of inflammatory bowel disease. Aging is a major contributing factor for trabecular bone loss. We found that old mice have a dramatically decreased number of endosteal mesenchymal progenitors compared to young mice. Parathyroid hormone (PTH) treatment potently stimulates bone formation. A single PTH injection greatly increased the number of endosteal mesenchymal progenitors, particularly those located at the metaphyseal bone, but had no effect on their central counterparts. In summary, endosteal mesenchymal progenitors are more metabolically active and relevant to physiological bone formation than central mesenchymal progenitors. Hence, they represent a biologically important target for future mesenchymal stem cell studies. PMID:23274348

Radiation Induced Chromatin Conformation Changes Analysed by Fluorescent Localization Microscopy, Statistical Physics, and Graph Theory

PubMed Central

Müller, Patrick; Hillebrandt, Sabina; Krufczik, Matthias; Bach, Margund; Kaufmann, Rainer; Hausmann, Michael; Heermann, Dieter W.

2015-01-01

It has been well established that the architecture of chromatin in cell nuclei is not random but functionally correlated. Chromatin damage caused by ionizing radiation raises complex repair machineries. This is accompanied by local chromatin rearrangements and structural changes which may for instance improve the accessibility of damaged sites for repair protein complexes. Using stably transfected HeLa cells expressing either green fluorescent protein (GFP) labelled histone H2B or yellow fluorescent protein (YFP) labelled histone H2A, we investigated the positioning of individual histone proteins in cell nuclei by means of high resolution localization microscopy (Spectral Position Determination Microscopy = SPDM). The cells were exposed to ionizing radiation of different doses and aliquots were fixed after different repair times for SPDM imaging. In addition to the repair dependent histone protein pattern, the positioning of antibodies specific for heterochromatin and euchromatin was separately recorded by SPDM. The present paper aims to provide a quantitative description of structural changes of chromatin after irradiation and during repair. It introduces a novel approach to analyse SPDM images by means of statistical physics and graph theory. The method is based on the calculation of the radial distribution functions as well as edge length distributions for graphs defined by a triangulation of the marker positions. The obtained results show that through the cell nucleus the different chromatin re-arrangements as detected by the fluorescent nucleosomal pattern average themselves. In contrast heterochromatic regions alone indicate a relaxation after radiation exposure and re-condensation during repair whereas euchromatin seemed to be unaffected or behave contrarily. SPDM in combination with the analysis techniques applied allows the systematic elucidation of chromatin re-arrangements after irradiation and during repair, if selected sub-regions of nuclei are investigated. PMID:26042422

Radiation induced chromatin conformation changes analysed by fluorescent localization microscopy, statistical physics, and graph theory.

PubMed

Zhang, Yang; Máté, Gabriell; Müller, Patrick; Hillebrandt, Sabina; Krufczik, Matthias; Bach, Margund; Kaufmann, Rainer; Hausmann, Michael; Heermann, Dieter W

2015-01-01

It has been well established that the architecture of chromatin in cell nuclei is not random but functionally correlated. Chromatin damage caused by ionizing radiation raises complex repair machineries. This is accompanied by local chromatin rearrangements and structural changes which may for instance improve the accessibility of damaged sites for repair protein complexes. Using stably transfected HeLa cells expressing either green fluorescent protein (GFP) labelled histone H2B or yellow fluorescent protein (YFP) labelled histone H2A, we investigated the positioning of individual histone proteins in cell nuclei by means of high resolution localization microscopy (Spectral Position Determination Microscopy = SPDM). The cells were exposed to ionizing radiation of different doses and aliquots were fixed after different repair times for SPDM imaging. In addition to the repair dependent histone protein pattern, the positioning of antibodies specific for heterochromatin and euchromatin was separately recorded by SPDM. The present paper aims to provide a quantitative description of structural changes of chromatin after irradiation and during repair. It introduces a novel approach to analyse SPDM images by means of statistical physics and graph theory. The method is based on the calculation of the radial distribution functions as well as edge length distributions for graphs defined by a triangulation of the marker positions. The obtained results show that through the cell nucleus the different chromatin re-arrangements as detected by the fluorescent nucleosomal pattern average themselves. In contrast heterochromatic regions alone indicate a relaxation after radiation exposure and re-condensation during repair whereas euchromatin seemed to be unaffected or behave contrarily. SPDM in combination with the analysis techniques applied allows the systematic elucidation of chromatin re-arrangements after irradiation and during repair, if selected sub-regions of nuclei are investigated.

Reconfiguring the AR-TIF2 Protein–Protein Interaction HCS Assay in Prostate Cancer Cells and Characterizing the Hits from a LOPAC Screen

PubMed Central

Fancher, Ashley T.; Hua, Yun; Camarco, Daniel P.; Close, David A.; Strock, Christopher J.

2016-01-01

Abstract The continued activation of androgen receptor (AR) transcription and elevated expression of AR and transcriptional intermediary factor 2 (TIF2) coactivator observed in prostate cancer (CaP) recurrence and the development of castration-resistant CaP (CRPC) support a screening strategy for small-molecule inhibitors of AR-TIF2 protein–protein interactions (PPIs) to find new drug candidates. Small molecules can elicit tissue selective effects, because the cells of distinct tissues express different levels and cohorts of coregulatory proteins. We reconfigured the AR-TIF2 PPI biosensor (PPIB) assay in the PC-3 CaP cell line to determine whether AR modulators and hits from an AR-TIF2 PPIB screen conducted in U-2 OS cells would behave differently in the CaP cell background. Although we did not observe any significant differences in the compound responses between the assay performed in osteosarcoma and CaP cells, the U-2 OS AR-TIF2 PPIB assay would be more amenable to screening, because both the virus and cell culture demands are lower. We implemented a testing paradigm of counter-screens and secondary hit characterization assays that allowed us to identify and deprioritize hits that inhibited/disrupted AR-TIF2 PPIs and AR transcriptional activation (AR-TA) through antagonism of AR ligand binding or by non-specifically blocking nuclear receptor trafficking. Since AR-TIF2 PPI inhibitor/disruptor molecules act distally to AR ligand binding, they have the potential to modulate AR-TA in a cell-specific manner that is distinct from existing anti-androgen drugs, and to overcome the development of resistance to AR antagonism. We anticipate that the application of this testing paradigm to characterize the hits from an AR-TIF2 PPI high-content screening campaign will enable us to prioritize the AR-TIF2 PPI inhibitor/disruptor leads that have potential to be developed into novel therapeutics for CaP and CRPC. PMID:27606620

Non-linear macro evolution of a dc driven micro atmospheric glow discharge

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xu, S. F.; Zhong, X. X., E-mail: xxzhong@sjtu.edu.cn

2015-10-15

We studied the macro evolution of the micro atmospheric glow discharge generated between a micro argon jet into ambient air and static water. The micro discharge behaves similarly to a complex ecosystem. Non-linear behaviors are found for the micro discharge when the water acts as a cathode, different from the discharge when water behaves as an anode. Groups of snapshots of the micro discharge formed at different discharge currents are captured by an intensified charge-coupled device with controlled exposure time, and each group consisted of 256 images taken in succession. Edge detection methods are used to identify the water surfacemore » and then the total brightness is defined by adding up the signal counts over the area of the micro discharge. Motions of the water surface at different discharge currents show that the water surface lowers increasingly rapidly when the water acts as a cathode. In contrast, the water surface lowers at a constant speed when the water behaves as an anode. The light curves are similar to logistic growth curves, suggesting that a self-inhibition process occurs in the micro discharge. Meanwhile, the total brightness increases linearly during the same time when the water acts as an anode. Discharge-water interactions cause the micro discharge to evolve. The charged particle bomb process is probably responsible for the different behaviors of the micro discharges when the water acts as cathode and anode.« less

Selfish cells in altruistic cell society - a theoretical oncology.

PubMed

Chigira, M

1993-09-01

In multicellular organisms, internal evolution of individual cells is strictly forbidden and 'evolutional' DNA replication should be performed only by the sexual reproduction system. Wholistic negative control system called 'homeostasis' serves all service to germ line cells. All somatic cells are altruistic to the germ line cells. However, in malignant tumors, it seems that individual cells replicate and behave 'selfishly' and evolve against the internal microenvironment. Tumor cells only express the occult selfishness which is programmed in normal cells a priori. This phenomenon is based on the failure of identical DNA replication, and results in 'autonomy' and 'anomie' of cellular society as shown in tumor cells. Genetic programs of normal cells connote this cellular autonomy and anomie introduced by the deletion of regulators on structure genes. It is rather paradoxical that the somatic cells get their freedom from wholistic negative regulation programmed internally. However, this is not a true paradox, since multicellular organisms have clearly been evolved from 'monads' in which cells proliferate without wholistic regulation. Somatic cells revolt against germ cell DNA, called 'selfish replicator' by Dawkins. It is an inevitable destiny that the 'selfishness' coded in genome should be revenged by itself. Selfish replicator in germ cell line should be revolted by its selfishness in the expansion of somatic cells, since they have an orthogenesis to get more selfishness in order to increase their genome. Tumor heterogeneity and progression can be fully explained by this self-contradictory process which produces heterogeneous gene copies different from the original clone in the tumor, although 'selfish' gene replication is the final target of being. Furthermore, we have to discard the concept of clonality of tumor cells since genetic instability is a fundamental feature of tumors. Finally, tumor cells and proto-oncogenes can be considered as the ultimate parasite to germ line cells.

Energy distributions in rods and beams

NASA Technical Reports Server (NTRS)

Wohlever, J. C.; Bernhard, R. J.

1989-01-01

A hypothesis proposed by Nefske and Sung (1987) that the mechanical energy flow in acoustic/structural systems can be modeled using a thermal energy flow analogy was tested for both longitudinal vibration in rods and transverse flexural vibrations in beams. It was found that the rod behaves according to the energy flow analogy. However, the beam solutions behaved significantly differently than predicted by the thermal analogy, unless spatially averaged energy and power flow were considered. Otherwise, the beam analysis is restricted to frequencies where the near-field terms in the displacement solution are negligible over most of the beam.

Combining the absorptive and radiative loss in metasurfaces for multi-spectral shaping of the electromagnetic scattering.

PubMed

Pan, Wenbo; Huang, Cheng; Pu, Mingbo; Ma, Xiaoliang; Cui, Jianhua; Zhao, Bo; Luo, Xiangang

2016-02-19

The absorptive and radiative losses are two fundamental aspects of the electromagnetic responses, which are widely occurring in many different systems such as waveguides, solar cells, and antennas. Here we proposed a metasurface to realize the control of the absorptive and radiative loss and to reduce the radar cross section (RCS) in multi-frequency bands. The anti-phase gradient and absorptive metasurfaces were designed that consists of metallic square patch and square loop structure inserted with resistors, acting as an phase gradient material in the X and Ku band, while behaving as an absorber in the S band. The simulation and experiment results verified the double-band, wideband and polarization-independent RCS reduction by the absorptive and anti-phase gradient metasurfaces.

A numerical study of blood flow using mixture theory

PubMed Central

Wu, Wei-Tao; Aubry, Nadine; Massoudi, Mehrdad; Kim, Jeongho; Antaki, James F.

2014-01-01

In this paper, we consider the two dimensional flow of blood in a rectangular microfluidic channel. We use Mixture Theory to treat this problem as a two-component system: One component is the red blood cells (RBCs) modeled as a generalized Reiner–Rivlin type fluid, which considers the effects of volume fraction (hematocrit) and influence of shear rate upon viscosity. The other component, plasma, is assumed to behave as a linear viscous fluid. A CFD solver based on OpenFOAM® was developed and employed to simulate a specific problem, namely blood flow in a two dimensional micro-channel, is studied. Finally to better understand this two-component flow system and the effects of the different parameters, the equations are made dimensionless and a parametric study is performed. PMID:24791016

A numerical study of blood flow using mixture theory.

PubMed

Wu, Wei-Tao; Aubry, Nadine; Massoudi, Mehrdad; Kim, Jeongho; Antaki, James F

2014-03-01

In this paper, we consider the two dimensional flow of blood in a rectangular microfluidic channel. We use Mixture Theory to treat this problem as a two-component system: One component is the red blood cells (RBCs) modeled as a generalized Reiner-Rivlin type fluid, which considers the effects of volume fraction (hematocrit) and influence of shear rate upon viscosity. The other component, plasma, is assumed to behave as a linear viscous fluid. A CFD solver based on OpenFOAM ® was developed and employed to simulate a specific problem, namely blood flow in a two dimensional micro-channel, is studied. Finally to better understand this two-component flow system and the effects of the different parameters, the equations are made dimensionless and a parametric study is performed.

BIOAVAILABILITY OF PAHS FROM PYROGENIC AND PETROGENIC SOURCES MEASURED USING GLASS FISH

EPA Science Inventory

Geochemical evidence indicates PAHs associated with pyrogenic sources behave differently than PAHs from petrogenic sources. There is also some evidence and supposition that PAHs from pyrogenic and petrogenic sources demonstrate differing bioavailability. In this study, we evaluat...

Neoadjuvant sirolimus for a large hepatic perivascular epithelioid cell tumor (PEComa).

PubMed

Bergamo, Francesca; Maruzzo, Marco; Basso, Umberto; Montesco, Maria Cristina; Zagonel, Vittorina; Gringeri, Enrico; Cillo, Umberto

2014-02-27

Perivascular epithelioid cell tumors (PEComas) are rare soft-tissue tumors with an extremely heterogeneous clinical behavior. They may arise in different organs and may behave indolently or sometimes metastasize with different grades of biological aggressiveness. We report the case of a young woman with a primary inoperable PEComa of the liver with malignant histological features. Since the mTOR pathway is often altered in PEComas and responses have been reported with mTOR-inhibitors such as sirolimus or temsirolimus, we decided to start a neoadjuvant treatment with sirolimus. The patient tolerated the treatment fairly well and after 8 months a favorable tumor shrinkage was obtained. The patient then stopped sirolimus and 2 weeks later underwent partial liver resection, with complete clinical recovery and normal liver function. The histological report confirmed a malignant PEComa with vascular invasion and negative margins. Then 6 additional months of post-operative sirolimus treatment were administered, followed by regular radiological follow-up. For patients with a large and histologically aggressive PEComa, we think that neoadjuvant treatment with mTOR-inhibitor sirolimus may be considered to facilitate surgery and allow early control of a potentially metastatic disease. For selected high-risk patients, the option of adjuvant treatment may be discussed.

Nanomechanical properties of phospholipid microbubbles.

PubMed

Buchner Santos, Evelyn; Morris, Julia K; Glynos, Emmanouil; Sboros, Vassilis; Koutsos, Vasileios

2012-04-03

This study uses atomic force microscopy (AFM) force-deformation (F-Δ) curves to investigate for the first time the Young's modulus of a phospholipid microbubble (MB) ultrasound contrast agent. The stiffness of the MBs was calculated from the gradient of the F-Δ curves, and the Young's modulus of the MB shell was calculated by employing two different mechanical models based on the Reissner and elastic membrane theories. We found that the relatively soft phospholipid-based MBs behave inherently differently to stiffer, polymer-based MBs [Glynos, E.; Koutsos, V.; McDicken, W. N.; Moran, C. M.; Pye, S. D.; Ross, J. A.; Sboros, V. Langmuir2009, 25 (13), 7514-7522] and that elastic membrane theory is the most appropriate of the models tested for evaluating the Young's modulus of the phospholipid shell, agreeing with values available for living cell membranes, supported lipid bilayers, and synthetic phospholipid vesicles. Furthermore, we show that AFM F-Δ curves in combination with a suitable mechanical model can assess the shell properties of phospholipid MBs. The "effective" Young's modulus of the whole bubble was also calculated by analysis using Hertz theory. This analysis yielded values which are in agreement with results from studies which used Hertz theory to analyze similar systems such as cells.

Numerical investigation for one bad-behaved flow in a Pelton turbine

NASA Astrophysics Data System (ADS)

Wei, X. Z.; Yang, K.; Wang, H. J.; Gong, R. Z.; Li, D. Y.

2015-01-01

The gas-liquid two-phase flow in pelton turbines is very complicated, there are many kinds of bad-behaved flow in pelton turbines. In this paper, CFD numerical simulation for the pelton turbine was conducted using VOF two-phase model. One kind of bad-behaved flow caused by the two jets was captured, and the bad-behaved flow was analysed by torque on buckets. It can be concluded that the angle between the two jets and the value of ratio of runner diameter and jet diameter are important parameters for the bad-behaved flow. Furthermore, the reason why the efficiency of some multi-jet type turbines is very low can be well explained by the analysis of bad-behaved flow. Finally, some suggestions for improvement were also provided in present paper.

Cell membrane causes the lipid bilayers to behave as variable capacitors: A resonance with self-induction of helical proteins.

PubMed

Monajjemi, Majid

2015-12-01

Cell membrane has a unique feature of storing biological energies in a physiologically relevant environment. This study illustrates a capacitor model of biological cell membrane including DPPC structures. The electron density profile models, electron localization function (ELF) and local information entropy have been applied to study the interaction of proteins with lipid bilayers in the cell membrane. The quantum and coulomb blockade effects of different thicknesses in the membrane have also been specifically investigated. It has been exhibited the quantum effects can appear in a small region of the free space within the membrane thickness due to the number and type of phospholipid layers. In addition, from the viewpoint of quantum effects by Heisenberg rule, it is shown the quantum tunneling is allowed in some micro positions while it is forbidden in other forms of membrane capacitor systems. Due to the dynamical behavior of the cell membrane, its capacitance is not fixed which results a variable capacitor. In presence of the external fields through protein trance membrane or ions, charges exert forces that can influence the state of the cell membrane. This causes to appear the charge capacitive susceptibility that can resonate with self-induction of helical coils; the resonance of which is the main reason for various biological pulses. Copyright © 2015 Elsevier B.V. All rights reserved.

Forced expression of the Ikaros 6 isoform in human placental blood CD34(+) cells impairs their ability to differentiate toward the B-lymphoid lineage.

PubMed

Tonnelle, C; Bardin, F; Maroc, C; Imbert, A M; Campa, F; Dalloul, A; Schmitt, C; Chabannon, C

2001-11-01

Studies in mice suggest that the Ikaros (Ik) gene encodes several isoforms and is a critical regulator of hematolymphoid differentiation. Little is known on the role of Ikaros in human stem cell differentiation. Herein, the biological consequences of the forced expression of Ikaros 6 (Ik6) in human placental blood CD34(+) progenitors are evaluated. Ik6 is one of the isoforms produced from the Ikaros premessenger RNA by alternative splicing and is thought to behave as a dominant negative isoform of the gene product because it lacks the DNA binding domain present in transcriptionally active isoforms. The results demonstrate that human cord blood CD34(+) cells that express high levels of Ik6 as a result of retrovirally mediated gene transfer have a reduced capacity to produce lymphoid B cells in 2 independent assays: (1) in vitro reinitiation of human hematopoiesis during coculture with the MS-5 murine stromal cell line and (2) xenotransplantation in nonobese diabetic-severe combined immunodeficient mice. These results suggest that Ikaros plays an important role in stem cell commitment in humans and that the balance between the different isoforms is a key element of this regulatory system; they support the hypothesis that posttranscriptional events can participate in the control of human hematopoietic differentiation.

Calcium transient prevalence across the dendritic arbour predicts place field properties.

PubMed

Sheffield, Mark E J; Dombeck, Daniel A

2015-01-08

Establishing the hippocampal cellular ensemble that represents an animal's environment involves the emergence and disappearance of place fields in specific CA1 pyramidal neurons, and the acquisition of different spatial firing properties across the active population. While such firing flexibility and diversity have been linked to spatial memory, attention and task performance, the cellular and network origin of these place cell features is unknown. Basic integrate-and-fire models of place firing propose that such features result solely from varying inputs to place cells, but recent studies suggest instead that place cells themselves may play an active role through regenerative dendritic events. However, owing to the difficulty of performing functional recordings from place cell dendrites, no direct evidence of regenerative dendritic events exists, leaving any possible connection to place coding unknown. Using multi-plane two-photon calcium imaging of CA1 place cell somata, axons and dendrites in mice navigating a virtual environment, here we show that regenerative dendritic events do exist in place cells of behaving mice, and, surprisingly, their prevalence throughout the arbour is highly spatiotemporally variable. Furthermore, we show that the prevalence of such events predicts the spatial precision and persistence or disappearance of place fields. This suggests that the dynamics of spiking throughout the dendritic arbour may play a key role in forming the hippocampal representation of space.

Calcium transient prevalence across the dendritic arbor predicts place field properties

PubMed Central

Sheffield, Mark E. J.; Dombeck, Daniel A.

2014-01-01

Establishing the hippocampal cellular ensemble that represents an animal’s environment involves the emergence and disappearance of place fields in specific CA1 pyramidal neurons1–4, and the acquisition of different spatial firing properties across the active population5. While such firing flexibility and diversity have been linked to spatial memory, attention and task performance6,7, the cellular and network origin of these place cell features is unknown. Basic integrate-and-fire models of place firing propose that such features result solely from varying inputs to place cells8,9, but recent studies3,10 instead suggest that place cells themselves may play an active role through regenerative dendritic events. However, due to the difficulty of performing functional recordings from place cell dendrites, no direct evidence of regenerative dendritic events exists, leaving any possible connection to place coding unknown. Using multi-plane two-photon calcium imaging of CA1 place cell somata, axons, and dendrites in mice navigating a virtual environment, we show that regenerative dendritic events do exist in place cells of behaving mice and, surprisingly, their prevalence throughout the arbor is highly spatiotemporally variable. Further, we show that the prevalence of such events predicts the spatial precision and persistence or disappearance of place fields. This suggests that the dynamics of spiking throughout the dendritic arbor may play a key role in forming the hippocampal representation of space. PMID:25363782

Co-Culture with Listeria monocytogenes within a Dual-Species Biofilm Community Strongly Increases Resistance of Pseudomonas putida to Benzalkonium Chloride

PubMed Central

Giaouris, Efstathios; Chorianopoulos, Nikos; Doulgeraki, Agapi; Nychas, George-John

2013-01-01

Biofilm formation is a phenomenon occurring almost wherever microorganisms and surfaces exist in close proximity. This study aimed to evaluate the possible influence of bacterial interactions on the ability of Listeria monocytogenes and Pseudomonas putida to develop a dual-species biofilm community on stainless steel (SS), as well as on the subsequent resistance of their sessile cells to benzalkonium chloride (BC) used in inadequate (sub-lethal) concentration (50 ppm). The possible progressive adaptability of mixed-culture biofilms to BC was also investigated. To accomplish these, 3 strains per species were left to develop mixed-culture biofilms on SS coupons, incubated in daily renewable growth medium for a total period of 10 days, under either mono- or dual-species conditions. Each day, biofilm cells were exposed to disinfection treatment. Results revealed that the simultaneous presence of L. monocytogenes strongly increased the resistance of P. putida biofilm cells to BC, while culture conditions (mono-/dual-species) did not seem to significantly influence the resistance of L. monocytogenes biofilm cells. BC mainly killed L. monocytogenes cells when this was applied against the dual-species sessile community during the whole incubation period, despite the fact that from the 2nd day this community was mainly composed (>90%) of P. putida cells. No obvious adaptation to BC was observed in either L. monocytogenes or P. putida biofilm cells. Pulsed field gel electrophoresis (PFGE) analysis showed that the different strains behaved differently with regard to biofilm formation and antimicrobial resistance. Such knowledge on the physiological behavior of mixed-culture biofilms could provide the information necessary to control their formation. PMID:24130873

Lumbar hemangioma masking a plasma cell tumor--case report and review of the literature.

PubMed

Haque, Maahir U; Wilson, Adam N; Blecher, Haim D; Reich, Steven M

2013-08-01

Vertebral hemangiomata are ubiquitous bone tumors. Often multiple, they are generally benign in nature and slow growing. They typically have a predictable radiographic appearance. Occasionally, hemangiomata may behave in a more aggressive manner, causing pathologic fracture or even symptoms/signs of nerve compression. In such cases, one must be careful not to assume that an atypical hemangioma is responsible. Coexisting, more malignant processes may be present and sometimes may be radiographically undetectable in the setting of acute fracture. This was the case in our patient. Case report/university spine surgery center. The patient underwent a corpectomy of her affected vertebra with conversion to a total spondylectomy when intraoperative frozen section was consistent with plasma cell neoplasm. A reconstruction with vertebral body replacement and fusion through anterior and posterior approaches was completed. Subsequently, the literature was reviewed for other cases of atypical hemangiomata to investigate the incidence of coexistent lesions. This patient presented with pain secondary to an unstable pathologic vertebral body fracture. Surgery to stabilize her spine was elected. Intraoperative recognition of abnormal-appearing tissue led to the diagnosis of a plasma cell neoplasm that was not seen on imaging. Coexistent in the same vertebra was hemangiomatous tissue that was visible on preoperative imaging. There are rare reports of aggressively behaving hemangiomata that mainly have occurred in the thoracic spine. There have been no reports of the coexistence of a hemangioma and a plasma cell tumor in the same vertebral level in the setting of acute compression fracture. Copyright © 2013 Elsevier Inc. All rights reserved.

Intra-islet endothelial cell and β-cell crosstalk: Implication for islet cell transplantation

PubMed Central

Narayanan, Siddharth; Loganathan, Gopalakrishnan; Dhanasekaran, Maheswaran; Tucker, William; Patel, Ankit; Subhashree, Venugopal; Mokshagundam, SriPrakash; Hughes, Michael G; Williams, Stuart K; Balamurugan, Appakalai N

2017-01-01

The intra-islet microvasculature is a critical interface between the blood and islet endocrine cells governing a number of cellular and pathophysiological processes associated with the pancreatic tissue. A growing body of evidence indicates a strong functional and physical interdependency of β-cells with endothelial cells (ECs), the building blocks of islet microvasculature. Intra-islet ECs, actively regulate vascular permeability and appear to play a role in fine-tuning blood glucose sensing and regulation. These cells also tend to behave as “guardians”, controlling the expression and movement of a number of important immune mediators, thereby strongly contributing to the physiology of islets. This review will focus on the molecular signalling and crosstalk between the intra-islet ECs and β-cells and how their relationship can be a potential target for intervention strategies in islet pathology and islet transplantation. PMID:28507914

Effect of procaine on cultivated human WI-38 fibroblasts.

PubMed

Pigeolet, E; Raes, M; Houbion, A; Remacle, J

1988-01-01

Procaine is a local anesthetic, also used in experimental gerontology and has been tested in cultivated human WI-38 fibroblasts. This molecule was found to enhance growth rate and cell densities in actively dividing cultures. As the cells aged, however, this stimulatory effect diminished and finally vanished. In a long term experiment the enhancement of growth of procaine treated cultures was finally replaced by a toxic effect even at low concentration. The amount of the thermolabile enzyme found in phase III cells did not change when procaine was added to the culture medium. In this cellular aging model, procaine behaved like a metabolic stimulator of actively dividing cells but not as an "antiaging" molecule as it is sometimes assumed.

Ethnicity, gender socialization, and children’s attitudes towards gay men and lesbian women

PubMed Central

Bos, Henny M.W.; Picavet, Charles; Sandfort, Theo G. M.

2011-01-01

The aim of the present study was to assess whether children’s attitudes towards gay men and lesbian women differ in relation to their ethnic backgrounds, and whether ethnic differences are a result of perceived differential gender socialization practices. Data were collected from children in eight Dutch elementary schools by means of a paper-and-pencil questionnaire administered in the classroom. All children (mean age 11.47; N = 229) lived in the Netherlands; 50.2% had non-Western and 49.8% Western ethnic backgrounds. Children with non-Western ethnic backgrounds reported more negative attitudes towards gays and lesbians. These children perceived more parental pressure to behave in accordance with their gender and showed more negative attitudes towards gender-nonconforming behaviour by peers. Hierarchical regression analyses revealed that cultural differences in attitudes towards gay men and lesbian women are partly mediated by differentially perceived parental pressure to behave in accordance with their gender. PMID:23162164

Ethics and synthetic gametes.

PubMed

Testa, Giuseppe; Harris, John

2005-04-01

The recent in vitro derivation of gamete-like cells from mouse embryonic stem (mES) cells is a major breakthrough and lays down several challenges, both for the further scientific investigation and for the bioethical and biolegal discourse. We refer here to these cells as gamete-like (sperm-like or oocyte-like, respectively), because at present there is still no evidence that these cells behave fully like bona fide sperm or oocytes, lacking the fundamental proof, i.e. combination with a normally derived gamete of the opposite sex to yield a normal individual. However, the results published so far do show that these cells share some defining features of gametes. We discuss these results in the light of the bioethical and legal questions that are likely to arise would the same process become possible with human embryonic stem (hES) cells.

Characterization of a continuous agitated cell reactor for oxygen dependent biocatalysis.

PubMed

Toftgaard Pedersen, Asbjørn; de Carvalho, Teresa Melo; Sutherland, Euan; Rehn, Gustav; Ashe, Robert; Woodley, John M

2017-06-01

Biocatalytic oxidation reactions employing molecular oxygen as the electron acceptor are difficult to conduct in a continuous flow reactor because of the requirement for high oxygen transfer rates. In this paper, the oxidation of glucose to glucono-1,5-lactone by glucose oxidase was used as a model reaction to study a novel continuous agitated cell reactor (ACR). The ACR consists of ten cells interconnected by small channels. An agitator is placed in each cell, which mixes the content of the cell when the reactor body is shaken by lateral movement. Based on tracer experiments, a hydrodynamic model for the ACR was developed. The model consisted of ten tanks-in-series with back-mixing occurring within and between each cell. The back-mixing was a necessary addition to the model in order to explain the observed phenomenon that the ACR behaved as two continuous stirred tank reactors (CSTRs) at low flow rates, while it at high flow rates behaved as the expected ten CSTRs in series. The performance of the ACR was evaluated by comparing the steady state conversion at varying residence times with the conversion observed in a stirred batch reactor of comparable size. It was found that the ACR could more than double the overall reaction rate, which was solely due to an increased oxygen transfer rate in the ACR caused by the intense mixing as a result of the spring agitators. The volumetric oxygen transfer coefficient, k L a, was estimated to be 344 h -1 in the 100 mL ACR, opposed to only 104 h -1 in a batch reactor of comparable working volume. Interestingly, the large deviation from plug flow behavior seen in the tracer experiments was found to have little influence on the conversion in the ACR, since both a plug flow reactor (PFR) model and the backflow cell model described the data sufficiently well. Biotechnol. Bioeng. 2017;114: 1222-1230. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Generators of the brainstem auditory evoked potential in cat. III: Identified cell populations.

PubMed

Melcher, J R; Kiang, N Y

1996-04-01

This paper examines the relationship between different brainstem cell populations and the brainstem auditory evoked potential (BAEP). First, we present a mathematical model relating the BAEP to underlying cellular activity. Then, we identify specific cellular generators of the click-evoked BAEP in cats by combining model-derived insights with key experimental data. These data include (a) a correspondence between particular brainstem regions and specific extrema in the BAEP waveform, determined from lesion experiments, and (b) values for model parameters derived from published physiological and anatomical information. Ultimately, we conclude (with varying degrees of confidence) that: (1) the earliest extrema in the BAEP are generated by spiral ganglion cells, (2) P2 is mainly generated by cochlear nucleus (CN) globular cells, (3) P3 is partly generated by CN spherical cells and partly by cells receiving inputs from globular cells, (4) P4 is predominantly generated by medial superior olive (MSO) principal cells, which are driven by spherical cells, (5) the generators of P5 are driven by MSO principal cells, and (6) the BAEP, as a whole, is generated mainly by cells with characteristic frequencies above 2 kHz. Thus, the BAEP in cats mainly reflects cellular activity in two parallel pathways, one originating with globular cells and the other with spherical cells. Since the globular cell pathway is poorly represented in humans, we suggest that the human BAEP is largely generated by brainstem cells in the spherical cell pathway. Given our conclusions, it should now be possible to relate activity in specific cell populations to psychophysical performance since the BAEP can be recorded in behaving humans and animals.

Heterogeneous Households A within-subject test of asymmetric information between spouses in Kenya

PubMed Central

Hoel, Jessica B.

2015-01-01

To identify which spouses respond to asymmetric information, I play two dictator games with each member of the couple. One decision is kept secret from the respondent's spouse, while another choice is public. Most people give the same amount in public and secret, while a minority behave opportunistically and give more to their spouse in public and less in secret. The types identified in the lab also behave differently at home. For those who behave opportunistically in the lab, greater knowledge about finances at home is associated with worse opportunism in the lab, suggesting that for these couples complete information at home is not due to trust but rather is an endogenous response to non-cooperative behavior. The paper highlights that allowing for heterogeneous types changes the conclusions we draw about appropriate models of the household and suggests that laboratory games can be used to identify household types useful in the interpretation of field data. PMID:26504256

When Lying Feels the Right Thing to Do.

PubMed

Van Der Zee, Sophie; Anderson, Ross; Poppe, Ronald

2016-01-01

Fraud is a pervasive and challenging problem that costs society large amounts of money. By no means all fraud is committed by 'professional criminals': much is done by ordinary people who indulge in small-scale opportunistic deception. In this paper, we set out to investigate when people behave dishonestly, for example by committing fraud, in an online context. We conducted three studies to investigate how the rejection of one's efforts, operationalized in different ways, affected the amount of cheating and information falsification. Study 1 demonstrated that people behave more dishonestly when rejected. Studies 2 and 3 were conducted in order to disentangle the confounding factors of the nature of the rejection and the financial rewards that are usually associated with dishonest behavior. It was demonstrated that rejection in general, rather than the nature of a rejection, caused people to behave more dishonestly. When a rejection was based on subjective grounds, dishonest behavior increased with approximately 10%, but this difference was not statistically significant. We subsequently measured whether dishonesty was driven by the financial loss associated with rejection, or emotional factors such as a desire for revenge. We found that rejected participants were just as dishonest when their cheating did not led to financial gain. However, they felt stronger emotions when there was no money involved. This seems to suggest that upon rejection, emotional involvement, especially a reduction in happiness, drives dishonest behavior more strongly than a rational cost-benefit analysis. These results indicate that rejection causes people to behave more dishonestly, specifically in online settings. Firms wishing to deter customers and employees from committing fraud may therefore benefit from transparency and clear policy guidelines, discouraging people to submit claims that are likely to be rejected.

When Lying Feels the Right Thing to Do

PubMed Central

Van Der Zee, Sophie; Anderson, Ross; Poppe, Ronald

2016-01-01

Fraud is a pervasive and challenging problem that costs society large amounts of money. By no means all fraud is committed by ‘professional criminals’: much is done by ordinary people who indulge in small-scale opportunistic deception. In this paper, we set out to investigate when people behave dishonestly, for example by committing fraud, in an online context. We conducted three studies to investigate how the rejection of one’s efforts, operationalized in different ways, affected the amount of cheating and information falsification. Study 1 demonstrated that people behave more dishonestly when rejected. Studies 2 and 3 were conducted in order to disentangle the confounding factors of the nature of the rejection and the financial rewards that are usually associated with dishonest behavior. It was demonstrated that rejection in general, rather than the nature of a rejection, caused people to behave more dishonestly. When a rejection was based on subjective grounds, dishonest behavior increased with approximately 10%, but this difference was not statistically significant. We subsequently measured whether dishonesty was driven by the financial loss associated with rejection, or emotional factors such as a desire for revenge. We found that rejected participants were just as dishonest when their cheating did not led to financial gain. However, they felt stronger emotions when there was no money involved. This seems to suggest that upon rejection, emotional involvement, especially a reduction in happiness, drives dishonest behavior more strongly than a rational cost-benefit analysis. These results indicate that rejection causes people to behave more dishonestly, specifically in online settings. Firms wishing to deter customers and employees from committing fraud may therefore benefit from transparency and clear policy guidelines, discouraging people to submit claims that are likely to be rejected. PMID:27313549

Monitoring of Vibrio harveyi quorum sensing activity in real time during infection of brine shrimp larvae.

PubMed

Defoirdt, Tom; Sorgeloos, Patrick

2012-12-01

Quorum sensing, bacterial cell-to-cell communication, has been linked to the virulence of pathogenic bacteria. Indeed, in vitro experiments have shown that many bacterial pathogens regulate the expression of virulence genes by this cell-to-cell communication process. Moreover, signal molecules have been detected in samples retrieved from infected hosts and quorum sensing disruption has been reported to result in reduced virulence in different host-pathogen systems. However, data on in vivo quorum sensing activity of pathogens during infection of a host are currently lacking. We previously reported that quorum sensing regulates the virulence of Vibrio harveyi in a standardised model system with gnotobiotic brine shrimp (Artemia franciscana) larvae. Here, we monitored quorum sensing activity in Vibrio harveyi during infection of the shrimp, using bioluminescence as a read-out. We found that wild-type Vibrio harveyi shows a strong increase in quorum sensing activity early during infection. In this respect, the bacteria behave remarkably similar in different larvae, despite the fact that only half of them survive the infection. Interestingly, when expressed per bacterial cell, Vibrio harveyi showed around 200-fold higher maximal quorum sensing-regulated bioluminescence when associated with larvae than in the culture water. Finally, the in vivo quorum sensing activity of mutants defective in the production of one of the three signal molecules is consistent with their virulence, with no detectable in vivo quorum sensing activity in AI-2- and CAI-1-deficient mutants. These results indicate that AI-2 and CAI-1 are the dominant signals during infection of brine shrimp.

Monitoring of Vibrio harveyi quorum sensing activity in real time during infection of brine shrimp larvae

PubMed Central

Defoirdt, Tom; Sorgeloos, Patrick

2012-01-01

Quorum sensing, bacterial cell-to-cell communication, has been linked to the virulence of pathogenic bacteria. Indeed, in vitro experiments have shown that many bacterial pathogens regulate the expression of virulence genes by this cell-to-cell communication process. Moreover, signal molecules have been detected in samples retrieved from infected hosts and quorum sensing disruption has been reported to result in reduced virulence in different host–pathogen systems. However, data on in vivo quorum sensing activity of pathogens during infection of a host are currently lacking. We previously reported that quorum sensing regulates the virulence of Vibrio harveyi in a standardised model system with gnotobiotic brine shrimp (Artemia franciscana) larvae. Here, we monitored quorum sensing activity in Vibrio harveyi during infection of the shrimp, using bioluminescence as a read-out. We found that wild-type Vibrio harveyi shows a strong increase in quorum sensing activity early during infection. In this respect, the bacteria behave remarkably similar in different larvae, despite the fact that only half of them survive the infection. Interestingly, when expressed per bacterial cell, Vibrio harveyi showed around 200-fold higher maximal quorum sensing-regulated bioluminescence when associated with larvae than in the culture water. Finally, the in vivo quorum sensing activity of mutants defective in the production of one of the three signal molecules is consistent with their virulence, with no detectable in vivo quorum sensing activity in AI-2- and CAI-1-deficient mutants. These results indicate that AI-2 and CAI-1 are the dominant signals during infection of brine shrimp. PMID:22673627

Evaluation of role of Notch3 signaling pathway in human lung cancer cells.

PubMed

Hassan, Wael Abdo; Yoshida, Ryoji; Kudoh, Shinji; Motooka, Yamato; Ito, Takaaki

2016-05-01

There is still a debate on the extent to which Notch3 signaling is involved in lung carcinogenesis and whether such function is dependent on cancer type or not. To evaluate Notch3 expression in different types of human lung cancer cells. Notch3 was detected in human lung cancer cell lines and in tissues. Then, small interfering RNA (siRNA) was used to down-regulate the expression of Notch3 in H69AR small cell lung carcinoma (SCLC) cells; two non-small cell lung carcinoma (NSCLC) cells; A549 adenocarcinoma (ADC); and H2170 squamous cell carcinoma (SCC). In addition, Notch3 intracellular domain (N3ICD) plasmid was transfected into H1688 human SCLC cells. We observed the effect of deregulating Notch3 signaling on the following cell properties: Notch-related proteins, cell morphology, adhesion, epithelial-mesenchymal transition (EMT), motility, proliferation and neuroendocrine (NE) features of SCLC. Notch3 is mainly expressed in NSCLC, and the expression of Notch1, Hes1 and Jagged1 is affected by Notch3. Notch3 has opposite functions in SCLC and NSCLC, being a tumor suppressor in the former and tumor promoting in the latter, in the context of cell adhesion, EMT and motility. Regarding cell proliferation, we found that inhibiting Notch3 in NSCLC decreases cell proliferation and induces apoptosis in NSCLC. Notch3 has no effect on cell proliferation or NE features of SCLC. Notch3 signaling in lung carcinoma is dependent on cell type. In SCLC, Notch3 behaves as a tumor suppressor pathway, while in NSCLC it acts as a tumor-promoting pathway.

Single cell cultures of Drosophila neuroectodermal and mesectodermal central nervous system progenitors reveal different degrees of developmental autonomy.

PubMed

Lüer, Karin; Technau, Gerhard M

2009-08-03

The Drosophila embryonic central nervous system (CNS) develops from two sets of progenitor cells, neuroblasts and ventral midline progenitors, which behave differently in many respects. Neuroblasts derive from the neurogenic region of the ectoderm and form the lateral parts of the CNS. Ventral midline precursors are formed by two rows of mesectodermal cells and build the CNS midline. There is plenty of evidence that individual identities are conferred to precursor cells by positional information in the ectoderm. It is unclear, however, how far the precursors can maintain their identities and developmental properties in the absence of normal external signals. To separate the respective contributions of autonomous properties versus extrinsic signals during their further development, we isolated individual midline precursors and neuroectodermal precursors at the pre-mitotic gastrula stage, traced their development in vitro, and analyzed the characteristics of their lineages in comparison with those described for the embryo. Although individually cultured mesectodermal cells exhibit basic characteristics of CNS midline progenitors, the clones produced by these progenitors differ from their in situ counterparts with regard to cell numbers, expression of molecular markers, and the separation of neuronal and glial fate. In contrast, clones derived from individually cultured precursors taken from specific dorsoventral zones of the neuroectoderm develop striking similarities to the lineages of neuroblasts that normally delaminate from these zones and develop in situ. This in vitro analysis allows for the first time a comparison of the developmental capacities in situ and in vitro of individual neural precursors of defined spatial and temporal origin. The data reveal that cells isolated at the pre-mitotic and pre-delamination stage express characteristics of the progenitor type appropriate to their site of origin in the embryo. However, presumptive neuroblasts, once specified in the neuroectoderm, exhibit a higher degree of autonomy regarding generation of their lineages compared to mesectodermal midline progenitors.

Algivore or Phototroph? Plakobranchus ocellatus (Gastropoda) Continuously Acquires Kleptoplasts and Nutrition from Multiple Algal Species in Nature

PubMed Central

Maeda, Taro; Hirose, Euichi; Chikaraishi, Yoshito; Kawato, Masaru; Takishita, Kiyotaka; Yoshida, Takao; Verbruggen, Heroen; Tanaka, Jiro; Shimamura, Shigeru; Takaki, Yoshihiro; Tsuchiya, Masashi; Iwai, Kenji; Maruyama, Tadashi

2012-01-01

The sea slug Plakobranchus ocellatus (Sacoglossa, Gastropoda) retains photosynthetically active chloroplasts from ingested algae (functional kleptoplasts) in the epithelial cells of its digestive gland for up to 10 months. While its feeding behavior has not been observed in natural habitats, two hypotheses have been proposed: 1) adult P. ocellatus uses kleptoplasts to obtain photosynthates and nutritionally behaves as a photoautotroph without replenishing the kleptoplasts; or 2) it behaves as a mixotroph (photoautotroph and herbivorous consumer) and replenishes kleptoplasts continually or periodically. To address the question of which hypothesis is more likely, we examined the source algae for kleptoplasts and temporal changes in kleptoplast composition and nutritional contribution. By characterizing the temporal diversity of P. ocellatus kleptoplasts using rbcL sequences, we found that P. ocellatus harvests kleptoplasts from at least 8 different siphonous green algal species, that kleptoplasts from more than one species are present in each individual sea slug, and that the kleptoplast composition differs temporally. These results suggest that wild P. ocellatus often feed on multiple species of siphonous algae from which they continually obtain fresh chloroplasts. By estimating the trophic position of wild and starved P. ocellatus using the stable nitrogen isotopic composition of amino acids, we showed that despite the abundance of kleptoplasts, their photosynthates do not contribute greatly to the nutrition of wild P. ocellatus, but that kleptoplast photosynthates form a significant source of nutrition for starved sea slugs. The herbivorous nature of wild P. ocellatus is consistent with insights from molecular analyses indicating that kleptoplasts are frequently replenished from ingested algae, leading to the conclusion that natural populations of P. ocellatus do not rely on photosynthesis but mainly on the digestion of ingested algae. PMID:22848693

Ectoenzymes and innate immunity: the role of human CD157 in leukocyte trafficking.

PubMed

Funaro, Ada; Ortolan, Erika; Bovino, Paola; Lo Buono, Nicola; Nacci, Giulia; Parrotta, Rossella; Ferrero, Enza; Malavasi, Fabio

2009-01-01

CD157 is a glycosylphosphatidylinositol-anchored molecule encoded by a member of the CD38/ADP-ribosyl cyclase gene family, involved in the metabolism of NAD. Expressed mainly by cells of the myeloid lineage and by vascular endothelial cells, CD157 has a dual nature behaving both as an ectoenzyme and as a receptor. Although it lacks a cytoplasmic domain, and cannot transduce signals on its own, the molecule compensates for this structural limit by interacting with conventional receptors. Recent experimental evidence suggests that CD157 orchestrates critical functions of human neutrophils. Indeed, CD157-mediated signals promote cell polarization, regulate chemotaxis induced through the high affinity fMLP receptor and control transendothelial migration.

Curvature-Guided Motility of Microalgae in Geometric Confinement

NASA Astrophysics Data System (ADS)

Ostapenko, Tanya; Schwarzendahl, Fabian Jan; Böddeker, Thomas J.; Kreis, Christian Titus; Cammann, Jan; Mazza, Marco G.; Bäumchen, Oliver

2018-02-01

Microorganisms, such as bacteria and microalgae, often live in habitats consisting of a liquid phase and a plethora of interfaces. The precise ways in which these motile microbes behave in their confined environment remain unclear. Using experiments and Brownian dynamics simulations, we study the motility of a single Chlamydomonas microalga in an isolated microhabitat with controlled geometric properties. We demonstrate how the geometry of the habitat controls the cell's navigation in confinement. The probability of finding the cell swimming near the boundary increases with the wall curvature, as seen for both circular and elliptical chambers. The theory, utilizing an asymmetric dumbbell model of the cell and steric wall interactions, captures this curvature-guided navigation quantitatively with no free parameters.

Targeting of regulated necrosis in kidney disease.

PubMed

Martin-Sanchez, Diego; Poveda, Jonay; Fontecha-Barriuso, Miguel; Ruiz-Andres, Olga; Sanchez-Niño, María Dolores; Ruiz-Ortega, Marta; Ortiz, Alberto; Sanz, Ana Belén

The term acute tubular necrosis was thought to represent a misnomer derived from morphological studies of human necropsies and necrosis was thought to represent an unregulated passive form of cell death which was not amenable to therapeutic manipulation. Recent advances have improved our understanding of cell death in acute kidney injury. First, apoptosis results in cell loss, but does not trigger an inflammatory response. However, clumsy attempts at interfering with apoptosis (e.g. certain caspase inhibitors) may trigger necrosis and, thus, inflammation-mediated kidney injury. Second, and most revolutionary, the concept of regulated necrosis emerged. Several modalities of regulated necrosis were described, such as necroptosis, ferroptosis, pyroptosis and mitochondria permeability transition regulated necrosis. Similar to apoptosis, regulated necrosis is modulated by specific molecules that behave as therapeutic targets. Contrary to apoptosis, regulated necrosis may be extremely pro-inflammatory and, importantly for kidney transplantation, immunogenic. Furthermore, regulated necrosis may trigger synchronized necrosis, in which all cells within a given tubule die in a synchronized manner. We now review the different modalities of regulated necrosis, the evidence for a role in diverse forms of kidney injury and the new opportunities for therapeutic intervention. Copyright © 2017 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

Hybrid nanocatalysts containing enzymes and metallic nanoparticles for ethanol/O2 biofuel cell

NASA Astrophysics Data System (ADS)

Aquino Neto, S.; Almeida, T. S.; Palma, L. M.; Minteer, S. D.; de Andrade, A. R.

2014-08-01

We report the preparation of hybrid nanostructured bioanodes containing the enzyme alcohol dehydrogenase (ADH) with either Au, Pt, or Pt0.75Sn0.25 nanoparticles for use in ethanol/O2 hybrid biofuel cells. We describe two different methodologies for the preparation of the bioanodes: in a first case, multi walled carbon nanotubes (MWCNTs) were employed as a support for the metallic nanoparticles and TBAB-modified Nafion® aided enzyme immobilization. In the second case, we immobilized the enzymes using dendrimers-encapsulated nanoparticles as the agent for enzyme anchoring. The biofuel cell tests showed that the addition of metallic nanoparticles to the bioanode structure enhanced the overall biofuel cell performance. The bioelectrode containing Au nanoparticles displaying the best performance, with an open circuit potential of 0.61 ± 0.05 V and a maximum power density of 155 ± 11 μW cm-2. NADH cyclic voltammetric experiments indicated that Au nanoparticles behaved as a catalyst toward NADH oxidation. Comparing the two protocols we used to synthetized nanoparticles, the sample containing the Au nanoparticles supported on MWCNTs furnished fourfold higher values. Therefore, from the satisfactory results obtained, it can be inferred that the combination of small amounts of metallic nanoparticles with enzymes improve bioanode performance.

Adipose cell differentiation: evidence for a two-step process in the polyamine-dependent Ob1754 clonal line.

PubMed Central

Amri, E Z; Dani, C; Doglio, A; Etienne, J; Grimaldi, P; Ailhaud, G

1986-01-01

A subclone of preadipocyte Ob17 cells has been isolated (Ob1754 clonal line). Confluent Ob1754 cells treated with an inhibitor of spermidine and spermine synthesis, methylglyoxal bis(guanylhydrazone), were totally dependent upon putrescine addition for the expression of glycerol-3-phosphate dehydrogenase which behaved as a late marker of adipose conversion. Under these conditions, the early expression of lipoprotein lipase during growth arrest remained unchanged. Studies at the mRNA level showed that the expression of unidentified pOb24 and pGH3 mRNAs, which was parallel to that of lipoprotein lipase, is independent of polyamine addition whereas the late emergence of glycerol-3-phosphate dehydrogenase mRNA was putrescine-dependent and co-ordinated with the expression of pAL422 mRNA encoding for a myelin-P2 homologue [Bernlohr, Angus, Lane, Bolanowski & Kelly (1984) Proc. Natl. Acad. Sci. U.S.A. 81, 5468-5472]. The appearance of lipoprotein lipase preceded DNA synthesis and post-confluent mitoses which were both putrescine-dependent and which took place before the appearance of glycerol-3-phosphate dehydrogenase. Thus the adipose conversion of Ob1754 cells involves the expression of at least two separate sets of markers which are differently regulated. Images Fig. 3. Fig. 6. PMID:3800927

DOE Office of Scientific and Technical Information (OSTI.GOV)

Alexandrov, L. B.

All cancers originate from a single cell that starts to behave abnormally, to divide uncontrollably, and, eventually, to invade adjacent tissues (1). The aberrant behavior of this single cell is due to somatic mutations—changes in the genomic DNA produced by the activity of different mutational processes (1). These various mutational processes include exposure to exogenous or endogenous mutagens, abnormal DNA editing, the incomplete fidelity of DNA polymerases, and failure of DNA repair mechanisms (2). Early studies that sequenced TP53, the most commonly mutated gene in human cancer, provided evidence that mutational processes leave distinct imprints of somatic mutations on themore » genome of a cancer cell (3). For example, C:G>A:T transversions predominate in smoking-associated lung cancer, whereas C:G>T:A transitions occurring mainly at dipyrimidines and CC:GG>TT:AA double-nucleotide substitutions are common in ultraviolet light–associated skin cancers. Moreover, these patterns of mutations matched the ones induced experimentally by tobacco mutagens and ultraviolet light, respectively, the major, known, exogenous carcinogenic influences in these cancer types, and demonstrated that examining patterns of mutations in cancer genomes can yield information about the mutational processes that cause human cancer (4).« less

Flow cytometry without alignment of collection optics.

PubMed

Sitton, Greg; Srienc, Friedrich

2009-12-01

This study describes the performance of a new waveguide flow cell constructed from Teflon AF (TFC) and the potential use of fiber optic splitters to replace collection objectives and dichroic mirrors. The TFC has the unique optical property that the refractive index of the polymer is lower than water and therefore, water filled TFC behaves and functions as a liquid core waveguide. Thus, as cells flow through the TFC and are illuminated by a laser orthogonal to the flow direction, scattered and fluorescent light is directed down the axis of the TFC to a fiber optic. The total signal in the fiber optic is then split into multiple fibers by fiber optic splitters to enable measurement of signal intensities at different wavelengths. Optical filters are placed at the terminus of each fiber before measurement of specific wavelengths by a PMT. The constructed system was used to measure DNA content of CHO and yeast cells. Polystyrene beads were used for alignment and to assess the performance of the system. Polystyrene beads were observed to produce light scattering signals with unique bimodal characteristics dependent on the direction of flow relative to the collecting fiber optic.

Understanding the origins of human cancer

DOE PAGES

Alexandrov, L. B.

2015-12-04

All cancers originate from a single cell that starts to behave abnormally, to divide uncontrollably, and, eventually, to invade adjacent tissues (1). The aberrant behavior of this single cell is due to somatic mutations—changes in the genomic DNA produced by the activity of different mutational processes (1). These various mutational processes include exposure to exogenous or endogenous mutagens, abnormal DNA editing, the incomplete fidelity of DNA polymerases, and failure of DNA repair mechanisms (2). Early studies that sequenced TP53, the most commonly mutated gene in human cancer, provided evidence that mutational processes leave distinct imprints of somatic mutations on themore » genome of a cancer cell (3). For example, C:G>A:T transversions predominate in smoking-associated lung cancer, whereas C:G>T:A transitions occurring mainly at dipyrimidines and CC:GG>TT:AA double-nucleotide substitutions are common in ultraviolet light–associated skin cancers. Moreover, these patterns of mutations matched the ones induced experimentally by tobacco mutagens and ultraviolet light, respectively, the major, known, exogenous carcinogenic influences in these cancer types, and demonstrated that examining patterns of mutations in cancer genomes can yield information about the mutational processes that cause human cancer (4).« less

Ferret-mouse differences in interkinetic nuclear migration and cellular densification in the neocortical ventricular zone.

PubMed

Okamoto, Mayumi; Shinoda, Tomoyasu; Kawaue, Takumi; Nagasaka, Arata; Miyata, Takaki

2014-09-01

The thick outer subventricular zone (OSVZ) is characteristic of the development of human neocortex. How this region originates from the ventricular zone (VZ) is largely unknown. Recently, we showed that over-proliferation-induced acute nuclear densification and thickening of the VZ in neocortical walls of mice, which lack an OSVZ, causes reactive delamination of undifferentiated progenitors and invasion by these cells of basal areas outside the VZ. In this study, we sought to determine how VZ cells behave in non-rodent animals that have an OSVZ. A comparison of mid-embryonic mice and ferrets revealed: (1) the VZ is thicker and more pseudostratified in ferrets. (2) The soma and nuclei of VZ cells were horizontally and apicobasally denser in ferrets. (3) Individual endfeet were also denser on the apical (ventricular) surface in ferrets. (4) In ferrets, apicalward nucleokinesis was less directional, whereas basalward nucleokinesis was more directional; consequently, the nuclear density in the periventricular space (within 16 μm of the apical surface) was smaller in ferrets than in mice, despite the nuclear densification seen basally in ferrets. These results suggest that species-specific differences in nucleokinesis strategies may have evolved in close association with the magnitudes and patterns of nuclear stratification in the VZ. Copyright © 2014 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Comparing Crystals

ERIC Educational Resources Information Center

Sharp, Janet; Hoiberg, Karen; Chumbley, Scott

2003-01-01

This standard lesson on identifying salt and sugar crystals expands into an opportunity for students to develop their observation, questioning, and modeling skills. Although sugar and salt may look similar, students discovered that they looked very different under a magnifying glass and behaved differently when dissolved in water. In addition,…

A comparative study of behavioral and psychological signs and symptoms of dementia in patients with dementia referred to psychogeriatric services in Korea and the United Kingdom.

PubMed

Shah, Ajit; Ellanchenny, Nalini; Suh, Guk-Hee

2004-06-01

There is a paucity of cross-cultural studies of behavioral and psychological symptoms of dementia (BPSD). BPSD were examined in a consecutive series of referrals to a psychogeriatric service in the United Kingdom (U.K.) and in Korea, using the BEHAVE-AD, the Cornell Scale for Depression in Dementia and the Mini-mental State Examination (MMSE). The U.K. service served a well-defined geographical catchment area with a multidisciplinary team and emphasis on home assessments. The Korean service was a nationwide service with limited community resources. The correlates of individual BPSD in each country and the differences between the two countries were examined. Koreans were younger, were more likely to be married, less likely to be single, had a greater number of people in their household and were more likely to live in their own homes than the U.K. sample. Koreans were more likely to be referred by general psychiatrists or family members, and the U.K. sample was more likely to be referred by general practitioners. Koreans were more likely to have Alzheimer's disease and the U.K. sample to have vascular dementia. The Korean sample had a lower MMSE score than the U.K. sample. In both countries, the total BEHAVE-AD score and most subscale scores were negatively correlated with the MMSE score. The total BEHAVE-AD score and all subscale scores were higher in the Korean sample than in the U.K. sample. The prevalence of all BPSD measured with the BEHAVE-AD were higher in the Korean sample (except aggressivity). These differences may be explained by differing interpretation and administration of the measurement instruments, models of service delivery, availability of primary and secondary care services, health seeking behavior of patients and families, cultural influences, and knowledge, expectations and recognition of BPSD by professionals in primary and secondary care. However, despite this, there was possible evidence of genuine differences worthy of further cross-cultural population-based epidemiological study of BPSD between these two countries.

Creep Function of a Single Living Cell

PubMed Central

Desprat, Nicolas; Richert, Alain; Simeon, Jacqueline; Asnacios, Atef

2005-01-01

We used a novel uniaxial stretching rheometer to measure the creep function J(t) of an isolated living cell. We show, for the first time at the scale of the whole cell, that J(t) behaves as a power-law J(t) = Atα. For N = 43 mice myoblasts (C2-7), we find α = 0.24 ± 0.01 and A = (2.4 ± 0.3) 10−3 Pa−1 s−α. Using Laplace Transforms, we compare A and α to the parameters G0 and β of the complex modulus G*(ω) = G0ωβ measured by other authors using magnetic twisting cytometry and atomic force microscopy. Excellent agreement between A and G0 on the one hand, and between α and β on the other hand, indicated that the power-law is an intrinsic feature of cell mechanics and not the signature of a particular technique. Moreover, the agreement between measurements at very different size scales, going from a few tens of nanometers to the scale of the whole cell, suggests that self-similarity could be a central feature of cell mechanical structure. Finally, we show that the power-law behavior could explain previous results first interpreted as instantaneous elasticity. Thus, we think that the living cell must definitely be thought of as a material with a large and continuous distribution of relaxation time constants which cannot be described by models with a finite number of springs and dash-pots. PMID:15596508

Creep function of a single living cell.

PubMed

Desprat, Nicolas; Richert, Alain; Simeon, Jacqueline; Asnacios, Atef

2005-03-01

We used a novel uniaxial stretching rheometer to measure the creep function J(t) of an isolated living cell. We show, for the first time at the scale of the whole cell, that J(t) behaves as a power-law J(t) = At(alpha). For N = 43 mice myoblasts (C2-7), we find alpha = 0.24 +/- 0.01 and A = (2.4 +/- 0.3) 10(-3) Pa(-1) s(-alpha). Using Laplace Transforms, we compare A and alpha to the parameters G(0) and beta of the complex modulus G*(omega) = G(0)omega(beta) measured by other authors using magnetic twisting cytometry and atomic force microscopy. Excellent agreement between A and G(0) on the one hand, and between alpha and beta on the other hand, indicated that the power-law is an intrinsic feature of cell mechanics and not the signature of a particular technique. Moreover, the agreement between measurements at very different size scales, going from a few tens of nanometers to the scale of the whole cell, suggests that self-similarity could be a central feature of cell mechanical structure. Finally, we show that the power-law behavior could explain previous results first interpreted as instantaneous elasticity. Thus, we think that the living cell must definitely be thought of as a material with a large and continuous distribution of relaxation time constants which cannot be described by models with a finite number of springs and dash-pots.

Monocarboxylate transporters in the brain and in cancer.

PubMed

Pérez-Escuredo, Jhudit; Van Hée, Vincent F; Sboarina, Martina; Falces, Jorge; Payen, Valéry L; Pellerin, Luc; Sonveaux, Pierre

2016-10-01

Monocarboxylate transporters (MCTs) constitute a family of 14 members among which MCT1-4 facilitate the passive transport of monocarboxylates such as lactate, pyruvate and ketone bodies together with protons across cell membranes. Their anchorage and activity at the plasma membrane requires interaction with chaperon protein such as basigin/CD147 and embigin/gp70. MCT1-4 are expressed in different tissues where they play important roles in physiological and pathological processes. This review focuses on the brain and on cancer. In the brain, MCTs control the delivery of lactate, produced by astrocytes, to neurons, where it is used as an oxidative fuel. Consequently, MCT dysfunctions are associated with pathologies of the central nervous system encompassing neurodegeneration and cognitive defects, epilepsy and metabolic disorders. In tumors, MCTs control the exchange of lactate and other monocarboxylates between glycolytic and oxidative cancer cells, between stromal and cancer cells and between glycolytic cells and endothelial cells. Lactate is not only a metabolic waste for glycolytic cells and a metabolic fuel for oxidative cells, but it also behaves as a signaling agent that promotes angiogenesis and as an immunosuppressive metabolite. Because MCTs gate the activities of lactate, drugs targeting these transporters have been developed that could constitute new anticancer treatments. This article is part of a Special Issue entitled: Mitochondrial Channels edited by Pierre Sonveaux, Pierre Maechler and Jean-Claude Martinou. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Rapid cell-free forward engineering of novel genetic ring oscillators

PubMed Central

Niederholtmeyer, Henrike; Sun, Zachary Z; Hori, Yutaka; Yeung, Enoch; Verpoorte, Amanda; Murray, Richard M; Maerkl, Sebastian J

2015-01-01

While complex dynamic biological networks control gene expression in all living organisms, the forward engineering of comparable synthetic networks remains challenging. The current paradigm of characterizing synthetic networks in cells results in lengthy design-build-test cycles, minimal data collection, and poor quantitative characterization. Cell-free systems are appealing alternative environments, but it remains questionable whether biological networks behave similarly in cell-free systems and in cells. We characterized in a cell-free system the ‘repressilator’, a three-node synthetic oscillator. We then engineered novel three, four, and five-gene ring architectures, from characterization of circuit components to rapid analysis of complete networks. When implemented in cells, our novel 3-node networks produced population-wide oscillations and 95% of 5-node oscillator cells oscillated for up to 72 hr. Oscillation periods in cells matched the cell-free system results for all networks tested. An alternate forward engineering paradigm using cell-free systems can thus accurately capture cellular behavior. DOI: http://dx.doi.org/10.7554/eLife.09771.001 PMID:26430766

A Novel c.125 T>G (p.Val42Gly) Mutation in The Human INS Gene Leads to Neonatal Diabetes Mellitus via a Decrease in Insulin Synthesis.

PubMed

Sun, Fei; Du, Wenhua; Ma, Junhua; Gu, Mingjun; Wang, Jingnan; Zhu, Hongling; Song, Huaidong; Gao, Guanqi

2018-06-11

Neonatal diabetes mellitus is likely caused by monogenic mutations, several of which have been identified. INS mutations have a broad spectrum of clinical presentations, ranging from severe neonatal onset to mild adult onset, which suggests that the products of different mutant INS alleles behave differently and utilize distinct mechanisms to induce diabetes. In this study, a neonatal diabetes mellitus patient's INS gene was sequenced, and functional experiments were conducted. The neonatal diabetes mellitus patient's genomic DNA was extracted, and the patient's KCNJ11, ABCC8, and INS genes were sequenced. A novel mutation was identified in INS, and the open reading frame of this human mutant INS gene was inserted into the pMSCV-PIG plasmid. The constructed pMSCV-PIG plasmid was combined with VSV-g and Gag-pol and transfected into 293T cells to package the lentivirus. To stably overexpress the mutant gene, INS-1 cells were infected with the virus. The levels of insulin in the cell culture medium and cytoplasm were determined by ELISA and immunocytochemistry, respectively. A heterozygous mutation, c.125T>G (p. Val42Gly), was identified in a neonatal diabetes mellitus patient's INS gene. The human mutant INS open reading frame was overexpressed in INS-1 cells, and the mutant insulin was undetectable in the cell culture medium and cytoplasm. The novel heterozygous activating mutation c.125 T>G (p.Val42Gly) impairs the synthesis of insulin by pancreatic beta cells, resulting in diabetes. © Georg Thieme Verlag KG Stuttgart · New York.

Leadership Behaviors of School Administrators: Do Men and Women Differ?

ERIC Educational Resources Information Center

Johnson, Shirley; Busch, Steve; Slate, John R.

2008-01-01

In this study, the reasons why men and women behave differently in leadership roles in schools were investigated because of recent research on the indirect nature of the school principal's impact on learning and on gender differences in leadership behaviors. Practicing principals (109 males, 172 females) from two Southwestern states were surveyed…

Novice and Expert Physical Education Teachers: They May Think and Decide Differently...But Do They Behave Differently?

ERIC Educational Resources Information Center

van der Mars, Hans; And Others

The purpose of this study was to determine whether varying levels of expertise would produce differences in selected indicators of effective teaching performance. Eighteen elementary physical education teachers were grouped based on stages of pedagogical expertise development as suggested by Berliner (1988). The three groups included…

Solubilization of active opiate receptors.

PubMed Central

Simonds, W F; Koski, G; Streaty, R A; Hjelmeland, L M; Klee, W A

1980-01-01

Receptors that reversibly bind opiates and opioid peptides have been solubilized from brain and neuroblastoma-glioma hybrid cell NG108-15 membranes. Active receptors are specifically solubilized with a new type of detergent 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate, which is a zwitterionic derivative of cholic acid. The solubilized receptor complexes behave as large molecules with a Stokes radius of 70 A and contain protein as an essential constituent. PMID:6254034

Smurf2 Regulates DNA Repair and Packaging to Prevent Tumors | Center for Cancer Research

Cancer.gov

The blueprint for all of a cell’s functions is written in the genetic code of DNA sequences as well as in the landscape of DNA and histone modifications. DNA is wrapped around histones to package it into chromatin, which is stored in the nucleus. It is important to maintain the integrity of the chromatin structure to ensure that the cell continues to behave appropriately.

Bioavailability of Oral Pyridostigmine and Inhibition of Red Blood Cell Acetylcholinesterase by Oral and Intravenous Pyridostigmine

DTIC Science & Technology

1989-03-22

Case Report Forms 134 1. INTRODUCTION Studies in animals have indicated that carbamate acetyl- cholinesterase inhibitors have protective effects...effect compartment with a rate constant KE0. Furthermore, it was assumed that pyridostigmine behaves as a standard competitive inhibitor of the...really reversible, at least in the classical sense of almost instantaneous association and dissociation of eruzyme with inhibitor . After carbamylation

An open source, wireless capable miniature microscope system

NASA Astrophysics Data System (ADS)

Liberti, William A., III; Perkins, L. Nathan; Leman, Daniel P.; Gardner, Timothy J.

2017-08-01

Objective. Fluorescence imaging through head-mounted microscopes in freely behaving animals is becoming a standard method to study neural circuit function. Flexible, open-source designs are needed to spur evolution of the method. Approach. We describe a miniature microscope for single-photon fluorescence imaging in freely behaving animals. The device is made from 3D printed parts and off-the-shelf components. These microscopes weigh less than 1.8 g, can be configured to image a variety of fluorophores, and can be used wirelessly or in conjunction with active commutators. Microscope control software, based in Swift for macOS, provides low-latency image processing capabilities for closed-loop, or BMI, experiments. Main results. Miniature microscopes were deployed in the songbird premotor region HVC (used as a proper name), in singing zebra finches. Individual neurons yield temporally precise patterns of calcium activity that are consistent over repeated renditions of song. Several cells were tracked over timescales of weeks and months, providing an opportunity to study learning related changes in HVC. Significance. 3D printed miniature microscopes, composed completely of consumer grade components, are a cost-effective, modular option for head-mounting imaging. These easily constructed and customizable tools provide access to cell-type specific neural ensembles over timescales of weeks.

The binding of calcium ions by erythrocytes and `ghost'-cell membranes

PubMed Central

Long, C.; Mouat, Barbara

1971-01-01

1. Washed human erythrocytes, suspended in iso-osmotic sucrose containing 2.5mm-calcium chloride, bind about 400μg-atoms of calcium/litre of packed cells. Sucrose may be replaced by other sugars. 2. Partial replacement of sucrose by iso-osmotic potassium chloride diminishes the uptake of calcium, 50% inhibition occurring at about 50mm-potassium chloride. 3. Other univalent cations behave like potassium, whereas bivalent cations are much more inhibitory. The tervalent cations, yttrium and lanthanum, however, are the most effective inhibitors of calcium uptake. 4. An approximate correlation exists between the calcium uptake and the sialic acid content of erythrocytes of various species and of human erythrocytes that have been partially depleted of sialic acid by treatment with neuraminidase. However, even after complete removal of sialic acid, human erythrocytes still bind about 140μg-atoms of calcium/litre of packed cells. 5. A Scatchard (1949) plot of calcium uptake at various Ca2+ concentrations in the suspending media shows the presence of three different binding sites on the external surface of the human erythrocyte membrane. 6. Erythrocyte `ghost' cells, the membranes of which appear to be permeable to Ca2+ ions, can bind about 1000μg-atoms of calcium per `ghost'-cell equivalent of 1 litre of packed erythrocytes. This indicates that there are also binding sites for calcium on the internal surface of the erythrocyte membrane. PMID:5124387

Effect of ambient light on monoclonal antibody product quality during small-scale mammalian cell culture process in clear glass bioreactors.

PubMed

Mallaney, Mary; Wang, Szu-Han; Sreedhara, Alavattam

2014-01-01

During a small-scale cell culture process producing a monoclonal antibody, a larger than expected difference was observed in the charge variants profile of the harvested cell culture fluid (HCCF) between the 2 L and larger scales (e.g., 400 L and 12 kL). Small-scale studies performed at the 2 L scale consistently showed an increase in acidic species when compared with the material made at larger scale. Since the 2 L bioreactors were made of clear transparent glass while the larger scale reactors are made of stainless steel, the effect of ambient laboratory light on cell culture process in 2 L bioreactors as well as handling the HCCF was carefully evaluated. Photoreactions in the 2 L glass bioreactors including light mediated increase in acidic variants in HCCF and formulation buffers were identified and carefully analyzed. While the acidic variants comprised of a mixture of sialylated, reduced disulfide, crosslinked (nonreducible), glycated, and deamidated forms, an increase in the nonreducible forms, deamidation and Met oxidation was predominantly observed under light stress. The monoclonal antibody produced in glass bioreactors that were protected from light behaved similar to the one produced in the larger scale. Our data clearly indicate that care should be taken when glass bioreactors are used in cell culture studies during monoclonal antibody production. © 2014 American Institute of Chemical Engineers.

Modeling the Treatment of Glioblastoma Multiforme and Cancer Stem Cells with Ordinary Differential Equations.

PubMed

Abernathy, Kristen; Burke, Jeremy

2016-01-01

Despite improvements in cancer therapy and treatments, tumor recurrence is a common event in cancer patients. One explanation of recurrence is that cancer therapy focuses on treatment of tumor cells and does not eradicate cancer stem cells (CSCs). CSCs are postulated to behave similar to normal stem cells in that their role is to maintain homeostasis. That is, when the population of tumor cells is reduced or depleted by treatment, CSCs will repopulate the tumor, causing recurrence. In this paper, we study the application of the CSC Hypothesis to the treatment of glioblastoma multiforme by immunotherapy. We extend the work of Kogan et al. (2008) to incorporate the dynamics of CSCs, prove the existence of a recurrence state, and provide an analysis of possible cancerous states and their dependence on treatment levels.

Effect of growth conditions on production of rhamnose-containing cell wall and capsular polysaccharides by strains of Lactobacillus casei subsp. rhamnosus.

PubMed

Wicken, A J; Ayres, A; Campbell, L K; Knox, K W

1983-01-01

Strains of Lactobacillus casei subsp. rhamnosus possessing two cell wall polysaccharides, a hexosamine-containing H-polysaccharide and a rhamnose-containing R-polysaccharide, were examined for the effect of growth conditions on the production of these two components. In strain NCTC 6375, R- and H-polysaccharides accounted for an estimated 44 and 20%, respectively, of the cell wall for organisms grown in batch culture with glucose as the carbohydrate source. Growth on fructose-containing media reduced the amount of R-polysaccharide by approximately 50% without affecting the amount of H-polysaccharide. Subculture of fructose-grown organisms in glucose restored the original proportions of the two polysaccharides. Galactose- and sucrose-grown cells behaved similarly to glucose-grown cells with respect to polysaccharide production, whereas growth in rhamnose or ribose showed values close to those for fructose-grown cells. Continuous culture of strain NCTC 6375 for more than 100 generations showed a gradual and irreversible reduction of the R-polysaccharide to less than 5% of the cell wall and an increase of the H-polysaccharide to 40% of the cell wall. Other type culture strains of L. casei subsp. rhamnosus, NCIB 7473 and ATCC 7469, behaved similarly in batch and continuous culture. In contrast, strains of L. casei subsp. rhamnosus isolated at the Institute of Dental Research showed phenotypic stability with respect to the relative proportions of R- and H-polysaccharides in both batch and continuous culture. Changes in polysaccharide composition of type culture strains were also mirrored in changes in the immunogenicity of the two components and resistance to the rate of enzymic lysis of whole organisms. For L. casei subsp. rhamnosus strain NCTC 10302 the R-polysaccharide is present entirely as capsular material. The amount of R-polysaccharide produced was also markedly dependent on the carbohydrate component of the medium in batch culture and both dilution rate and nature of the limiting carbohydrate in continuous culture, varying over a 10-fold range, whereas the cell wall H-polysaccharide remained constant.

Effect of growth conditions on production of rhamnose-containing cell wall and capsular polysaccharides by strains of Lactobacillus casei subsp. rhamnosus.

PubMed Central

Wicken, A J; Ayres, A; Campbell, L K; Knox, K W

1983-01-01

Strains of Lactobacillus casei subsp. rhamnosus possessing two cell wall polysaccharides, a hexosamine-containing H-polysaccharide and a rhamnose-containing R-polysaccharide, were examined for the effect of growth conditions on the production of these two components. In strain NCTC 6375, R- and H-polysaccharides accounted for an estimated 44 and 20%, respectively, of the cell wall for organisms grown in batch culture with glucose as the carbohydrate source. Growth on fructose-containing media reduced the amount of R-polysaccharide by approximately 50% without affecting the amount of H-polysaccharide. Subculture of fructose-grown organisms in glucose restored the original proportions of the two polysaccharides. Galactose- and sucrose-grown cells behaved similarly to glucose-grown cells with respect to polysaccharide production, whereas growth in rhamnose or ribose showed values close to those for fructose-grown cells. Continuous culture of strain NCTC 6375 for more than 100 generations showed a gradual and irreversible reduction of the R-polysaccharide to less than 5% of the cell wall and an increase of the H-polysaccharide to 40% of the cell wall. Other type culture strains of L. casei subsp. rhamnosus, NCIB 7473 and ATCC 7469, behaved similarly in batch and continuous culture. In contrast, strains of L. casei subsp. rhamnosus isolated at the Institute of Dental Research showed phenotypic stability with respect to the relative proportions of R- and H-polysaccharides in both batch and continuous culture. Changes in polysaccharide composition of type culture strains were also mirrored in changes in the immunogenicity of the two components and resistance to the rate of enzymic lysis of whole organisms. For L. casei subsp. rhamnosus strain NCTC 10302 the R-polysaccharide is present entirely as capsular material. The amount of R-polysaccharide produced was also markedly dependent on the carbohydrate component of the medium in batch culture and both dilution rate and nature of the limiting carbohydrate in continuous culture, varying over a 10-fold range, whereas the cell wall H-polysaccharide remained constant. PMID:6401290

Relationship between unit cell type and porosity and the fatigue behavior of selective laser melted meta-biomaterials.

PubMed

Amin Yavari, S; Ahmadi, S M; Wauthle, R; Pouran, B; Schrooten, J; Weinans, H; Zadpoor, A A

2015-03-01

Meta-materials are structures when their small-scale properties are considered, but behave as materials when their homogenized macroscopic properties are studied. There is an intimate relationship between the design of the small-scale structure and the homogenized properties of such materials. In this article, we studied that relationship for meta-biomaterials that are aimed for biomedical applications, otherwise known as meta-biomaterials. Selective laser melted porous titanium (Ti6Al4V ELI) structures were manufactured based on three different types of repeating unit cells, namely cube, diamond, and truncated cuboctahedron, and with different porosities. The morphological features, static mechanical properties, and fatigue behavior of the porous biomaterials were studied with a focus on their fatigue behavior. It was observed that, in addition to static mechanical properties, the fatigue properties of the porous biomaterials are highly dependent on the type of unit cell as well as on porosity. None of the porous structures based on the cube unit cell failed after 10(6) loading cycles even when the applied stress reached 80% of their yield strengths. For both other unit cells, higher porosities resulted in shorter fatigue lives for the same level of applied stress. When normalized with respect to their yield stresses, the S-N data points of structures with different porosities very well (R(2)>0.8) conformed to one single power law specific to the type of the unit cell. For the same level of normalized applied stress, the truncated cuboctahedron unit cell resulted in a longer fatigue life as compared to the diamond unit cell. In a similar comparison, the fatigue lives of the porous structures based on both truncated cuboctahedron and diamond unit cells were longer than that of the porous structures based on the rhombic dodecahedron unit cell (determined in a previous study). The data presented in this study could serve as a basis for design of porous biomaterials as well as for corroboration of relevant analytical and computational models. Copyright © 2014 Elsevier Ltd. All rights reserved.

Effects of Insecticidal Ketones Present in Mint Plants on GABAA Receptor from Mammalian Neurons

PubMed Central

Sánchez-Borzone, Mariela Eugenia; Marin, Leticia Delgado; García, Daniel Asmed

2017-01-01

Background: The genus Mentha, an important member of the Lamiaceae family, is represented by many species commonly known as mint. The insecticidal activity of Mentha oil and its main components has been tested and established against various insects/pests. Among these, the ketone monoterpenes that are most common in different Mentha species demonstrated insect toxicity, with pulegone being the most active, followed by carvone and menthone. Considering that the GABAA receptor (GABAA-R) is one of the main insecticide targets on neurons, and that pulegone would modulate the insect GABA system, it may be expected that the insecticidal properties of Mentha ketones are mediated by their interaction with this receptor. Objective: In order to discern the pharmacological actions of these products when used as insecticides on mammalian organisms, we evaluated the pharmacologic activity of ketones, commonly present in Mentha plants, on native GABAA-R from rats. Materials and Methods: Determination of ketones effects on allosterically enhanced benzodiazepine binding, using primary cultures of cortical neurons, which express functional receptors and MTT assay to evaluate their cell toxicity. Results: Our results seem to indicate that ketone components of Mentha, with proven repellent or insecticide activity, were able to behave as GABAA-R negative allosteric modulators in murine cells and consequently could exhibit convulsant activity in mammalians. Only pulegone at the highest assayed concentration (2 mM) showed a significant reduction in cell viability after exposure for 24 hr. Conclusion: The present results strongly suggest that the ketone components of Mentha are able to exhibit convulsant activity in mammalian organisms, but functional assays and in vivo experiments would be necessary to corroborate this proposed action. SUMMARY The pharmacological activity of insecticide ketones, commonly present in Mentha plants, was evaluated on native GABAA receptor from mammalian neurons.All studied compounds: pulegone, menthone and dihydrocarvone, were able to behave as negative allosteric modulators and could exhibit convulsant activity in mammalian organisms.Citotoxicity assays demonstrated that only pulegone affected the cell viability. Abbreviations used: GABA: gamma aminobutyric acid, GABAA-R: GABAA receptor, MTT: 1-(4,5-dimethylthiazol-2-yl)-3,5-diphenylformazam, DMEM: Dulbecco's modified minimum essential mèdium, [3H]TBOB: [3H] t-Butylbicycloorthobenzoate PMID:28216893

Roles of different IRES-dependent FGF2 isoforms in the acquisition of the major aggressive features of human metastatic melanoma.

PubMed

Andreucci, Elena; Bianchini, Francesca; Biagioni, Alessio; Del Rosso, Mario; Papucci, Laura; Schiavone, Nicola; Magnelli, Lucia

2017-01-01

Fibroblast growth factor 2 (FGF2) is involved in many physiological and pathological processes. Fgf2 deregulation contributes to the acquisition of malignant features of melanoma and other cancers. FGF2 is an alternative translation product expressed as five isoforms, a low-molecular-weight (18 KDa) and four high-molecular-weight (22, 22.5, 24, 34 KDa) isoforms, with different subcellular distributions. An internal ribosomal entry site (IRES) in its mRNA controls the translation of all the isoforms with the exception for the cap-dependent 34 KDa. The 18-KDa isoform has been extensively studied, while very few is known about the roles of high molecular weight isoforms. FGF2 is known to promote melanoma development and progression. To disclose the differential contribution of FGF2 isoforms in melanoma, we forced the expression of IRES-dependent low-molecular-weight (LMW, 18 KDa) and high-molecular-weight (HMW, 22, 22.5, 24 KDa) isoforms in a human metastatic melanoma cell line. This comparative study highlights that, while LMW isoform confers stem-like features to melanoma cells and promotes angiogenesis, HMW isoforms induce higher migratory ability and contribute to tumor perfusion by promoting vasculogenic mimicry (VM) when endothelial cell-driven angiogenesis is lacking. To conclude, FGF2 isoforms mainly behave in specific, antithetical manners, but can cooperate in different steps of tumor progression, providing melanoma cells with major malignant features. FGF2 is an alternative translation product expressed as different isoforms termed LMW and HMW. FGF2 is involved in melanoma development and progression. HMW FGF2 isoforms enhance in vitro motility of melanoma cells. LMW FGF2 confers stem-like features and increases in vivo metastasization. LMW FGF2 promotes angiogenesis while HMW FGF2 induces vasculogenic mimicry.

Visual interaction in recently admitted and chronic long-stay schizophrenic patients.

PubMed

Rutter, D R

1976-09-01

Several reports have suggested that schizophrenic patients engage in very little Looking and eye-contact. However, previous work, much of it methodologically unsatisfactory, has been based almost always on the clinical psychiatric interview, with the result that several important questions remain unanswered. In particular, we do not know how schizophrenic patients behave in free conversation, how their behaviour with another patient may differ from their behaviour with a psychiatrically normal partner, nor even whether they show individual consistency across encounters. The first study was designed to examine these questions, by observing recently admitted schizophrenic patients in two free dyadic conversations, one with a schizophrenic partner and one with a psychiatrically normal partner, and comparing them with three control groups: depressive patients; patients suffering from neurotic or personality disorders; and psychiatrically normal chest patients. The second study went on to test whether the early descriptions of gross abnormality may be more appropriate to chronic long-stay patients than to recently admitted patients, and the design consisted of a comparison between the two groups. The first study revealed a quite unexpected pattern of results. Consistently across their two encounters, schizophrenic subjects behaved similarly for the most part to all three control groups, normal and abnormal alike. Moreover, the few differences which did emerge conflicted sharply with previous findings, including the writer's, and were no more marked in patient-patient than patient-normal encounters. The second study revealed no differences between chronic long-stay and recently admitted schizophrenic patients. It is suggested that the differences in findings between the present two studies and previous reports are most likely to be attributable to differences in verbal content: schizophrenic patients show abnormalities of visual interaction when talking about personal matters, but behave quite normally when the topic is not of immediate personal relevance.

ITO/InP solar cells: A comparison of devices fabricated by ion beam and RF sputtering of the ITO

NASA Technical Reports Server (NTRS)

Coutts, T. J.

1987-01-01

This work was performed with the view of elucidating the behavior of indium tin oxide/indium phosphide (ITO/InP) solar cells prepared by RF and ion beam sputtering. It was found that using RF sputter deposition of the ITO always leads to more efficient devices than ion beam sputter deposition. An important aspect of the former technique is the exposure of the single crystal p-InP substrates to a very low plasma power prior to deposition. Substrates treated in this manner have also been used for ion beam deposition of ITO. In this case the cells behave very similarly to the RF deposited cells, thus suggesting that the lower power plasma exposure (LPPE) is the crucial process step.

P2X receptors, sensory neurons and pain.

PubMed

Bele, Tanja; Fabbretti, Elsa

2015-01-01

Pain represents a very large social and clinical problem since the current treatment provides insufficient pain relief. Plasticity of pain receptors together with sensitisation of sensory neurons, and the role of soluble mediators released from non-neuronal cells render difficult to understand the spatial and temporal scale of pain development, neuronal responses and disease progression. In pathological conditions, ATP is one of the most powerful mediators that activates P2X receptors that behave as sensitive ATP-detectors, such as neuronal P2X3 receptor subtypes and P2X4 and P2X7 receptors expressed on non-neuronal cells. Dissecting the molecular mechanisms occurring in sensory neurons and in accessory cells allows to design appropriate tissue- and cell- targeted approaches to treat chronic pain.

Polymeric Nanoelectrodes for Investigating Cellular Adhesion

NASA Astrophysics Data System (ADS)

Thapa, Prem; Paneru, Govind; Flanders, Bret

2011-03-01

Polyethylene dioxythiophene nano-filaments were grown on lithographic electrode arrays by the recently developed directed electrochemical nanowire assembly technique. These filaments are firmly attached to the electrode but are not attached to the glass substrate. Hence, they behave like cantilevered rods (with one free end). Individual cells of the slime mold Dictystolium discoideum initiate contact by extending pseudopods to the nanoelectrodes when cultured on the electrode arrays. Scanning electron micrographs of the interfaces show the contact area to be of the order of 0.1 μ m 2 . Confocal images reveal the focal adhesions in the cell-electrode contact region. Deflection of the nanoelectrode by an individual cell can be used to measure the force exerted by the cell. Recent results on this innovative force sensing approach will be discussed. NSF.

What kind of crisis for capitalism?

NASA Astrophysics Data System (ADS)

1982-09-01

This week's meeting of the International Monetary Fund at Toronto will avoid an immediate crisis. But more international credit will not allow rich and poor to behave as if they live on different planets.

Correlation Scales of the Turbulent Cascade at 1 au

NASA Astrophysics Data System (ADS)

Smith, Charles W.; Vasquez, Bernard J.; Coburn, Jesse T.; Forman, Miriam A.; Stawarz, Julia E.

2018-05-01

We examine correlation functions of the mixed, third-order expressions that, when ensemble-averaged, describe the cascade of energy in the inertial range of magnetohydrodynamic turbulence. Unlike the correlation function of primitive variables such as the magnetic field, solar wind velocity, temperature, and density, the third-order expressions decorrelate at a scale that is approximately 20% of the lag. This suggests the nonlinear dynamics decorrelate in less than one wavelength. Therefore, each scale can behave differently from one wavelength to the next. In the same manner, different scales within the inertial range can behave independently at any given time or location. With such a cascade that can be strongly patchy and highly variable, it is often possible to obtain negative cascade rates for short periods of time, as reported earlier for individual samples of data.

Addressing gaps in the maturity of judgment literature: age differences and delinquency.

PubMed

Modecki, Kathryn Lynn

2008-02-01

Over the past decade, a majority of states have legislated to expand their capacity to try adolescents as adults [Griffin (2003). Trying and sentencing juveniles as adults: An analysis of state transfer and blended sentencing laws. Pittsburgh, PA: National Center for Juvenile Justice]. In response, researchers have investigated factors that may affect adolescent culpability [Steinberg and Scott (Am Psychol 58(12):1009-1018, 2003)]. Research on immature judgment posits that psychosocial influences on adolescent decision processes results in reduced criminal responsibility [Cauffman and Steinberg (Behav Sci Law 18(6):741-760, 2000); Scott, Reppucci, and Woolard (Law Hum Behav 19(3):221-244, 1995); Steinberg and Cauffman (Law Hum Behav 20(3):249-272, 1996)]. The current study utilizes hypothetical vignettes and standardized measures of maturity of judgment (responsibility, temperance, and perspective) to examine gaps in previous maturity of judgment findings (Cauffman and Steinberg 2000). This work suggests that adolescents (ages 14-17) display less responsibility and perspective relative to college students (ages 18-21), young-adults (ages 22-27), and adults (ages 28-40). Further, this research finds no maturity of judgment differences between delinquent and non-delinquent youth, but does find significant maturity of judgment differences between high and low delinquency male youth. Finally, results show that maturity of judgment predicts self-reported delinquency beyond the contributions of age, gender, race, education level, SES, and antisocial decision making. Implications for the juvenile justice system are discussed.

Rheological behaviour of a suspension of microswimmers varying in motor characteristics

NASA Astrophysics Data System (ADS)

Tirumkudulu, Mahesh; Karmakar, Richa; Gulvady, Ranjit; Venkatesh, K. V.

2013-11-01

A suspension of motile cells exhibits complex rheological properties due to their collective motion. We measure the shear viscosity of suspensions of Escherichia coli strains varying in motor characteristics such as duration of run and tumble. At low cell densities, all strains irrespective of their motor characteristics exhibiting a linear increase in viscosity with cell density suggesting that the cells behave as a suspension of rods with an effective aspect ratio set by the motor characteristics of the bacteria. As the cell density is increased beyond a critical value, the viscosity drops sharply signaling the presence of strongly coordinated motion among bacteria. The critical density depends not only on the magnitude of shear but also the motor characteristics of individual cells. High shear rate disrupts the coordinated motion reducing its behavior, once again, to a suspension of inactive particles. The authors acknowldege financial support from Department of Science and Technology, India.

Motor characteristics determine the rheological behavior of a suspension of microswimmers

NASA Astrophysics Data System (ADS)

Karmakar, Richa; Gulvady, Ranjit; Tirumkudulu, Mahesh S.; Venkatesh, K. V.

2014-07-01

A suspension of motile cells exhibits complex rheological properties due to their collective motion. We measure the shear viscosity of a suspension of Escherichia coli strains varying in motor characteristics such as duration of run and tumble. At low cell densities, all strains irrespective of their motor characteristics exhibit a linear increase in viscosity with cell density suggesting that the cells behave as a suspension of passive rods with an effective aspect ratio set by the motor characteristics of the bacteria. As the cell density is increased beyond a critical value, the viscosity drops sharply signaling the presence of strongly coordinated motion among bacteria. The critical density depends not only on the magnitude of shear but also the motor characteristics of individual cells. High shear rate disrupts the coordinated motion reducing its behavior, once again, to a suspension of inactive particles.

Vitronectin--master controller or micromanager?

PubMed

Leavesley, David I; Kashyap, Abhishek S; Croll, Tristan; Sivaramakrishnan, Manaswini; Shokoohmand, Ali; Hollier, Brett G; Upton, Zee

2013-10-01

The concept that the mammalian glycoprotein vitronectin acts as a biological 'glue' and key controller of mammalian tissue repair and remodelling activity is emerging from nearly 50 years of experimental in vitro and in vivo data. Unexpectedly, the vitronectin-knockout (VN-KO) mouse was found to be viable and to have largely normal phenotype. However, diligent observation revealed that the VN-KO animal exhibits delayed coagulation and poor wound healing. This is interpreted to indicate that VN occupies a role in the earliest events of thrombogenesis and tissue repair. VN is the foundation upon which the thrombus grows in an organised structure. In addition to sealing the wound, the thrombus also serves to protect the underlying tissue from oxidation, is a reservoir of mitogens and tissue repair mediators, and provides a provisional scaffold for the repairing tissue. In the absence of VN (e.g., VN-KO animal), this cascade is disrupted before it begins. A wide variety of biologically active species associate with VN. Although initial studies were focused on mitogens, other classes of bioactives (e.g., glycosaminoglycans and metalloproteinases) are now also known to specifically interact with VN. Although some interactions are transient, others are long-lived and often result in multi-protein complexes. Multi-protein complexes provide several advantages: prolonging molecular interactions, sustaining local concentrations, facilitating co-stimulation of cell surface receptors and thereby enhancing cellular/biological responses. We contend that these, or equivalent, multi-protein complexes facilitate VN polyfunctionality in vivo. It is also likely that many of the species demonstrated to associate with VN in vitro, also associate with VN in vivo in similar multi-protein complexes. Thus, the predominant biological function of VN is that of a master controller of the extracellular environment; informing, and possibly instructing cells 'where' to behave, 'when' to behave and 'how' to behave (i.e., appropriately for the current circumstance). © 2013 International Union of Biochemistry and Molecular Biology.

Analysis of inflammasomes and antiviral sensing components reveals decreased expression of NLRX1 in HIV-positive patients assuming efficient antiretroviral therapy.

PubMed

Nasi, Milena; De Biasi, Sara; Bianchini, Elena; Digaetano, Margherita; Pinti, Marcello; Gibellini, Lara; Pecorini, Simone; Carnevale, Gianluca; Guaraldi, Giovanni; Borghi, Vanni; Mussini, Cristina; Cossarizza, Andrea

2015-09-24

Few studies have investigated the importance of different components of the inflammasome system and of innate mitochondrial sensing (IMS) pathways in HIV infection and its treatment. We analysed the expression of several components of the inflammasome and of the IMS in HIV-positive patients taking successful combination antiretroviral therapy (cART). We enrolled 20 HIV-positive patients under cART, who achieved viral suppression since at least 10 months and 20 age and sex-matched healthy donors. By RT-PCR, using peripheral blood mononuclear cells (PBMCs), we quantified the mRNA expression of 16 genes involved in inflammasome activation and regulation (AIM2, NAIP, PYCARD, CASP1, CASP5, NLRP6, NLRP1, NLRP3, TXNIP, BCL2, NLRC4, PANX1, P2RX7, IL-18, IL-1β, SUGT1) and eight genes involved in IMS (MFN2, MFN1, cGAS, RIG-I, MAVS, NLRX1, RAB32, STING). Compared with controls, HIV-positive patients showed significantly lower mRNA levels of the mitochondrial protein NLRX1, which plays a key role in regulating apoptotic cell death; main PBMC subpopulations behave in a similar manner. No differences were observed in the expression of inflammasome components, which however showed complex correlations. The decreased level of NLRX1 in HIV infection could suggest that the virus is able to downregulate mechanisms linked to triggering of cell death in several immune cell types. The fact that HIV-positive patients did not show altered expression of inflammasome components, nor of most genes involved in IMS, suggests that the infection and/or the chronic immune activation does not influence the transcriptional machinery of innate mechanisms able to trigger inflammation at different levels.

Histomorphometric analysis of nuclear and cellular volumetric alterations in oral lichen planus, lichenoid lesions and normal oral mucosa using image analysis software.

PubMed

Venkatesiah, Sowmya S; Kale, Alka D; Hallikeremath, Seema R; Kotrashetti, Vijayalakshmi S

2013-01-01

Lichen planus is a chronic inflammatory mucocutaneous disease that clinically and histologically resembles lichenoid lesions, although the latter has a different etiology. Though criteria have been suggested for differentiating oral lichen planus from lichenoid lesions, confusion still prevails. To study the cellular and nuclear volumetric features in the epithelium of normal mucosa, lichen planus, and lichenoid lesions to determine variations if any. A retrospective study was done on 25 histologically diagnosed cases each of oral lichen planus, oral lichenoid lesions, and normal oral mucosa. Cellular and nuclear morphometric measurements were assessed on hematoxylin and eosin sections using image analysis software. Analysis of variance test (ANOVA) and Tukey's post-hoc test. The basal cells of oral lichen planus showed a significant increase in the mean nuclear and cellular areas, and in nuclear volume; there was a significant decrease in the nuclear-cytoplasmic ratio as compared to normal mucosa. The suprabasal cells showed a significant increase in nuclear and cellular areas, nuclear diameter, and nuclear and cellular volumes as compared to normal mucosa. The basal cells of oral lichenoid lesions showed significant difference in the mean cellular area and the mean nuclear-cytoplasmic ratio as compared to normal mucosa, whereas the suprabasal cells differed significantly from normal mucosa in the mean nuclear area and the nuclear and cellular volumes. Morphometry can differentiate lesions of oral lichen planus and oral lichenoid lesions from normal oral mucosa. Thus, morphometry may serve to discriminate between normal and premalignant lichen planus and lichenoid lesions. These lesions might have a high risk for malignant transformation and may behave in a similar manner with respect to malignant transformation.

Alternative activation of STAT1 and STAT3 in response to interferon-gamma.

PubMed

Qing, Yulan; Stark, George R

2004-10-01

Interferon-gamma (IFNgamma) is a pluripotent cytokine whose major biological effects are mediated through a pathway in which STAT1 is the predominant and essential transcription factor. STAT3 can also be activated weakly by IFNgamma, but the mechanism of activation and function of STAT3 as a part of the interferon response are not known. Here we show that STAT3 activation is much stronger and more prolonged in STAT1-null mouse embryo fibroblasts than in wild-type cells. In response to IFNgamma, SRC-family kinases are required to activate STAT3 (but not STAT1) through tyrosine phosphorylation, whereas the receptor-bound kinases JAK1 and JAK2 are required to activate both STATs. Tyrosine 419 of the IFNgamma receptor subunit 1 (IFNGR1) is required to activate both STATs, suggesting that STAT1 and STAT3 compete with each other for the same receptor phosphotyrosine motif. Activated STAT3 can replace STAT1 in STAT1-null cells to drive the transcription of certain genes, for example, socs-3 and c/ebpdelta, which have gamma-activated sequence motifs in their promoters. Work from Ian Kerr's laboratory reveals that the gp130-linked interleukin-6 receptor, which usually activates STAT3 predominantly, activates STAT1 efficiently when STAT3 is absent. Because STAT1 and STAT3 have opposing biological effects (STAT3 is an oncogene, and STAT1 is a tumor suppressor), the reciprocal activation of these two transcription factors in response to IFNgamma or interleukin-6 suggests that their relative abundance, which may vary substantially in different normal cell types, under different conditions or in tumors is likely to have a major impact on how cells behave in response to different cytokines.

Isolation of Optically Targeted Single Bacteria by Application of Fluidic Force Microscopy to Aerobic Anoxygenic Phototrophs from the Phyllosphere

PubMed Central

Stiefel, Philipp; Zambelli, Tomaso

2013-01-01

In their natural environment, bacteria often behave differently than they do under laboratory conditions. To gain insight into the physiology of bacteria in situ, dedicated approaches are required to monitor their adaptations and specific behaviors under environmental conditions. Optical microscopy is crucial for the observation of fundamental characteristics of bacteria, such as cell shape, size, and marker gene expression. Here, fluidic force microscopy (FluidFM) was exploited to isolate optically selected bacteria for subsequent identification and characterization. In this study, bacteriochlorophyll-producing bacteria, which can be visualized due to their characteristic fluorescence in the infrared range, were isolated from leaf washes. Bacterial communities from the phyllosphere were investigated because they harbor genes indicative of aerobic anoxygenic photosynthesis. Our data show that different species of Methylobacterium express their photosystem in planta, and they show a distinct pattern of bacteriochlorophyll production under laboratory conditions that is dependent on supplied carbon sources. PMID:23770907

The use of the decision tree technique and image cytometry to characterize aggressiveness in World Health Organization (WHO) grade II superficial transitional cell carcinomas of the bladder.

PubMed

Decaestecker, C; van Velthoven, R; Petein, M; Janssen, T; Salmon, I; Pasteels, J L; van Ham, P; Schulman, C; Kiss, R

1996-03-01

The aggressiveness of human bladder tumours can be assessed by means of various classification systems, including the one proposed by the World Health Organization (WHO). According to the WHO classification, three levels of malignancy are identified as grades I (low), II (intermediate), and III (high). This classification system operates satisfactorily for two of the three grades in forecasting clinical progression, most grade I tumours being associated with good prognoses and most grade III with bad. In contrast, the grade II group is very heterogeneous in terms of their clinical behaviour. The present study used two computer-assisted methods to investigate whether it is possible to sub-classify grade II tumours: computer-assisted microscope analysis (image cytometry) of Feulgen-stained nuclei and the Decision Tree Technique. This latter technique belongs to the Supervised Learning Algorithm and enables an objective assessment to be made of the diagnostic value associated with a given parameter. The combined use of these two methods in a series of 292 superficial transitional cell carcinomas shows that it is possible to identify one subgroup of grade II tumours which behave clinically like grade I tumours and a second subgroup which behaves clinically like grade III tumours. Of the nine ploidy-related parameters computed by means of image cytometry [the DNA index (DI), DNA histogram type (DHT), and the percentages of diploid, hyperdiploid, triploid, hypertriploid, tetraploid, hypertetraploid, and polyploid cell nuclei], it was the percentage of hyperdiploid and hypertetraploid cell nuclei which enabled identification, rather than conventional parameters such as the DI or the DHT.

Three dimensional cultures: a tool to study normal acinar architecture vs. malignant transformation of breast cells.

PubMed

Pal, Anupama; Kleer, Celina G

2014-04-25

Invasive breast carcinomas are a group of malignant epithelial tumors characterized by the invasion of adjacent tissues and propensity to metastasize. The interplay of signals between cancer cells and their microenvironment exerts a powerful influence on breast cancer growth and biological behavior(1). However, most of these signals from the extracellular matrix are lost or their relevance is understudied when cells are grown in two dimensional culture (2D) as a monolayer. In recent years, three dimensional (3D) culture on a reconstituted basement membrane has emerged as a method of choice to recapitulate the tissue architecture of benign and malignant breast cells. Cells grown in 3D retain the important cues from the extracellular matrix and provide a physiologically relevant ex vivo system(2,3). Of note, there is growing evidence suggesting that cells behave differently when grown in 3D as compared to 2D(4). 3D culture can be effectively used as a means to differentiate the malignant phenotype from the benign breast phenotype and for underpinning the cellular and molecular signaling involved(3). One of the distinguishing characteristics of benign epithelial cells is that they are polarized so that the apical cytoplasm is towards the lumen and the basal cytoplasm rests on the basement membrane. This apico-basal polarity is lost in invasive breast carcinomas, which are characterized by cellular disorganization and formation of anastomosing and branching tubules that haphazardly infiltrates the surrounding stroma. These histopathological differences between benign gland and invasive carcinoma can be reproduced in 3D(6,7). Using the appropriate read-outs like the quantitation of single round acinar structures, or differential expression of validated molecular markers for cell proliferation, polarity and apoptosis in combination with other molecular and cell biology techniques, 3D culture can provide an important tool to better understand the cellular changes during malignant transformation and for delineating the responsible signaling.

PASTA repeats of the protein kinase StkP interconnect cell constriction and separation of Streptococcus pneumoniae.

PubMed

Zucchini, Laure; Mercy, Chryslène; Garcia, Pierre Simon; Cluzel, Caroline; Gueguen-Chaignon, Virginie; Galisson, Frédéric; Freton, Céline; Guiral, Sébastien; Brochier-Armanet, Céline; Gouet, Patrice; Grangeasse, Christophe

2018-02-01

Eukaryotic-like serine/threonine kinases (eSTKs) with extracellular PASTA repeats are key membrane regulators of bacterial cell division. How PASTA repeats govern eSTK activation and function remains elusive. Using evolution- and structural-guided approaches combined with cell imaging, we disentangle the role of each PASTA repeat of the eSTK StkP from Streptococcus pneumoniae. While the three membrane-proximal PASTA repeats behave as interchangeable modules required for the activation of StkP independently of cell wall binding, they also control the septal cell wall thickness. In contrast, the fourth and membrane-distal PASTA repeat directs StkP localization at the division septum and encompasses a specific motif that is critical for final cell separation through interaction with the cell wall hydrolase LytB. We propose a model in which the extracellular four-PASTA domain of StkP plays a dual function in interconnecting the phosphorylation of StkP endogenous targets along with septal cell wall remodelling to allow cell division of the pneumococcus.

Zolpidem Reduces Hippocampal Neuronal Activity in Freely Behaving Mice: A Large Scale Calcium Imaging Study with Miniaturized Fluorescence Microscope

PubMed Central

Berdyyeva, Tamara; Otte, Stephani; Aluisio, Leah; Ziv, Yaniv; Burns, Laurie D.; Dugovic, Christine; Yun, Sujin; Ghosh, Kunal K.; Schnitzer, Mark J.; Lovenberg, Timothy; Bonaventure, Pascal

2014-01-01

Therapeutic drugs for cognitive and psychiatric disorders are often characterized by their molecular mechanism of action. Here we demonstrate a new approach to elucidate drug action on large-scale neuronal activity by tracking somatic calcium dynamics in hundreds of CA1 hippocampal neurons of pharmacologically manipulated behaving mice. We used an adeno-associated viral vector to express the calcium sensor GCaMP3 in CA1 pyramidal cells under control of the CaMKII promoter and a miniaturized microscope to observe cellular dynamics. We visualized these dynamics with and without a systemic administration of Zolpidem, a GABAA agonist that is the most commonly prescribed drug for the treatment of insomnia in the United States. Despite growing concerns about the potential adverse effects of Zolpidem on memory and cognition, it remained unclear whether Zolpidem alters neuronal activity in the hippocampus, a brain area critical for cognition and memory. Zolpidem, when delivered at a dose known to induce and prolong sleep, strongly suppressed CA1 calcium signaling. The rate of calcium transients after Zolpidem administration was significantly lower compared to vehicle treatment. To factor out the contribution of changes in locomotor or physiological conditions following Zolpidem treatment, we compared the cellular activity across comparable epochs matched by locomotor and physiological assessments. This analysis revealed significantly depressive effects of Zolpidem regardless of the animal’s state. Individual hippocampal CA1 pyramidal cells differed in their responses to Zolpidem with the majority (∼65%) significantly decreasing the rate of calcium transients, and a small subset (3%) showing an unexpected and significant increase. By linking molecular mechanisms with the dynamics of neural circuitry and behavioral states, this approach has the potential to contribute substantially to the development of new therapeutics for the treatment of CNS disorders. PMID:25372144

Connecting single cell to collective cell behavior in a unified theoretical framework

NASA Astrophysics Data System (ADS)

George, Mishel; Bullo, Francesco; Campàs, Otger

Collective cell behavior is an essential part of tissue and organ morphogenesis during embryonic development, as well as of various disease processes, such as cancer. In contrast to many in vitro studies of collective cell migration, most cases of in vivo collective cell migration involve rather small groups of cells, with large sheets of migrating cells being less common. The vast majority of theoretical descriptions of collective cell behavior focus on large numbers of cells, but fail to accurately capture the dynamics of small groups of cells. Here we introduce a low-dimensional theoretical description that successfully captures single cell migration, cell collisions, collective dynamics in small groups of cells, and force propagation during sheet expansion, all within a common theoretical framework. Our description is derived from first principles and also includes key phenomenological aspects of cell migration that control the dynamics of traction forces. Among other results, we explain the counter-intuitive observations that pairs of cells repel each other upon collision while they behave in a coordinated manner within larger clusters.

Electrical Behavior of Copper Mine Tailings During EKR with Modified Electric Fields.

PubMed

Rojo, Adrian; Hansen, Henrik K; Monárdez, Omara; Jorquera, Carlos; Santis, Paulina; Inostroza, Paula

2017-03-01

Electro-kinetic remediation (EKR) with sinusoidal electric field obtained simultaneously with DC/AC voltage reduce the polarization of the EKR with DC voltage. The DC voltage value defines the presence of a periodic polarity reversal of the cell and the electrical charge for electro-kinetic transport. In this case, the AC frequency favors the breaking of polarization conditions resulting from the EKR with DC voltage. However, with high frequencies a negative effect occurs where the tailings behave as a filter circuit, discriminating frequencies of an electric signal. The goal of this work is to analyse the electrical behaviour of tailings in EKR experiments. The conditions selected were: DC/AC voltages: 10/15 and 20/25 V (peak values), and AC voltage frequencies 50-2000 Hz. When the AC frequency reaches 2000 Hz, the copper removal tends to zero, indicating that the tailing behaves as a high-pass filter in which the DC voltage was filtered out.

Mononuclear cell membranes: stabilization by reproterol and cromoglycate, destabilization by fenoterol and salbutamol.

PubMed

Zimmer, Guido; Bernhörster, Markus; Pilz, Patrizius; Schuchmann-Fix, Jutta; Hüggelmeier, Rolf; Blüm, Nicole; Libertus, Herman

2006-01-01

Electron paramagnetic resonance (EPR) spectroscopy with spin labels 5- and 16-doxyl-stearic acid (DSA) was used to differentiate between actions of beta-agonists on human mononuclear cell membrane. Reproterol (CAS 13055-82-8), salbutamol (CAS 51022-70-9) and fenoterol (CAS 1944-12-3) compared to cromoglycate (CAS 15826-37-6) were used at concentrations of 10-100 nmol/l per 10(7) cells. With reproterol, order and polarity was not much changed, whereas salbutamol and fenoterol significantly destabilized the membrane to similar extent. Cromoglycate acted in a stabilizing fashion. With trypan blue exclusion, reproterol and cromoglycate showed stable values, whereas salbutamol and fenoterol augmented permeability. Thus, by conventional lipid spin labeling the discrimination between salbutamol and fenoterol could not be carried out. In contrast, previous lipid peroxidation studies in a model system had revealed a decrease by reproterol, no change by salbutamol and an increase by fenoterol. Also, using fenoterol, protein spin label 4-maleimido-TEMPO (2, 2, 6, 6-tetramethyl-1-piperidinyloxy) showed an increase of membrane rigidity of mononuclear cells. Moreover, mast cells of different origin were previously found tween beta-agonists. Reproterol in all tests behaved in a therapeutically profitable way. In conclusion, in addition to lipid spin labeling other methods and materials should be considered, to finally arrive at a more realistic differentiation between, for instance, salbutamol and fenoterol. The term "membrane (de) stabilization" should not generally be used without careful consideration of the type of cell/membrane in question.

Platinum nanoparticles and their cellular uptake and DNA platination at non-cytotoxic concentrations.

PubMed

Gehrke, Helge; Pelka, Joanna; Hartinger, Christian G; Blank, Holger; Bleimund, Felix; Schneider, Reinhard; Gerthsen, Dagmar; Bräse, Stefan; Crone, Marlene; Türk, Michael; Marko, Doris

2011-07-01

Three differently sized, highly dispersed platinum nanoparticle (Pt-NP) preparations were generated by supercritical fluid reactive deposition (SFRD) and deposited on a β-cyclodextrin matrix. The average particle size and size distribution were steered by the precursor reduction conditions, resulting in particle preparations of <20, <100 and >100 nm as characterised by TEM and SEM. As reported previously, these Pt-NPs were found to cause DNA strand breaks in human colon carcinoma cells (HT29) in a concentration- and time-dependent manner and a distinct size dependency. Here, we addressed the question whether Pt-NPs might affect directly DNA integrity in these cells and thus behave analogous to platinum-based chemotherapeutics such as cisplatin. Therefore, DNA-associated Pt as well as the translocation of Pt-NPs through a Caco-2 monolayer was quantified by ICP-MS. STEM imaging demonstrated that Pt-NPs were taken up into HT29 cells in their particulate and aggregated form, but appear not to translocate into the nucleus or interact with mitochondria. The platinum content of the DNA of HT29 cells was found to increase in a time- and concentration-dependent manner with a maximal effect at 1,000 ng/cm(2). ICP-MS analysis of the cell culture medium indicated the formation of soluble Pt species, although to a limited extent. The observations suggest that DNA strand breaks mediated by metallic Pt-NPs are caused by Pt ions forming during the incubation of cells with these nanoparticles.

Ability of primary auditory cortical neurons to detect amplitude modulation with rate and temporal codes: neurometric analysis

PubMed Central

Johnson, Jeffrey S.; Yin, Pingbo; O'Connor, Kevin N.

2012-01-01

Amplitude modulation (AM) is a common feature of natural sounds, and its detection is biologically important. Even though most sounds are not fully modulated, the majority of physiological studies have focused on fully modulated (100% modulation depth) sounds. We presented AM noise at a range of modulation depths to awake macaque monkeys while recording from neurons in primary auditory cortex (A1). The ability of neurons to detect partial AM with rate and temporal codes was assessed with signal detection methods. On average, single-cell synchrony was as or more sensitive than spike count in modulation detection. Cells are less sensitive to modulation depth if tested away from their best modulation frequency, particularly for temporal measures. Mean neural modulation detection thresholds in A1 are not as sensitive as behavioral thresholds, but with phase locking the most sensitive neurons are more sensitive, suggesting that for temporal measures the lower-envelope principle cannot account for thresholds. Three methods of preanalysis pooling of spike trains (multiunit, similar to convergence from a cortical column; within cell, similar to convergence of cells with matched response properties; across cell, similar to indiscriminate convergence of cells) all result in an increase in neural sensitivity to modulation depth for both temporal and rate codes. For the across-cell method, pooling of a few dozen cells can result in detection thresholds that approximate those of the behaving animal. With synchrony measures, indiscriminate pooling results in sensitive detection of modulation frequencies between 20 and 60 Hz, suggesting that differences in AM response phase are minor in A1. PMID:22422997

Characterization, cell-surface expression and ligand-binding properties of different truncated N-terminal extracellular domains of the ionotropic glutamate receptor subunit GluR1.

PubMed

McIlhinney, R A; Molnár, E

1996-04-01

To identify the location of the first transmembrane segment of the GluR1 glutamate receptor subunit artificial stop codons have been introduced into the N-terminal domain at amino acid positions 442, 510, and 563, namely just before and spanning the proposed first two transmembrane regions. The resultant truncated N-terminal fragments of GluR1, termed NT1, NT2, and NT3 respectively were expressed in Cos-7 cells and their cellular distribution and cell-surface expression analysed using an N-terminal antibody to GluR1. All of the fragments were fully glycosylated and were found to be associated with cell membranes but none was secreted. Differential extraction of the cell membranes indicated that both NT1 and NT2 behave as peripheral membrane proteins. In contrast NT3, like the full subunit, has integral membrane protein properties. Furthermore only NT3 is expressed at the cell surface as determined by immunofluorescence and cell-surface biotinylation. Protease protection assays indicated that only NT3 had a cytoplasmic tail. Binding studies using the selective ligand [(3)H]alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate ([(3)H]AMPA) demonstrated that NT3 does not bind ligand. Together these results indicate that the first transmembrane domain of the GluR1 subunit lies between residues 509 and 562, that the N-terminal domain alone cannot form a functional ligand-binding site and that this domain can be targeted to the cell surface provided that it has a transmembrane-spanning region.

A precisely substituted benzopyran targets androgen refractory prostate cancer cells through selective modulation of estrogen receptors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kumar, Rajeev; Verma, Vikas; Sharma, Vikas

Dietary consumption of phytoestrogens like genistein has been linked with lower incidence of prostate cancer. The estradiol-like benzopyran core of genistein confers estrogen receptor-β (ER-β) selectivity that imparts weak anti-proliferative activity against prostate cancer cells. DL-2-[4-(2-piperidinoethoxy)phenyl]-3-phenyl-2H-1-benzopyran (BP), a SERM designed with benzopyran core, targeted androgen independent prostate cancer (PC-3) cells 14-times more potently than genistein, ~ 25% more efficiently than tamoxifen and 6.5-times more actively than ICI-182780, without forfeiting significant specificity in comparison to genistein. BP increased apoptosis (annexin-V and TUNEL labeling), arrested cell cycle, and significantly increased caspase-3 activity along with mRNA expressions of estrogen receptor (ER)-β and FasLmore » (qPCR) in PC-3 cells. In classical ERE-luc reporter assay BP behaved as a potent ER-α antagonist and ER-β agonist. Accordingly, it decreased expression of ER-α target PS2 (P < 0.01) and increased expression of ER-β target TNF-α (P < 0.05) genes in PC-3. ER-β deficient PC-3 (siRNA-transfected) was resistant to apoptotic and anti-proliferative actions of SERMs, including stimulation of FasL expression by BP. BP significantly inhibited phosphorylation of Akt and ERK-1/2, JNK and p38 in PC-3 (immunoblotting), and thus adopted a multi-pathway mechanism to exert a more potent anti-proliferative activity against prostate cancer cells than natural and synthetic SERMs. Its precise ER-subtype specific activity presents a unique lead structure for further optimization. - Highlights: • BP with benzopyran core of genistein was identified for ER-β selective action. • BP was 14-times more potent than genistien in targeting prostate cancer cells. • It behaved as a potent ER-β agonist and ER-α antagonist in gene reporter assays. • BP's anti-proliferative action was inhibited significantly in ER-β deficient cells. • BP — a unique lead structure for further optimization.« less

Noninvasive High-Throughput Single-Cell Analysis of the Intracellular pH of Saccharomyces cerevisiae by Ratiometric Flow Cytometry

PubMed Central

Valkonen, Mari; Mojzita, Dominik; Penttilä, Merja

2013-01-01

The ability of cells to maintain pH homeostasis in response to environmental changes has elicited interest in basic and applied research and has prompted the development of methods for intracellular pH measurements. Many traditional methods provide information at population level and thus the average values of the studied cell physiological phenomena, excluding the fact that cell cultures are very heterogeneous. Single-cell analysis, on the other hand, offers more detailed insight into population variability, thereby facilitating a considerably deeper understanding of cell physiology. Although microscopy methods can address this issue, they suffer from limitations in terms of the small number of individual cells that can be studied and complicated image processing. We developed a noninvasive high-throughput method that employs flow cytometry to analyze large populations of cells that express pHluorin, a genetically encoded ratiometric fluorescent probe that is sensitive to pH. The method described here enables measurement of the intracellular pH of single cells with high sensitivity and speed, which is a clear improvement compared to previously published methods that either require pretreatment of the cells, measure cell populations, or require complex data analysis. The ratios of fluorescence intensities, which correlate to the intracellular pH, are independent of the expression levels of the pH probe, making the use of transiently or extrachromosomally expressed probes possible. We conducted an experiment on the kinetics of the pH homeostasis of Saccharomyces cerevisiae cultures grown to a stationary phase after ethanol or glucose addition and after exposure to weak acid stress and glucose pulse. Minor populations with pH homeostasis behaving differently upon treatments were identified. PMID:24038689

Noninvasive high-throughput single-cell analysis of the intracellular pH of Saccharomyces cerevisiae by ratiometric flow cytometry.

PubMed

Valkonen, Mari; Mojzita, Dominik; Penttilä, Merja; Bencina, Mojca

2013-12-01

The ability of cells to maintain pH homeostasis in response to environmental changes has elicited interest in basic and applied research and has prompted the development of methods for intracellular pH measurements. Many traditional methods provide information at population level and thus the average values of the studied cell physiological phenomena, excluding the fact that cell cultures are very heterogeneous. Single-cell analysis, on the other hand, offers more detailed insight into population variability, thereby facilitating a considerably deeper understanding of cell physiology. Although microscopy methods can address this issue, they suffer from limitations in terms of the small number of individual cells that can be studied and complicated image processing. We developed a noninvasive high-throughput method that employs flow cytometry to analyze large populations of cells that express pHluorin, a genetically encoded ratiometric fluorescent probe that is sensitive to pH. The method described here enables measurement of the intracellular pH of single cells with high sensitivity and speed, which is a clear improvement compared to previously published methods that either require pretreatment of the cells, measure cell populations, or require complex data analysis. The ratios of fluorescence intensities, which correlate to the intracellular pH, are independent of the expression levels of the pH probe, making the use of transiently or extrachromosomally expressed probes possible. We conducted an experiment on the kinetics of the pH homeostasis of Saccharomyces cerevisiae cultures grown to a stationary phase after ethanol or glucose addition and after exposure to weak acid stress and glucose pulse. Minor populations with pH homeostasis behaving differently upon treatments were identified.

Predicting efficiency of solar cells based on transparent conducting electrodes

NASA Astrophysics Data System (ADS)

Kumar, Ankush

2017-01-01

Efficiency of a solar cell is directly correlated with the performance of its transparent conducting electrodes (TCEs) which dictates its two core processes, viz., absorption and collection efficiencies. Emerging designs of a TCE involve active networks of carbon nanotubes, silver nanowires and various template-based techniques providing diverse structures; here, voids are transparent for optical transmittance while the conducting network acts as a charge collector. However, it is still not well understood as to which kind of network structure leads to an optimum solar cell performance; therefore, mostly an arbitrary network is chosen as a solar cell electrode. Herein, we propose a new generic approach for understanding the role of TCEs in determining the solar cell efficiency based on analysis of shadowing and recombination losses. A random network of wires encloses void regions of different sizes and shapes which permit light transmission; two terms, void fraction and equivalent radius, are defined to represent the TCE transmittance and wire spacings, respectively. The approach has been applied to various literature examples and their solar cell performance has been compared. To obtain high-efficiency solar cells, optimum density of the wires and their aspect ratio as well as active layer thickness are calculated. Our findings show that a TCE well suitable for one solar cell may not be suitable for another. For high diffusion length based solar cells, the void fraction of the network should be low while for low diffusion length based solar cells, the equivalent radius should be lower. The network with less wire spacing compared to the diffusion length behaves similar to continuous film based TCEs (such as indium tin oxide). The present work will be useful for architectural as well as material engineering of transparent electrodes for improvisation of solar cell performance.

Nuclear Autonomy in Multinucleate Fungi

PubMed Central

Roberts, Samantha E.; Gladfelter, Amy S.

2015-01-01

Within many fungal syncytia, nuclei behave independently despite sharing a common cytoplasm. Creation of independent nuclear zones of control in one cell is paradoxical considering random protein synthesis sites, predicted rapid diffusion rates, and well-mixed cytosol. In studying the surprising fungal nuclear autonomy, new principles of cellular organization are emerging. We discuss the current understanding of nuclear autonomy, focusing on asynchronous cell cycle progression where most work has been directed. Mechanisms underlying nuclear autonomy are diverse including mRNA localization, ploidy variability, and nuclear spacing control. With the challenges fungal syncytia face due to cytoplasmic size and shape, they serve as powerful models for uncovering new subcellular organization modes, variability sources among isogenic uninucleate cells, and the evolution of multicellularity. PMID:26379197

Belonging, believing, bonding, and behaving: the relationship between religion and business ownership at the country level.

PubMed

Hoogendoorn, Brigitte; Rietveld, Cornelius A; van Stel, André

2016-01-01

This cross-country study adopts a competing theories approach in which both a value perspective and a social capital perspective are used to understand the relation between religion and a country's business ownership rate. We distinguish among four dimensions of religion: belonging to a religious denomination, believing certain religious propositions, bonding to religious practices, and behaving in a religious manner. An empirical analysis of data from 30 OECD countries with multiple data points per country covering the period 1984-2010 suggests a positive relationship between religion and business ownership based on those dimensions that reflect the internal aspects of religiosity (i.e., believing and behaving). We do not observe a significant association for those dimensions that reflect more external aspects of religion (i.e., belonging and bonding). These results suggest that the social capital perspective prevails the value perspective, at least when internal aspects of religiosity are concerned. More generally, our study demonstrates the importance of distinguishing between different dimensions of religion when investigating the link between religion and entrepreneurship.

Statistical mechanics of tuned cell signalling: sensitive collective response by synthetic biological circuits

NASA Astrophysics Data System (ADS)

Voliotis, M.; Liverpool, T. B.

2017-03-01

Living cells sense and process environmental cues through noisy biochemical mechanisms. This apparatus limits the scope of engineering cells as viable sensors. Here, we highlight a mechanism that enables robust, population-wide responses to external stimulation based on cellular communication, known as quorum sensing. We propose a synthetic circuit consisting of two mutually repressing quorum sensing modules. At low cell densities the system behaves like a genetic toggle switch, while at higher cell densities the behaviour of nearby cells is coupled via diffusible quorum sensing molecules. We show by systematic coarse graining that at large length and timescales that the system can be described using the Ising model of a ferromagnet. Thus, in analogy with magnetic systems, the sensitivity of the population-wide response, or its ‘susceptibility’ to a change in the external signal, is highly enhanced for a narrow range of cell-cell coupling close to a critical value. We expect that our approach will be used to enhance the sensitivity of synthetic bio-sensing networks.

Multicellular contractility contributes to the emergence of mesothelioma nodules

NASA Astrophysics Data System (ADS)

Czirok, Andras

Malignant pleural mesothelioma (MPM) nodules arise from the mesothelial lining of the pleural cavity by a poorly understood mechanism. We demonstrate that macroscopic multicellular aggregates, reminiscent of the MPM nodules found in patients, develop when MPM cell lines are cultured at high cell densities for several weeks. Surprisingly, the nodule-like aggregates do not arise by excessive local cell proliferation, but by myosin II-driven cell contractility. Contractile nodules contain prominent actin cables that can span several cells. Several features of the in vitro MPM nodule development can be explained by a computational model that assumes uniform and steady intercellular contractile forces within a monolayer of cells, and a mechanical load-dependent lifetime of cell-cell contacts. The model behaves as a self-tensioned Maxwell fluid and exhibits an instability that leads to pattern formation. Altogether, our findings suggest that inhibition of the actomyosin system may provide a hitherto not utilized therapeutic approach to affect MPM growth. NIH R01-GM102801.

A rare case of failed healing in previously burned skin after a secondary burns.

PubMed

Goldie, Stephen J; Parsons, Shaun; Menezes, Hana; Ives, Andrew; Cleland, Heather

2017-01-01

Patients presenting with large surface area burns are common in our practice; however, patients with a secondary large burn on pre-existing burn scars and grafts are rare and not reported. We report on an unusual case of a patient sustaining a secondary large burn to areas previously injured by a burn from a different mechanism. We discuss the potential implications when managing a case like this and suggest potential biological reasons why the skin may behave differently. Our patient was a 33-year-old man who presented with a 5% TBSA burn on skin scarred by a previous 40% total body surface area (TBSA) burn and skin grafts. Initially assessed as superficial partial thickness in depth, the wounds were treated conservatively with dressings; however, they failed to heal and became infected requiring surgical management. Burns sustained in areas of previous burn scars and grafts may behave differently to normal patterns of healing, requiring more aggressive management and surgical intervention at an early stage.

Assessment of Adeno-Associated Virus Serotype Tropism in Human Retinal Explants.

PubMed

Wiley, Luke A; Burnight, Erin R; Kaalberg, Emily E; Jiao, Chunhua; Riker, Megan J; Halder, Jennifer A; Luse, Meagan A; Han, Ian C; Russell, Stephen R; Sohn, Elliott H; Stone, Edwin M; Tucker, Budd A; Mullins, Robert F

2018-04-01

Advances in the discovery of the causes of monogenic retinal disorders, combined with technologies for the delivery of DNA to the retina, offer enormous opportunities for the treatment of previously untreatable blinding diseases. However, for gene augmentation to be most effective, vectors that have the correct cell-type specificity are needed. While animal models are very useful, they often exhibit differences in retinal cell surface receptors compared to the human retina. This study evaluated the use of an ex vivo organotypic explant system to test the transduction efficiency and tropism of seven different adeno-associated virus type 2 (AAV2) serotypes in the human retina and retinal pigment epithelium-choroid-AAV2/1, AAV2/2, AAV2/4, AAV2/5, AAV2/6, AAV2/8, and AAV2/9-all driving expression of GFP under control of the cytomegalovirus promoter. After 7 days in culture, it was found that AAV2/4 and AAV2/5 were particularly efficient at transducing photoreceptor cells and that AAV2/5 was highly specific to the outer nuclear layer, whereas AAV2/8 displayed consistently low transduction of photoreceptors. To validate the authenticity of the organotypic culture system, the transduction of the same set of AAVs was also compared in a pig model, in which sub-retinal injections in vivo were compared to cultured and transduced organotypic cultures ex vivo. This study shows how different AAV serotypes behave in the human retina and provides insight for further investigation of each of these serotypes for gene augmentation-based treatment of inherited retinal degeneration.

A novel antibody engineering strategy for making monovalent bispecific heterodimeric IgG antibodies by electrostatic steering mechanism.

PubMed

Liu, Zhi; Leng, Esther C; Gunasekaran, Kannan; Pentony, Martin; Shen, Min; Howard, Monique; Stoops, Janelle; Manchulenko, Kathy; Razinkov, Vladimir; Liu, Hua; Fanslow, William; Hu, Zhonghua; Sun, Nancy; Hasegawa, Haruki; Clark, Rutilio; Foltz, Ian N; Yan, Wei

2015-03-20

Producing pure and well behaved bispecific antibodies (bsAbs) on a large scale for preclinical and clinical testing is a challenging task. Here, we describe a new strategy for making monovalent bispecific heterodimeric IgG antibodies in mammalian cells. We applied an electrostatic steering mechanism to engineer antibody light chain-heavy chain (LC-HC) interface residues in such a way that each LC strongly favors its cognate HC when two different HCs and two different LCs are co-expressed in the same cell to assemble a functional bispecific antibody. We produced heterodimeric IgGs from transiently and stably transfected mammalian cells. The engineered heterodimeric IgG molecules maintain the overall IgG structure with correct LC-HC pairings, bind to two different antigens with comparable affinity when compared with their parental antibodies, and retain the functionality of parental antibodies in biological assays. In addition, the bispecific heterodimeric IgG derived from anti-HER2 and anti-EGF receptor (EGFR) antibody was shown to induce a higher level of receptor internalization than the combination of two parental antibodies. Mouse xenograft BxPC-3, Panc-1, and Calu-3 human tumor models showed that the heterodimeric IgGs strongly inhibited tumor growth. The described approach can be used to generate tools from two pre-existent antibodies and explore the potential of bispecific antibodies. The asymmetrically engineered Fc variants for antibody-dependent cellular cytotoxicity enhancement could be embedded in monovalent bispecific heterodimeric IgG to make best-in-class therapeutic antibodies. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

The genetic network controlling plasma cell differentiation.

PubMed

Nutt, Stephen L; Taubenheim, Nadine; Hasbold, Jhagvaral; Corcoran, Lynn M; Hodgkin, Philip D

2011-10-01

Upon activation by antigen, mature B cells undergo immunoglobulin class switch recombination and differentiate into antibody-secreting plasma cells, the endpoint of the B cell developmental lineage. Careful quantitation of these processes, which are stochastic, independent and strongly linked to the division history of the cell, has revealed that populations of B cells behave in a highly predictable manner. Considerable progress has also been made in the last few years in understanding the gene regulatory network that controls the B cell to plasma cell transition. The mutually exclusive transcriptomes of B cells and plasma cells are maintained by the antagonistic influences of two groups of transcription factors, those that maintain the B cell program, including Pax5, Bach2 and Bcl6, and those that promote and facilitate plasma cell differentiation, notably Irf4, Blimp1 and Xbp1. In this review, we discuss progress in the definition of both the transcriptional and cellular events occurring during late B cell differentiation, as integrating these two approaches is crucial to defining a regulatory network that faithfully reflects the stochastic features and complexity of the humoral immune response. 2011 Elsevier Ltd. All rights reserved.

Triticum aestivum WRAB18 functions in plastids and confers abiotic stress tolerance when overexpressed in Escherichia coli and Nicotiania benthamiana.

PubMed

Wang, Xiaoyu; Zhang, Linsheng; Zhang, Yane; Bai, Zhenqing; Liu, Hao; Zhang, Dapeng

2017-01-01

WRAB18, an ABA-inducible protein belongs to the third family of late embryogenesis abundant (LEA) proteins which can be induced by different biotic or abiotic stresses. In the present study, WRAB18 was cloned from the Zhengyin 1 cultivar of Triticum aestivum and overexpressed in Escherichia coli to explore its effects on the growth of E. coli under different abiotic stresses. Results suggested the enhanced exhibition of tolerance of E. coli to these stresses. Meanwhile, the WRAB18-transgenic tobacco plants were obtained to analyze the stress-related enzymatic activities of ascorbate peroxidase (APX), peroxidase (POD) and superoxide dismutase (SOD), and to quantify the content of malonaldehyde (MDA) under osmotic stress, high salinity, and low and high temperature stress. The activities of APX, POD and SOD in the transgenic tobacco lines were higher while the content of MDA was lower than those of WT lines. Moreover, plastid localization of WRAB18 in Nicotiana benthamiana plasma cells were found fusing with GFP. In addition, purified WRAB18 protein protected LDH (Lactate dehydrogenase) enzyme activity in vitro from various stress conditions. In brief, WRAB18 protein shows protective action behaving as a "molecular shield" in both prokaryotic and eukaryotic cells under various abiotic stresses, not only during ABA stress.

An adaptable neuromorphic model of orientation selectivity based on floating gate dynamics

PubMed Central

Gupta, Priti; Markan, C. M.

2014-01-01

The biggest challenge that the neuromorphic community faces today is to build systems that can be considered truly cognitive. Adaptation and self-organization are the two basic principles that underlie any cognitive function that the brain performs. If we can replicate this behavior in hardware, we move a step closer to our goal of having cognitive neuromorphic systems. Adaptive feature selectivity is a mechanism by which nature optimizes resources so as to have greater acuity for more abundant features. Developing neuromorphic feature maps can help design generic machines that can emulate this adaptive behavior. Most neuromorphic models that have attempted to build self-organizing systems, follow the approach of modeling abstract theoretical frameworks in hardware. While this is good from a modeling and analysis perspective, it may not lead to the most efficient hardware. On the other hand, exploiting hardware dynamics to build adaptive systems rather than forcing the hardware to behave like mathematical equations, seems to be a more robust methodology when it comes to developing actual hardware for real world applications. In this paper we use a novel time-staggered Winner Take All circuit, that exploits the adaptation dynamics of floating gate transistors, to model an adaptive cortical cell that demonstrates Orientation Selectivity, a well-known biological phenomenon observed in the visual cortex. The cell performs competitive learning, refining its weights in response to input patterns resembling different oriented bars, becoming selective to a particular oriented pattern. Different analysis performed on the cell such as orientation tuning, application of abnormal inputs, response to spatial frequency and periodic patterns reveal close similarity between our cell and its biological counterpart. Embedded in a RC grid, these cells interact diffusively exhibiting cluster formation, making way for adaptively building orientation selective maps in silicon. PMID:24765062

Invasion in breast lesions: the role of the epithelial-stroma barrier.

PubMed

Rakha, Emad A; Miligy, Islam M; Gorringe, Kylie L; Toss, Michael S; Green, Andrew R; Fox, Stephen B; Schmitt, Fernando C; Tan, Puay-Hoon; Tse, Gary M; Badve, Sunil; Decker, Thomas; Vincent-Salomon, Anne; Dabbs, David J; Foschini, Maria P; Moreno, Filipa; Wentao, Yang; Geyer, Felipe C; Reis-Filho, Jorge S; Pinder, Sarah E; Lakhani, Sunil R; Ellis, Ian O

2018-06-01

Despite the significant biological, behavioural and management differences between ductal carcinoma in situ (DCIS) and invasive carcinoma of the breast, they share many morphological and molecular similarities. Differentiation of these two different lesions in breast pathological diagnosis is based typically on the presence of an intact barrier between the malignant epithelial cells and stroma; namely, the myoepithelial cell (MEC) layer and surrounding basement membrane (BM). Despite being robust diagnostic criteria, the identification of MECs and BM to differentiate in-situ from invasive carcinoma is not always straightforward. The MEC layer around DCIS may be interrupted and/or show an altered immunoprofile. MECs may be absent in some benign locally infiltrative lesions such as microglandular adenosis and infiltrating epitheliosis, and occasionally in non-infiltrative conditions such as apocrine lesions, and in these contexts this does not denote malignancy or invasive disease with metastatic potential. MECs may also be absent around some malignant lesions such as some forms of papillary carcinoma, yet these behave in an indolent fashion akin to some DCIS. In Paget's disease, malignant mammary epithelial cells extend anteriorly from the ducts to infiltrate the epidermis of the nipple but do not typically infiltrate through the BM into the dermis. Conversely, BM-like material can be seen around invasive carcinoma cells and around metastatic tumour cell deposits. Here, we review the role of MECs and BM in breast pathology and highlight potential clinical implications. We advise caution in interpretation of MEC features in breast pathology and mindfulness of the substantive evidence base in the literature associated with behaviour and clinical outcome of lesions classified as benign on conventional morphological examination before changing classification to an invasive lesion on the sole basis of MEC characteristics. © 2017 John Wiley & Sons Ltd.

Liquid crystal polymers: evidence of hairpin defects in nematic main chains, comparison with side chain polymers

NASA Astrophysics Data System (ADS)

Li, M. H.; Brûlet, A.; Keller, P.; Cotton, J. P.

1996-09-01

This article describes the conformation of two species of liquid crystalline polymers as revealed by small angle neutron scattering. The results obtained with side chain polymers are recalled. The procedure used to analyze the scattering data of main chains in the nematic phase is reported in this paper. It permits a demonstration of the existence of hairpins. Comparison of both polymer species shows that in the isotropic phase, the two polymers adopt a random coil conformation. In the nematic phase, the conformations are very different; the side chains behave as a melt of penetrable random coils whereas the main chains behave as a nematic phase of non penetrable cylinders.

A biopolymer transistor: electrical amplification by microtubules.

PubMed

Priel, Avner; Ramos, Arnolt J; Tuszynski, Jack A; Cantiello, Horacio F

2006-06-15

Microtubules (MTs) are important cytoskeletal structures engaged in a number of specific cellular activities, including vesicular traffic, cell cyto-architecture and motility, cell division, and information processing within neuronal processes. MTs have also been implicated in higher neuronal functions, including memory and the emergence of "consciousness". How MTs handle and process electrical information, however, is heretofore unknown. Here we show new electrodynamic properties of MTs. Isolated, taxol-stabilized MTs behave as biomolecular transistors capable of amplifying electrical information. Electrical amplification by MTs can lead to the enhancement of dynamic information, and processivity in neurons can be conceptualized as an "ionic-based" transistor, which may affect, among other known functions, neuronal computational capabilities.

Cancer: a profit-driven biosystem?

PubMed

Deisboeck, Thomas S

2008-08-01

The argument is made that solid malignant tumors behave as profit-driven biological systems in that they expand their nutrient-uptaking surface to increase energetic revenue, at a comparably low metabolic cost. Within this conceptual framework, cancer cell migration is a critical mechanism as it maximizes systemic surface expansion while minimizing diffusion distance. Treating these tumor systems with adjuvant anti-proliferative regimen only should increase the energetic net gain of the viable cancer cells left behind, hence would facilitate tumor recurrence. Therapeutic attempts to better control tumor (re)growth should therefore aim primarily at containing its surface expansion, thus reducing its energetic revenue, or increasing its metabolic costs or better yet, both.

Cancer: A profit-driven biosystem ?

PubMed Central

Deisboeck, Thomas S.

2008-01-01

The argument is made that solid malignant tumors behave as profit-driven biological systems in that they expand their nutrient-uptaking surface to increase energetic revenue, at a comparably low metabolic cost. Within this conceptual framework, cancer cell migration is a critical mechanism as it maximizes systemic surface expansion while minimizing diffusion distance. Treating these tumor systems with adjuvant anti-proliferative regimen only should increase the energetic net gain of the viable cancer cells left behind, hence would facilitate tumor recurrence. Therapeutic attempts to better control tumor (re)growth should therefore aim primarily at containing its surface expansion, thus reducing its energetic revenue, or increasing its metabolic costs or better yet, both. PMID:18420354

Multiple subclasses of Purkinje cells in the primate floccular complex provide similar signals to guide learning in the vestibulo-ocular reflex

NASA Technical Reports Server (NTRS)

Raymond, J. L.; Lisberger, S. G.

1997-01-01

The neural "learning rules" governing the induction of plasticity in the cerebellum were analyzed by recording the patterns of neural activity in awake, behaving animals during stimuli that induce a form of cerebellum-dependent learning. We recorded the simple- and complex-spike responses of a broad sample of Purkinje cells in the floccular complex during a number of stimulus conditions that induce motor learning in the vestibulo-ocular reflex (VOR). Each subclass of Purkinje cells carried essentially the same information about required changes in the gain of the VOR. The correlation of simple-spike activity in Purkinje cells with activity in vestibular pathways could guide learning during low-frequency but not high-frequency stimuli. Climbing fiber activity could guide learning during all stimuli tested but only if compared with the activity present approximately 100 msec earlier in either vestibular pathways or Purkinje cells.

Normal and leukaemic human haemopoietic cells in diffusion chamber. A morphological and functional CFU-C study.

PubMed

Laurent, M; Clémancey-Marcille, G; Hollard, D

1980-03-01

Leukaemic human bone marrow and peripheral blood cells were cultured for 25 d in diffusion chambers implanted into cyclophosphamide treated mice. Normal bone marrow cells were cultured simultaneously. These cells were studied both morphologically and functionally (CFU-C). The leukaemic cells behaved heterogeneously, 2 groups being distinguishable in accordance with their initial in vitro growth pattern (1: no growth or microcluster growth. 2: macrocluster growth). Group I showed progressive cellular death with a diminution of granulocytic progenitors and the appearance of a predominantly macrophagic population. This behaviour resembled that of the control group. The initial microcluster growth pattern remained identical throughout the entire culture period. Group 2, after considerable cellular death up to d 5, showed an explosive proliferation of the granulocytic progenitors and incomplete differentiation (up to myelocyte). The initial macrocluster growth pattern remained identical.

Dual behavior of caustic optical beams facing obstacles

NASA Astrophysics Data System (ADS)

Vaveliuk, Pablo; Martínez-Matos, Óscar; Ren, Yu-Xuan; Lu, Rong-De

2017-06-01

A full propagation analysis on both fold-type and cusp-type caustic optical beams under various setups of obstructions is theoretically and experimentally performed. It is demonstrated that the self-healing property of caustic optical beams that include the famous Airy beam is a quite relative property. In fact, fold-type and cusp-type beams cannot only behave as self-healing beams by blocking the main intensity peak, but also behave as self-breaking ones in a nonintuitive manner: by blocking a lateral side of the beam without touching the central intensity peak. The regeneration and rupture processes of caustic beams follow a nonlocal propagation dynamic unlike the other conventional beams. Moreover, deep differences between fold and cusp caustic beams are pointed out once facing certain obstructions. The cusp-caustic beam can be broken down by the obstacle placed in a dark zone outside the caustic region, while the fold-type one remains unaltered. This beam rupture confirms the key role of a hidden propagating field in the shadow region for cusp beams that coexist with the evanescent one. The obtained results cast down the established idea that the Airy beam is a robust self-healing beam since any caustic beam can behave in a dual manner depending on the obstruction location. These facts open up different perspectives for the applications in which the self-healing properties of the beam are relevant.

Majorana Fermion and bound states in the continuum on a cross-shaped quantum dot hybrid structure

NASA Astrophysics Data System (ADS)

Zambrano, David; Ramos, Juan Pablo; Orellana, Pedro

We show how transmission, differential conductance and density of states (DOS) behave when two superconductor/semiconductors topological nanowires are placed next to the ends of a quantum-dot (QD) chain, where the central QD is attached to normal conductors leads. Results in a single QD coupled to two Kitaev chains within the topological phase and a T-shaped QD hybrid structure suggest these kind of system are strong candidates for qubits. We show how bound states in the continuum (BICs) arise as zero energy modes on conductance and DOS for different sets of system parameters showing evidence of Majorana fermions, and we also study how they behave for different numbers (even/odd) of QD in the cross-shaped structure. The authors acknowledge financial support from CONICYT, under Grant PAI-79140064, scholarship 21141034 and from FONDECYT, under Grant 1140571.

Expression of FLNa in human melanoma cells regulates the function of integrin α1β1 and phosphorylation and localisation of PKB/AKT/ERK1/2 kinases.

PubMed

Krebs, Kristi; Ruusmann, Anu; Simonlatser, Grethel; Velling, Teet

2015-12-01

FLNa is a ubiquitous cytoskeletal protein that links transmembrane receptors, including integrins, to F-actin and functions as a signalling intermediate. We investigated FLNa's role in the function of integrin-type collagen receptors, EGF-EGFR signalling and regulation of PKB/Akt and ERK1/2. Using FLNa-deficient M2 human melanoma cells, and same cells expressing EGFP-FLNa (M2F) or its Ig-like repeats 1-8+24, 8-15+24 and 16-24, we found that in M2F and M2 8-15+24 cells, EGF induced the increased phosphorylation of PKB/Akt and ERK1/2. In M2F cells EGF induced the localisation of these kinases to cell nucleus and lamellipodia, respectively, and the ERK1/2 phosphorylation-dependent co-immunoprecipitation of FLNa with ERK1/2. Only M2F and M2 8-15+24 cells adhered to and spread on type I collagen whereas on fibronectin all cells behaved similarly. α1β1 and α2β1 were the integrin-type collagen receptors expressed on these cells with primarily α1β1 localising to focal contacts and affecting cell adhesion and migration in a manner dependent on FLNa or its Ig-like repeats 8-15. Our results suggest a role for FLNa repeats 8-15 in the α1-subunit-dependent regulation of integrin α1β1 function, EGF-EGFR signalling to PKB/Akt and ERK1/2, identify ERK1/2 in EGF-induced FLNa-associated protein complexes, and show that the function of different integrins is subjected to differential regulation by FLNa. Copyright © 2015. Published by Elsevier GmbH.

Cross-situational consistency of trait expressions and injunctive norms among Asian Canadian and European Canadian undergraduates.

PubMed

Locke, Kenneth D; Sadler, Pamela; McDonald, Kelly

2018-06-14

In the current paper, we sought to clarify when and why Asian Americans/Canadians and European Americans/Canadians differ in self-consistency (the consistency of personality traits across situations). European Canadian (n = 220) and second-generation Asian Canadian (n = 166) undergraduates (Mage = 19 years) described the traits they expressed and the traits others wanted them to express (i.e., injunctive norms, or injunctions) in four different social situations (i.e., with parents, with friends, with siblings, and with professors). Self-consistency was greater among European Canadians than Asian Canadians, but only when comparing behavior with parents versus with peers (i.e., friends and siblings). The same pattern was found for injunctive consistency (cross-situational consistency of trait injunctions). Injunctions strongly predicted the behavior of both Asian and European Canadians, but because the injunctions from parents versus peers diverged more for Asian Canadians, so did their behaviors. Controlling for the effect of inconsistent injunctions across situations eliminated the ethnic difference in self-consistency. Finally, Asian Canadians who perceived their immigrant parents as embracing a Canadian identity were as cross-situationally consistent as European Canadians because they tended to behave-and believe their parents approved of their behaving-with parents similarly to how they behaved with peers (e.g., more carefree and outspoken). Contrary to previous theorizing, cultural influences on broad cognitive or motivational dispositions (e.g., dialecticism, collectivism) alone cannot explain the observed pattern of ethnic differences in consistency. To understand when bicultural individuals are less consistent across situations also requires an understanding of the specific situations across which they tend to encounter divergent social norms. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

The Effects of Ultra Thin Films on Dynamic Wetting

NASA Astrophysics Data System (ADS)

Chen, Xia; Garoff, Stephen; Rame, Enrique

2002-11-01

Dynamic wetting, the displacement of one fluid by another immiscible fluid on a surface, controls many natural and technological phenomena, such as coating, printing, spray painting and lubricating. Particularly in coating and spraying applications, contact lines advance across pre-existing fluid films. Most previous work has focused on contact lines advancing across films sufficiently thick that they behave as simple Newtonian fluids. Ultrathin films, where the film thickness may impinge on fundamental length scales in the fluid, have received less attention. In this talk, we will discuss the effects of ultrathin polymer films on dynamic wetting. We measure the interface shape within microns of moving contact lines advancing across preexisting films and compare the measurements to existing models of viscous bending for interfaces advancing across dry surfaces and 'thick' (in the sense that they behave as liquids) films. In the experiments, we advance a contact line of 10-poise and 1-poise polydimethylsiloxane (silicone oil) across pre-coated films of the same fluid with thickness from a single chain thickness (approx. 10 A) through a couple of radii of gyration (100-200 A) to films so thick they are likely bulk in behavior (103 A). All films are physisorbed, i.e. they readily rinse from the surface. Thus, molecules in the film are not anchored to the surface and can move within the film if the hydrodynamics dictate such motion. For films of the thickness of a single chain (approx. 10 A), our experiments indicate that the advancing fluid behaves just as it would if it advanced over a dry surface. For the thicker films (103 A), we find behavior indicating that the molecules in the film are acting as a fluid with the bulk properties. In this regime, results for the two different fluids are identical when the experiments are performed at the same pre-existing film thickness and advancing capillary number, Ca. For film of thickness of a few radii of gyration (approx. 100-200 A), the behavior depends on Ca of the advancing meniscus. At low Ca, the viscous bending of the interface near the contact line does not behave as it would on a dry surface. It has a lower curvature than expected. However, at higher Ca, the viscous bending is described by the model for spreading over a dry surface. These results show that the fluid flow in the film does behave differently than bulk as the film thickness becomes comparable to molecular length scale. But even more intriguing is the unusual velocity dependence of that behavior where the film behaves more solid-like at higher contact line speeds. We will discuss these results in terms of the properties of confined polymer melts.

The Effects of Ultra Thin Films on Dynamic Wetting

NASA Technical Reports Server (NTRS)

Chen, Xia; Garoff, Stephen; Rame, Enrique

2002-01-01

Dynamic wetting, the displacement of one fluid by another immiscible fluid on a surface, controls many natural and technological phenomena, such as coating, printing, spray painting and lubricating. Particularly in coating and spraying applications, contact lines advance across pre-existing fluid films. Most previous work has focused on contact lines advancing across films sufficiently thick that they behave as simple Newtonian fluids. Ultrathin films, where the film thickness may impinge on fundamental length scales in the fluid, have received less attention. In this talk, we will discuss the effects of ultrathin polymer films on dynamic wetting. We measure the interface shape within microns of moving contact lines advancing across preexisting films and compare the measurements to existing models of viscous bending for interfaces advancing across dry surfaces and 'thick' (in the sense that they behave as liquids) films. In the experiments, we advance a contact line of 10-poise and 1-poise polydimethylsiloxane (silicone oil) across pre-coated films of the same fluid with thickness from a single chain thickness (approx. 10 A) through a couple of radii of gyration (100-200 A) to films so thick they are likely bulk in behavior (10(exp 3) A). All films are physisorbed, i.e. they readily rinse from the surface. Thus, molecules in the film are not anchored to the surface and can move within the film if the hydrodynamics dictate such motion. For films of the thickness of a single chain (approx. 10 A), our experiments indicate that the advancing fluid behaves just as it would if it advanced over a dry surface. For the thicker films (10(exp 3) A), we find behavior indicating that the molecules in the film are acting as a fluid with the bulk properties. In this regime, results for the two different fluids are identical when the experiments are performed at the same pre-existing film thickness and advancing capillary number, Ca. For film of thickness of a few radii of gyration (approx. 100-200 A), the behavior depends on Ca of the advancing meniscus. At low Ca, the viscous bending of the interface near the contact line does not behave as it would on a dry surface. It has a lower curvature than expected. However, at higher Ca, the viscous bending is described by the model for spreading over a dry surface. These results show that the fluid flow in the film does behave differently than bulk as the film thickness becomes comparable to molecular length scale. But even more intriguing is the unusual velocity dependence of that behavior where the film behaves more solid-like at higher contact line speeds. We will discuss these results in terms of the properties of confined polymer melts.

Gravity and the cells of gravity receptors in mammals

NASA Technical Reports Server (NTRS)

Ross, M. D.

1983-01-01

A model of the mammalian gravity receptor system is presented, with attention given to the effects of weightlessness. Two receptors are on each side of the head, with end organs in the saccule and utricle of the vestibular membranous labyrinth of the inner ear, embedded in the temporal bone. Each end organ has a macula, containing hair cells and supporting cells, and an otoconial complex, an otoconial membrane and mineral masses called otoconia. X ray powder diffraction examinations have revealed that the otoconia can behave like crystals, i.e., with piezoelectric properties, due to the mineral deposits. Bending of the hair cells because of acceleration can put pressure on the otoconial mineral, producing an electrical signal in the absence of a gravitational field. The possibility that pyroelectricity, as well as piezoelectricity, is present in the otoconial complexes, is discussed.

Disability Hate Crime: Persecuted for Difference

ERIC Educational Resources Information Center

Ralph, Sue; Capewell, Carmel; Bonnett, Elizabeth

2016-01-01

This article briefly discusses the long history of violence towards disabled people which sets the context for an analysis of the modern-day form of violence known as disability hate crime (DHC). People who look or behave differently to others often find themselves victims of violent crimes. The language used to describe disabled people…

Depth of Processing and Age Differences

ERIC Educational Resources Information Center

Kheirzadeh, Shiela; Pakzadian, Sarah Sadat

2016-01-01

The present article is aimed to investigate whether there are any differences between youngsters and adults in their working and long-term memory functioning. The theory of Depth of Processing (Craik and Lockhart in "J Verbal Learning Verbal Behav" 11:671-684, 1972) discusses the varying degrees of strengths of memory traces as the…

Faithful anaphase is ensured by Mis4, a sister chromatid cohesion molecule required in S phase and not destroyed in G1 phase

PubMed Central

Furuya, Kanji; Takahashi, Kohta; Yanagida, Mitsuhiro

1998-01-01

The loss of sister chromatid cohesion triggers anaphase spindle movement. The budding yeast Mcd1/Scc1 protein, called cohesin, is required for associating chromatids, and proteins homologous to it exist in a variety of eukaryotes. Mcd1/Scc1 is removed from chromosomes in anaphase and degrades in G1. We show that the fission yeast protein, Mis4, which is required for equal sister chromatid separation in anaphase is a different chromatid cohesion molecule that behaves independent of cohesin and is conserved from yeast to human. Its inactivation in G1 results in cell lethality in S phase and subsequent premature sister chromatid separation. Inactivation in G2 leads to cell death in subsequent metaphase–anaphase progression but missegregation occurs only in the next round of mitosis. Mis4 is not essential for condensation, nor does it degrade in G1. Rather, it associates with chromosomes in a punctate fashion throughout the cell cycle. mis4 mutants are hypersensitive to hydroxyurea (HU) and UV irradiation but retain the ability to restrain cell cycle progression when damaged or sustaining a block to replication. The mis4 mutation results in synthetic lethality with a DNA ligase mutant. Mis4 may form a stable link between chromatids in S phase that is split rather than removed in anaphase. PMID:9808627

Asymptotics and numerics of a family of two-dimensional generalized surface quasi-geostrophic equations

NASA Astrophysics Data System (ADS)

Ohkitani, Koji

2012-09-01

We study the generalised 2D surface quasi-geostrophic (SQG) equation, where the active scalar is given by a fractional power α of Laplacian applied to the stream function. This includes the 2D SQG and Euler equations as special cases. Using Poincaré's successive approximation to higher α-derivatives of the active scalar, we derive a variational equation for describing perturbations in the generalized SQG equation. In particular, in the limit α → 0, an asymptotic equation is derived on a stretched time variable τ = αt, which unifies equations in the family near α = 0. The successive approximation is also discussed at the other extreme of the 2D Euler limit α = 2-0. Numerical experiments are presented for both limits. We consider whether the solution behaves in a more singular fashion, with more effective nonlinearity, when α is increased. Two competing effects are identified: the regularizing effect of a fractional inverse Laplacian (control by conservation) and cancellation by symmetry (nonlinearity depletion). Near α = 0 (complete depletion), the solution behaves in a more singular fashion as α increases. Near α = 2 (maximal control by conservation), the solution behave in a more singular fashion, as α decreases, suggesting that there may be some α in [0, 2] at which the solution behaves in the most singular manner. We also present some numerical results of the family for α = 0.5, 1, and 1.5. On the original time t, the H1 norm of θ generally grows more rapidly with increasing α. However, on the new time τ, this order is reversed. On the other hand, contour patterns for different α appear to be similar at fixed τ, even though the norms are markedly different in magnitude. Finally, point-vortex systems for the generalized SQG family are discussed to shed light on the above problems of time scale.

Enantiomer‐specific measurements of current‐use pesticides in aquatic systems

EPA Science Inventory

Some current‐use pesticides are chiral and have nonsuperimposable mirror images called enantiomers that exhibit identical physical–chemical properties but can behave differently when in contact with other chiral molecules (e.g., regarding degradation and uptake). Thes...

The Use of Comprehensive Molecular Profiling With Network and Control Theory to Better Understand GWI and Model Therapeutic Strategies

DTIC Science & Technology

2010-07-01

we excluded subjects with DSM IV diagnoses for psychotic or melancholic depression , panic attacks, substance dependency, or psychoses as well as any...with endothelial cells: evidence for depression -induced athero- sclerotic risk. Brain Behav Immun 2008, 2:215-23. 31. Ariza ME, Glaser R, Kaumaya PT...medications, and a past or present psychiatric diagnosis of psychosis (e.g., schizophrenia), dementia, major depressive disorder with psychotic or

Twisted bilayer blue phosphorene: A direct band gap semiconductor

NASA Astrophysics Data System (ADS)

Ospina, D. A.; Duque, C. A.; Correa, J. D.; Suárez Morell, Eric

2016-09-01

We report that two rotated layers of blue phosphorene behave as a direct band gap semiconductor. The optical spectrum shows absorption peaks in the visible region of the spectrum and in addition the energy of these peaks can be tuned with the rotational angle. These findings makes twisted bilayer blue phosphorene a strong candidate as a solar cell or photodetection device. Our results are based on ab initio calculations of several rotated blue phosphorene layers.

Protoplasts Obtained from Candida tropicalis Grown on Alkanes

PubMed Central

Lebeault, J. M.; Roche, B.; Duvnjak, Z.; Azoulay, E.

1969-01-01

A method for the preparation of protoplasts from Candida tropicalis cultivated on n-tetradecane is described. This essentially consists of replacing the mannitol-sorbitol solution of the classical helicase technique by 1 m magnesium sulfate and lowering the pH to 4.1 during incubation in the presence of helicase. The protoplasts thus prepared behave like intact cells and are capable of consuming oxygen in the presence of n-tetradecane, n-decane, 1-decanol, and glucose. Images PMID:5361212

Bioengineered II-VI semiconductor quantum dot-carboxymethylcellulose nanoconjugates as multifunctional fluorescent nanoprobes for bioimaging live cells

NASA Astrophysics Data System (ADS)

Mansur, Alexandra A. P.; Mansur, Herman S.; Mansur, Rafael L.; de Carvalho, Fernanda G.; Carvalho, Sandhra M.

2018-01-01

Colloidal semiconductor quantum dots (QDs) are light-emitting ultra-small nanoparticles, which have emerged as a new class of nanoprobes with unique optical properties for bioimaging and biomedical diagnostic. However, to be used for most biomedical applications the biocompatibility and water-solubility are mandatory that can achieved through surface modification forming QD-nanoconjugates. In this study, semiconductor II-VI quantum dots of type MX (M = Cd, Pb, Zn, X = S) were directly synthesized in aqueous media and at room temperature using carboxymethylcellulose sodium salt (CMC) behaving simultaneously as stabilizing and surface biofunctional ligand. These nanoconjugates were extensively characterized using UV-visible spectroscopy, photoluminescence spectroscopy, X-ray photoelectron spectroscopy, Fourier transform infrared spectroscopy, X-ray diffraction, transmission electron microscopy, dynamic light scattering and zeta potential. The results demonstrated that the biopolymer was effective on nucleating and stabilizing the colloidal nanocrystals of CdS, ZnS, and PbS with the average diameter ranging from 2.0 to 5.0 nm depending on the composition of the semiconductor core, which showed quantum-size confinement effect. These QD/polysaccharide conjugates showed luminescent activity from UV-visible to near-infrared range of the spectra under violet laser excitation. Moreover, the bioassays performed proved that these novel nanoconjugates were biocompatible and behaved as composition-dependent fluorescent nanoprobes for in vitro live cell bioimaging with very promising perspectives to be used in numerous biomedical applications and nanomedicine.

The complex role of NOTCH receptors and their ligands in the development of hepatoblastoma, cholangiocarcinoma and hepatocellular carcinoma.

PubMed

Gil-García, Borja; Baladrón, Victoriano

2016-02-01

The NOTCH signalling pathway is one of the key molecular pathways of embryonic development and adult tissues homeostasis in mammals. Mammals have four NOTCH receptors and various ligands that modulate their activity. Many cell disorders, whose genesis involves the NOTCH signalling pathway, have been discovered, including cancer. The mechanisms by which these receptors and their ligands affect liver cell transformation are not yet well understood, and they seem to behave as both oncogenes and tumour-suppressor proteins. In this review, we discuss the published data regarding the role of these proteins in the development of hepatoblastoma, cholangiocarcinoma and hepatocellular carcinoma malignancies. The alteration of the NOTCH signalling pathway may be one of the main drivers of hepatic neoplastic growth. However, this signalling pathway might also modulate the development of specific liver tumour features. The complexity of the function of NOTCH receptors and their ligands may be due to their interactions with many other cell signalling pathways. Furthermore, the different levels of expression and activation of these receptors could be a reason for their distinct and sometimes contradictory effects. © 2015 Société Française des Microscopies and Société de Biologie Cellulaire de France. Published by John Wiley & Sons Ltd.

Role of ionotropic glutamate receptors in LTP in rat hippocampal CA1 oriens-lacunosum moleculare interneurons

PubMed Central

Oren, Iris; Nissen, Wiebke; Kullmann, Dimitri M.; Somogyi, Peter; Lamsa, Karri P.

2009-01-01

Some interneurons of the hippocampus exhibit NMDA receptor-independent long-term potentiation (LTP) that is induced by presynaptic glutamate release when the postsynaptic membrane potential is hyperpolarized. This ‘anti-Hebbian’ form of LTP is prevented by postsynaptic depolarization or by blocking AMPA and kainate receptors. Although both AMPA and kainate receptors are expressed in hippocampal interneurons, their relative roles in anti-Hebbian LTP are not known. Because interneuron diversity potentially conceals simple rules underlying different forms of plasticity, we focus on glutamatergic synapses onto a subset of interneurons with dendrites in stratum oriens and a main ascending axon that projects to stratum lacunosum-moleculare, the O-LM cells. We show that anti-Hebbian LTP in O-LM interneurons has consistent induction and expression properties, and is prevented by selective inhibition of AMPA receptors. The majority of the ionotropic glutamatergic synaptic current in these cells is mediated by inwardly rectifying Ca2+ -permeable AMPA receptors. Although GluR5-containing kainate receptors contribute to synaptic currents at high stimulus frequency, they are not required for LTP induction. Glutamatergic synapses on O-LM cells thus behave in a homogeneous manner, and exhibit LTP dependent on Ca2+-permeable AMPA receptors. PMID:19176803

Current status and future needs of the BehavePlus Fire Modeling System

Treesearch

Patricia L. Andrews

2014-01-01

The BehavePlus Fire Modeling System is among the most widely used systems for wildland fire prediction. It is designed for use in a range of tasks including wildfire behaviour prediction, prescribed fire planning, fire investigation, fuel hazard assessment, fire model understanding, communication and research. BehavePlus is based on mathematical models for fire...

Switchable genetic oscillator operating in quasi-stable mode

PubMed Central

Strelkowa, Natalja; Barahona, Mauricio

2010-01-01

Ring topologies of repressing genes have qualitatively different long-term dynamics if the number of genes is odd (they oscillate) or even (they exhibit bistability). However, these attractors may not fully explain the observed behaviour in transient and stochastic environments such as the cell. We show here that even repressilators possess quasi-stable, travelling wave periodic solutions that are reachable, long-lived and robust to parameter changes. These solutions underlie the sustained oscillations observed in even rings in the stochastic regime, even if these circuits are expected to behave as switches. The existence of such solutions can also be exploited for control purposes: operation of the system around the quasi-stable orbit allows us to turn on and off the oscillations reliably and on demand. We illustrate these ideas with a simple protocol based on optical interference that can induce oscillations robustly both in the stochastic and deterministic regimes. PMID:20097721

Role of Pullulan in preparation of ceria nanoparticles and investigation of their biological activities

NASA Astrophysics Data System (ADS)

Khorrami, Mohammad Bagher; Sadeghnia, Hamid Reza; Pasdar, Alireza; Ghayour-Mobarhan, Majid; Riahi-Zanjani, Bamdad; Darroudi, Majid

2018-04-01

Throughout this work, a facile, environmental-friendly, and "green" method is delineated for preparing ceria nanoparticles (CNPs), which utilizes nontoxic and renewable degraded polysaccharide polymer including pullulan as a natural matrix. Pullulan behaves as a suitable stabilizing (capping) agent for CNPs that are effectively formed at various high temperatures, while they are structurally analyzed through different techniques such as TGA/DTG, XRD, FESEM, and FTIR instruments. This procedure was found to be comparable to the ones that were acquired from conventional preparation methods that employ hazardous materials, which confirms this approach to be an exquisite alternative in preparing CNPs through the benefit of bioorganic materials. The in vitro cytotoxicity studies on Neuro2A cells have mentioned nontoxic particles in a range of concentrations (0.97-125 μg/ml) and thus, we reckon that the prepared particular CNPs will have persistent utilization in various fields of biology and medicine.

Follicle-stimulating hormone synthesis and fertility are intact in mice lacking SMAD3 DNA binding activity and SMAD2 in gonadotrope cells

PubMed Central

Fortin, Jérôme; Boehm, Ulrich; Weinstein, Michael B.; Graff, Jonathan M.; Bernard, Daniel J.

2014-01-01

The activin/inhibin system regulates follicle-stimulating hormone (FSH) synthesis and release by pituitary gonadotrope cells in mammals. In vitro cell line data suggest that activins stimulate FSH β-subunit (Fshb) transcription via complexes containing the receptor-regulated SMAD proteins SMAD2 and SMAD3. Here, we used a Cre-loxP approach to determine the necessity for SMAD2 and/or SMAD3 in FSH synthesis in vivo. Surprisingly, mice with conditional mutations in both Smad2 and Smad3 specifically in gonadotrope cells are fertile and produce FSH at quantitatively normal levels. Notably, however, we discovered that the recombined Smad3 allele produces a transcript that encodes the entirety of the SMAD3 C-terminal Mad homology 2 (MH2) domain. This protein behaves similarly to full-length SMAD3 in Fshb transcriptional assays. As the truncated protein lacks the N-terminal Mad homology 1 (MH1) domain, these results show that SMAD3 DNA-binding activity as well as SMAD2 are dispensable for normal FSH synthesis in vivo. Furthermore, the observation that deletion of proximal exons does not remove all SMAD3 function may facilitate interpretation of divergent phenotypes previously described in different Smad3 knockout mouse lines.—Fortin, J., Boehm, U., Weinstein, M. B., Graff, J. M., Bernard, D. J. Follicle-stimulating hormone synthesis and fertility are intact in mice lacking SMAD3 DNA binding activity and SMAD2 in gonadotrope cells. PMID:24308975

Transplantation of prokaryotic two-component signaling pathways into mammalian cells.

PubMed

Hansen, Jonathan; Mailand, Erik; Swaminathan, Krishna Kumar; Schreiber, Joerg; Angelici, Bartolomeo; Benenson, Yaakov

2014-11-04

Signaling pathway engineering is a promising route toward synthetic biological circuits. Histidine-aspartate phosphorelays are thought to have evolved in prokaryotes where they form the basis for two-component signaling. Tyrosine-serine-threonine phosphorelays, exemplified by MAP kinase cascades, are predominant in eukaryotes. Recently, a prokaryotic two-component pathway was implemented in a plant species to sense environmental trinitrotoluene. We reasoned that "transplantation" of two-component pathways into mammalian host could provide an orthogonal and diverse toolkit for a variety of signal processing tasks. Here we report that two-component pathways could be partially reconstituted in mammalian cell culture and used for programmable control of gene expression. To enable this reconstitution, coding sequences of histidine kinase (HK) and response regulator (RR) components were codon-optimized for human cells, whereas the RRs were fused with a transactivation domain. Responsive promoters were furnished by fusing DNA binding sites in front of a minimal promoter. We found that coexpression of HKs and their cognate RRs in cultured mammalian cells is necessary and sufficient to strongly induce gene expression even in the absence of pathways' chemical triggers in the medium. Both loss-of-function and constitutive mutants behaved as expected. We further used the two-component signaling pathways to implement two-input logical AND, NOR, and OR gene regulation. Thus, two-component systems can be applied in different capacities in mammalian cells and their components can be used for large-scale synthetic gene circuits.

Conserved pattern of tangential neuronal migration during forebrain development.

PubMed

Métin, Christine; Alvarez, Chantal; Moudoux, David; Vitalis, Tania; Pieau, Claude; Molnár, Zoltán

2007-08-01

Origin, timing and direction of neuronal migration during brain development determine the distinct organization of adult structures. Changes in these processes might have driven the evolution of the forebrain in vertebrates. GABAergic neurons originate from the ganglionic eminence in mammals and migrate tangentially to the cortex. We are interested in differences and similarities in tangential migration patterns across corresponding telencephalic territories in mammals and reptiles. Using morphological criteria and expression patterns of Darpp-32, Tbr1, Nkx2.1 and Pax6 genes, we show in slice cultures of turtle embryos that early cohorts of tangentially migrating cells are released from the medial ganglionic eminence between stages 14 and 18. Additional populations migrate tangentially from the dorsal subpallium. Large cohorts of tangentially migrating neurons originate ventral to the dorsal ventricular ridge at stage 14 and from the lateral ganglionic eminence from stage 15. Release of GABAergic cells from these regions was investigated further in explant cultures. Tangential migration in turtle proceeds in a fashion similar to mammals. In chimeric slice culture and in ovo graft experiments, the tangentially migrating cells behaved according to the host environment - turtle cells responded to the available cues in mouse slices and mouse cells assumed characteristic migratory routes in turtle brains, indicating highly conserved embryonic signals between these distant species. Our study contributes to the evaluation of theories on the origin of the dorsal cortex and indicates that tangential migration is universal in mammals and sauropsids.

Agonist-induced modulation of inverse agonist efficacy at the beta 2-adrenergic receptor.

PubMed

Chidiac, P; Nouet, S; Bouvier, M

1996-09-01

Sustained stimulation of several G protein-coupled receptors is known to lead to a reduction in the signaling efficacy. This phenomenon, named agonist-induced desensitization, has been best studied for the beta 2-adrenergic receptor (AR) and is characterized by a decreased efficacy of beta-adrenergic agonists to stimulate the adenylyl cyclase activity. Recently, several beta-adrenergic ligands were found to inhibit the spontaneous agonist-independent activity of the beta 2AR. These compounds, termed inverse agonists, have different inhibitory efficacies, ranging from almost neutral antagonists to full inverse agonists. The current study was undertaken to determine whether, as is the case for agonists, desensitization can affect the efficacies of inverse agonists. Agonist-promoted desensitization of the human beta 2AR expressed in Sf9 cells potentiated the inhibitory actions of the inverse agonists, with the extent of the potentiation being inversely proportional to their intrinsic activity. For example, desensitization increased the inhibitory action of the weak inverse agonist labetalol by 29%, whereas inhibition of the spontaneous activity by the strong inverse agonist timolol was not enhanced by the desensitizing stimuli. Interestingly, dichloroisoproterenol acted stochastically as either a weak partial agonist or a weak inverse agonist in control conditions but always behaved as an inverse agonist after desensitization. These data demonstrate that like for agonists, the efficacies of inverse agonists can be modulated by a desensitizing treatment. Also, the data show that the initial state of the receptor can determine whether a ligand behaves as a partial agonist or an inverse agonist.

Bioprinting for Neural Tissue Engineering.

PubMed

Knowlton, Stephanie; Anand, Shivesh; Shah, Twisha; Tasoglu, Savas

2018-01-01

Bioprinting is a method by which a cell-encapsulating bioink is patterned to create complex tissue architectures. Given the potential impact of this technology on neural research, we review the current state-of-the-art approaches for bioprinting neural tissues. While 2D neural cultures are ubiquitous for studying neural cells, 3D cultures can more accurately replicate the microenvironment of neural tissues. By bioprinting neuronal constructs, one can precisely control the microenvironment by specifically formulating the bioink for neural tissues, and by spatially patterning cell types and scaffold properties in three dimensions. We review a range of bioprinted neural tissue models and discuss how they can be used to observe how neurons behave, understand disease processes, develop new therapies and, ultimately, design replacement tissues. Copyright © 2017 Elsevier Ltd. All rights reserved.

Research Tool to Evaluate the Safety Response of Lithium Batteries to an Internal Short Circuit

DOE Office of Scientific and Technical Information (OSTI.GOV)

Keyser, Matthew; Darcy, Eric; Pesaran, Ahmad

Li-ion cells provide the highest specific energy and energy density rechargeable battery with the longest life. Many safety incidents that take place in the field originate due to an internal short that was not detectable or predictable at the point of manufacture. NREL's internal short circuit (ISC) device is capable of simulating shorts and produces consistent and reproducible results. The cell behaves normally until the ISC device is activated wherein a latent defect (i.e., built into the cell during manufacturing) gradually moves into position to create an internal short while the battery is in use, providing relevant data to verifymore » abuse models. The ISC device is an effective tool for studying the safety features of parts of Li-ion batteries.« less

Effects of Misbehaving Common Items on Aggregate Scores and an Application of the Mantel-Haenszel Statistic in Test Equating. CSE Report 688

ERIC Educational Resources Information Center

Michaelides, Michalis P.

2006-01-01

Consistent behavior is a desirable characteristic that common items are expected to have when administered to different groups. Findings from the literature have established that items do not always behave in consistent ways; item indices and IRT item parameter estimates of the same items differ when obtained from different administrations.…

Education and Competitive Economy: How Do Cultural Dimensions Fit In?

ERIC Educational Resources Information Center

Cheung, Hoi Yan; Chan, Alex Wing Ho

2010-01-01

Globalization has changed the way people behave in different aspects of life. One of the significant differences is that people are now competing with everyone around the world, not just people within or near their own regions. A good way of remaining competitive is to provide quality education that can help students meet the needs of the…

Low- and High-IQ Learning Disabled Children in the Mainstream.

ERIC Educational Resources Information Center

Gottlieb, Jay; And Others

1983-01-01

Nine low IQ (less than 80) and 12 high IQ (100 plus) learning disabled children (grades four through six) who attended resource room programs were observed in regular classes. Results indicated that teachers did not perceive the two groups of LD children differently but that the teachers behaved differently toward the two groups. (Author/MC)

Echoes of the embryo: using the developmental biology toolkit to study cancer.

PubMed

Aiello, Nicole M; Stanger, Ben Z

2016-02-01

The hallmark of embryonic development is regulation - the tendency for cells to find their way into organized and 'well behaved' structures - whereas cancer is characterized by dysregulation and disorder. At face value, cancer biology and developmental biology would thus seem to have little to do with each other. But if one looks beneath the surface, embryos and cancers share a number of cellular and molecular features. Embryos arise from a single cell and undergo rapid growth involving cell migration and cell-cell interactions: features that are also seen in the context of cancer. Consequently, many of the experimental tools that have been used to study embryogenesis for over a century are well-suited to studying cancer. This article will review the similarities between embryogenesis and cancer progression and discuss how some of the concepts and techniques used to understand embryos are now being adapted to provide insight into tumorigenesis, from the origins of cancer cells to metastasis. © 2016. Published by The Company of Biologists Ltd.

An integrated system for synchronous culture of animal cells under controlled conditions.

PubMed

Mendoza-Pérez, Elena; Hernández, Vanessa; Palomares, Laura A; Serrato, José A

2016-01-01

The cell cycle has fundamental effects on cell cultures and their products. Tools to synchronize cultured cells allow the study of cellular physiology and metabolism at particular cell cycle phases. However, cells are most often arrested by methods that alter their homeostasis and are then cultivated in poorly controlled environments. Cell behavior could then be affected by the synchronization method and culture conditions used, and not just by the particular cell cycle phase under study. Moreover, only a few viable cells are recovered. Here, we designed an integrated system where a large number of cells from a controlled bioreactor culture is separated by centrifugal elutriation at high viabilities. In contrast to current elutriation methods, cells are injected directly from a bioreactor into an injection loop, allowing the introduction of a large number of cells into the separation chamber without stressful centrifugation. A low pulsation peristaltic pump increases the stability of the elutriation chamber. Using this approach, a large number of healthy cells at each cell cycle phase were obtained, allowing their direct inoculation into fully instrumented bioreactors. Hybridoma cells synchronized and cultured in this system behaved as expected for a synchronous culture.

Piezo- and Flexoelectric Membrane Materials Underlie Fast Biological Motors in the Ear

PubMed Central

Breneman, Kathryn D.; Rabbitt, Richard D.

2010-01-01

The mammalian inner ear is remarkably sensitive to quiet sounds, exhibits over 100dB dynamic range, and has the exquisite ability to discriminate closely spaced tones even in the presence of noise. This performance is achieved, in part, through active mechanical amplification of vibrations by sensory hair cells within the inner ear. All hair cells are endowed with a bundle of motile microvilli, stereocilia, located at the apical end of the cell, and the more specialized outer hair cells (OHC’s) are also endowed with somatic electromotility responsible for changes in cell length in response to perturbations in membrane potential. Both hair bundle and somatic motors are known to feed energy into the mechanical vibrations in the inner ear. The biophysical origin and relative significance of the motors remains a subject of intense research. Several biological motors have been identified in hair cells that might underlie the motor(s), including a cousin of the classical ATP driven actin-myosin motor found in skeletal muscle. Hydrolysis of ATP, however, is much too slow to be viable at audio frequencies on a cycle-by-cycle basis. Heuristically, the OHC somatic motor behaves as if the OHC lateral wall membrane were a piezoelectric material and the hair bundle motor behaves as if the plasma membrane were a flexoelectric material. We propose these observations from a continuum materials perspective are literally true. To examine this idea, we formulated mathematical models of the OHC lateral wall “piezoelectric” motor and the more ubiquitous “flexoelectric” hair bundle motor. Plausible biophysical mechanisms underlying piezo- and flexoelectricity were established. Model predictions were compared extensively to the available data. The models were then applied to study the power conversion efficiency of the motors. Results show that the material properties of the complex membranes in hair cells provide them with the ability to convert electrical power available in the inner ear cochlea into useful mechanical amplification of sound induced vibrations at auditory frequencies. We also examined how hair cell amplification might be controlled by the brain through efferent synaptic contacts on hair cells and found a simple mechanism to tune hearing to signals of interest to the listener by electrical control of these motors. PMID:21188296

Laser-modified titanium surfaces enhance the osteogenic differentiation of human mesenchymal stem cells.

PubMed

Bressel, Tatiana A B; de Queiroz, Jana Dara Freires; Gomes Moreira, Susana Margarida; da Fonseca, Jéssyca T; Filho, Edson A; Guastaldi, Antônio Carlos; Batistuzzo de Medeiros, Silvia Regina

2017-11-28

Titanium surfaces have been modified by various approaches with the aim of improving the stimulation of osseointegration. Laser beam (Yb-YAG) treatment is a controllable and flexible approach to modifying surfaces. It creates a complex surface topography with micro and nano-scaled patterns, and an oxide layer that can improve the osseointegration of implants, increasing their usefulness as bone implant materials. Laser beam irradiation at various fluences (132, 210, or 235 J/cm 2 ) was used to treat commercially pure titanium discs to create complex surface topographies. The titanium discs were investigated by scanning electron microscopy, X-ray diffraction, and measurement of contact angles. The surface generated at a fluence of 235 J/cm 2 was used in the biological assays. The behavior of mesenchymal stem cells from an umbilical cord vein was evaluated using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, a mineralization assay, and an alkaline phosphatase activity assay and by carrying out a quantitative real-time polymerase chain reaction for osteogenic markers. CHO-k1 cells were also exposed to titanium discs in the MTT assay. The best titanium surface was that produced by laser beam irradiation at 235 J/cm 2 fluence. Cell proliferation analysis revealed that the CHO-k1 and mesenchymal stem cells behaved differently. The laser-processed titanium surface increased the proliferation of CHO-k1 cells, reduced the proliferation of mesenchymal stem cells, upregulated the expression of the osteogenic markers, and enhanced alkaline phosphatase activity. The laser-treated titanium surface modulated cellular behavior depending on the cell type, and stimulated osteogenic differentiation. This evidence supports the potential use of laser-processed titanium surfaces as bone implant materials, and their use in regenerative medicine could promote better outcomes.

The games economists play: Why economics students behave more selfishly than other students

PubMed Central

Gerlach, Philipp

2017-01-01

Do economics students behave more selfishly than other students? Experiments involving monetary allocations suggest so. This article investigates the underlying motives for the economic students’ more selfish behavior by separating three potential explanatory mechanisms: economics students are less concerned with fairness when making allocation decisions; have a different notion of what is fair in allocations; or are more skeptical about other people’s allocations, which in turn makes them less willing to comply with a shared fairness norm. The three mechanisms were tested by inviting students from various disciplines to participate in a relatively novel experimental game and asking all participants to give reasons for their choices. Compared with students of other disciplines, economics students were about equally likely to mention fairness in their comments; had a similar notion of what was fair in the situation; however, they expected lower offers, made lower offers, and were less willing to enforce compliance with a fair allocation at a cost to themselves. The economics students’ lower expectations mediated their allocation decisions, suggesting that economics students behaved more selfishly because they expected others not to comply with the shared fairness norm. PMID:28873465

The games economists play: Why economics students behave more selfishly than other students.

PubMed

Gerlach, Philipp

2017-01-01

Do economics students behave more selfishly than other students? Experiments involving monetary allocations suggest so. This article investigates the underlying motives for the economic students' more selfish behavior by separating three potential explanatory mechanisms: economics students are less concerned with fairness when making allocation decisions; have a different notion of what is fair in allocations; or are more skeptical about other people's allocations, which in turn makes them less willing to comply with a shared fairness norm. The three mechanisms were tested by inviting students from various disciplines to participate in a relatively novel experimental game and asking all participants to give reasons for their choices. Compared with students of other disciplines, economics students were about equally likely to mention fairness in their comments; had a similar notion of what was fair in the situation; however, they expected lower offers, made lower offers, and were less willing to enforce compliance with a fair allocation at a cost to themselves. The economics students' lower expectations mediated their allocation decisions, suggesting that economics students behaved more selfishly because they expected others not to comply with the shared fairness norm.

Detection of biotin in individual sea urchin oocytes using a bioluminescence binding assay.

PubMed

Feltus, A; Grosvenor, A L; Conover, R C; Anderson, K W; Daunert, S

2001-04-01

The ability to detect biomolecules in single cells is important in order to fully understand the processes by which many biochemical events occur. To that end, we have developed a bioluminescence binding assay capable of measuring the intracellular biotin content of individual cells. The assay depends on competition between an aequorin-biotin conjugate (AEQ-biotin) and free biotin within the oocytes for binding sites on the protein avidin. The assay is performed by microinjecting each component into the oocytes and following the resulting bioluminescence within the oocyte upon triggering of aequorin. Results obtained using sea urchin oocytes show that the assay performed within the cells behaves in a manner consistent with assay theory. Using the assay, the individual biotin content of the oocytes is an average of approximately 20 amol. To our knowledge, this is the first reported multicomponent binding assay to be performed inside an intact single cell.

Changes in Somatosensory Responsiveness in Behaving Primates

DTIC Science & Technology

1988-08-01

visually vs. vibratory-triggered movements; 2) to record from the cerebral cortex of awake , behaving monkeys during the performance of these sensory...vibratory-triggered movements; 2) to record from the cerebral cortex of awake , behaving monkeys during the performance of these sensory-triggered...recording chamber was implanted over the forelimb * region of the left sensorimotor cortices following a craniotomy and secured with smaller bolts and the

Changes in Sensory Responsiveness in Behaving Primates.

DTIC Science & Technology

1986-07-14

controlled behavioral training and monitoring, and electrophysiological recording in awake , behaving monkeys. All I, research equipment listed in the original...recording from the sensorimotor cortices was conducted on May 21. Under general anesthesia, a craniotomy was performed over the pre- and postcentral cortices...Department of Neurosurgery at U.T. Dr. Klein is somewhat unusual in that he has had previous experience recording from awake , behaving monkeys. The experience

Validation of BEHAVE fire behavior predictions in oak savannas using five fuel models

Treesearch

Keith Grabner; John Dwyer; Bruce Cutter

1997-01-01

Prescribed fire is a valuable tool in the restoration and management of oak savannas. BEHAVE, a fire behavior prediction system developed by the United States Forest Service, can be a useful tool when managing oak savannas with prescribed fire. BEHAVE predictions of fire rate-of-spread and flame length were validated using four standardized fuel models: Fuel Model 1 (...

Noise as a Public Health Problem: Proceedings of the International Congress (4th) Held at Turin (Italy) on June 21-25, 1983. Volume 1.

DTIC Science & Technology

1983-11-01

22 , 821-825. Peters, D.A.V., Prenatal stress: effects on brain biogenic amine and plasma corticosterone levels. Pharmacol., Biochem. and Behav., 17...527 Late Postnatal Effect on Corticosterone Blood Level, of an Acoustical Stimulation Previously Applied to Mice During Pre or Early Postnatal...evaluated threshold shifts and/or hair cell destruction as indicatozs of damage. The aim has particularly been focused on the effect of systema- tically

Pathophysiological Alterations In The Basolateral Amygdala And Neurodegeneration Of Limbic Structures During Epileptogenesis Induced By Status Epilepticus

DTIC Science & Technology

2009-02-05

Crestani F, Martin JR, Möhler H, and Rudolph U (2000) Mechanism of action of the hypnotic zolpidem in vivo. Br J Pharmacol 131:1251–56...epilepsy laterality and reproductive hormone levels in women. Epilepsy Behav 4:407-13. Houser CR (1990) Granule cell dispersion in the dentate gyrus of...cortex from epileptic patients. Neurobiol Dis 8:459- 68. Kostarczyk EM (1986) The amygdala and male reproductive functions. I. Anatomical and

Proceedings of the Quantum Computation for Physical Modeling Workshop Held in North Falmouth, Massachusetts on October 18-19, 2000

DTIC Science & Technology

2002-01-01

1-3], a task that is exponen- algorithms to model quantum mechanical systems. tially complex in the number of particles treated and A starting point ...cell size approaches zero). There- tion were presented by Succi and Benzi [10,11] and fore, from the point -of-view of the modeler, there ex- by... point regarding this particular In both cases, the model behaves as expected. gate is that when measurements are periodically made Third, in Section 4

Genomes Behave as Social Entities: Alien Chromatin Minorities Evolve Through Specificities Reduction

USDA-ARS?s Scientific Manuscript database

Hybridization and chromosome doubling entailed by allopolyploidization requires genetic and epigenetic modifications, resulting in the adjustment of different genomes to the same nuclear environment. Recently, the main role of retrotransposon/microsatellite-rich regions of the genome in DNA sequenc...

Fluorescent Photo-conversion: A second chance to label unique cells.

PubMed

Mellott, Adam J; Shinogle, Heather E; Moore, David S; Detamore, Michael S

2015-03-01

Not all cells behave uniformly after treatment in tissue engineering studies. In fact, some treated cells display no signs of treatment or show unique characteristics not consistent with other treated cells. What if the "unique" cells could be isolated from a treated population, and further studied? Photo-convertible reporter proteins, such as Dendra2 , allow for the ability to selectively identify unique cells with a secondary label within a primary labeled treated population. In the current study, select cells were identified and labeled through photo-conversion of Dendra2 -transfected human Wharton's Jelly cells (hWJCs) for the first time. Robust photo-conversion of green-to-red fluorescence was achieved consistently in arbitrarily selected cells, allowing for precise cell identification of select hWJCs. The current study demonstrates a method that offers investigators the opportunity to selectively label and identify unique cells within a treated population for further study or isolation from the treatment population. Photo-convertible reporter proteins, such as Dendra2 , offer the ability over non-photo-convertible reporter proteins, such as green fluorescent protein, to analyze unique individual cells within a treated population, which allows investigators to gain more meaningful information on how a treatment affects all cells within a target population.

Time Correlations of Lightning Flash Sequences in Thunderstorms Revealed by Fractal Analysis

NASA Astrophysics Data System (ADS)

Gou, Xueqiang; Chen, Mingli; Zhang, Guangshu

2018-01-01

By using the data of lightning detection and ranging system at the Kennedy Space Center, the temporal fractal and correlation of interevent time series of lightning flash sequences in thunderstorms have been investigated with Allan factor (AF), Fano factor (FF), and detrended fluctuation analysis (DFA) methods. AF, FF, and DFA methods are powerful tools to detect the time-scaling structures and correlations in point processes. Totally 40 thunderstorms with distinguishing features of a single-cell storm and apparent increase and decrease in the total flash rate were selected for the analysis. It is found that the time-scaling exponents for AF (αAF) and FF (αFF) analyses are 1.62 and 0.95 in average, respectively, indicating a strong time correlation of the lightning flash sequences. DFA analysis shows that there is a crossover phenomenon—a crossover timescale (τc) ranging from 54 to 195 s with an average of 114 s. The occurrence of a lightning flash in a thunderstorm behaves randomly at timescales <τc but shows strong time correlation at scales >τc. Physically, these may imply that the establishment of an extensive strong electric field necessary for the occurrence of a lightning flash needs a timescale >τc, which behaves strongly time correlated. But the initiation of a lightning flash within a well-established extensive strong electric field may involve the heterogeneities of the electric field at a timescale <τc, which behave randomly.

Semi- and thiosemicarbazide Mn(II) complexes: Characterization, DFT and biological studies

NASA Astrophysics Data System (ADS)

Yousef, T. A.; Alduaij, O. K.; Ahmed, Sara F.; Abu El-Reash, G. M.; El-Gammal, O. A.

2016-09-01

One NO and two NOS donor ligands have been prepared by addition ethanolic suspension of 2-hydrazino-2-oxo-N-phenyl-acetamide to phenyl isocyanate (H2PAPS), phenyl isothiocyanate (H2PAPT) and benzoyl isothiocyanate (H2PABT). The Mn (II) complexes were prepared from the chloride salt and characterized by conventional techniques. The isolated complexes were assigned the formulaes, [Mn(HPAPS)2], [Mn(HPAPT)Cl] and [Mn(HPABT)Cl(H2O)2], respectively. The IR study of ligands and their complexes shows that H2PAPS behaves as a mononegative tridentate via both CO of hydrazide moiety in keto and deprotonated enol form and CN (azomethine) due to enolization of CO cyanate moiety without deprotonation. H2PAPT behaves as mononegative tridentate via CO of hydrazide moiety, deprotonated thiol CS and NH group. Finally H2PABT behaves as mononegative tridentate via deprotonated enolized CO of hydrazide moiety, CO of benzoyl moiety and NH group. The IR spectra of ligands from DFT calculations are compared with those obtained experimentally. Also, HOMO, LUMO, the bond lengths, bond angles, and dipole moments have been calculated. The calculated HOMO-LUMO energy gap reveals that charge transfer occurs within the molecule. The binding energy values display the high stability of complexes. The kinetic and thermodynamic parameters were determined by Coats-Redfern and Horowitz-Metzger methods. The antibacterial activities were also tested against Bacillus subtilis and Escherichia coli bacteria. Finally, the antitumor activities of the Ligands and their Mn(II) complexes have been evaluated against liver (HePG2) and breast (MCF-7) cancer cells.

Developmental change in the contribution of voltage-gated Ca(2+) channels to the pacemaking of deep cerebellar nuclei neurons.

PubMed

Alviña, K; Tara, E; Khodakhah, K

2016-05-13

The activity of the deep cerebellar nuclei (DCN) neurons conveys the bulk of the output of the cerebellum. To generate these motor signals, DCN neurons integrate synaptic inputs with their own spontaneous activity. We have previously reported that N-type voltage-gated Ca(2+) channels modulate the spontaneous activity of the majority of juvenile DCN neurons in vitro. Specifically, pharmacologically blocking N-type Ca(2+) channels increases their firing rate causing DCN cells to burst. Adult DCN neurons however, behaved differently. To further investigate this change, we have studied here the effect of cadmium on the firing rate of DCN neurons in acute cerebellar slices obtained from adult (>2 months old) or juvenile (12-21 days old) rats and mice. Strikingly, and in contrast to juvenile DCN cells, cadmium did not affect the pacemaking of adult DCN cells. The activity of Purkinje cells (PCs) however was transformed into high-frequency bursting, regardless the age. Further, we questioned whether these findings could be due to an artifact associated with the added difficulty of preparing adult DCN slices. Hence we proceeded to examine the spontaneous activity of DCN neurons in anesthetized juvenile and adult rats and mice in vivo. When cadmium was injected into the DCN in vivo no significant change in firing rate was observed, conversely to most juvenile DCN neurons which showed high-frequency bursts after cadmium injection. In these same animals, PCs pacemaking showed no developmental difference. Thus our results demonstrate a remarkable age-dependent functional modification in the regulation of DCN neurons pacemaking. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Chiral Thioxanthones as Modulators of P-glycoprotein: Synthesis and Enantioselectivity Studies.

PubMed

Lopes, Ana; Martins, Eva; Silva, Renata; Pinto, Madalena M M; Remião, Fernando; Sousa, Emília; Fernandes, Carla

2018-03-10

Recently, thioxanthone derivatives were found to protect cells against toxic P-glycoprotein (P-gp) substrates, acting as potent inducers/activators of this efflux pump. The study of new P-gp chiral modulators produced from thioxanthone derivatives could clarify the enantioselectivity of this ABC transporter towards this new class of modulators. The aim of this study was to evaluate the P-gp modulatory ability of four enantiomeric pairs of new synthesized chiral aminated thioxanthones (ATxs) 1 - 8 , studying the influence of the stereochemistry on P-gp induction/ activation in cultured Caco-2 cells. The data displayed that all the tested compounds (at 20 μM) significantly decreased the intracellular accumulation of a P-gp fluorescent substrate (rhodamine 123) when incubated simultaneously for 60 min, demonstrating an increased activity of the efflux, when compared to control cells. Additionally, all of them except ATx 3 (+), caused similar results when the accumulation of the P-gp fluorescent substrate was evaluated after pre-incubating cells with the test compounds for 24 h, significantly reducing the rhodamine 123 intracellular accumulation as a result of a significant increase in P-gp activity. However, ATx 2 (-) was the only derivative that, after 24 h of incubation, significantly increased P-gp expression. These results demonstrated a significantly increased P-gp activity, even without an increase in P-gp expression. Therefore, ATxs 1 - 8 were shown to behave as P-gp activators. Furthermore, no significant differences were detected in the activity of the protein when comparing the enantiomeric pairs. Nevertheless, ATx 2 (-) modulates P-gp expression differently from its enantiomer, ATx 1 (+). These results disclosed new activators and inducers of P-gp and highlight the existence of enantioselectivity in the induction mechanism.

Two-photon imaging of neuronal activity in motor cortex of marmosets during upper-limb movement tasks.

PubMed

Ebina, Teppei; Masamizu, Yoshito; Tanaka, Yasuhiro R; Watakabe, Akiya; Hirakawa, Reiko; Hirayama, Yuka; Hira, Riichiro; Terada, Shin-Ichiro; Koketsu, Daisuke; Hikosaka, Kazuo; Mizukami, Hiroaki; Nambu, Atsushi; Sasaki, Erika; Yamamori, Tetsuo; Matsuzaki, Masanori

2018-05-14

Two-photon imaging in behaving animals has revealed neuronal activities related to behavioral and cognitive function at single-cell resolution. However, marmosets have posed a challenge due to limited success in training on motor tasks. Here we report the development of protocols to train head-fixed common marmosets to perform upper-limb movement tasks and simultaneously perform two-photon imaging. After 2-5 months of training sessions, head-fixed marmosets can control a manipulandum to move a cursor to a target on a screen. We conduct two-photon calcium imaging of layer 2/3 neurons in the motor cortex during this motor task performance, and detect task-relevant activity from multiple neurons at cellular and subcellular resolutions. In a two-target reaching task, some neurons show direction-selective activity over the training days. In a short-term force-field adaptation task, some neurons change their activity when the force field is on. Two-photon calcium imaging in behaving marmosets may become a fundamental technique for determining the spatial organization of the cortical dynamics underlying action and cognition.

Experimental determination of dynamic parameters of an industrial robot

NASA Astrophysics Data System (ADS)

Banas, W.; Cwikła, G.; Foit, K.; Gwiazda, A.; Monica, Z.; Sekala, A.

2017-08-01

In an industry increasingly used are industrial robots. Commonly used are two basic methods of programming, on-line programming and off-line programming. In both cases, the programming consists in getting to the selected points record this position, and set the order of movement of the robot, and the introduction of logical tests. Such a program is easy to write, and it is suitable for most industrial applications. Especially when the process is known, respectively slow and unchanging. In this case, the program is being prepared for a universal model of the robot with the appropriate geometry and are checked only collisions. Is not taken into account the dynamics of the robot and how it will really behave while in motion. For this reason, the robot programmed to be tested at a reduced speed, which is raised gradually to the final value. Depending on the complexity of the move and the proximity of the elements it takes a lot of time. It is easy to notice that the robot at different speeds have different trajectories and behaves differently.

Game location and aggression in rugby league.

PubMed

Jones, Marc V; Bray, Steven R; Olivier, Stephen

2005-04-01

The present study examined the relationship between aggression and game location in rugby league. We videotaped a random sample of 21 professional rugby league games played in the 2000 Super League season. Trained observers recorded the frequency of aggressive behaviours. Consistent with previous research, which used territoriality theories as a basis for prediction, we hypothesized that the home team would behave more aggressively than the away team. The results showed no significant difference in the frequency of aggressive behaviours exhibited by the home and away teams. However, the away teams engaged in substantially more aggressive behaviours in games they lost compared with games they won. No significant differences in the pattern of aggressive behaviours for home and away teams emerged as a function of game time (i.e. first or second half) or game situation (i.e. when teams were winning, losing or drawing). The findings suggest that while home and away teams do not display different levels of aggression, the cost of behaving aggressively (in terms of game outcome) may be greater for the away team.

Studies on Rapidly Frozen Suspensions of Yeast Cells by Differential Thermal Analysis and Conductometry

PubMed Central

Mazur, Peter

1963-01-01

Few, if any, yeast cells survived rapid cooling to -196°C and subsequent slow warming. After rapid freezing, the suspensions absorbed latent heat of fusion between -15° and 0°C during warming, and the relation between the amount of heat absorbed and the concentration of cells was the same as that in equivalent KCl solutions, indicating that frozen suspensions behave thermally like frozen solutions. The amount of heat absorbed was such that more than 80 per cent of the intracellular solution had to be frozen. The conductometric behavior of frozen suspensions showed that cell solutes were still inside the cells and surrounded by an intact cell membrane at the time heat was being absorbed. Two models are consistent with these findings. The first assumes that intracellular freezing has taken place; the second that all freezable water has left the cells and frozen externally. The latter model is ruled out because rapidly cooled cells do not shrink by an amount equal to the volume of water that would have to be withdrawn to prevent internal freezing. PMID:13934216

BK Polyomavirus Genotypes Represent Distinct Serotypes with Distinct Entry Tropism

PubMed Central

Pastrana, Diana V.; Ray, Upasana; Magaldi, Thomas G.; Schowalter, Rachel M.; Çuburu, Nicolas

2013-01-01

BK polyomavirus (BKV) causes significant urinary tract pathogenesis in immunosuppressed individuals, including kidney and bone marrow transplant recipients. It is currently unclear whether BKV-neutralizing antibodies can moderate or prevent BKV disease. We developed reporter pseudoviruses based on seven divergent BKV isolates and performed neutralization assays on sera from healthy human subjects. The results demonstrate that BKV genotypes I, II, III, and IV are fully distinct serotypes. While nearly all healthy subjects had BKV genotype I-neutralizing antibodies, a majority of subjects did not detectably neutralize genotype III or IV. Surprisingly, BKV subgenotypes Ib1 and Ib2 can behave as fully distinct serotypes. This difference is governed by as few as two residues adjacent to the cellular glycan receptor-binding site on the virion surface. Serological analysis of mice given virus-like particle (VLP)-based BKV vaccines confirmed these findings. Mice administered a multivalent VLP vaccine showed high-titer serum antibody responses that potently cross-neutralized all tested BKV genotypes. Interestingly, each of the neutralization serotypes bound a distinct spectrum of cell surface receptors, suggesting a possible connection between escape from recognition by neutralizing antibodies and cellular attachment mechanisms. The finding implies that different BKV genotypes have different cellular tropisms and pathogenic potentials in vivo. Individuals who are infected with one BKV serotype may remain humorally vulnerable to other BKV serotypes after implementation of T cell immunosuppression. Thus, prevaccinating organ transplant recipients with a multivalent BKV VLP vaccine might reduce the risk of developing posttransplant BKV disease. PMID:23843634

CXCL4L1 inhibits angiogenesis and induces undirected endothelial cell migration without affecting endothelial cell proliferation and monocyte recruitment.

PubMed

Sarabi, A; Kramp, B K; Drechsler, M; Hackeng, T M; Soehnlein, O; Weber, C; Koenen, R R; Von Hundelshausen, P

2011-01-01

The non-allelic variant of CXCL4/PF4, CXCL4L1/PF4alt, differs from CXCL4 in three amino acids of the C-terminal α-helix and has been characterized as a potent anti-angiogenic regulator. Although CXCL4 structurally belongs to the chemokine family, it does not behave like a 'classical' chemokine, lacking significant chemotactic properties. Specific hallmarks are its angiostatic, anti-proliferative activities, and proinflammatory functions, which can be conferred by heteromer-formation with CCL5/RANTES enhancing monocyte recruitment. Here we show that tube formation of endothelial cells was inhibited by CXCL4L1 and CXCL4, while only CXCL4L1 triggered chemokinesis of endothelial cells. The chemotactic response towards VEGF and bFGF was attenuated by both variants and CXCL4L1-induced chemokinesis was blocked by bFGF or VEGF. Endothelial cell proliferation was inhibited by CXCL4 (IC(50) 6.9 μg mL(-1)) but not by CXCL4L1, while both chemokines bound directly to VEGF and bFGF. Moreover, CXCL4 enhanced CCL5-induced monocyte arrest in flow adhesion experiments and monocyte recruitment into the mouse peritoneal cavity in vivo, whereas CXCL4L1 had no effect. CXCL4L1 revealed lower affinity to CCL5 than CXCL4, as quantified by isothermal fluorescence titration. As evidenced by the reduction of the activated partial thromboplastin time, CXCL4L1 showed a tendency towards less heparin-neutralizing activity than CXCL4 (IC(50) 2.45 vs 0.98 μg mL(-1)).  CXCL4L1 may act angiostatically by causing random endothelial cell locomotion, disturbing directed migration towards angiogenic chemokines, serving as a homeostatic chemokine with a moderate structural distinction yet different functional profile from CXCL4. © 2010 International Society on Thrombosis and Haemostasis.

Physical and chemical differences between one-stage and two-stage hydrothermal pretreated hardwood substrates for use in cellulosic ethanol production

DOE PAGES

Guilliams, Andrew; Pattathil, Sivakumar; Willies, Deidre; ...

2016-02-03

Here, there are many different types of pretreatment carried out to prepare cellulosic substrates for fermentation. In this study, one- and two-stage hydrothermal pretreatment were carried out to determine their effects on subsequent fermentations. The two substrates were found to behave differently during fermentation. The two substrates were then characterized using physical and chemical parameters.

Gap junctions between interneurons are required for normal spatial coding in the hippocampus and short-term spatial memory

PubMed Central

Allen, Kevin; Fuchs, Elke C.; Jaschonek, Hannah; Bannerman, David M.; Monyer, Hannah

2011-01-01

Gap junctions containing connexin-36 (Cx36) electrically couple interneurons in many brain regions and synchronize their activity. We used Cx36 knockout mice (Cx36−/−) to study the importance of electrical coupling between interneurons for spatial coding in the hippocampus and for different forms of hippocampus-dependent spatial memory. Recordings in behaving mice revealed that the spatial selectivity of hippocampal pyramidal neurons was reduced and less stable in Cx36−/− mice. Altered network activity was reflected in slower theta oscillations in the mutants. Temporal coding, assessed by determining the presence and characteristics of theta phase precession, had different dynamics in Cx36−/− mice compared to controls. At the behavioral level, Cx36−/− mice displayed impaired short-term spatial memory but normal spatial reference memory. These results highlight the functional role of electrically coupled interneurons for spatial coding and cognition. Moreover, they suggest that the precise spatial selectivity of place cells is not essential for normal performance on spatial tasks assessing associative long-term memory. PMID:21525295

Design, synthesis, and action of oxotremorine-related hybrid-type allosteric modulators of muscarinic acetylcholine receptors.

PubMed

Disingrini, Teresa; Muth, Mathias; Dallanoce, Clelia; Barocelli, Elisabetta; Bertoni, Simona; Kellershohn, Kerstin; Mohr, Klaus; De Amici, Marco; Holzgrabe, Ulrike

2006-01-12

A novel series of muscarinic receptor ligands of the hexamethonio-type was prepared which contained, on one side, the phthalimidopropane or 1,8-naphthalimido-2,2-dimethylpropane moiety typical for subtype selective allosteric antagonists and, on the other, the acetylenic fragment typical for the nonselective orthosteric muscarinic agonists oxotremorine, oxotremorine-M, and related muscarinic agonists. Binding experiments in M(2) receptors using [(3)H]N-methylscopolamine as an orthosteric probe proved an allosteric action of both groups of hybrids, 7a-10a and 8b-10b. The difference in activity between a-group and b-group hybrids corresponded with the activity difference between the allosteric parent compounds. In M(1)-M(3) muscarinic isolated organ preparations, most of the hybrids behaved as subtype selective antagonists. [(35)S]GTPgammaS binding assays using human M(2) receptors overexpressed in CHO cells revealed that a weak intrinsic efficacy was preserved in 8b-10b. Thus, attaching muscarinic allosteric antagonist moieties to orthosteric muscarinic agonists may lead to hybrid compounds in which functions of both components are mixed.

Current directions in behavioral medicine research on genetic testing for disease susceptibility: introduction to the special section.

PubMed

Sherman, Kerry A; Cameron, Linda D

2015-10-01

The aim of this special section is to showcase research contributing to our understanding of factors influencing decisions to undergo genetic testing and the impact of the genetic testing process on health-related behaviors of tested individuals. The first two articles report studies investigating factors associated with interest in genetic testing and acceptance of test results (Sherman et al. in J Behav Med doi: 10.1007/s10865-015-9630-9 , 2015; Taber et al. in J Behav Med doi: 10.1007/s10865-015-9642-5 , 2015b). The next two papers address the unique contribution of genetic risk information to understanding risk beyond genetic counseling alone (Heiniger et al. in J Behav Med doi 10.1007/s10865-015-9632-7 , 2015; Taber et al. in J Behav Med doi: 10.1007/s10865-015-9648-z , 2015a). The final three articles investigate the effects of genetic risk information on beliefs about disease control and prevention (Aspinwall et al. in J Behav Med doi: 10.1007/s10865-015-9631-8 , 2015; Kelly et al. in J Behav Med doi 10.1007/s10865-014-9613-2 , 2014; Myers et al. in J Behav Med doi: 10.1007/s10865-015-9626-5 , 2015). Collectively, the special section of papers highlights the diverse ways in which behavioural medicine contributes to our understanding of genetic testing for disease risk, and points to the value of further research to better understand ways in which individuals perceive, interpret and respond to genetic risk information.

A numerical study of slope and fuel structure effects on coupled wildfire behaviour

Treesearch

Rodman R. Linn; Judith L. Winterkamp; David R. Weise; Carleton Edminster

2010-01-01

Slope and fuel structure are commonly accepted as major factors affecting theway wildfires behave. However, it is possible that slope affects fire differently depending on the fuel bed. Six FIRETEC simulations using three different fuel beds on flat and upslope topography were used to examine this possibility. Fuel beds resembling grass, chaparral, and ponderosa pine...

Women Behaving Badly: Dahl's Witches Meet the Women of the Eighties.

ERIC Educational Resources Information Center

Bird, Anne-Marie

1998-01-01

Investigates the issue of misogyny in Roald Dahl's 1983 book and Nicolas Roeg's 1989 film, "The Witches." Looks at the general differences in the two texts--the most explicit difference is in the film's ending. Explores the significance of the witch in the book and to what extent Roeg's film uses the implied connection between evil and gender. (PA)

Glucagon signaling modulates sweet taste responsiveness.

PubMed

Elson, Amanda E T; Dotson, Cedrick D; Egan, Josephine M; Munger, Steven D

2010-10-01

The gustatory system provides critical information about the quality and nutritional value of food before it is ingested. Thus, physiological mechanisms that modulate taste function in the context of nutritional needs or metabolic status could optimize ingestive decisions. We report that glucagon, which plays important roles in the maintenance of glucose homeostasis, enhances sweet taste responsiveness through local actions in the mouse gustatory epithelium. Using immunohistochemistry and confocal microscopy, we found that glucagon and its receptor (GlucR) are coexpressed in a subset of mouse taste receptor cells. Most of these cells also express the T1R3 taste receptor implicated in sweet and/or umami taste. Genetic or pharmacological disruption of glucagon signaling in behaving mice indicated a critical role for glucagon in the modulation of taste responsiveness. Scg5(-/-) mice, which lack mature glucagon, had significantly reduced responsiveness to sucrose as compared to wild-type littermates in brief-access taste tests. No significant differences were seen in responses to prototypical salty, sour, or bitter stimuli. Taste responsiveness to sucrose was similarly reduced upon acute and local disruption of glucagon signaling by the GlucR antagonist L-168,049. Together, these data indicate a role for local glucagon signaling in the peripheral modulation of sweet taste responsiveness.

Cytoplasmic flows as signatures for the mechanics of mitotic positioning

PubMed Central

Nazockdast, Ehssan; Rahimian, Abtin; Needleman, Daniel; Shelley, Michael

2017-01-01

The proper positioning of mitotic spindle in the single-cell Caenorhabditis elegans embryo is achieved initially by the migration and rotation of the pronuclear complex (PNC) and its two associated astral microtubules (MTs). Pronuclear migration produces global cytoplasmic flows that couple the mechanics of all MTs, the PNC, and the cell periphery with each other through their hydrodynamic interactions (HIs). We present the first computational study that explicitly accounts for detailed HIs between the cytoskeletal components and demonstrate the key consequences of HIs for the mechanics of pronuclear migration. First, we show that, because of HIs between the MTs, the cytoplasm-filled astral MTs behave like a porous medium, with its permeability decreasing with increasing the number of MTs. We then directly study the dynamics of PNC migration under various force-transduction models, including the pushing or pulling of MTs at the cortex and the pulling of MTs by cytoplasmically bound force generators. Although achieving proper position and orientation on reasonable time scales does not uniquely choose a model, we find that each model produces a different signature in its induced cytoplasmic flow. We suggest that cytoplasmic flows can be used to differentiate between mechanisms. PMID:28331070

Dynamics and Size of Cross-Linking-Induced Lipid Nanodomains in Model Membranes

PubMed Central

Štefl, Martin; Šachl, Radek; Humpolíčková, Jana; Cebecauer, Marek; Macháň, Radek; Kolářová, Marie; Johansson, Lennart B.-Å.; Hof, Martin

2012-01-01

Changes of membrane organization upon cross-linking of its components trigger cell signaling response to various exogenous factors. Cross-linking of raft gangliosides GM1 with cholera toxin (CTxB) was shown to cause microscopic phase separation in model membranes, and the CTxB-GM1 complexes forming a minimal lipid raft unit are the subject of ongoing cell membrane research. Yet, those subdiffraction sized rafts have never been described in terms of size and dynamics. By means of two-color z-scan fluorescence correlation spectroscopy, we show that the nanosized domains are formed in model membranes at lower sphingomyelin (Sph) content than needed for the large-scale phase separation and that the CTxB-GM1 complexes are confined in the domains poorly stabilized with Sph. Förster resonance energy transfer together with Monte Carlo modeling of the donor decay response reveal the domain radius of ∼8 nm, which increases at higher Sph content. We observed two types of domains behaving differently, which suggests a dual role of the cross-linker: first, local transient condensation of the GM1 molecules compensating for a lack of Sph and second, coalescence of existing nanodomains ending in large-scale phase separation. PMID:22824274

[Gut barrier in the critically ill patient: facts and trends].

PubMed

Velasco, Nicolás

2006-08-01

The disturbances of gut barrier in critically ill patients may influence their outcome and prognosis. Experiments in animals show that fasting and stress collaborate to produce intestinal atrophy and translocation of microorganisms and toxins. This fact is one of the main arguments to promote the use of early enteral feeding in critically ill patients. However, the intestinal barrier behaves differently in humans than in animals. The human enteral cells have a good tolerance to fasting and stress, mucosal atrophy is mild and it is not always associated with changes in intestinal permeability. Moreover, the relationship between intestinal permeability with sepsis and bacterial translocation is controversial. This last phenomenon also happens in normal subjects and may be a mechanism to build immunological memory. One of the most important factors that influence bacterial translocation is the microorganism, that under stress conditions can adhere to the intestinal cell and penetrate the intestinal barrier. Splanchnic ischemia and reperfusion is one of the main pathogenic factors in the failure of intestinal barrier. Finally, the fact that the small bowel is an inflammatory target of extra intestinal injuries, explains several clinical situations. The pathophysiology of the intestinal barrier definitely requires more research.

What If? Conditionals in Educational Registers

ERIC Educational Resources Information Center

Louwerse, Max M.; Crossley, Scott A.; Jeuniaux, Patrick

2008-01-01

Many corpus linguistic studies have investigated classification of texts into genres and registers, but relatively few of these studies have looked at linguistic features in educational registers. From a pedagogical perspective it is important to determine whether certain linguistic features behave differently across registers within particular…

Taking Care of Risky Business.

ERIC Educational Resources Information Center

Powell, Tammie; Taylor, Stephen

1994-01-01

American children do not bring uniform characteristics to the school setting. The at-risk student actually learns, behaves, and thinks differently from the student considered ideally suited to traditional programming. The poor "fit" between the at-risk students' natural characteristics and the expectations of the traditional school…

Outlines on nanotechnologies applied to bladder tissue engineering.

PubMed

Alberti, C

2012-01-01

Tissue engineering technologies are more and more expanding as consequence of recent developments in the field of biomaterial science and nanotechnology research. An important issue in designing scaffold materials is that of recreating the ECM (extra-cellular matrix) functional features - particularly ECM-derived complex molecule signalling - to mimic its capability of directing cell-growth and neotissue morphogenesis. In this way the nanotechnology may offer intriguing chances, biomaterial nanoscale-based scaffold geometry behaving as nanomechanotransducer complex interacting with different cell nanosize proteins, especially with those of cell surface mechanoreceptors. To fabricate 3D-scaffold complex architectures, endowed with controlled geometry and functional properties, bottom-up approaches, based on molecular self-assembling of small building polymer units, are used, sometimes functionalizing them by incorporation of bioactive peptide sequences such as RDG (arginine - glycine - aspartic acid, a cell-integrin binding domain of fibronectin), whereas the top-down approaches are useful to fabricate micro/nanoscale structures, such as a microvasculature within an existing complex bioarchitecture. Synthetic polymer-based nanofibers, produced by electrospinning process, may be used to create fibrous scaffolds that can facilitate, given their nanostructured geometry and surface roughness, cell adhesion and growth. Also bladder tissue engineering may benefit by nanotechnology advances to achieve a better reliability of the bladder engineered tissue. Particularly, bladder smooth muscle cell adhesion to nanostructured polymeric surfaces is significantly enhanced in comparison with that to conventional biomaterials. Moreover nanostructured surfaces of bladder engineered tissue show a decreased calcium stone production. In a bladder tumor animal model, the dispersion of carbon nanofibers in a polymeric scaffold-based tissue engineered replacement neobladder, appears to inhibit a carcinogenic relapse in bladder prosthetic material. Facing the future, a full success of bladder tissue engineering will mainly depend on the progress of both biomaterial nanotechnologies and stem cell biology research.

Mobility and Oxidation of Adsorbed CO on Shape-Controlled Pt Nanoparticles in Acidic Medium.

PubMed

Farias, Manuel J S; Busó-Rogero, Carlos; Vidal-Iglesias, Francisco J; Solla-Gullón, José; Camara, Giuseppe A; Feliu, Juan M

2017-01-31

The knowledge about how CO occupies and detaches from specific surface sites on well-structured Pt surfaces provides outstanding information on both dynamics/mobility of CO ads and oxidation of this molecule under electrochemical conditions. This work reports how the potentiostatic growth of different coverage CO adlayers evolves with time on both cubic and octahedral Pt nanoparticles in acidic medium. Data suggest that during the growth of the CO adlayer, CO ads molecules slightly shift toward low coordination sites only on octahedral Pt nanoparticles, so that these undercoordinated sites are the first filled on octahedral Pt nanoparticles. Conversely, on cubic Pt nanoparticles, adsorbed CO behaves as an immobile species, and low coordinated sites as well as (100) terraces are apparently filled uniformly and simultaneously. However, once the adlayer is complete, irrespectively of whether the CO is oxidized in a single step or in a sequence of different potential steps, results suggest that CO ads behaves as an immobile species during its oxidation on both octahedral and cubic Pt nanoparticles.

Non-criticality of interaction network over system's crises: A percolation analysis.

PubMed

Shirazi, Amir Hossein; Saberi, Abbas Ali; Hosseiny, Ali; Amirzadeh, Ehsan; Toranj Simin, Pourya

2017-11-20

Extraction of interaction networks from multi-variate time-series is one of the topics of broad interest in complex systems. Although this method has a wide range of applications, most of the previous analyses have focused on the pairwise relations. Here we establish the potential of such a method to elicit aggregated behavior of the system by making a connection with the concepts from percolation theory. We study the dynamical interaction networks of a financial market extracted from the correlation network of indices, and build a weighted network. In correspondence with the percolation model, we find that away from financial crises the interaction network behaves like a critical random network of Erdős-Rényi, while close to a financial crisis, our model deviates from the critical random network and behaves differently at different size scales. We perform further analysis to clarify that our observation is not a simple consequence of the growth in correlations over the crises.

Papillary fibroblasts differentiate into reticular fibroblasts after prolonged in vitro culture.

PubMed

Janson, David; Saintigny, Gaëlle; Mahé, Christian; El Ghalbzouri, Abdoelwaheb

2013-01-01

The dermis can be divided into two morphologically different layers: the papillary and reticular dermis. Fibroblasts isolated from these layers behave differently when cultured in vitro. During skin ageing, the papillary dermis decreases in volume. Based on the functional differences in vitro, it is hypothesized that the loss of papillary fibroblasts contributes to skin ageing. In this study, we aimed to mimic certain aspects of skin ageing by using high-passage cultures of reticular and papillary fibroblasts and investigated the effect of these cells on skin morphogenesis in reconstructed human skin equivalents. Skin equivalents generated with reticular fibroblasts showed a reduced terminal differentiation and fewer proliferating basal keratinocytes. Aged in vitro papillary fibroblasts had increased expression of biomarkers specific to reticular fibroblasts. The phenotype and morphology of skin equivalents generated with high-passage papillary fibroblasts resembled that of reticular fibroblasts. This demonstrates that papillary fibroblasts can differentiate into reticular fibroblasts in vitro. Therefore, we hypothesize that papillary fibroblasts represent an undifferentiated phenotype, while reticular fibroblasts represent a more differentiated population. The differentiation process could be a new target for anti-skin-ageing strategies. © 2013 John Wiley & Sons A/S.

Dietary unsaturated fatty acids differently affect catecholamine handling by adrenal chromaffin cells.

PubMed

Gomes, Andreia; Correia, Gustavo; Coelho, Marisa; Araújo, João Ricardo; Pinho, Maria João; Teixeira, Ana Luisa; Medeiros, Rui; Ribeiro, Laura

2015-05-01

Catecholamines (CA) play an important role in cardiovascular (CDV) disease risk. Namely, noradrenaline (NA) levels positively correlate whereas adrenaline (AD) levels negatively correlate with obesity and/or CDV disease. Western diets, which are tipically rich in Ω-6 fatty acids (FAs) and deficient in Ω-3 FAs, may contribute to the development of obesity, type 2 diabetes and/or coronary artery disease. Taking this into consideration and the fact that our group has already described that saturated FAs affect catecholamine handling by adrenal chromaffin cells, this work aimed to investigate the effect of unsaturated FAs upon catecholamine handling in the same model. Our results showed that chronic exposure to unsaturated FAs differently modulated CA cellular content and release, regardless of both FA series and number of carbon atoms. Namely, the Ω-6 arachidonic and linoleic acids, based on their effect on CA release and cellular content, seemed to impair NA and AD vesicular transport, whereas γ-linolenic acid selectively impaired AD synthesis and release. Within the Ω-9 FAs, oleic acid was devoid of effect, and elaidic acid behaved similarly to γ-linolenic acid. Eicosapentaenoic and docosahexaenoic acids (Ω-3 series) impaired the synthesis and release of both NA and AD. These results deserve attention and future development, namely, in what concerns the mechanisms involved and correlative effects in vivo. Copyright © 2015 Elsevier Inc. All rights reserved.

Radiation damage buildup and dislocation evolution in Ni and equiatomic multicomponent Ni-based alloys

NASA Astrophysics Data System (ADS)

Levo, E.; Granberg, F.; Fridlund, C.; Nordlund, K.; Djurabekova, F.

2017-07-01

Single-phase multicomponent alloys of equal atomic concentrations ("equiatomic") have proven to exhibit promising mechanical and corrosion resistance properties, that are sought after in materials intended for use in hazardous environments like next-generation nuclear reactors. In this article, we investigate the damage production and dislocation mobility by simulating irradiation of elemental Ni and the alloys NiCo, NiCoCr, NiCoFe and NiFe, to assess the effect of elemental composition. We compare the defect production and the evolution of dislocation networks in the simulation cells of two different sizes, for all five studied materials. We find that the trends in defect evolution are in good agreement between the different cell sizes. The damage is generally reduced with increased alloy complexity, and the dislocation evolution is specific to each material, depending on its complexity. We show that increasing complexity of the alloys does not always lead to decreased susceptibility to damage accumulation under irradiation. We show that, for instance, the NiCo alloy behaves very similarly to Ni, while presence of Fe or Cr in the alloy even as a third component reduces the saturated level of damage substantially. Moreover, we linked the defect evolution with the dislocation transformations in the alloys. Sudden drops in defect number and large defect fluctuations from the continuous irradiation can be explained from the dislocation activity.

Active Tension Network model reveals an exotic mechanical state realized in epithelial tissues

NASA Astrophysics Data System (ADS)

Noll, Nicholas; Mani, Madhav; Heemskerk, Idse; Streicha, Sebastian; Shraiman, Boris

Mechanical interactions play a crucial role in epithelial morphogenesis, yet understanding the complex mechanisms through which stress and deformation affect cell behavior remains an open problem. Here we formulate and analyze the Active Tension Network (ATN) model, which assumes that mechanical balance of cells is dominated by cortical tension and introduces tension dependent active remodeling of the cortex. We find that ATNs exhibit unusual mechanical properties: i) ATN behaves as a fluid at short times, but at long times it supports external tension, like a solid; ii) its mechanical equilibrium state has extensive degeneracy associated with a discrete conformal - ''isogonal'' - deformation of cells. ATN model predicts a constraint on equilibrium cell geometry, which we demonstrate to hold in certain epithelial tissues. We further show that isogonal modes are observed in a fruit fly embryo, accounting for the striking variability of apical area of ventral cells and helping understand the early phase of gastrulation. Living matter realizes new and exotic mechanical states, understanding which helps understand biological phenomena.

HLA-B27.

PubMed

Bowness, Paul

2015-01-01

Possession of the human leukocyte antigen (HLA) class I molecule B27 is strongly associated with ankylosing spondylitis (AS), but the pathogenic role of HLA-B27 is unknown. Two broad theories most likely explain the role of HLA-B27 in AS pathogenesis. The first is based on the natural immunological function of HLA-B27 of presenting antigenic peptides to cytotoxic T cells. Thus, HLA-B27-restricted immune responses to self-antigens, or arthritogenic peptides, might drive immunopathology. B27 can also "behave badly," misfolding during assembly and leading to endoplasmic reticulum stress and autophagy responses. β2m-free B27 heavy chain structures including homodimers (B272) can also be expressed at the cell surface following endosomal recycling of cell surface heterotrimers. Cell surface free heavy chains and B272 bind to innate immune receptors on T, NK, and myeloid cells with proinflammatory effects. This review describes the natural function of HLA-B27, its disease associations, and the current theories as to its pathogenic role.

Heterostructured TiO2/NiTiO3 Nanorod Arrays for Inorganic Sensitized Solar Cells with Significantly Enhanced Photovoltaic Performance and Stability.

PubMed

Li, Yue-Ying; Wang, Jian-Gan; Sun, Huan-Huan; Wei, Bingqing

2018-04-11

Organic dyes used in the conventional dye-sensitized solar cells (DSSCs) suffer from poor light stability and high cost. In this work, we demonstrate a new inorganic sensitized solar cell based on ordered one-dimensional semiconductor nanorod arrays of TiO 2 /NiTiO 3 (NTO) heterostructures prepared via a facile two-step hydrothermal approach. The semiconductor heterostructure arrays are highly desirable and promising for DSSCs because of their direct charge transport capability and slow charge recombination rate. The low-cost NTO inorganic semiconductor possesses an appropriate band gap that matches well with TiO 2 , which behaves like a "dye" to enable efficient light harvesting and fast electron-hole separation. The solar cells constructed by the ordered TiO 2 /NTO heterostructure photoanodes show a significantly improved power conversion efficiency, high fill factor, and more promising, outstanding life stability. The present work will open up an avenue to design heterostructured inorganics for high-performance solar cells.

Arabidopsis EDS1 connects pathogen effector recognition to cell compartment-specific immune responses.

PubMed

Heidrich, Katharina; Wirthmueller, Lennart; Tasset, Céline; Pouzet, Cécile; Deslandes, Laurent; Parker, Jane E

2011-12-09

Pathogen effectors are intercepted by plant intracellular nucleotide binding-leucine-rich repeat (NB-LRR) receptors. However, processes linking receptor activation to downstream defenses remain obscure. Nucleo-cytoplasmic basal resistance regulator EDS1 (ENHANCED DISEASE SUSCEPTIBILITY1) is indispensible for immunity mediated by TIR (Toll-interleukin-1 receptor)-NB-LRR receptors. We show that Arabidopsis EDS1 molecularly connects TIR-NB-LRR disease resistance protein RPS4 recognition of bacterial effector AvrRps4 to defense pathways. RPS4-EDS1 and AvrRps4-EDS1 complexes are detected inside nuclei of living tobacco cells after transient coexpression and in Arabidopsis soluble leaf extracts after resistance activation. Forced AvrRps4 localization to the host cytoplasm or nucleus reveals cell compartment-specific RPS4-EDS1 defense branches. Although nuclear processes restrict bacterial growth, programmed cell death and transcriptional resistance reinforcement require nucleo-cytoplasmic coordination. Thus, EDS1 behaves as an effector target and activated TIR-NB-LRR signal transducer for defenses across cell compartments.

Structure/function relationships of calcitonin analogues as agonists, antagonists, or inverse agonists in a constitutively activated receptor cell system.

PubMed

Pozvek, G; Hilton, J M; Quiza, M; Houssami, S; Sexton, P M

1997-04-01

The structure/function relationship of salmon calcitonin (sCT) analogues was investigated in heterologous calcitonin receptor (CTR) expression systems. sCT analogues with progressive amino-terminal truncations intermediate of sCT-(1-32) to sCT-(8-32) were examined for their ability to act as agonists, antagonists, or inverse agonists. Two CTR cell clones, B8-H10 and G12-E12, which express approximately 5 million and 25,000 C1b receptors/cell, respectively, were used for this study. The B8-H10 clone has an approximately 80-fold increase in basal levels of intracellular cAMP due to constitutive activation of the overexpressed receptor. In whole-cell competition binding studies, sCT-(1-32) was more potent than any of its amino-terminally truncated analogues in competition for 125I-sCT binding. In cAMP accumulation studies, sCT-(1-32) and modified analogues sCT-(2-32) and sCT-(3-32) had agonist activities. SDZ-216-710, with an amino-terminal truncation of four amino acids, behaved as a partial agonist/antagonist, whereas amino-terminal truncations of six or seven amino acid residues produced a 16-fold reduction in basal cAMP levels and attenuated the response to the agonist sCT-(1-32) in the constitutively active CTR system. This inverse agonist effect was insensitive to pertussis toxin inhibition. In contrast, the inverse agonist activity of these peptides was not observed in the nonconstitutively active CTR system, in which sCT analogues with amino-terminal truncations of four or more amino acids behaved as neutral competitive antagonists. These results suggest that the inverse agonist activity is mediated by stabilization of the inactive state of the receptor, which does not couple to G protein, and attenuates basal signaling initiated by ligand-independent activation of the effector adenylyl cyclase.

Unipolar distributions of junctional Myosin II identify cell stripe boundaries that drive cell intercalation throughout Drosophila axis extension

PubMed Central

Tetley, Robert J; Blanchard, Guy B; Fletcher, Alexander G; Adams, Richard J; Sanson, Bénédicte

2016-01-01

Convergence and extension movements elongate tissues during development. Drosophila germ-band extension (GBE) is one example, which requires active cell rearrangements driven by Myosin II planar polarisation. Here, we develop novel computational methods to analyse the spatiotemporal dynamics of Myosin II during GBE, at the scale of the tissue. We show that initial Myosin II bipolar cell polarization gives way to unipolar enrichment at parasegmental boundaries and two further boundaries within each parasegment, concomitant with a doubling of cell number as the tissue elongates. These boundaries are the primary sites of cell intercalation, behaving as mechanical barriers and providing a mechanism for how cells remain ordered during GBE. Enrichment at parasegment boundaries during GBE is independent of Wingless signaling, suggesting pair-rule gene control. Our results are consistent with recent work showing that a combinatorial code of Toll-like receptors downstream of pair-rule genes contributes to Myosin II polarization via local cell-cell interactions. We propose an updated cell-cell interaction model for Myosin II polarization that we tested in a vertex-based simulation. DOI: http://dx.doi.org/10.7554/eLife.12094.001 PMID:27183005

Reciprocity Outperforms Conformity to Promote Cooperation.

PubMed

Romano, Angelo; Balliet, Daniel

2017-10-01

Evolutionary psychologists have proposed two processes that could give rise to the pervasiveness of human cooperation observed among individuals who are not genetically related: reciprocity and conformity. We tested whether reciprocity outperformed conformity in promoting cooperation, especially when these psychological processes would promote a different cooperative or noncooperative response. To do so, across three studies, we observed participants' cooperation with a partner after learning (a) that their partner had behaved cooperatively (or not) on several previous trials and (b) that their group members had behaved cooperatively (or not) on several previous trials with that same partner. Although we found that people both reciprocate and conform, reciprocity has a stronger influence on cooperation. Moreover, we found that conformity can be partly explained by a concern about one's reputation-a finding that supports a reciprocity framework.

4-Amino-N-(3-meth­oxy­pyrazin-2-yl)benzene­sulfonamide

PubMed Central

Bruni, Bruno; Coran, Silvia A.; Bartolucci, Gianluca; Di Vaira, Massimo

2010-01-01

The overall mol­ecular geometry of the title compound, C11H12N4O3S, is bent, with a dihedral angle of 89.24 (5)° between the best planes through the two aromatic rings. Each mol­ecule behaves as a hydrogen-bond donor toward three different mol­ecules, through its amidic and the two aminic H atoms, and it behaves as a hydrogen-bond acceptor from two other mol­ecules via one of its sulfonamidic O atoms. In the crystal, mol­ecules linked by N—H⋯N and N—H⋯O hydrogen bonds form kinked layers parallel to (001), adjacent layers being connected by van der Waals inter­actions. PMID:21587634

Mirrored morality: an exploration of moral choice in video games.

PubMed

Weaver, Andrew J; Lewis, Nicky

2012-11-01

This exploratory study was designed to examine how players make moral choices in video games and what effects these choices have on emotional responses to the games. Participants (n=75) filled out a moral foundations questionnaire (MFQ) and then played through the first full act of the video game Fallout 3. Game play was recorded and content analyzed for the moral decisions made. Players also reported their enjoyment of and emotional reactions to the game and reflected on the decisions they made. The majority of players made moral decisions and behaved toward the nonplayer game characters they encountered as if these were actual interpersonal interactions. Individual differences in decision making were predicted by the MFQ. Behaving in antisocial ways did increase guilt, but had no impact on enjoyment.

Physics of interplanetary dust capture via impact into organic polymer foams

NASA Technical Reports Server (NTRS)

Anderson, William W.; Ahrens, Thomas J.

1994-01-01

The physics of hypervelocity impacts into foams is of interest because of the possible application to interplanetary dust particle (IDP) capture by spacecraft. We present a model for the phenomena occurring in such impacts into low-density organic polymer foams. Particles smaller than foam cells behave as if the foam is a series of solid slabs and are fragmented and, at higher velocities, thermally altered. Particles much larger than the foam cells behave as if the foam were a continuum, allowing the use of a continuum mechanics model to describe the effects of drag and ablation. Fragmentation is expected to be a major process, especially for aggregates of small grains. Calculations based on these arguments accurately predict experimental data and, for hypothetical IDPs, indicate that recovery of organic materials will be low for encounter velocities greater than 5 km/s. For an organic particle 100 micrometers in diameter, approx. 35% of the original mass would be collected in an impact at 5 km/s, dropping to approx. 10% at 10 km/s and approx. 0% at 15 km/s. For the same velocities the recovery ratios for troilite (FeS) are approx. 95%, 65%, and 50%, and for olivine (Mg2SiO4) they are approx. 98%, 80%, and 65%, demonstrating that inorganic materials are much more easily collected. The density of the collector material has only a second-order effect, changing the recovered mass by less than 10% of the original mass.

Enhancing thermoelectrochemical properties by tethering ferrocene to the anion or cation of ionic liquids: altered thermodynamics and solubility.

PubMed

Aldous, Leigh; Black, Jeffrey J; Elias, Maximo C; Gélinas, Bruno; Rochefort, Dominic

2017-09-13

Entropic changes inherent within a redox process typically result in significant temperature sensitivity. This can be utilised positively or can be a detrimental process. This study has investigated the thermoelectrochemical properties (temperature-dependant electrochemistry) of the ferrocenium|ferrocene redox couple in an ionic liquid, and in particular the effect of covalently tethering this redox couple to fixed positive or negative charges. As such, the ionic liquid 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide was employed to dissolve ferrocene, as well as cationic-tethered ferrocene (the 1-ethyl-3-(methylferrocenyl)imidazolium cation) and anionic-tethered ferrocene (the ferrocenylsulfonyl(trifluoromethylsulfonyl)imide anion). These systems were characterised in terms of their voltammetry (apparent formal potentials, diffusion coefficients and electron transfer rate constants) and thermoelectrochemistry (temperature coefficients of the cell potential or 'Seebeck coefficients', short circuit current densities and power density outputs). The oxidised cationic species behaved like a dicationic species and was thus 6-fold more effective at converting waste thermal energy to electrical power within a thermoelectrochemical cell than unmodified ferrocene. This was almost exclusively due to a significant boost in the Seebeck coefficient of this redox couple. Conversely, the oxidised anionic species was formally a zwitterion, but this zwitterionic species behaved thermodynamically like a neutral species. The inverted entropic change upon going from ferrocene to anion-tethered ferrocene allowed development of a largely temperature-insensitive reference potential based upon a mixture of acetylferrocene and ferricenyl(iii)sulfonyl(trifluoromethylsulfonyl)imide.

Nanofibers of Human Tropoelastin-inspired peptides: Structural characterization and biological properties.

PubMed

Secchi, Valeria; Franchi, Stefano; Fioramonti, Marco; Polzonetti, Giovanni; Iucci, Giovanna; Bochicchio, Brigida; Battocchio, Chiara

2017-08-01

Regenerative medicine is taking great advantage from the use of biomaterials in the treatments of a wide range of diseases and injuries. Among other biomaterials, self-assembling peptides are appealing systems due to their ability to spontaneously form nanostructured hydrogels that can be directly injected into lesions. Indeed, self-assembling peptide scaffolds are expected to behave as biomimetic matrices able to surround cells, to promote specific interactions, and to control and modify cell behavior by mimicking the native environment as well. We selected three pentadecapeptides inspired by Human Tropoelastin, a natural protein of the extracellular matrix, expected to show high biocompatibility. Moreover, the here proposed self-assembling peptides (SAPs) are able to spontaneously aggregate in nanofibers in biological environment, as revealed by AFM (Atomic Force Microscopy). Peptides were characterized by XPS (X-ray Photoelectron Spectroscopy) and IRRAS (Infrared Reflection Absorption Spectroscopy) both as lyophilized (not aggregated) and as aggregated (nanofibers) samples in order to investigate some potential differences in their chemical composition and intermolecular interactions, and to analyze the surface and interface of nanofibers. Finally, an accurate investigation of the biological properties of the SAPs and of their interaction with cells was performed by culturing for the first time human Mesenchymal Stem Cells (hMSCs) in presence of SAPs. The final aim of this work was to assess if Human Tropoelastin-inspired nanostructured fibers could exert a cytotoxic effect and to evaluate their biocompatibility, cellular adhesion and proliferation. Copyright © 2017 Elsevier B.V. All rights reserved.

The interaction of spatial scale and predator-prey functional response

USGS Publications Warehouse

Blaine, T.W.; DeAngelis, D.L.

1997-01-01

Predator-prey models with a prey-dependent functional response have the property that the prey equilibrium value is determined only by predator characteristics. However, in observed natural systems (for instance, snail-periphyton interactions in streams) the equilibrium periphyton biomass has been shown experimentally to be influenced by both snail numbers and levels of available limiting nutrient in the water. Hypothesizing that the observed patchiness in periphyton in streams may be part of the explanation for the departure of behavior of the equilibrium biomasses from predictions of the prey-dependent response of the snail-periphyton system, we developed and analyzed a spatially-explicit model of periphyton in which snails were modeled as individuals in their movement and feeding, and periphyton was modeled as patches or spatial cells. Three different assumptions on snail movement were used: (1) random movement between spatial cells, (2) tracking by snails of local abundances of periphyton, and (3) delayed departure of snails from cells to reduce costs associated with movement. Of these assumptions, only the third strategy, based on an herbivore strategy of staying in one patch until local periphyton biomass concentration falls below a certain threshold amount, produced results in which both periphyton and snail biomass increased with nutrient input. Thus, if data are averaged spatially over the whole system, we expect that a ratio-dependent functional response may be observed if the herbivore behaves according to the third assumption. Both random movement and delayed cell departure had the result that spatial heterogeneity of periphyton increased with nutrient input.

Multi-scale modelling of the dynamics of cell colonies: insights into cell-adhesion forces and cancer invasion from in silico simulations.

PubMed

Schlüter, Daniela K; Ramis-Conde, Ignacio; Chaplain, Mark A J

2015-02-06

Studying the biophysical interactions between cells is crucial to understanding how normal tissue develops, how it is structured and also when malfunctions occur. Traditional experiments try to infer events at the tissue level after observing the behaviour of and interactions between individual cells. This approach assumes that cells behave in the same biophysical manner in isolated experiments as they do within colonies and tissues. In this paper, we develop a multi-scale multi-compartment mathematical model that accounts for the principal biophysical interactions and adhesion pathways not only at a cell-cell level but also at the level of cell colonies (in contrast to the traditional approach). Our results suggest that adhesion/separation forces between cells may be lower in cell colonies than traditional isolated single-cell experiments infer. As a consequence, isolated single-cell experiments may be insufficient to deduce important biological processes such as single-cell invasion after detachment from a solid tumour. The simulations further show that kinetic rates and cell biophysical characteristics such as pressure-related cell-cycle arrest have a major influence on cell colony patterns and can allow for the development of protrusive cellular structures as seen in invasive cancer cell lines independent of expression levels of pro-invasion molecules.

Characterization of the biomechanical properties of T4 pili expressed by Streptococcus pneumoniae--a comparison between helix-like and open coil-like pili.

PubMed

Castelain, Mickaël; Koutris, Efstratios; Andersson, Magnus; Wiklund, Krister; Björnham, Oscar; Schedin, Staffan; Axner, Ove

2009-07-13

Bacterial adhesion organelles, known as fimbria or pili, are expressed by gram-positive as well as gram-negative bacteria families. These appendages play a key role in the first steps of the invasion and infection processes, and they therefore provide bacteria with pathogenic abilities. To improve the knowledge of pili-mediated bacterial adhesion to host cells and how these pili behave under the presence of an external force, we first characterize, using force measuring optical tweezers, open coil-like T4 pili expressed by gram-positive Streptococcus pneumoniae with respect to their biomechanical properties. It is shown that their elongation behavior can be well described by the worm-like chain model and that they possess a large degree of flexibility. Their properties are then compared with those of helix-like pili expressed by gram-negative uropathogenic Escherichia coli (UPEC), which have different pili architecture. The differences suggest that these two types of pili have distinctly dissimilar mechanisms to adhere and sustain external forces. Helix-like pili expressed by UPEC bacteria adhere to host cells by single adhesins located at the distal end of the pili while their helix-like structures act as shock absorbers to dampen the irregularly shear forces induced by urine flow and to increase the cooperativity of the pili ensemble, whereas open coil-like pili expressed by S. pneumoniae adhere to cells by a multitude of adhesins distributed along the pili. It is hypothesized that these two types of pili represent different strategies of adhering to host cells in the presence of external forces. When exposed to significant forces, bacteria expressing helix-like pili remain attached by distributing the external force among a multitude of pili, whereas bacteria expressing open coil-like pili sustain large forces primarily by their multitude of binding adhesins which presumably detach sequentially.

Optimization of an integrated electrodisinfection/electrocoagulation process with Al bipolar electrodes for urban wastewater reclamation.

PubMed

Cotillas, Salvador; Llanos, Javier; Cañizares, Pablo; Mateo, Sara; Rodrigo, Manuel A

2013-04-01

In this work, a novel integrated electrochemical process for urban wastewater regeneration is described. The electrochemical cell consists in a Boron Doped Diamond (BDD) or a Dimensionally Stable Anode (DSA) as anode, a Stainless Steel (SS) as cathode and a perforated aluminum plate, which behaves as bipolar electrode, between anode and cathode. Thus, in this cell, it is possible to carry out, at the same time, two different electrochemical processes: electrodisinfection (ED) and electrocoagulation (EC). The treatment of urban wastewater with different anodes and different operating conditions is studied. First of all, in order to check the process performance, experiments with synthetic wastewaters were carried out, showing that it is possible to achieve a 100% of turbidity removal by the electrodissolution of the bipolar electrode. Next, the effect of the current density and the anode material are studied during the ED-EC process of actual effluents. Results show that it is possible to remove Escherichia coli and turbidity simultaneously of an actual effluent from a WasteWater Treatment Facility (WWTF). The use of BDD anodes allows to remove the E. coli completely at an applied electric charge of 0.0077 A h dm(-3) when working with a current density of 6.65 A m(-2). On the other hand, with DSA anodes, the current density necessary to achieve the total removal of E. coli is higher (11.12 A m(-2)) than that required with BDD anodes. Finally, the influence of cell flow path and flow rate have been studied. Results show that the performance of the process strongly depends on the characteristics of the initial effluent (E. coli concentration and Cl(-)/NH(4)(+) initial ratio) and that a cell configuration cathode (inlet)-anode (outlet) and a higher flow rate enhance the removal of the turbidity from the treated effluent. Copyright © 2013 Elsevier Ltd. All rights reserved.

Use Your Imagination: What UK Universities Want You to Think of Them

ERIC Educational Resources Information Center

Huisman, Jeroen; Mampaey, Jelle

2018-01-01

In higher education research, theoretical approaches stressing isomorphism dominate the discourse on how higher education institutions 'behave' in their higher education and research systems. We argue that research should address both instances of similarity and differences. Using theoretical notions from institutionalism and the…

Applications of discrete element method in modeling of grain postharvest operations

USDA-ARS?s Scientific Manuscript database

Grain kernels are finite and discrete materials. Although flowing grain can behave like a continuum fluid at times, the discontinuous behavior exhibited by grain kernels cannot be simulated solely with conventional continuum-based computer modeling such as finite-element or finite-difference methods...

A microfluidics assay to study invasion of human placental trophoblast cells.

PubMed

Abbas, Yassen; Oefner, Carolin Melati; Polacheck, William J; Gardner, Lucy; Farrell, Lydia; Sharkey, Andrew; Kamm, Roger; Moffett, Ashley; Oyen, Michelle L

2017-05-01

Pre-eclampsia, fetal growth restriction and stillbirth are major pregnancy disorders throughout the world. The underlying pathogenesis of these diseases is defective placentation characterized by inadequate invasion of extravillous placental trophoblast cells into the uterine arteries. How trophoblast invasion is controlled remains an unanswered question but is influenced by maternal uterine immune cells called decidual natural killer cells. Here, we describe an in vitro microfluidic invasion assay to study the migration of primary human trophoblast cells. Each experiment can be performed with a small number of cells making it possible to conduct research on human samples despite the challenges of isolating primary trophoblast cells. Cells are exposed to a chemical gradient and tracked in a three-dimensional microenvironment using real-time high-resolution imaging, so that dynamic readouts on cell migration such as directionality, motility and velocity are obtained. The microfluidic system was validated using isolated trophoblast and a gradient of granulocyte-macrophage colony-stimulating factor, a cytokine produced by activated decidual natural killer cells. This microfluidic model provides detailed analysis of the dynamics of trophoblast migration compared to previous assays and can be modified in future to study in vitro how human trophoblast behaves during placentation. © 2017 The Authors.

Airway Basal Cells. The “Smoking Gun” of Chronic Obstructive Pulmonary Disease

PubMed Central

2014-01-01

The earliest abnormality in the lung associated with smoking is hyperplasia of airway basal cells, the stem/progenitor cells of the ciliated and secretory cells that are central to pulmonary host defense. Using cell biology and ’omics technologies to assess basal cells isolated from bronchoscopic brushings of nonsmokers, smokers, and smokers with chronic obstructive pulmonary disease (COPD), compelling evidence has been provided in support of the concept that airway basal cells are central to the pathogenesis of smoking-associated lung diseases. When confronted by the chronic stress of smoking, airway basal cells become disorderly, regress to a more primitive state, behave as dictated by their inheritance, are susceptible to acquired changes in their genome, lose the capacity to regenerate the epithelium, are responsible for the major changes in the airway that characterize COPD, and, with persistent stress, can undergo malignant transformation. Together, these observations led to the conclusion that accelerated loss of lung function in susceptible individuals begins with disordered airway basal cell biology (i.e., that airway basal cells are the “smoking gun” of COPD, a potential target for the development of therapies to prevent smoking-related lung disorders). PMID:25354273

Proliferation of epithelial cell rests, formation of apical cysts, and regression of apical cysts after periapical wound healing.

PubMed

Lin, Louis M; Huang, George T-J; Rosenberg, Paul A

2007-08-01

There is continuing controversy regarding the potential for inflammatory apical cysts to heal after nonsurgical endodontic therapy. Molecular cell biology may provide answers to a series of related questions. How are the epithelial cell rests of Malassez stimulated to proliferate? How are the apical cysts formed? How does the lining epithelium of apical cysts regress after endodontic therapy? Epithelial cell rests are induced to divide and proliferate by inflammatory mediators, proinflammatory cytokines, and growth factors released from host cells during periradicular inflammation. Quiescent epithelial cell rests can behave like restricted-potential stem cells if stimulated to proliferate. Formation of apical cysts is most likely caused by the merging of proliferating epithelial strands from all directions to form a three-dimensional ball mass. After endodontic therapy, epithelial cells in epithelial strands of periapical granulomas and the lining epithelium of apical cysts may stop proliferating because of a reduction in inflammatory mediators, proinflammatory cytokines, and growth factors. Epithelial cells will also regress because of activation of apoptosis or programmed cell death through deprivation of survival factors or by receiving death signals during periapical wound healing.

Nanomechanical properties of hybrid coatings for bone tissue engineering.

PubMed

Skarmoutsou, Amalia; Lolas, Georgios; Charitidis, Costas A; Chatzinikolaidou, Maria; Vamvakaki, Maria; Farsari, Maria

2013-09-01

Bone tissue engineering has emerged as a promising alternative approach in the treatment of bone injuries and defects arising from malformation, osteoporosis, and tumours. In this approach, a temporary scaffold possessing mechanical properties resembling those of natural bone is needed to serve as a substrate enhancing cell adhesion and growth, and a physical support to guide the formation of the new bone. In this regard, the scaffold should be biocompatible, biodegradable, malleable and mechanically strong. Herein, we investigate the mechanical properties of three coatings of different chemical compositions onto silanized glass substrates; a hybrid material consisting of methacryloxypropyl trimethoxysilane and zirconium propoxide, a type of a hybrid organic-inorganic material of the above containing also 50 mol% 2-(dimethylamino)ethyl methacrylate (DMAEMA) moieties and a pure organic material, based on PDMAEMA. This study investigates the variations in the measured hardness and reduced modulus values, wear resistance and plastic behaviour before and after samples' submersion in cell culture medium. Through this analysis we aim to explain how hybrid materials behave under applied stresses (pile-up formations), how water uptake changes this behaviour, and estimate how these materials will react while interaction with cells in tissue engineering applications. Finally, we report on the pre-osteoblastic cell adhesion and proliferation on three-dimensional structures of the hybrid materials within the first hour and up to 7 days in culture. It was evident that hybrid structure, consisting of 50 mol% organic-inorganic material, reveals good mechanical behaviour, wear resistance and cell adhesion and proliferation, suggesting a possible candidate in bone tissue engineering. Copyright © 2013 Elsevier Ltd. All rights reserved.

Multi-scale modelling of the dynamics of cell colonies: insights into cell-adhesion forces and cancer invasion from in silico simulations

PubMed Central

Schlüter, Daniela K.; Ramis-Conde, Ignacio; Chaplain, Mark A. J.

2015-01-01

Studying the biophysical interactions between cells is crucial to understanding how normal tissue develops, how it is structured and also when malfunctions occur. Traditional experiments try to infer events at the tissue level after observing the behaviour of and interactions between individual cells. This approach assumes that cells behave in the same biophysical manner in isolated experiments as they do within colonies and tissues. In this paper, we develop a multi-scale multi-compartment mathematical model that accounts for the principal biophysical interactions and adhesion pathways not only at a cell–cell level but also at the level of cell colonies (in contrast to the traditional approach). Our results suggest that adhesion/separation forces between cells may be lower in cell colonies than traditional isolated single-cell experiments infer. As a consequence, isolated single-cell experiments may be insufficient to deduce important biological processes such as single-cell invasion after detachment from a solid tumour. The simulations further show that kinetic rates and cell biophysical characteristics such as pressure-related cell-cycle arrest have a major influence on cell colony patterns and can allow for the development of protrusive cellular structures as seen in invasive cancer cell lines independent of expression levels of pro-invasion molecules. PMID:25519994

Tumor suppressors Sav/Scrib and oncogene Ras regulate stem cell transformation in adult Drosophila Malpighian Tubules

PubMed Central

Zeng, Xiankun; Singh, Shree Ram; Hou, David; Hou, Steven X.

2012-01-01

An increasing body of evidence suggests that tumors might originate from a few transformed cells that share many properties with normal stem cells. However, it remains unclear how normal stem cells are transformed into cancer stem cells. Here, we demonstrated that mutations causing the loss of tumor suppressor Sav or Scrib or activation of the oncogene Ras transform normal stem cells into cancer stem cells through a multistep process in the adult Drosophila Malpighian Tubules (MTs). In wild-type MTs, each stem cell generates one self-renewing and one differentiating daughter cell. However, in flies with loss-of-function sav or scrib or gain-of-function Ras mutations, both daughter cells grew and behaved like stem cells, leading to the formation of tumors in MTs. Ras functioned downstream of Sav and Scrib in regulating the stem cell transformation. The Ras-transformed stem cells exhibited many of the hallmarks of cancer, such as increased proliferation, reduced cell death, and failure to differentiate. We further demonstrated that several signal transduction pathways (including MEK/MAPK, RhoA, PKA, and TOR) mediate Rasṕ function in the stem cell transformation. Therefore, we have identified a molecular mechanism that regulates stem cell transformation, and this finding may lead to strategies for preventing tumor formation in certain organs. PMID:20432470

Do gray wolves (Canis lupus) support pack mates during aggressive inter-pack interactions?

PubMed

Cassidy, Kira A; McIntyre, Richard T

2016-09-01

For group-living mammals, social coordination increases success in everything from hunting and foraging (Crofoot and Wrangham in Mind the Gap, Springer, Berlin, 2010; Bailey et al. in Behav Ecol Sociobiol 67:1-17, 2013) to agonism (Mosser and Packer in Anim Behav 78:359-370, 2009; Wilson et al. in Anim Behav 83:277-291, 2012; Cassidy et al. in Behav Ecol 26:1352-1360, 2015). Cooperation is found in many species and, due to its low costs, likely is a determining factor in the evolution of living in social groups (Smith in Anim Behav 92:291-304, 2014). Beyond cooperation, many mammals perform costly behaviors for the benefit of group mates (e.g., parental care, food sharing, grooming). Altruism is considered the most extreme case of cooperation where the altruist increases the fitness of the recipient while decreasing its own fitness (Bell in Selection: the mechanism of evolution. Oxford University Press, Oxford 2008). Gray wolf life history requires intra-pack familiarity, communication, and cooperation in order to succeed in hunting (MacNulty et al. in Behav Ecol doi: 10.1093/beheco/arr159 2011) and protecting group resources (Stahler et al. in J Anim Ecol 82: 222-234, 2013; Cassidy et al. in Behav Ecol 26:1352-1360, 2015). Here, we report 121 territorial aggressive inter-pack interactions in Yellowstone National Park between 1 April 1995 and 1 April 2011 (>5300 days of observation) and examine each interaction where one wolf interferes when its pack mate is being attacked by a rival group. This behavior was recorded six times (17.6 % of interactions involving an attack) and often occurred between dyads of closely related individuals. We discuss this behavior as it relates to the evolution of cooperation, sociality, and altruism.

Construction of Microdrive Arrays for Chronic Neural Recordings in Awake Behaving Mice

PubMed Central

Chang, Eric H.; Frattini, Stephen A.; Robbiati, Sergio; Huerta, Patricio T.

2013-01-01

State-of-the-art electrophysiological recordings from the brains of freely behaving animals allow researchers to simultaneously examine local field potentials (LFPs) from populations of neurons and action potentials from individual cells, as the animal engages in experimentally relevant tasks. Chronically implanted microdrives allow for brain recordings to last over periods of several weeks. Miniaturized drives and lightweight components allow for these long-term recordings to occur in small mammals, such as mice. By using tetrodes, which consist of tightly braided bundles of four electrodes in which each wire has a diameter of 12.5 μm, it is possible to isolate physiologically active neurons in superficial brain regions such as the cerebral cortex, dorsal hippocampus, and subiculum, as well as deeper regions such as the striatum and the amygdala. Moreover, this technique insures stable, high-fidelity neural recordings as the animal is challenged with a variety of behavioral tasks. This manuscript describes several techniques that have been optimized to record from the mouse brain. First, we show how to fabricate tetrodes, load them into driveable tubes, and gold-plate their tips in order to reduce their impedance from MΩ to KΩ range. Second, we show how to construct a custom microdrive assembly for carrying and moving the tetrodes vertically, with the use of inexpensive materials. Third, we show the steps for assembling a commercially available microdrive (Neuralynx VersaDrive) that is designed to carry independently movable tetrodes. Finally, we present representative results of local field potentials and single-unit signals obtained in the dorsal subiculum of mice. These techniques can be easily modified to accommodate different types of electrode arrays and recording schemes in the mouse brain. PMID:23851569

The Modification of Fuel Cell-Based Breath Alcohol Sensor Materials to Improve Water Retention of Sensing Performance

NASA Astrophysics Data System (ADS)

Allan, Jesse

Fuel cell based breath alcohol sensors (BrASs) are one of the most important tools used by law enforcement today. The ability to screen potentially intoxicated subjects with the ease, speed, and flexibility the BrAS can provide is unmatched by any other device of its kind. While these devices are used globally, they all suffer from a common deficiency: reliance on water. The ability of the fuel cell sensor to manage water content is one of the greatest fundamental challenges facing this technology today. In order to evaluate the fuel cell sensor device, a methodology was required that would allow in-house sensor testing to be coupled with a diagnostic testing method to not only test materials sensing performance, but also determine why a sensor behaved how it did. To do this, a next-generation fuel cell was designed specifically for sensor testing along with a test station that allowed for rapid response and sensor characteristics of a given material. The fuel cell was designed to allow in-situ testing of a membrane electrode assembly (MEA) of interest using cyclic voltammetry and electrochemical impedance spectroscopy. The in-house design was validated against a commercial cell to provide feedback on how materials in the in-house cell would behave in a commercial designed unit. The results showed that our cell with a commercial MEA behaved identically to a commercial cell with the same MEA. Following validation of our cell, common membrane materials were investigated to identify their suitability in a senor role. The materials chosen were designed for power generating devices, so they provided a benchmark to identify which properties would be important for sensor operation. It was found that while the Nafion membrane and sulfonated poly (ether ether ketone) did show performance increases over the commercial MEA, the thin characteristics of these membranes limited performance in drier conditions. From these results, it was determined that thicker membrane materials are better suited for sensor applications. The commercially used porous poly-vinyl chloride (PVC) membrane was investigated and modified to improve performance of this material. As PVC does not contain any natural hydroscopic properties, the addition of various hydrophilic groups to the PVC would aid in water management. It was found that while chemical modification could improve water retention, optimization of the modifications would be required to ensure flooding was not an issue. Composites of PVC and sulfonated silica showed performance that matched that of the commercial PVC, whilst using significantly less water to achieve those results. By reducing the water required for sensing, leaching of acid, as well as flooding could be reduced. Finally, the catalyst layer and gas diffusion layer (GDL) were investigated to understand what properties of these would impart the best performance increases for the sensor. For the catalyst layer, it was found that platinum black and 20% platinum supported on carbon achieved similar results. Platinum black has excellent catalytic activity for the ethanol oxidation reaction, while the surface area of the 20% platinum supported on carbon would allow for more ethanol to react, increasing the overall sensor capability. The choice of catalyst was less of an issue than the choice of GDL. It was found that using carbon fiber paper GDLs lead to greater retention of water in the MEA compared to carbon cloth GDLs due to the lower air permeability. This came at a cost however in that with a lower air permeability, less ethanol vapour would reach the catalytic sites, reducing sensing performance. Depending on the choice of membrane, removal of the GDL could impart performance increases, but could also cause detrimental failure in the case of Nafion based systems.

Preparation, in vitro degradability, cytotoxicity, and in vivo biocompatibility of porous hydroxyapatite whisker-reinforced poly(L-lactide) biocomposite scaffolds.

PubMed

Xie, Lu; Yu, Haiyang; Yang, Weizhong; Zhu, Zhuoli; Yue, Li

2016-01-01

Biodegradable and bioactive scaffolds with interconnected macroporous structures, suitable biodegradability, adequate mechanical property, and excellent biocompatibility have drawn increasing attention in bone tissue engineering. Hence, in this work, porous hydroxyapatite whisker-reinforced poly(L-lactide) (HA-w/PLLA) composite scaffolds with different ratios of HA and PLLA were successfully developed through compression molding and particle leaching. The microstructure, in vitro mineralization, cytocompatibility, hemocompatibility, and in vivo biocompatibility of the porous HA-w/PLLA were investigated for the first time. The SEM results revealed that these HA-w/PLLA scaffolds possessed interconnected pore structures. Compared with porous HA powder-reinforced PLLA (HA-p/PLLA) scaffolds, HA-w/PLLA scaffolds exhibited better mechanical property and in vitro bioactivity, as more formation of bone-like apatite layers were induced on these scaffolds after mineralization in SBF. Importantly, in vitro cytotoxicity displayed that porous HA-w/PLLA scaffold with HA/PLLA ratio of 1:1 (HA-w1/PLLA1) produced no deleterious effect on human mesenchymal stem cells (hMSCs), and cells performed elevated cell proliferation, indicating a good cytocompatibility. Simultaneously, well-behaved hemocompatibility and favorable in vivo biocompatibility determined from acute toxicity test and histological evaluation were also found in the porous HA-w1/PLLA1 scaffold. These findings may provide new prospects for utilizing the porous HA whisker-based biodegradable scaffolds in bone repair, replacement, and augmentation applications.

Defect States Emerging from a Non-Hermitian Flatband of Photonic Zero Modes

NASA Astrophysics Data System (ADS)

Qi, Bingkun; Zhang, Lingxuan; Ge, Li

2018-03-01

We show the existence of a flatband consisting of photonic zero modes in a gain and loss modulated lattice system as a result of the underlying non-Hermitian particle-hole symmetry. This general finding explains the previous observation in parity-time symmetric systems where non-Hermitian particle-hole symmetry is hidden. We further discuss the defect states in these systems, whose emergence can be viewed as an unconventional alignment of a pseudospin under the influence of a complex-valued pseudomagnetic field. These defect states also behave as a chain with two types of links, one rigid in a unit cell and one soft between unit cells, as the defect states become increasingly localized with the gain and loss strength.

Young children are more generous when others are aware of their actions.

PubMed

Leimgruber, Kristin L; Shaw, Alex; Santos, Laurie R; Olson, Kristina R

2012-01-01

Adults frequently employ reputation-enhancing strategies when engaging in prosocial acts, behaving more generously when their actions are likely to be witnessed by others and even more so when the extent of their generosity is made public. This study examined the developmental origins of sensitivity to cues associated with reputationally motivated prosociality by presenting five-year-olds with the option to provide one or four stickers to a familiar peer recipient at no cost to themselves. We systematically manipulated the recipient's knowledge of the actor's choices in two different ways: (1) occluding the recipient's view of both the actor and the allocation options and (2) presenting allocations in opaque containers whose contents were visible only to the actor. Children were consistently generous only when the recipient was fully aware of the donation options; in all cases in which the recipient was not aware of the donation options, children were strikingly ungenerous. These results demonstrate that five-year-olds exhibit "strategic prosociality," behaving differentially generous as a function of the amount of information available to the recipient about their actions. These findings suggest that long before they develop a rich understanding of the social significance of reputation or are conscious of complex strategic reasoning, children behave more generously when the details of their prosocial actions are available to others.

Do different strains of E. faecalis have the same behavior towards intracanal medications in in vitro research?

PubMed

Zancan, Rafaela Fernandes; Canali, Lyz Cristina Furquim; Tartari, Talita; Andrade, Flaviana Bombarda de; Vivan, Rodrigo Ricci; Duarte, Marco Antonio Hungaro

2018-05-24

The aim of this study was to evaluate the antimicrobial action of different endodontic pastes against Enterococcus faecalis ATCC 29212, isolated from the urinary tract, and compare the action with E. faecalis ATCC 4083, isolated from the root canal. For this purpose, dentin blocks were infected for 21 days with both bacteria at different time-intervals to ensure there would be no cross contamination. After this period, blocks were immersed in the test medications for 7 days, according to the following groups: CH/S, CH/P, CH/CMCP, CH/CHX, CH/DAP and TAP. Images of the samples were captured with a confocal microscope and the percentage of live cells was computed by means of the Bioimage program. The ATCC 29212 strain was shown to be more resistant to CH/SS, Calen, CH/DAP, and TAP than the ATCC 4083 strain. The antimicrobial action of the medications against each strain were divergent concerning the order of susceptibility. The authors concluded that the strains behaved in a different manner: in general, those extracted from the urinary tract were more resistant to the tested medications. Therefore, when E. faecalis must be used for in vitro research in endodontics, we suggest the use of ATCC 4083 strain to obtain results that are closer to the clinical reality.

Pasteurella multocida Toxin Manipulates T Cell Differentiation

PubMed Central

Hildebrand, Dagmar; Heeg, Klaus; Kubatzky, Katharina F.

2015-01-01

Pasteurella multocida causes various diseases in a broad range of wild and domestic animals. Toxigenic strains of the serotypes A and D produce an AB protein toxin named Pasteurella multocida toxin (PMT). PMT constitutively activates the heterotrimeric G protein subunits Gαq, Gα13, and Gαi through deamidation of a glutamine residue, which results in cytoskeletal rearrangements as well as increased proliferation and survival of the host cell. In human monocytes, PMT alters the lipopolysaccharide (LPS)-induced activation toward a phenotype that suppresses T cell activation. Here we describe that the toxin also modulates CD4-positive T helper (Th) cells directly. PMT amplifies the expansion of Th cells through enhanced cell cycle progression and suppression of apoptosis and manipulates the differentiation of Th subclasses through activation of Signal Transducers and Activators of Transcription (STAT) family members and induction of subtype-specific master transcription factors. A large population of toxin-treated T cells is double-positive for Foxp3 and RORγt, the transcription factors expressed by Treg and Th17 cells, respectively. This suggests that these cells could have the potential to turn into Th17 cells or suppressive Treg cells. However, in terms of function, the PMT-differentiated cells behave as inflammatory Th17 cells that produce IL-17 and trigger T cell proliferation. PMID:26635744

The effects of simulated hypogravity on murine bone marrow cells

NASA Technical Reports Server (NTRS)

Lawless, Desales

1989-01-01

Mouse bone marrow cells grown in complete medium at unit gravity were compared with a similar population cultured in conditions that mimic some aspects of microgravity. After the cells adjusted to the conditions that simulated microgravity, they proliferated as fetal or oncogenic populations; their numbers doubled in twelve hour periods. Differentiated subpopulations were depleted from the heterogeneous mixture with time and the undifferentiated hematopoietic stem cells increased in numbers. The cells in the control groups in unit gravity and those in the bioreactors in conditions of microgravity were monitored under a number of parameters. Each were phenotyped as to cell surface antigens using a panel of monoclonal antibodies and flow cytometry. Other parameters compared included: pH, glucose uptake, oxygen consumption and carbon-dioxide production. Nuclear DNA was monitored by flow cytometry. Functional responses were studied by mitogenic stimulation by various lectins. The importance of these findings should have relevance to the space program. Cells should behave predictably in zero gravity; specific populations can be eliminated from diverse populations and other populations isolated. The availability of stem cell populations will enhance both bone marrow and gene transplant programs. Stem cells will permit developmental biologists study the paths of hematopoiesis.

CHO-cell mutant with a defect in cytokinesis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thompson, L.H.; Lindl, P.A.

1976-01-01

In a selection procedure designed to enrich for temperature-sensitive mutant cells blocked in mitosis a CHO-cell mutant was isolated which has a defect in cytokinesis as the basis of its temperature-sensitive phenotype. Cultures of the mutant had an abnormally high percentage (ie, 34 percent) of polyploid cells at the permissive temperature of 34/sup 0/C and showed further increased frequencies of polyploidy as well as many multinucleated cells at 38.5/sup 0/ and 39.5/sup 0/. When the mutant cells were synchronized in metaphase by Colcemid arrest and then placed into fresh medium at nonpermissive temperature, they did not divide although the completionmore » of mitosis appeared cytologically normal. Ultrastructural examination by electron microscopy of such synchronized cells at telophase revealed no specific defects in cellular components other than failure of development of a normal midbody. The sensitivity of the mutant to cytochalasin B and to Colcemid was the same as for wild-type cells. This mutation behaved as recessive in tetraploid cell hybrids constructed by fusing the mutant with a CHO strain which was wild-type with respect to temperature sensitivity.« less

Dietary Phenolic Acids Act as Effective Antioxidants in Membrane Models and in Cultured Cells, Exhibiting Proapoptotic Effects in Leukaemia Cells

PubMed Central

Zambonin, Laura; Caliceti, Cristiana; Vieceli Dalla Sega, Francesco; Fiorentini, Diana; Hrelia, Silvana; Landi, Laura; Prata, Cecilia

2012-01-01

Caffeic, syringic, and protocatechuic acids are phenolic acids derived directly from food intake or come from the gut metabolism of polyphenols. In this study, the antioxidant activity of these compounds was at first evaluated in membrane models, where caffeic acid behaved as a very effective chain-breaking antioxidant, whereas syringic and protocatechuic acids were only retardants of lipid peroxidation. However, all three compounds acted as good scavengers of reactive species in cultured cells subjected to exogenous oxidative stress produced by low level of H2O2. Many tumour cells are characterised by increased ROS levels compared with their noncancerous counterparts. Therefore, we investigated whether phenolic acids, at low concentrations, comparable to those present in human plasma, were able to decrease basal reactive species. Results show that phenolic acids reduced ROS in a leukaemia cell line (HEL), whereas no effect was observed in normal cells, such as HUVEC. The compounds exhibited no toxicity to normal cells while they decreased proliferation in leukaemia cells, inducing apoptosis. In the debate on optimal ROS-manipulating strategies in cancer therapy, our work in leukaemia cells supports the antioxidant ROS-depleting approach. PMID:22792417

A Cross-National Perspective on Bullying

ERIC Educational Resources Information Center

Borntrager, Cameo; Davis, Joanne L.; Bernstein, Adam; Gorman, Heather

2009-01-01

Despite international recognition, few comparison studies examining bullying have been conducted due to methodological differences. Within the US, bullying studies are often conducted in isolation and no consistent prevalence rates have been established (Griffin and Gross in Aggress Violent Behav 9:379-400, 2004). The purpose of this study was to…

Uncertainty plus Prior Equals Rational Bias: An Intuitive Bayesian Probability Weighting Function

ERIC Educational Resources Information Center

Fennell, John; Baddeley, Roland

2012-01-01

Empirical research has shown that when making choices based on probabilistic options, people behave as if they overestimate small probabilities, underestimate large probabilities, and treat positive and negative outcomes differently. These distortions have been modeled using a nonlinear probability weighting function, which is found in several…

Acquisition of Multiple Questions in English, Russian, and Malayalam

ERIC Educational Resources Information Center

Grebenyova, Lydia

2011-01-01

This article presents the results of four studies exploring the acquisition of the language-specific syntactic and semantic properties of multiple interrogatives in English, Russian, and Malayalam, languages that behave differently with respect to the syntax and semantics of multiple interrogatives. A corpus analysis investigated the frequency of…

Understanding and Teaching Generation Y

ERIC Educational Resources Information Center

Reilly, Peter

2012-01-01

English teaching professionals working with children in primary school, adolescents in secondary school, or adults at university know that learners nowadays think and behave differently than those from previous generations. These students were born into a world of information technology; they prefer to multitask rather than focus on one thing at a…

Professors Behaving Badly: Faculty Misconduct in Graduate Education

ERIC Educational Resources Information Center

Braxton, John M.; Proper, Eve; Bayer, Alan E.

2011-01-01

A faculty member publishes an article without offering coauthorship to a graduate assistant who has made a substantial conceptual or methodological contribution to the article. A professor does not permit graduate students to express viewpoints different from her own. A graduate student close to finishing his dissertation cannot reach his…

Judging Mental Disorder in Youths: Effects of Client, Clinician, and Contextual Differences

ERIC Educational Resources Information Center

Pottick, Kathleen J.; Kirk, Stuart A.; Hsieh, Derek K.; Tian, Xin

2007-01-01

Using a vignette-based, mailed survey of 1,401 experienced psychologists, psychiatrists, and social workers, the authors examined how clients' race/ethnicity and clinicians' professional and social characteristics affect their judgment of mental disorder among antisocially behaving youths. Vignettes described problematic behaviors meeting the …

Impression Management in the Psychiatric Interview: Quality, Style, and Individual Differences

ERIC Educational Resources Information Center

Sherman, Mark; And Others

1975-01-01

The ability of 24 Veterans Administration Day Treatment Center psychiatric outpatients to vary intentionally their degree of apparent psychopathology during structured interviews was studied. Patients defined as sick presenters behaved in a significantly more pathological manner during an interview preceded by "fake sick" instructions than they…

On being the right size: scaling effects in designing a human-on-a-chip

PubMed Central

Moraes, Christopher; Labuz, Joseph M.; Leung, Brendan M.; Inoue, Mayumi; Chun, Tae-Hwa; Takayama, Shuichi

2013-01-01

Developing a human-on-a-chip by connecting multiple model organ systems would provide an intermediate screen for therapeutic efficacy and toxic side effects of drugs prior to conducting expensive clinical trials. However, correctly designing individual organs and scaling them relative to each other to make a functional microscale human analog is challenging, and a generalized approach has yet to be identified. In this work, we demonstrate the importance of rational design of both the individual organ and its relationship with other organs, using a simple two-compartment system simulating insulin-dependent glucose uptake in adipose tissues. We demonstrate that inter-organ scaling laws depend on both the number of cells, and on the spatial arrangement of those cells within the microfabricated construct. We then propose a simple and novel inter-organ ‘metabolically-supported functional scaling’ approach predicated on maintaining in vivo cellular basal metabolic rates, by limiting resources available to cells on the chip. This approach leverages findings from allometric scaling models in mammals that limited resources in vivo prompts cells to behave differently than in resource-rich in vitro cultures. Although applying scaling laws directly to tissues can result in systems that would be quite challenging to implement, engineering workarounds may be used to circumvent these scaling issues. Specific workarounds discussed include the limited oxygen carrying capacity of cell culture media when used as a blood substitute and the ability to engineer non-physiological structures to augment organ function, to create the transport-accessible, yet resource-limited environment necessary for cells to mimic in vivo functionality. Furthermore, designing the structure of individual tissues in each organ compartment may be a useful strategy to bypass scaling concerns at the inter-organ level. PMID:23925524

Changes in Simple Spike Activity of some Purkinje cells in the Oculomotor Vermis during Saccade Adaptation are Appropriate to Participate in Motor Learning

PubMed Central

Kojima, Yoshiko; Soetedjo, Robijanto; Fuchs, Albert F.

2010-01-01

Adaptation of saccadic eye movements provides an excellent motor learning model to study theories of neuronal plasticity. When primates make saccades to a jumping target, a backward step of the target during the saccade can make it appear to overshoot. If this deception continues for many trials, saccades gradually decrease in amplitude to go directly to the back-stepped target location. We used this adaptation paradigm to evaluate the Marr-Albus hypothesis that such motor learning occurs at the Purkinje (P-) cell of the cerebellum. We recorded the activity of identified P-cells in the oculomotor vermis, lobules VIc and VII. After determining the on and off error directions of a P-cell’s complex spike activity, we determined whether its saccade-related simple spike (SS) activity changed during saccade adaptation in those two directions. Before adaptation, 57 of 61 P-cells exhibited a clear burst, pause or a combination of both for saccades in one or both directions. Sixty-two percent of all cells, including 2 of the 4 initially unresponsive ones, behaved differently for saccades whose size changed because of adaptation than for saccades of similar sizes gathered before adaptation. In at least 42% of these, the changes were appropriate to decrease saccade amplitude based on our current knowledge of cerebellum and brain stem saccade circuitry. Changes in activity during adaptation were not compensating for the potential fatigue associated with performing many saccades. Therefore, many P-cells in the oculomotor vermis exhibit changes in SS activity specific to adapted saccades and therefore appropriate to induce adaptation. PMID:20220005

A composite model of the human postcapillary venule for investigation of microvascular leukocyte recruitment

PubMed Central

Lauridsen, Holly M.; Pober, Jordan S.; Gonzalez, Anjelica L.

2014-01-01

Neutrophil extravasation occurs across postcapillary venules, structures composed of endothelial cells (ECs), pericytes (PCs), and basement membrane (BM). We constructed composite models of the human postcapillary venule, combining ECs with PCs or PC-deposited BM, to better study this process. Quiescent and tumor necrosis factor α (TNF-α)-activated composites demonstrated in situ-like expression of cadherins, E-selectin, intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), platelet-endothelial cell adhesion molecule 1 (PECAM-1), CD99, and interleukin 8 (IL-8). After TNF-α activation, the ECs supported greater neutrophil adhesion (66.1 vs. 23.7% of input cells) and transmigration (35.1 vs. 7.20% of input cells) than did the PCs, but the composites behaved comparably (no significant difference) to ECs in both assays. TNF-α-activated EC-conditioned medium (CM) increased transmigration across the PCs, whereas TNF-α-activated PC-CM decreased transmigration across the ECs, and culturing on PC-derived BM decreased both adhesion to and transmigration across the ECs. Anti-very late antigen 4 (VLA-4; on neutrophils) inhibited adhesion to TNF-α-activated composites, but not to ECs alone. Anti-CD99 (expressed on all 3 cell types) inhibited transmigration across the composites (14.5% of control) more than across the ECs (39.0% of control), and venular shear stress reduced transmigration across the ECs (17.3% of static) more than across the composites (36.7% of static). These results provide proof of concept that our composite human EC/PC/BM venular construct can reveal new interactions in the inflammatory cascade.—Lauridsen, H. M., Pober, J. S., Gonzalez, A. L. A composite model of the human postcapillary venule for investigation of microvascular leukocyte recruitment. PMID:24297702

Developmental Dyspraxia

MedlinePlus

... disorder may be of average or above average intelligence, they may behave immaturely. × Definition Developmental dyspraxia is ... disorder may be of average or above average intelligence, they may behave immaturely. View Full Definition Treatment ...

Colon cancer cells adopt an invasive phenotype without mesenchymal transition in 3-D but not 2-D culture upon combined stimulation with EGF and crypt growth factors.

PubMed

Ludwig, Kirsten; Tse, Edison S; Wang, Jean Yj

2013-05-02

The intestinal crypt homeostasis is maintained by a combination of growth factors including Wnt, R-Spondin1, Noggin and the epidermal growth factor (EGF). In human colorectal cancer, the Wnt pathway is constitutively activated through genetic and epigenetic alterations in as many as 11 genes encoding components of this crypt stem-cell maintenance mechanism. Although the proliferation of colon cancer cells does not require Wnt, it is possible that colon cancer cells can still respond to the crypt growth factors in the colonic microenvironment. A number of studies have shown that epithelial cells behave differently in 3-D versus 2-D cultures. Because the 3-D conditions more closely mimic the in vivo environment, we examined the effects of Wnt and other crypt growth factors on colon cancer cell growth in 3-D culture. Colon cancer cells were grown in 3-D matrigel supplemented with different combinations of crypt growth factors and colonies were examined for morphology and pathways. When colon cancer cells were cultured in 3-D with EGF, they grew as round spheroid colonies. However, colon cancer cells also grew as flat, disc-like colonies when cultured with EGF plus Wnt, R-Spondin1 and Noggin. Disc colonies were found to have comparable levels of E-cadherin as the spheroid colonies, but showed decreased E-cadherin at the cell-matrix contact sites. Disc colonies also elaborated F-actin rich protrusions (FRP) at the cell-matrix edge, reminiscent of an invasive phenotype but without the expression of vimentin. These E-cadherin and F-actin alterations were not induced by the four growth factors in 2-D culture. Formation of the disc colonies was inhibited by the knockdown of β-catenin and by protein kinase inhibitors such as gefitinib, imatinib and MK-2206. Furthermore, withdrawal of the crypt growth factors was able to revert the disc colonies to spheroid growth, showing that the invasive phenotype was reversible dependent on the availability of growth factors. These findings show that colon cancer cells remain responsive to the growth factors in the crypt microenvironment and can be induced to undergo morphological transformation in the more physiologically relevant 3-D culture.

512-Channel and 13-Region Simultaneous Recordings Coupled with Optogenetic Manipulation in Freely Behaving Mice

PubMed Central

Xie, Kun; Fox, Grace E.; Liu, Jun; Tsien, Joe Z.

2016-01-01

The development of technologies capable of recording both single-unit activity and local field potentials (LFPs) over a wide range of brain circuits in freely behaving animals is the key to constructing brain activity maps. Although mice are the most popular mammalian genetic model, in vivo neural recording has been traditionally limited to smaller channel count and fewer brain structures because of the mouse’s small size and thin skull. Here, we describe a 512-channel tetrode system that allows us to record simultaneously over a dozen cortical and subcortical structures in behaving mice. This new technique offers two major advantages – namely, the ultra-low cost and the do-it-yourself flexibility for targeting any combination of many brain areas. We show the successful recordings of both single units and LFPs from 13 distinct neural circuits of the mouse brain, including subregions of the anterior cingulate cortices, retrosplenial cortices, somatosensory cortices, secondary auditory cortex, hippocampal CA1, dentate gyrus, subiculum, lateral entorhinal cortex, perirhinal cortex, and prelimbic cortex. This 512-channel system can also be combined with Cre-lox neurogenetics and optogenetics to further examine interactions between genes, cell types, and circuit dynamics across a wide range of brain structures. Finally, we demonstrate that complex stimuli – such as an earthquake and fear-inducing foot-shock – trigger firing changes in all of the 13 brain regions recorded, supporting the notion that neural code is highly distributed. In addition, we show that localized optogenetic manipulation in any given brain region could disrupt network oscillations and caused changes in single-unit firing patterns in a brain-wide manner, thereby raising the cautionary note of the interpretation of optogenetically manipulated behaviors. PMID:27378865

Sonic Hedgehog promotes the survival of neural crest cells by limiting apoptosis induced by the dependence receptor CDON during branchial arch development.

PubMed

Delloye-Bourgeois, Céline; Rama, Nicolas; Brito, José; Le Douarin, Nicole; Mehlen, Patrick

2014-09-26

Cell-adhesion molecule-related/Downregulated by Oncogenes (CDO or CDON) was identified as a receptor for the classic morphogen Sonic Hedgehog (SHH). It has been shown that, in cell culture, CDO also behaves as a SHH dependence receptor: CDO actively triggers apoptosis in absence of SHH via a proteolytic cleavage in CDO intracellular domain. We present evidence that CDO is also pro-apoptotic in the developing neural tube where SHH is known to act as a survival factor. SHH, produced by the ventral foregut endoderm, was shown to promote survival of facial neural crest cells (NCCs) that colonize the first branchial arch (BA1). We show here that the survival activity of SHH on neural crest cells is due to SHH-mediated inhibition of CDO pro-apoptotic activity. Silencing of CDO rescued NCCs from apoptosis observed upon SHH inhibition in the ventral foregut endoderm. Thus, the pair SHH/dependence receptor CDO may play an important role in neural crest cell survival during the formation of the first branchial arch. Copyright © 2014 Elsevier Inc. All rights reserved.

Microstructure based model for sound absorption predictions of perforated closed-cell metallic foams.

PubMed

Chevillotte, Fabien; Perrot, Camille; Panneton, Raymond

2010-10-01

Closed-cell metallic foams are known for their rigidity, lightness, thermal conductivity as well as their low production cost compared to open-cell metallic foams. However, they are also poor sound absorbers. Similarly to a rigid solid, a method to enhance their sound absorption is to perforate them. This method has shown good preliminary results but has not yet been analyzed from a microstructure point of view. The objective of this work is to better understand how perforations interact with closed-cell foam microstructure and how it modifies the sound absorption of the foam. A simple two-dimensional microstructural model of the perforated closed-cell metallic foam is presented and numerically solved. A rough three-dimensional conversion of the two-dimensional results is proposed. The results obtained with the calculation method show that the perforated closed-cell foam behaves similarly to a perforated solid; however, its sound absorption is modulated by the foam microstructure, and most particularly by the diameters of both perforation and pore. A comparison with measurements demonstrates that the proposed calculation method yields realistic trends. Some design guides are also proposed.

Heat-shock protein 60 is required for blastema formation and maintenance during regeneration

PubMed Central

Makino, Shinji; Whitehead, Geoffrey G.; Lien, Ching-Ling; Kim, Soo; Jhawar, Payal; Kono, Akane; Kawata, Yasushi; Keating, Mark T.

2005-01-01

Zebrafish fin regeneration requires the formation and maintenance of blastema cells. Blastema cells are not derived from stem cells but behave as such, because they are slow-cycling and are thought to provide rapidly proliferating daughter cells that drive regenerative outgrowth. The molecular basis of blastema formation is not understood. Here, we show that heat-shock protein 60 (hsp60) is required for blastema formation and maintenance. We used a chemical mutagenesis screen to identify no blastema (nbl), a zebrafish mutant with an early fin regeneration defect. Fin regeneration failed in nbl due to defective blastema formation. nbl also failed to regenerate hearts. Positional cloning and mutational analyses revealed that nbl results from a V324E missense mutation in hsp60. This mutation reduced hsp60 function in binding and refolding denatured proteins. hsp60 expression is increased during formation of blastema cells, and dysfunction leads to mitochondrial defects and apoptosis in these cells. These data indicate that hsp60 is required for the formation and maintenance of regenerating tissue. PMID:16204379

The Single Superoxide Dismutase of Rhodobacter capsulatus Is a Cambialistic, Manganese-Containing Enzyme

PubMed Central

Tabares, Leandro C.; Bittel, Cristian; Carrillo, Néstor; Bortolotti, Ana; Cortez, Néstor

2003-01-01

The phototrophic bacterium Rhodobacter capsulatus contains a single, oxygen-responsive superoxide dismutase (SODRc) homologous to iron-containing superoxide dismutase enzymes. Recombinant SODRc, however, displayed higher activity after refolding with Mn2+, especially when the pH of the assay mixture was raised. SODRc isolated from Rhodobacter cells also preferentially contains manganese, but metal discrimination depends on the culture conditions, with iron fractions increasing from 7% in aerobic cultures up to 40% in photosynthetic cultures. Therefore, SODRc behaves as a Mn-containing dismutase with cambialistic properties. PMID:12730184

An introduction to the mechanics of DNA.

PubMed

Travers, A A; Thompson, J M T

2004-07-15

This article gives an overview of recent research on the mechanical properties and spatial deformations of the DNA molecule. Globally the molecule behaves like a uniform elastic rod, and its twisting and writhing govern its compaction and packaging within a cell. Meanwhile high mechanical stresses can induce structural transitions of DNA giving, for example, a phase diagram in the space of the applied tension and torque. Locally, the mechanical properties vary according to the local sequence organization. These variations play a vital role in the biological functioning of the molecule.

Segregation of two spectrin isoforms: polarized membrane-binding sites direct polarized membrane skeleton assembly.

PubMed

Dubreuil, R R; Maddux, P B; Grushko, T A; MacVicar, G R

1997-10-01

Spectrin isoforms are often segregated within specialized plasma membrane subdomains where they are thought to contribute to the development of cell surface polarity. It was previously shown that ankyrin and beta spectrin are recruited to sites of cell-cell contact in Drosophila S2 cells expressing the homophilic adhesion molecule neuroglian. Here, we show that neuroglian has no apparent effect on a second spectrin isoform (alpha beta H), which is constitutively associated with the plasma membrane in S2 cells. Another membrane marker, the Na,K-ATPase, codistributes with ankyrin and alpha beta spectrin at sites of neuroglian-mediated contact. The distributions of these markers in epithelial cells in vivo are consistent with the order of events observed in S2 cells. Neuroglian, ankyrin, alpha beta spectrin, and the Na,K-ATPase colocalize at the lateral domain of salivary gland cells. In contrast, alpha beta H spectrin is sorted to the apical domain of salivary gland and somatic follicle cells. Thus, the two spectrin isoforms respond independently to positional cues at the cell surface: in one case an apically sorted receptor and in the other case a locally activated cell-cell adhesion molecule. The results support a model in which the membrane skeleton behaves as a transducer of positional information within cells.

Fluorescent Photo-conversion: A second chance to label unique cells

PubMed Central

Mellott, Adam J.; Shinogle, Heather E.; Moore, David S.; Detamore, Michael S.

2014-01-01

Not all cells behave uniformly after treatment in tissue engineering studies. In fact, some treated cells display no signs of treatment or show unique characteristics not consistent with other treated cells. What if the “unique” cells could be isolated from a treated population, and further studied? Photo-convertible reporter proteins, such as Dendra2, allow for the ability to selectively identify unique cells with a secondary label within a primary labeled treated population. In the current study, select cells were identified and labeled through photo-conversion of Dendra2-transfected human Wharton's Jelly cells (hWJCs) for the first time. Robust photo-conversion of green-to-red fluorescence was achieved consistently in arbitrarily selected cells, allowing for precise cell identification of select hWJCs. The current study demonstrates a method that offers investigators the opportunity to selectively label and identify unique cells within a treated population for further study or isolation from the treatment population. Photo-convertible reporter proteins, such as Dendra2, offer the ability over non-photo-convertible reporter proteins, such as green fluorescent protein, to analyze unique individual cells within a treated population, which allows investigators to gain more meaningful information on how a treatment affects all cells within a target population. PMID:25914756

Immortalisation of a human diploid fibroblast cell strain: a DT-diaphorase paradox.

PubMed Central

Kuehl, B. L.; Brezden, C. B.; Traver, R. D.; Siegel, D.; Ross, D.; Renzing, J.; Rauth, A. M.

1996-01-01

Transfection of a normal human diploid fibroblast cell strain, GM38, with a simian virus 40 (SV40) large T antigen containing plasmid, yielded an immortal cell line, G38-8X, which had a similar sensitivity as the parental cell strain to the quinone-containing chemotherapeutic agent mitomycin C (MMC), under both aerobic and hypoxic exposure conditions. The activity level of DT-diaphorase was similar in both the parental GM38 and G38-8X cells. Although DT-diaphorase could be detected by Western blot analysis, using two mouse anti-human monoclonal antibodies, in GM38 cells, it was not detected in the G38-8X cells. G38-8X cells have a slightly increased P450R activity (2-fold), and have elevated P-glycoprotein levels compared with the parental GM38 cell strain. The immortal G38-8X cell line is 2-fold more resistant to ionising radiation than the parental GM38 cell strain (D10 approximately 5 Gy). Although these SV40 large T antigen immortalised human diploid fibroblasts behaved similarly to their parental cell strain in terms of MMC sensitivity and DT-diaphorase activity, careful characterisation revealed that these cells had enhanced P-glycoprotein activity and had a decreased sensitivity to ionising radiation. Images Figure 3 PMID:8763839

A well-behaved class of charged analogue of Durgapal solution

NASA Astrophysics Data System (ADS)

Mehta, R. N.; Pant, Neeraj; Mahto, Dipo; Jha, J. S.

2013-02-01

We present a well behaved class of charged analogue of M.C. Durgapal (J. Phys. A, Math. Gen. 15:2637, 1982) solution. This solution describes charged fluid balls with positively finite central pressure, positively finite central density; their ratio is less than one and causality condition is obeyed at the centre. The outmarch of pressure, density, pressure-density ratio and the adiabatic speed of sound is monotonically decreasing, however, the electric intensity is monotonically increasing in nature. This solution gives us wide range of parameter for every positive value of n for which the solution is well behaved hence, suitable for modeling of super dense stars. Keeping in view of well behaved nature of this solution, one new class of solution is being studied extensively. Moreover, this class of solution gives us wide range of constant K (0≤ K≤2.2) for which the solution is well behaved hence, suitable for modeling of super dense stars like strange quark stars, neutron stars and pulsars. For this class of solution the mass of a star is maximized with all degree of suitability, compatible with quark stars, neutron stars and pulsars. By assuming the surface density ρ b =2×1014 g/cm3 (like, Brecher and Capocaso, Nature 259:377, 1976), corresponding to K=0 with X=0..235, the resulting well behaved model has the mass M=4.03 M Θ , radius r b =19.53 km and moment of inertia I=1.213×1046 g cm2; for K=1.5 with X=0.235, the resulting well behaved model has the mass M=4.43 M Θ , radius r b =18.04 km and moment of inertia I=1.136×1046 g cm2; for K=2.2 with X=0.235, the resulting well behaved model has the mass M=4.56 M Θ , radius r b =17.30 km and moment of inertia I=1.076×1046 g cm2. These values of masses and moment of inertia are found to be consistent with the crab pulsars.

Cooperative quantum-behaved particle swarm optimization with dynamic varying search areas and Lévy flight disturbance.

PubMed

Li, Desheng

2014-01-01

This paper proposes a novel variant of cooperative quantum-behaved particle swarm optimization (CQPSO) algorithm with two mechanisms to reduce the search space and avoid the stagnation, called CQPSO-DVSA-LFD. One mechanism is called Dynamic Varying Search Area (DVSA), which takes charge of limiting the ranges of particles' activity into a reduced area. On the other hand, in order to escape the local optima, Lévy flights are used to generate the stochastic disturbance in the movement of particles. To test the performance of CQPSO-DVSA-LFD, numerical experiments are conducted to compare the proposed algorithm with different variants of PSO. According to the experimental results, the proposed method performs better than other variants of PSO on both benchmark test functions and the combinatorial optimization issue, that is, the job-shop scheduling problem.

Blocking Blood Flow to Solid Tumors by Destabilizing Tubulin: An Approach to Targeting Tumor Growth.

PubMed

Pérez-Pérez, María-Jesús; Priego, Eva-María; Bueno, Oskía; Martins, Maria Solange; Canela, María-Dolores; Liekens, Sandra

2016-10-13

The unique characteristics of the tumor vasculature offer the possibility to selectively target tumor growth and vascularization using tubulin-destabilizing agents. Evidence accumulated with combretastatin A-4 (CA-4) and its prodrug CA-4P support the therapeutic value of compounds sharing this mechanism of action. However, the chemical instability and poor solubility of CA-4 demand alternative compounds that are able to surmount these limitations. This Perspective illustrates the different classes of compounds that behave similar to CA-4, analyzes their binding mode to αβ-tubulin according to recently available structural complexes, and includes described approaches to improve their delivery. In addition, dissecting the mechanism of action of CA-4 and analogues allows a closer insight into the advantages and drawbacks associated with these tubulin-destabilizing agents that behave as vascular disrupting agents (VDAs).

Brain state-dependence of electrically evoked potentials monitored with head-mounted electronics.

PubMed

Richardson, Andrew G; Fetz, Eberhard E

2012-11-01

Inferring changes in brain connectivity is critical to studies of learning-related plasticity and stimulus-induced conditioning of neural circuits. In addition, monitoring spontaneous fluctuations in connectivity can provide insight into information processing during different brain states. Here, we quantified state-dependent connectivity changes throughout the 24-h sleep-wake cycle in freely behaving monkeys. A novel, head-mounted electronic device was used to electrically stimulate at one site and record evoked potentials at other sites. Electrically evoked potentials (EEPs) revealed the connectivity pattern between several cortical sites and the basal forebrain. We quantified state-dependent changes in the EEPs. Cortico-cortical EEP amplitude increased during slow-wave sleep, compared to wakefulness, while basal-cortical EEP amplitude decreased. The results demonstrate the utility of using portable electronics to document state-dependent connectivity changes in freely behaving primates.

Information Processing Capabilities in Performers Differing in Levels of Motor Skill

DTIC Science & Technology

1979-01-01

F. I. 1. , ’ Lockhart , R. S. Levels of* processing : A framework for memory research. Journal of Verbal Learning and Verbal Behavior, 1972, 11, 671-684...ARI TECHNICAL REPORT LEVEr.79iA4 Information Processing Capabilities in Performers Differing In Levels of 00 Motor Skill ,4 by Robert N. Singer... PROCESSING CAPABILITIES IN PERFORMERS DIFFERING IN LEVELS OF MOTOR SKILL INTRODUCTION In the human behaving systems model developed by Singer, Gerson, and

Sensory Coding by Cerebellar Mossy Fibres through Inhibition-Driven Phase Resetting and Synchronisation

PubMed Central

Holtzman, Tahl; Jörntell, Henrik

2011-01-01

Temporal coding of spike-times using oscillatory mechanisms allied to spike-time dependent plasticity could represent a powerful mechanism for neuronal communication. However, it is unclear how temporal coding is constructed at the single neuronal level. Here we investigate a novel class of highly regular, metronome-like neurones in the rat brainstem which form a major source of cerebellar afferents. Stimulation of sensory inputs evoked brief periods of inhibition that interrupted the regular firing of these cells leading to phase-shifted spike-time advancements and delays. Alongside phase-shifting, metronome cells also behaved as band-pass filters during rhythmic sensory stimulation, with maximal spike-stimulus synchronisation at frequencies close to the idiosyncratic firing frequency of each neurone. Phase-shifting and band-pass filtering serve to temporally align ensembles of metronome cells, leading to sustained volleys of near-coincident spike-times, thereby transmitting synchronised sensory information to downstream targets in the cerebellar cortex. PMID:22046297

Activity-dependent self-regulation of viscous length scales in biological systems

NASA Astrophysics Data System (ADS)

Nandi, Saroj Kumar

2018-05-01

The cellular cortex, which is a highly viscous thin cytoplasmic layer just below the cell membrane, controls the cell's mechanical properties, which can be characterized by a hydrodynamic length scale ℓ . Cells actively regulate ℓ via the activity of force-generating molecules, such as myosin II. Here we develop a general theory for such systems through a coarse-grained hydrodynamic approach including activity in the static description of the system providing an experimentally accessible parameter and elucidate the detailed mechanism of how a living system can actively self-regulate its hydrodynamic length scale, controlling the rigidity of the system. Remarkably, we find that ℓ , as a function of activity, behaves universally and roughly inversely proportional to the activity of the system. Our theory rationalizes a number of experimental findings on diverse systems, and comparison of our theory with existing experimental data shows good agreement.

Pyramidal cell-interneuron interactions underlie hippocampal ripple oscillations.

PubMed

Stark, Eran; Roux, Lisa; Eichler, Ronny; Senzai, Yuta; Royer, Sebastien; Buzsáki, György

2014-07-16

High-frequency ripple oscillations, observed most prominently in the hippocampal CA1 pyramidal layer, are associated with memory consolidation. The cellular and network mechanisms underlying the generation, frequency control, and spatial coherence of the rhythm are poorly understood. Using multisite optogenetic manipulations in freely behaving rodents, we found that depolarization of a small group of nearby pyramidal cells was sufficient to induce high-frequency oscillations, whereas closed-loop silencing of pyramidal cells or activation of parvalbumin- (PV) or somatostatin-immunoreactive interneurons aborted spontaneously occurring ripples. Focal pharmacological blockade of GABAA receptors abolished ripples. Localized PV interneuron activation paced ensemble spiking, and simultaneous induction of high-frequency oscillations at multiple locations resulted in a temporally coherent pattern mediated by phase-locked interneuron spiking. These results constrain competing models of ripple generation and indicate that temporally precise local interactions between excitatory and inhibitory neurons support ripple generation in the intact hippocampus. Copyright © 2014 Elsevier Inc. All rights reserved.

Pyramidal Cell-Interneuron Interactions Underlie Hippocampal Ripple Oscillations

PubMed Central

Stark, Eran; Roux, Lisa; Eichler, Ronny; Senzai, Yuta; Royer, Sebastien; Buzsáki, György

2015-01-01

SUMMARY High-frequency ripple oscillations, observed most prominently in the hippocampal CA1 pyramidal layer, are associated with memory consolidation. The cellular and network mechanisms underlying the generation, frequency control, and spatial coherence of the rhythm are poorly understood. Using multisite optogenetic manipulations in freely behaving rodents, we found that depolarization of a small group of nearby pyramidal cells was sufficient to induce high-frequency oscillations, whereas closed-loop silencing of pyramidal cells or activation of parvalbumin-(PV) or somatostatin-immunoreactive interneurons aborted spontaneously occurring ripples. Focal pharmacological blockade of GABAA receptors abolished ripples. Localized PV inter-neuron activation paced ensemble spiking, and simultaneous induction of high-frequency oscillations at multiple locations resulted in a temporally coherent pattern mediated by phase-locked inter-neuron spiking. These results constrain competing models of ripple generation and indicate that temporally precise local interactions between excitatory and inhibitory neurons support ripple generation in the intact hippocampus. PMID:25033186

Supramolecular "Trojan Horse" for Nuclear Delivery of Dual Anticancer Drugs.

PubMed

Cai, Yanbin; Shen, Haosheng; Zhan, Jie; Lin, Mingliang; Dai, Liuhan; Ren, Chunhua; Shi, Yang; Liu, Jianfeng; Gao, Jie; Yang, Zhimou

2017-03-01

Nuclear delivery and accumulation are very important for many anticancer drugs that interact with DNA or its associated enzymes in the nucleus. However, it is very difficult for neutrally and negatively charged anticancer drugs such as 10-hydroxycamptothecine (HCPT). Here we report a simple strategy to construct supramolecular nanomedicines for nuclear delivery of dual synergistic anticancer drugs. Our strategy utilizes the coassembly of a negatively charged HCPT-peptide amphiphile and the positively charged cisplatin. The resulting nanomaterials behave as the "Trojan Horse" that transported soldiers (anticancer drugs) across the walls of the castle (cell and nucleus membranes). Therefore, they show improved inhibition capacity to cancer cells including the drug resistant cancer cell and promote the synergistic tumor suppression property in vivo. We envision that our strategy of constructing nanomaterials by metal chelation would offer new opportunities to develop nanomedicines for combination chemotherapy.

Gender differences in moral judgment and the evaluation of gender-specified moral agents.

PubMed

Capraro, Valerio; Sippel, Jonathan

2017-11-01

Whether, and if so, how exactly gender differences are manifested in moral judgment has recently been at the center of much research on moral decision making. Previous research suggests that women are more deontological than men in personal, but not impersonal, moral dilemmas. However, typical personal and impersonal moral dilemmas differ along two dimensions: Personal dilemmas are more emotionally salient than impersonal ones and involve a violation of Kant's practical imperative that humans must never be used as a mere means, but only as ends. Thus, it remains unclear whether the reported gender difference is due to emotional salience or to the violation of the practical imperative. To answer this question, we explore gender differences in three moral dilemmas: a typical personal dilemma, a typical impersonal dilemma, and an intermediate dilemma, which is not as emotionally salient as typical personal moral dilemmas, but contains an equally strong violation of Kant's practical imperative. While we replicate the result that women tend to embrace deontological ethics more than men in personal, but not impersonal, dilemmas, we find no gender differences in the intermediate situation. This suggests that gender differences in these type of dilemmas are driven by emotional salience, and not by the violation of the practical imperative. Additionally, we also explore whether people think that women should behave differently than men in these dilemmas. Across all three dilemmas, we find no statistically significant differences about how people think men and women should behave.

The End of Theory? Does the Data Deluge Make the Scientific Method Obsolete?

NASA Astrophysics Data System (ADS)

Kreinovich, Vladik; McClure, John; Symons, John

2008-10-01

Why do we need theory? One of the purposes of science is to predict: e.g., how a complex material behaves in different situations. There are a lot of records describing how different materials behave in different situations. In the past, it was not possible to find a similar record and simply recall what happened then. The only possibility was to extract, from the data, a simple dependence, and then use this dependence for predictions. For example, we can use Ohm's law V=I.R to predict the voltage V based on the current I and the resistance R. Nowadays, computer searches are so fast that there seems to be no need for any theoretical laws anymore: if we want to predict, we can simply search through all the records and find what happened in a similar situation. So maybe we do not need theory at all. This was the argument developed in a recent (June 2008) article in a popular Wired magazine. In our presentation, we will describe this argument in detail, and give our opinion on whether the computer progress will indeed lead to the end of the theory as we know it.

Automation of 3D cell culture using chemically defined hydrogels.

PubMed

Rimann, Markus; Angres, Brigitte; Patocchi-Tenzer, Isabel; Braum, Susanne; Graf-Hausner, Ursula

2014-04-01

Drug development relies on high-throughput screening involving cell-based assays. Most of the assays are still based on cells grown in monolayer rather than in three-dimensional (3D) formats, although cells behave more in vivo-like in 3D. To exemplify the adoption of 3D techniques in drug development, this project investigated the automation of a hydrogel-based 3D cell culture system using a liquid-handling robot. The hydrogel technology used offers high flexibility of gel design due to a modular composition of a polymer network and bioactive components. The cell inert degradation of the gel at the end of the culture period guaranteed the harmless isolation of live cells for further downstream processing. Human colon carcinoma cells HCT-116 were encapsulated and grown in these dextran-based hydrogels, thereby forming 3D multicellular spheroids. Viability and DNA content of the cells were shown to be similar in automated and manually produced hydrogels. Furthermore, cell treatment with toxic Taxol concentrations (100 nM) had the same effect on HCT-116 cell viability in manually and automated hydrogel preparations. Finally, a fully automated dose-response curve with the reference compound Taxol showed the potential of this hydrogel-based 3D cell culture system in advanced drug development.

CD40L+ CD4+ memory T cells migrate in a CD62P-dependent fashion into reactive lymph nodes and license dendritic cells for T cell priming

PubMed Central

Martín-Fontecha, Alfonso; Baumjohann, Dirk; Guarda, Greta; Reboldi, Andrea; Hons, Miroslav; Lanzavecchia, Antonio; Sallusto, Federica

2008-01-01

There is growing evidence that the maturation state of dendritic cells (DCs) is a critical parameter determining the balance between tolerance and immunity. We report that mouse CD4+ effector memory T (TEM) cells, but not naive or central memory T cells, constitutively expressed CD40L at levels sufficient to induce DC maturation in vitro and in vivo in the absence of antigenic stimulation. CD4+ TEM cells were excluded from resting lymph nodes but migrated in a CD62P-dependent fashion into reactive lymph nodes that were induced to express CD62P, in a transient or sustained fashion, on high endothelial venules. Trafficking of CD4+ TEM cells into chronic reactive lymph nodes maintained resident DCs in a mature state and promoted naive T cell responses and experimental autoimmune encephalomyelitis (EAE) to antigens administered in the absence of adjuvants. Antibodies to CD62P, which blocked CD4+ TEM cell migration into reactive lymph nodes, inhibited DC maturation, T cell priming, and induction of EAE. These results show that TEM cells can behave as endogenous adjuvants and suggest a mechanistic link between lymphocyte traffic in lymph nodes and induction of autoimmunity. PMID:18838544

Patterns of neural activity associated with honest and dishonest moral decisions

PubMed Central

Greene, Joshua D.; Paxton, Joseph M.

2009-01-01

What makes people behave honestly when confronted with opportunities for dishonest gain? Research on the interplay between controlled and automatic processes in decision making suggests 2 hypotheses: According to the “Will” hypothesis, honesty results from the active resistance of temptation, comparable to the controlled cognitive processes that enable the delay of reward. According to the “Grace” hypothesis, honesty results from the absence of temptation, consistent with research emphasizing the determination of behavior by the presence or absence of automatic processes. To test these hypotheses, we examined neural activity in individuals confronted with opportunities for dishonest gain. Subjects undergoing functional magnetic resonance imaging (fMRI) gained money by accurately predicting the outcomes of computerized coin-flips. In some trials, subjects recorded their predictions in advance. In other trials, subjects were rewarded based on self-reported accuracy, allowing them to gain money dishonestly by lying about the accuracy of their predictions. Many subjects behaved dishonestly, as indicated by improbable levels of “accuracy.” Our findings support the Grace hypothesis. Individuals who behaved honestly exhibited no additional control-related activity (or other kind of activity) when choosing to behave honestly, as compared with a control condition in which there was no opportunity for dishonest gain. In contrast, individuals who behaved dishonestly exhibited increased activity in control-related regions of prefrontal cortex, both when choosing to behave dishonestly and on occasions when they refrained from dishonesty. Levels of activity in these regions correlated with the frequency of dishonesty in individuals. PMID:19622733

Local viscoelasticity of living cells measured by rotational magnetic spectroscopy

PubMed Central

Berret, J.-F.

2016-01-01

When submitted to a magnetic field, micron-size wires with superparamagnetic properties behave as embedded rheometers and represent interesting sensors for microrheology. Here we use rotational magnetic spectroscopy to measure the shear viscosity of the cytoplasm of living cells. We address the question of whether the cytoplasm is a viscoelastic liquid or an elastic gel. The main result of the study is the observation of a rotational instability between a synchronous and an asynchronous regime of rotation, found for murine fibroblasts and human cancer cells. For wires of susceptibility 3.6, the transition occurs in the range 0.01–1 rad s−1. The determination of the shear viscosity (10–100 Pa s) and elastic modulus (5–20 Pa) confirms the viscoelastic character of the cytoplasm. In contrast to earlier studies, it is concluded that the interior of living cells can be described as a viscoelastic liquid, and not as an elastic gel. PMID:26729062

Optogenetic control of RhoA reveals zyxin-mediated elasticity of stress fibres

NASA Astrophysics Data System (ADS)

Oakes, Patrick W.; Wagner, Elizabeth; Brand, Christoph A.; Probst, Dimitri; Linke, Marco; Schwarz, Ulrich S.; Glotzer, Michael; Gardel, Margaret L.

2017-06-01

Cytoskeletal mechanics regulates cell morphodynamics and many physiological processes. While contractility is known to be largely RhoA-dependent, the process by which localized biochemical signals are translated into cell-level responses is poorly understood. Here we combine optogenetic control of RhoA, live-cell imaging and traction force microscopy to investigate the dynamics of actomyosin-based force generation. Local activation of RhoA not only stimulates local recruitment of actin and myosin but also increased traction forces that rapidly propagate across the cell via stress fibres and drive increased actin flow. Surprisingly, this flow reverses direction when local RhoA activation stops. We identify zyxin as a regulator of stress fibre mechanics, as stress fibres are fluid-like without flow reversal in its absence. Using a physical model, we demonstrate that stress fibres behave elastic-like, even at timescales exceeding turnover of constituent proteins. Such molecular control of actin mechanics likely plays critical roles in regulating morphodynamic events.

Characterization of the Ternary Compound Pd5Pt3Ni2 for PEMFC Cathode Electrocatalysts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jarvis, Karalee; Zhao, J; Allard Jr, Lawrence Frederick

2010-01-01

Research on proton exchange membrane fuel cells (PEMFC) has increased over the last decade due to an increasing demand for alternative energy solutions. Most PEMFCs use Pt on carbon support as electrocatalysts for oxygen reduction reactions (ORR) [1]. Due to the high cost of Pt, there is a strong drive to develop less expensive catalysts that meet or exceed the performance of Pt. Binary and ternary Pt alloys with less expensive metals are a possible route [1]. In this work, a ternary alloy with composition Pd5Pt3Ni2 was studied as a potential cathode material. Preliminary results showed similar catalytic performance tomore » pure Pt in single-cell tests. However, to enhance its performance, it is necessary to understand how this ternary catalyst behaves during fuel cell operation. Various electron microscopy techniques were used to characterize the ternary Pd5Pt3Ni2 catalysts within the membrane-electrode assembly (MEA) both before and after fuel cell operation.« less

Endoplasmic Reticulum-Localized Two-Photon-Absorbing Boron Dipyrromethenes as Advanced Photosensitizers for Photodynamic Therapy.

PubMed

Zhou, Yimin; Cheung, Ying-Kit; Ma, Chao; Zhao, Shirui; Gao, Di; Lo, Pui-Chi; Fong, Wing-Ping; Wong, Kam Sing; Ng, Dennis K P

2018-05-10

Two advanced boron dipyrromethene (BODIPY) based photosensitizers have been synthesized and characterized. With a glibenclamide analogous moiety, these compounds can localize in the endoplasmic reticulum (ER) of HeLa human cervical carcinoma cells and HepG2 human hepatocarcinoma cells. The BODIPY π skeleton is conjugated with two styryl or carbazolylethenyl groups, which can substantially red-shift the Q-band absorption and fluorescence emission and impart two-photon absorption (TPA) property to the chromophores. The TPA cross section of the carbazole-containing analogue reaches a value of 453 GM at 1010 nm. These compounds also behave as singlet oxygen generators with high photostability. Upon irradiation at λ > 610 nm, these photosensitizers cause photocytotoxicity to these two cell lines with IC 50 values down to 0.09 μM, for which the cell death is triggered mainly by ER stress. The two-photon photodynamic activity of the distyryl derivative upon excitation at λ = 800 nm has also been demonstrated.

The sociomicrobiology of antivirulence drug resistance: a proof of concept.

PubMed

Mellbye, Brett; Schuster, Martin

2011-01-01

Antivirulence drugs disarm rather than kill pathogens and are thought to alleviate the problem of resistance, although there is no evidence to support this notion. Quorum sensing (QS) often controls cooperative virulence factor production and is therefore an attractive antivirulence target, for which inhibitors (QSI) have been developed. We designed a proof-of-principle experiment to investigate the impact of bacterial social interactions on the evolution of QSI resistance. We cocultured Pseudomonas aeruginosa QS-deficient mutants with small proportions of the QS-proficient wild type, which in the absence of QSI mimic QSI-sensitive and -resistant variants, respectively. We employed two different QS-dependent nutrients that are degraded by extracellular (public) and cell-associated (private) enzymes. QS mutants (QSI-sensitive mimics) behaved as social cheaters that delayed population growth and prevented enrichment of wild-type cooperators (QSI-resistant mimics) only when nutrient acquisition was public, suggesting that QSI resistance would not spread. This highlights the potential for antivirulence strategies that target cooperative behaviors and provides a conceptual framework for future studies.

Multi-sensory integration in a small brain

NASA Astrophysics Data System (ADS)

Gepner, Ruben; Wolk, Jason; Gershow, Marc

Understanding how fluctuating multi-sensory stimuli are integrated and transformed in neural circuits has proved a difficult task. To address this question, we study the sensori-motor transformations happening in the brain of the Drosophila larva, a tractable model system with about 10,000 neurons. Using genetic tools that allow us to manipulate the activity of individual brain cells through their transparent body, we observe the stochastic decisions made by freely-behaving animals as their visual and olfactory environments fluctuate independently. We then use simple linear-nonlinear models to correlate outputs with relevant features in the inputs, and adaptive filtering processes to track changes in these relevant parameters used by the larva's brain to make decisions. We show how these techniques allow us to probe how statistics of stimuli from different sensory modalities combine to affect behavior, and can potentially guide our understanding of how neural circuits are anatomically and functionally integrated. Supported by NIH Grant 1DP2EB022359 and NSF Grant PHY-1455015.

Theory of compact nonporous windscreens for infrasonic measurements.

PubMed

Zuckerwar, Allan J

2010-06-01

The principle of the compact nonporous windscreen is based on the great penetrability of infrasound through matter. The windscreen performance is characterized by the ratio of the sound pressure at an interior microphone, located in the center of a windscreen, to the incident sound pressure in the free field. The frequency dependence of this pressure ratio is derived as a function of the windscreen material and geometric properties. Four different windscreen geometries are considered: a subsurface, box-shaped windscreen, a cylindrical windscreen of infinite length, a cylindrical windscreen of finite length, and a spherical windscreen. Results are presented for windscreens made of closed-cell polyurethane foam and for typical dimensions of each of the above geometries. The cylindrical windscreen of finite length, featuring evanescent radial modes, behaves as a unity-gain, low-pass filter, cutting off sharply at the end of the infrasonic range. The remaining geometries reveal a pass band that extends well into the audio range, terminated by a pronounced peak beyond which the response plummets rapidly.

Characterization of new drug delivery nanosystems using atomic force microscopy

NASA Astrophysics Data System (ADS)

Spyratou, Ellas; Mourelatou, Elena A.; Demetzos, C.; Makropoulou, Mersini; Serafetinides, A. A.

2015-01-01

Liposomes are the most attractive lipid vesicles for targeted drug delivery in nanomedicine, behaving also as cell models in biophotonics research. The characterization of the micro-mechanical properties of drug carriers is an important issue and many analytical techniques are employed, as, for example, optical tweezers and atomic force microscopy. In this work, polyol hyperbranched polymers (HBPs) have been employed along with liposomes for the preparation of new chimeric advanced drug delivery nanosystems (Chi-aDDnSs). Aliphatic polyester HBPs with three different pseudogenerations G2, G3 and G4 with 16, 32, and 64 peripheral hydroxyl groups, respectively, have been incorporated in liposomal formulation. The atomic force microscopy (AFM) technique was used for the comparative study of the morphology and the mechanical properties of Chi-aDDnSs and conventional DDnS. The effects of both the HBPs architecture and the polyesters pseudogeneration number in the stability and the stiffness of chi-aDDnSs were examined. From the force-distance curves of AFM spectroscopy, the Young's modulus was calculated.

Recently Identified Mutations in the Ebola Virus-Makona Genome Do Not Alter Pathogenicity in Animal Models.

PubMed

Marzi, Andrea; Chadinah, Spencer; Haddock, Elaine; Feldmann, Friederike; Arndt, Nicolette; Martellaro, Cynthia; Scott, Dana P; Hanley, Patrick W; Nyenswah, Tolbert G; Sow, Samba; Massaquoi, Moses; Feldmann, Heinz

2018-05-08

Ebola virus (EBOV), isolate Makona, the causative agent of the West African EBOV epidemic, has been the subject of numerous investigations to determine the genetic diversity and its potential implication for virus biology, pathogenicity, and transmissibility. Despite various mutations that have emerged over time through multiple human-to-human transmission chains, their biological relevance remains questionable. Recently, mutations in the glycoprotein GP and polymerase L, which emerged and stabilized early during the outbreak, have been associated with improved viral fitness in cell culture. Here, we infected mice and rhesus macaques with EBOV-Makona isolates carrying or lacking those mutations. Surprisingly, all isolates behaved very similarly independent of the genotype, causing severe or lethal disease in mice and macaques, respectively. Likewise, we could not detect any evidence for differences in virus shedding. Thus, no specific biological phenotype could be associated with these EBOV-Makona mutations in two animal models. Published by Elsevier Inc.

The Surface-to-Volume Ratio in Thermal Physics: From Cheese Cube Physics to Animal Metabolism

ERIC Educational Resources Information Center

Planinsic, Gorazd; Vollmer, Michael

2008-01-01

The surface-to-volume ratio is an important quantity in thermal physics. For example it governs the behaviour of heating or cooling of physical objects as a function of size like, e.g. cubes or spheres made of different material. The starting point in our paper is the simple physics problem of how cheese cubes of different sizes behave if heated…

Not so Individual after All: An Ecological Approach to Age as an Individual Difference Variable in a Classroom

ERIC Educational Resources Information Center

Pfenninger, Simone E.

2017-01-01

The main goal of this paper is to analyze how the age factor behaves as an alleged individual difference (ID) variable in SLA by focusing on the influence that the learning context exerts on the dynamics of age of onset (AO). The results of several long-term classroom studies on age effects will be presented, in which I have empirically analyzed…

CROSS-CULTURAL AGILITY IN LAW ENFORCEMENT: TYING IN THE INTERLOCUTORS CRAFT

DTIC Science & Technology

2017-02-10

think through novel and varied ways to DISTRIBUTION A. Approved for public release: distribution unlimited. 7 engage diversity. While basic...others think , behave, make decisions, view the world, and interpret actions assists in providing strategies and options in how best to engage them to...public release: distribution unlimited. 14 Different Modes of Thinking . But first, an officer might need to tap into a different thinking mode. Daniel

Insensitivity of chromosome I and the cell cycle to blockage of replication and segregation of Vibrio cholerae chromosome II.

PubMed

Kadoya, Ryosuke; Chattoraj, Dhruba K

2012-01-01

Vibrio cholerae has two chromosomes (chrI and chrII) whose replication and segregation are under different genetic controls. The region covering the replication origin of chrI resembles that of the Escherichia coli chromosome, and both origins are under control of the highly conserved initiator, DnaA. The origin region of chrII resembles that of plasmids that have iterated initiator-binding sites (iterons) and is under control of the chrII-specific initiator, RctB. Both chrI and chrII encode chromosome-specific orthologs of plasmid partitioning proteins, ParA and ParB. Here, we have interfered with chrII replication, segregation, or both, using extra copies of sites that titrate RctB or ParB. Under these conditions, replication and segregation of chrI remain unaffected for at least 1 cell cycle. In this respect, chrI behaves similarly to the E. coli chromosome when plasmid maintenance is disturbed in the same cell. Apparently, no checkpoint exists to block cell division before the crippled chromosome is lost by a failure to replicate or to segregate. Whether blocking chrI replication can affect chrII replication remains to be tested. Chromosome replication, chromosome segregation, and cell division are the three main events of the cell cycle. They occur in an orderly fashion once per cell cycle. How the sequence of events is controlled is only beginning to be answered in bacteria. The finding of bacteria that possess more than one chromosome raises the important question: how are different chromosomes coordinated in their replication and segregation? It appears that in the evolution of the two-chromosome genome of V. cholerae, either the secondary chromosome adapted to the main chromosome to ensure its maintenance or it is maintained independently, as are bacterial plasmids. An understanding of chromosome coordination is expected to bear on the evolutionary process of chromosome acquisition and on the efficacy of possible strategies for selective elimination of a pathogen by targeting a specific chromosome.

Edge-Dependent Electronic and Magnetic Characteristics of Freestanding β 12-Borophene Nanoribbons

NASA Astrophysics Data System (ADS)

Izadi Vishkayi, Sahar; Bagheri Tagani, Meysam

2018-03-01

This work presents an investigation of nanoribbons cut from β 12-borophene sheets by applying the density functional theory. In particular, the electronic and magnetic properties of borophene nanoribbons (BNR) are studied. It is found that all the ribbons considered in this work behave as metals, which is in good agreement with the recent experimental results. β 12-BNR has significant diversity due to the existence of five boron atoms in a unit cell of the sheet. The magnetic properties of the ribbons are strongly dependent on the cutting direction and edge profile. It is interesting that a ribbon with a specific width can behave as a normal or a ferromagnetic metal with magnetization at just one edge or two edges. Spin anisotropy is observed in some ribbons, and the magnetic moment is not found to be the same in both edges in an antiferromagnetic configuration. This effect stems from the edge asymmetry of the ribbons and results in the breaking of spin degeneracy in the band structure. Our findings show that β 12 BNRs are potential candidates for next-generation spintronic devices. [Figure not available: see fulltext.

Segregation of Two Spectrin Isoforms: Polarized Membrane-binding Sites Direct Polarized Membrane Skeleton Assembly

PubMed Central

Dubreuil, Ronald R.; Maddux, Pratumtip Boontrakulpoontawee; Grushko, Tanya A.; Macvicar, Gary R.

1997-01-01

Spectrin isoforms are often segregated within specialized plasma membrane subdomains where they are thought to contribute to the development of cell surface polarity. It was previously shown that ankyrin and β spectrin are recruited to sites of cell–cell contact in Drosophila S2 cells expressing the homophilic adhesion molecule neuroglian. Here, we show that neuroglian has no apparent effect on a second spectrin isoform (αβH), which is constitutively associated with the plasma membrane in S2 cells. Another membrane marker, the Na,K-ATPase, codistributes with ankyrin and αβ spectrin at sites of neuroglian-mediated contact. The distributions of these markers in epithelial cells in vivo are consistent with the order of events observed in S2 cells. Neuroglian, ankyrin, αβ spectrin, and the Na,K-ATPase colocalize at the lateral domain of salivary gland cells. In contrast, αβH spectrin is sorted to the apical domain of salivary gland and somatic follicle cells. Thus, the two spectrin isoforms respond independently to positional cues at the cell surface: in one case an apically sorted receptor and in the other case a locally activated cell–cell adhesion molecule. The results support a model in which the membrane skeleton behaves as a transducer of positional information within cells. PMID:9348534

Comparison of the Life Cycles of Genetically Distant Species C and Species D Human Adenoviruses Ad6 and Ad26 in Human Cells.

PubMed

Turner, Mallory A; Middha, Sumit; Hofherr, Sean E; Barry, Michael A

2015-12-01

Our understanding of adenovirus (Ad) biology is largely extrapolated from human species C Ad5. Most humans are immune to Ad5, so lower-seroprevalence viruses like human Ad6 and Ad26 are being tested as therapeutic vectors. Ad6 and Ad26 differ at the DNA level by 34%. To better understand how this might impact their biology, we examined the life cycle of the two viruses in human lung cells in vitro. Both viruses infected A549 cells with similar efficiencies, executed DNA replication with identical kinetics within 12 h, and began killing cells within 72 h. While Ad6-infected cells remained adherent until death, Ad26-infected cells detached within 12 h of infection but remained viable. Next-generation sequencing (NGS) of mRNA from infected cells demonstrated that viral transcripts constituted 1% of cellular mRNAs within 6 h and 8 to 16% within 12 h. Quantitative PCR and NGS revealed the activation of key early genes at 6 h and transition to late gene activation by 12 h by both viruses. There were marked differences in the balance of E1A and E1B activation by the two viruses and in the expression of E3 immune evasion mRNAs. Ad6 was markedly more effective at suppressing major histocompatibility complex class I (MHC I) display on the cell surface and in evading TRAIL-mediated apoptosis than was Ad26. These data demonstrate shared as well as divergent life cycles in these genetically distant human adenoviruses. An understanding of these differences expands the knowledge of alternative Ad species and may inform the selection of related Ads for therapeutic development. A burgeoning number of adenoviruses (Ads) are being harnessed as therapeutics, yet the biology of these viruses is generally extrapolated from Ad2 and Ad5. Here, we are the first to compare the transcriptional programs of two genetically distant Ads by mRNA next-generation sequencing (NGS). Species C Ad6 and Ad26 are being pursued as lower-seroprevalence Ad vectors but differ at the DNA level by 34%. Head-to-head comparison in human lung cells by NGS revealed that the two viruses generally conform to our general understanding of the Ad transcriptional program. However, fine mapping revealed subtle and strong differences in how these two viruses execute these programs, including differences in the balance of E1A and E1B mRNAs and in E3 immune evasion genes. This suggests that not all adenoviruses behave like Ad2 and Ad5 and that they may have unique strategies to infect cells and evade the immune system. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Fuel model selection for BEHAVE in midwestern oak savannas

USGS Publications Warehouse

Grabner, K.W.; Dwyer, J.P.; Cutter, B.E.

2001-01-01

BEHAVE, a fire behavior prediction system, can be a useful tool for managing areas with prescribed fire. However, the proper choice of fuel models can be critical in developing management scenarios. BEHAVE predictions were evaluated using four standardized fuel models that partially described oak savanna fuel conditions: Fuel Model 1 (Short Grass), 2 (Timber and Grass), 3 (Tall Grass), and 9 (Hardwood Litter). Although all four models yielded regressions with R2 in excess of 0.8, Fuel Model 2 produced the most reliable fire behavior predictions.

Developing Novel Automated Apparatus for Studying Battery of Social Behaviors in Mutant Mouse Models for Autism

DTIC Science & Technology

2013-06-01

Psychiatry, 2008. 13(1): p. 4-26. 2. McFarlane, H.G., et al., Autism -like behavioral phenotypes in BTBR T+tf/J mice. Genes Brain Behav, 2008. 7(2): p. 152...63. 3. Brodkin, E.S., BALB/c mice: low sociability and other phenotypes that may be relevant to autism . Behav Brain Res, 2007. 176(1): p. 53-65. 4...S.S., et al., Development of a mouse test for repetitive, restricted behaviors: relevance to autism . Behav Brain Res, 2008. 188(1): p. 178-94. 6

Functions of Japanese Exemplifying Particles in Spoken and Written Discourse

ERIC Educational Resources Information Center

Taylor, Yuki Io

2010-01-01

This dissertation examines how the Japanese particles "nado", "toka", and "tari" which all may be translated as "such as", "etc.", or "like" behave differently in written and spoken discourse. According to traditional analyses (e.g. Martin, 1987), these particles are assumed to be Exemplifying Particles (EP) used to provide concrete examples to…

Enhancing Appearance and Sports Performance: Are Female Collegiate Athletes Behaving More like Males?

ERIC Educational Resources Information Center

Muller, Susan M.; Gorrow, Teena R.; Schneider, Sidney R.

2009-01-01

Objective: The authors designed this study to determine if differences exist between male and female collegiate athletes' supplement use and behaviors to modify body appearance. Participants: Collegiate athletes who participated in this study were 241 females and 210 males, aged 17 to 28 years. Method: Participants completed a questionnaire about…

[The study and manufacture of spinning counter for experimental animals].

PubMed

Qi, X P; Zhou, C; Liu, F J; Chen, Z; Jiang, L; Yan, Z

1997-09-01

The single-chip microcomputer technique is used in the present study of spinning counter, which has 4 observation tunnels, the spinning behave of four experiment animals can be recorded at same time. The function of this instrument has four selections according to different experiment, and the recording data can be compute processed.

Acquisition of /S/ Clusters in English-Speaking Children with Phonological Disorders

ERIC Educational Resources Information Center

Yavas, Mehmet; McLeod, Sharynne

2010-01-01

Two member onset consonant clusters with /s/ as the first member (#sC onsets) behave differently from other double onset consonant clusters in English. Phonological explanations of children's consonant cluster production have been posited to predict children's speech acquisition. The aim of this study was to consider the role of the Sonority…

Idea-Centered Laboratory Science (I-CLS), [Unit] C, How a Scientist Expects His World To Behave.

ERIC Educational Resources Information Center

Van Deventer, William C.; Duyser, Lucille

The major ideas of this unit are: consistency and uniformity, cause and effect, and parsimony. Laboratory experiences consist of investigations into: projecting expectations, moon and stars, the relationships among different kinds of change (daily, monthly, annual temperature changes), force and motion, chemical reactions, superstitions, origin of…

Cliff or Step? Posture-Specific Learning at the Edge of a Drop-Off

ERIC Educational Resources Information Center

Kretch, Kari S.; Adolph, Karen E.

2013-01-01

Infants require locomotor experience to behave adaptively at a drop-off. However, different experimental paradigms (visual cliff and actual gaps and slopes) have generated conflicting findings regarding what infants learn and the specificity of their learning. An actual, adjustable drop-off apparatus was used to investigate whether learning to…

Understanding World Economic History

ERIC Educational Resources Information Center

Whaples, Robert

2013-01-01

One joy of studying history is discovering people living meaningful lives and behaving in unusual ways that are startling to the modern reader--young or old. Why did pre-modern people living hundreds or even thousands of years ago do things so differently than we do? Robert Whaples states that Economic historians conclude that the key difference…

A simple HPLC method for the comprehensive analysis of cis/trans (Z/E) geometrical isomers of carotenoids for nutritional studies

USDA-ARS?s Scientific Manuscript database

Geometrical isomers of carotenoids behave differently in aspects like stability towards oxidants, bioavailability, vitamin A activity and specificity for enzymes. The availability of HPLC methods for their detailed profiling is therefore advisable to expand our knowledge on their metabolism and biol...

Temperature Extremes, Health, and Human Capital

ERIC Educational Resources Information Center

Zivin, Joshua Graff; Shrader, Jeffrey

2016-01-01

The extreme temperatures expected under climate change may be especially harmful to children. Children are more vulnerable to heat partly because of their physiological features, but, perhaps more important, because they behave and respond differently than adults do. Children are less likely to manage their own heat risk and may have fewer ways to…

Comparison of Baseline Behavior and the Developmental Effects of Diazepam on Locomotor Activity in 3 Strains of Larval Zebrafish (Danio rerio)

EPA Science Inventory

Choice of strain is an important consideration in zebrafish husbandry and research. In the scientific literature there is concern that zebrafish strains may behave and respond differently to toxicants. A few studies have compared the baseline behavior of various strains of larv...

Beyond initial attraction: physical attractiveness in newlywed marriage.

PubMed

McNulty, James K; Neff, Lisa A; Karney, Benjamin R

2008-02-01

Physical appearance plays a crucial role in shaping new relationships, but does it continue to affect established relationships, such as marriage? In the current study, the authors examined how observer ratings of each spouse's facial attractiveness and the difference between those ratings were associated with (a) observations of social support behavior and (b) reports of marital satisfaction. In contrast to the robust and almost universally positive effects of levels of attractiveness on new relationships, the only association between levels of attractiveness and the outcomes of these marriages was that attractive husbands were less satisfied. Further, in contrast to the importance of matched attractiveness to new relationships, similarity in attractiveness was unrelated to spouses' satisfaction and behavior. Instead, the relative difference between partners' levels of attractiveness appeared to be most important in predicting marital behavior, such that both spouses behaved more positively in relationships in which wives were more attractive than their husbands, but they behaved more negatively in relationships in which husbands were more attractive than their wives. These results highlight the importance of dyadic examinations of the effects of spouses' qualities on their marriages.

Mapping the vestibular evoked myogenic potential (VEMP).

PubMed

Colebatch, James G

2012-01-01

Effects of different electrode placements and indifferent electrodes were investigated for the vestibular evoked myogenic potential (VEMP) recorded from the sternocleidomastoid muscle (SCM). In 5 normal volunteers, the motor point of the left SCM was identified and an electrode placed there. A grid of 7 additional electrodes was laid out, along and across the SCM, based upon the location of the motor point. One reference electrode was placed over the sternoclavicular joint and another over C7. There were clear morphological changes with differing recording sites and for the two reference electrodes, but the earliest and largest responses were recorded from the motor point. The C7 reference affected the level of rectified EMG and was associated with an initial negativity in some electrodes. The latencies of the p13 potentials increased with distance from the motor point but the n23 latencies did not. Thus the p13 potential behaved as a travelling wave whereas the n23 behaved as a standing wave. The C7 reference may be contaminated by other evoked myogenic activity. Ideally recordings should be made with an active electrode over the motor point.

Toward an epistemology of clinical psychoanalysis.

PubMed

Ahumada, J L

1997-01-01

Epistemology emerges from the study of the ways knowledge is gained in the different fields of scientific endeavor. Current polemics on the nature of psychoanalytic knowledge involve counterposed misconceptions of the nature of mind. On one side clinical psychoanalysis is under siege from philosophical "hard science" stalwarts who, upholding as the unitary model of scientific knowledge of Galilean model of science built around the "well-behaved" variables of mechanics and cosmology, argue clinical psychoanalysis does not meet empirical criteria for the validation of its claims. On the other side, its empirical character is renounced by hermeneuticists who, agreeing with "hard science" advocates on what science is, dismiss the animal nature of human beings and hold that clinical psychoanalysis is not an empirical science but a "human" interpretive one. Taking Adolf Grünbaum's critique as its referent, this paper examines how, by ignoring the differences between "exact" and observational science, the "hard science" demand for well-behaved variables misconstrues the nature of events in the realm of mind. Criteria for an epistemology fit for the facts of clinical psychoanalysis as an empirical, observational science of mind are then proposed.

Stabilization of Pt monolayer catalysts under harsh conditions of fuel cells

DOE PAGES

Zhang, Xiaoming; Liu, Ping; Yu, Shansheng; ...

2015-05-21

We employed density functional theory (DFT) to explore the stability of core (M = Cu, Ru, Rh, Pd, Ag, Os, Ir, Au)-shell (Pt) catalysts under harsh conditions, including solutions and reaction intermediates involved in the oxygen reduction reaction (ORR) in fuel cells. A pseudomorphic surface alloy (PSA) with a Pt monolayer (Pt 1ML) supported on an M surface, Pt 1ML/M(111) or (001), was considered as a model system. Different sets of candidate M cores were identified to achieve a stable Pt 1ML shell depending on the conditions. In vacuum conditions, the Pt 1ML shell can be stabilized on the mostmore » of M cores except Cu, Ag, and Au. The situation varies under various electrochemical conditions. Depending on the solutions and the operating reaction pathways of the ORR, different M should be considered. Pd and Ir are the only core metals studied, being able to keep the Pt ML shell intact in perchloric acid, sulfuric acid, phosphoric acid, and alkaline solutions as well as under the ORR conditions via different pathways. Ru and Os cores should also be paid attention, which only fall during the ORR via the *OOH intermediate. Rh core works well as long as the ORR does not undergo the pathway via *O intermediate. Our results show that PSAs can behave differently from the near surface alloy, Pt 1ML/M 1ML/Pt(111), highlighting the importance of considering both chemical environments and the atomic structures in rational design of highly stable core-shell nanocatalysts. Finally, the roles that d-band center of a core M played in determining the stability of supported Pt 1ML shell were also discussed.« less

Stabilization of Pt monolayer catalysts under harsh conditions of fuel cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Xiaoming; Yu, Shansheng; Zheng, Weitao, E-mail: wtzheng@jlu.edu.cn, E-mail: pingliu3@bnl.gov

2015-05-21

We employed density functional theory to explore the stability of core (M = Cu, Ru, Rh, Pd, Ag, Os, Ir, Au)-shell (Pt) catalysts under harsh conditions, including solutions and reaction intermediates involved in the oxygen reduction reaction (ORR) in fuel cells. A pseudomorphic surface alloy (PSA) with a Pt monolayer (Pt{sub 1ML}) supported on an M surface, Pt{sub 1ML}/M(111) or (001), was considered as a model system. Different sets of candidate M cores were identified to achieve a stable Pt{sub 1ML} shell depending on the conditions. In vacuum conditions, the Pt{sub 1ML} shell can be stabilized on the most ofmore » M cores except Cu, Ag, and Au. The situation varies under various electrochemical conditions. Depending on the solutions and the operating reaction pathways of the ORR, different M should be considered. Pd and Ir are the only core metals studied, being able to keep the Pt{sub ML} shell intact in perchloric acid, sulfuric acid, phosphoric acid, and alkaline solutions as well as under the ORR conditions via different pathways. Ru and Os cores should also be paid attention, which only fall during the ORR via the *OOH intermediate. Rh core works well as long as the ORR does not undergo the pathway via *O intermediate. Our results show that PSAs can behave differently from the near surface alloy, Pt{sub 1ML}/M{sub 1ML}/Pt(111), highlighting the importance of considering both chemical environments and the atomic structures in rational design of highly stable core-shell nanocatalysts. Finally, the roles that d-band center of a core M played in determining the stability of supported Pt{sub 1ML} shell were also discussed.« less

Role of cellular communication in the pathways of radiation-induced biological damage

NASA Astrophysics Data System (ADS)

Ballarini, Francesca; Facoetti, Angelica; Mariotti, Luca; Nano, Rosanna; Ottolenghi, Andrea

During the last decade, a large number of experimental studies on the so-called "non-targeted effects", in particular bystander effects, outlined that cellular communication plays a signifi- cant role in the pathways leading to radiation-induced biological damage. This might imply a paradigm shift in (low-dose) radiobiology, according to which one has to consider the response of groups of cells behaving like a population rather than single cells behaving as individuals. Furthermore, bystander effects, which are observed both for lethal endpoints (e.g. clonogenic inactivation and apoptosis) and for non-lethal ones (e.g. mutations and neoplastic transformation), tend to show non-linear dose responses characterized by a sharp increase followed by a plateau. This might have significant consequences in terms of low-dose risk, which is generally calculated on the basis of the "Linear No Threshold" hypothesis. Although it is known that two types of cellular communication (i.e. via gap junctions and/or molecular messengers diffusing in the extra-cellular environment, such as cytokines) play a major role, it is of utmost importance to better understand the underlying mechanisms, and how such mechanisms can be modulated by ionizing radiation. Though the "final" goal is to elucidate the in vivo scenario, in the meanwhile also in vitro studies can provide useful insights. In the present paper we will discuss key issues on the mechanisms underlying non-targeted effects and, more generally, cell communication, with focus on candidate molecular signals. Theoretical models and simulation codes can be of help in elucidating such mechanisms. In this framework, we will present a model and Monte Carlo code, under development at the University of Pavia, simulating the release, diffusion and internalization of candidate signals (typically cytokines) travelling in the extra-cellular environment, both by unirradiated (i.e., control) cells and by irradiated cells. The focus will be on the role of critical parameters such as the cell number and density, the amount of culture medium etc. Comparisons with ad hoc experimental data obtained in our laboratory will be presented, and possible implications in terms of low-dose risk assessment will be discussed. Work supported by the European Community (projects "RISC-RAD" and "NOTE") and the Italian Space Agency (project "MoMa/COUNT)

Electroluminescence of thin-film CdTe solar cells and modules

NASA Astrophysics Data System (ADS)

Raguse, John Michael

Thin-film photovoltaics has the potential to be a major source of world electricity. Mitigation of non-uniformities in thin-film solar cells and modules may help improve photovoltaic conversion efficiencies. In this manuscript, a measurement technique is discussed in detail which has the capability of detecting such non-uniformities in a form useful for analysis. Thin-film solar cells emit radiation while operating at forward electrical bias, analogous to an LED, a phenomena known as electroluminescence (EL). This process relatively is inefficient for polycrystalline CdTe devices, on the order of 10-4%, as most of the energy is converted into heat, but still strong enough for many valuable measurements. A EL system was built at the Colorado State University Photovoltaics Laboratory to measure EL from CdTe cells and modules. EL intensity normalized to exposure time and injection current density has been found to correlate very well with the difference between ideal and measured open-circuit voltage from devices that include a GaAs cell, an AlGaAs LED, and several CdTe cells with variations in manufacturing. Furthermore, these data points were found to be in good agreement when overlaid with calibrated data from two additional sources. The magnitude of the inverse slope of the fit is in agreement with the thermal voltage and the intercept was found to have a value near unity, in agreement with theory. The expanded data set consists of devices made from one of seven different band gaps and spans eight decades of EQELED efficiencies. As expected, cells which exhibit major failure of light-dark J-V superposition did not follow trend of well-behaved cells. EL images of selected defects from CdTe cells and modules are discussed and images are shown to be highly sensitive to defects in devices, since the intensity depends exponentially on the cells' voltages. The EL technique has proven to be a useful high-throughput tool for screening of cells. In addition to EL images, other opto-electronics characterization techniques were used to analyze defects in cells and modules such as weak-diode areas, cell delineation near substrate edge, non-uniform chlorine passivation, holes in back contact, high-resistance foreign layer, high back-contact sheet resistance, a discontinuous P3 line scribe (intercell shunt) and shunt through a cell (intracell shunt). Although EL images are proficient at illustrating the location and severity of defects with potentially high spatial resolution and short measurement times, their ability to identify the cause of such defects is limited. EL in concert with Light-Beam-Induced Current (LBIC), however, makes for a powerful ensemble as LBIC can probe different film layers at arbitrary voltage bias conditions, albeit with increased measurement times and potentially reduced spatial resolution.

Selective estrogen receptor modulation in pancreatic β-cells and the prevention of type 2 diabetes.

PubMed

Tiano, Joseph; Mauvais-Jarvis, Franck

2012-01-01

We recently showed that the female hormone 17β-estradiol (E2) protects against β-cell failure in rodent models of type 2 diabetes (T2D) by suppressing islet fatty acids and glycerolipids synthesis, thus preventing lipotoxic β-cell failure. E2 anti-lipogenic actions were recapitulated by pharmacological activation of the estrogen receptor (ER)α, ERβ and the G-protein coupled ER (GPER) in cultured rodent and human β-cells. In vivo, in mouse islets, ERα activation inhibited β-cell lipogenesis by suppressing fatty acid synthase expression (and activity) via an extranuclear, estrogen response element (ERE)-independent pathway requiring the signal transducer and activator of transcription 3. Here, we show that in INS-1 insulin-secreting cells, the selective ER modulator (SERM), Raloxifene, behaves both as ER antagonist with regard to nuclear ERE-dependent actions and as an ER agonist with regard to suppressing triglyceride accumulation. This additional finding opens the perspective that SERMs harboring ER agonistic activity in β-cells could have application in postmenopausal prevention of T2D. Additional studies using novel generation SERMs are needed to address this issue.

Urokinase links plasminogen activation and cell adhesion by cleavage of the RGD motif in vitronectin.

PubMed

De Lorenzi, Valentina; Sarra Ferraris, Gian Maria; Madsen, Jeppe B; Lupia, Michela; Andreasen, Peter A; Sidenius, Nicolai

2016-07-01

Components of the plasminogen activation system including urokinase (uPA), its inhibitor (PAI-1) and its cell surface receptor (uPAR) have been implicated in a wide variety of biological processes related to tissue homoeostasis. Firstly, the binding of uPA to uPAR favours extracellular proteolysis by enhancing cell surface plasminogen activation. Secondly, it promotes cell adhesion and signalling through binding of the provisional matrix protein vitronectin. We now report that uPA and plasmin induces a potent negative feedback on cell adhesion through specific cleavage of the RGD motif in vitronectin. Cleavage of vitronectin by uPA displays a remarkable receptor dependence and requires concomitant binding of both uPA and vitronectin to uPAR Moreover, we show that PAI-1 counteracts the negative feedback and behaves as a proteolysis-triggered stabilizer of uPAR-mediated cell adhesion to vitronectin. These findings identify a novel and highly specific function for the plasminogen activation system in the regulation of cell adhesion to vitronectin. The cleavage of vitronectin by uPA and plasmin results in the release of N-terminal vitronectin fragments that can be detected in vivo, underscoring the potential physiological relevance of the process. © 2016 The Authors.

Mate retention behavior of men and women in heterosexual and homosexual relationships.

PubMed

Vanderlaan, Doug P; Vasey, Paul L

2008-08-01

Comparing the behavior of heterosexual and homosexual persons can provide insight into the origins of heterosexual sex differences in psychology. Evidence indicates that, aside from sexual partner preference, the mating psychology of homosexual men is sex-typical whereas that of homosexual women tends to be more sex-atypical. The current study examined one aspect of mating psychology, mate retention behavior, and tested whether homosexual men and women were sex-typical or sex-atypical for those mate retention tactics where heterosexual men and women differed. Men and women in heterosexual and homosexual relationships were asked to provide information regarding their partners' mate retention behavior by using the Mate Retention Inventory Questionnaire. Heterosexual men and women differed significantly for six of the 19 mate retention tactics considered. With respect to the six mate retention tactics where heterosexual sex differences existed, homosexual men behaved in a sex-typical manner for five of the tactics, whereas homosexual women behaved in a sex-atypical manner for all six tactics. We discuss the significance of these findings for explaining the origins of the mate retention behavior of heterosexual men and women. In addition, we consider what the pattern of sex-typical and sex-atypical mating psychology among homosexual men and women, respectively, suggests in regard to sex differences in the development of mating psychology and the development of homosexual persons.

Advancing osteochondral tissue engineering: bone morphogenetic protein, transforming growth factor, and fibroblast growth factor signaling drive ordered differentiation of periosteal cells resulting in stable cartilage and bone formation in vivo.

PubMed

Mendes, L F; Katagiri, H; Tam, W L; Chai, Y C; Geris, L; Roberts, S J; Luyten, F P

2018-02-21

Chondrogenic mesenchymal stem cells (MSCs) have not yet been used to address the clinical demands of large osteochondral joint surface defects. In this study, self-assembling tissue intermediates (TIs) derived from human periosteum-derived stem/progenitor cells (hPDCs) were generated and validated for stable cartilage formation in vivo using two different animal models. hPDCs were aggregated and cultured in the presence of a novel growth factor (GF) cocktail comprising of transforming growth factor (TGF)-β1, bone morphogenetic protein (BMP)2, growth differentiation factor (GDF)5, BMP6, and fibroblast growth factor (FGF)2. Quantitative polymerase chain reaction (PCR) and immunohistochemistry were used to study in vitro differentiation. Aggregates were then implanted ectopically in nude mice and orthotopically in critical-size osteochondral defects in nude rats and evaluated by microcomputed tomography (µCT) and immunohistochemistry. Gene expression analysis after 28 days of in vitro culture revealed the expression of early and late chondrogenic markers and a significant upregulation of NOGGIN as compared to human articular chondrocytes (hACs). Histological examination revealed a bilayered structure comprising of chondrocytes at different stages of maturity. Ectopically, TIs generated both bone and mineralized cartilage at 8 weeks after implantation. Osteochondral defects treated with TIs displayed glycosaminoglycan (GAG) production, type-II collagen, and lubricin expression. Immunostaining for human nuclei protein suggested that hPDCs contributed to both subchondral bone and articular cartilage repair. Our data indicate that in vitro derived osteochondral-like tissues can be generated from hPDCs, which are capable of producing bone and cartilage ectopically and behave orthotopically as osteochondral units.

Population Coding of Visual Space: Comparison of Spatial Representations in Dorsal and Ventral Pathways

PubMed Central

Sereno, Anne B.; Lehky, Sidney R.

2011-01-01

Although the representation of space is as fundamental to visual processing as the representation of shape, it has received relatively little attention from neurophysiological investigations. In this study we characterize representations of space within visual cortex, and examine how they differ in a first direct comparison between dorsal and ventral subdivisions of the visual pathways. Neural activities were recorded in anterior inferotemporal cortex (AIT) and lateral intraparietal cortex (LIP) of awake behaving monkeys, structures associated with the ventral and dorsal visual pathways respectively, as a stimulus was presented at different locations within the visual field. In spatially selective cells, we find greater modulation of cell responses in LIP with changes in stimulus position. Further, using a novel population-based statistical approach (namely, multidimensional scaling), we recover the spatial map implicit within activities of neural populations, allowing us to quantitatively compare the geometry of neural space with physical space. We show that a population of spatially selective LIP neurons, despite having large receptive fields, is able to almost perfectly reconstruct stimulus locations within a low-dimensional representation. In contrast, a population of AIT neurons, despite each cell being spatially selective, provide less accurate low-dimensional reconstructions of stimulus locations. They produce instead only a topologically (categorically) correct rendition of space, which nevertheless might be critical for object and scene recognition. Furthermore, we found that the spatial representation recovered from population activity shows greater translation invariance in LIP than in AIT. We suggest that LIP spatial representations may be dimensionally isomorphic with 3D physical space, while in AIT spatial representations may reflect a more categorical representation of space (e.g., “next to” or “above”). PMID:21344010

Fluorescent indicators for Akt/protein kinase B and dynamics of Akt activity visualized in living cells.

PubMed

Sasaki, Kazuki; Sato, Moritoshi; Umezawa, Yoshio

2003-08-15

Akt/protein kinase B (PKB) is a serine/threonine kinase that regulates a variety of cellular responses. To provide information on the spatial and temporal dynamics of Akt/PKB activity, we have developed genetically encoded fluorescent indicators for Akt/PKB. The indicators contain two green fluorescent protein mutants, an Akt/PKB substrate domain, flexible linker sequence, and phosphorylation recognition domain. A phosphorylation of the substrate domain in the indicators caused change in the emission ratio based on fluorescent resonance energy transfer between the two green fluorescent protein mutants. To let the fluorescent indicators behave as endothelial nitric-oxide synthase and Bad, which are endogenous Akt/PKB substrates, they were fused with the Golgi target domain and mitochondria target domain, respectively. The indicators thus colocalized with the endogenous substrates conferred their susceptibilities to phosphorylation by Akt/PKB. We showed that the Golgi-localized indicator responded to the stimulation with 17beta-estradiol (E2) and insulin in endothelial cells. In addition, E2 elicited the phosphorylation of the mitochondria-localized indicator in the endothelial cells, but no phosphorylation was observed by E2 or by insulin of the diffusible indicator that has no targeting domain. The difference in the results with the three indicators suggests that the activated Akt/PKB is localized to subcellular compartments, including the Golgi apparatus and/or mitochondria, rather than diffusing in the cytosol, thereby efficiently phosphorylating its substrate proteins. E2 triggered the phosphorylation of the mitochondria-localized indicator, whereas insulin did not induce this phosphorylation, which suggests that the localization of the activated Akt/PKB to the mitochondria is directed differently between insulin and E2 via distinct mechanisms.

The concept of the eudicot shoot apical meristem as it applies to four Spiraea (Rosaceae), one Mentha (Lamiaceae) and one Euonymus (Celastraceae) cultivars based on chimeric analysis.

PubMed

Korn, Robert W

2013-05-01

Eversporting eudicots were sought to see if they behave like gymnosperms. Behaviour of eversporting gymnosperm chimeras indicates a single apical cell is present in SAM and it would be of interest to see if eudicot chimeras have the same behaviour. Four eversporting spireas, the pineapple mint and the Silver King euonymus were inspected for the fate of the yellow (mutant)-green (wild type) chimeras. As with gymnosperms, unstable eudicot chimeras in the four spireas, the pineapple mint and the Silver King euonymus became stable yellow about 80 % or more of the time and 20 % or less became stable green. The statistically significant preponderance of chimeric fates becoming all yellow suggests that a single apical cell resides in the yellow tunica. As with gymnosperms, descendent cells of the yellow replacement corpus cell eventually take over the corpus. Here is the first chimeric set of data to support the hypothesis of a one-celled meristem in eudicots rather than the traditional view of a muticellular meristem.

An Analogue VLSI Implementation of the Meddis Inner Hair Cell Model

NASA Astrophysics Data System (ADS)

McEwan, Alistair; van Schaik, André

2003-12-01

The Meddis inner hair cell model is a widely accepted, but computationally intensive computer model of mammalian inner hair cell function. We have produced an analogue VLSI implementation of this model that operates in real time in the current domain by using translinear and log-domain circuits. The circuit has been fabricated on a chip and tested against the Meddis model for (a) rate level functions for onset and steady-state response, (b) recovery after masking, (c) additivity, (d) two-component adaptation, (e) phase locking, (f) recovery of spontaneous activity, and (g) computational efficiency. The advantage of this circuit, over other electronic inner hair cell models, is its nearly exact implementation of the Meddis model which can be tuned to behave similarly to the biological inner hair cell. This has important implications on our ability to simulate the auditory system in real time. Furthermore, the technique of mapping a mathematical model of first-order differential equations to a circuit of log-domain filters allows us to implement real-time neuromorphic signal processors for a host of models using the same approach.

Tissue‐specific reactions to positional discontinuities in the regenerating axolotl limb

PubMed Central

Avila, Daima; Roy, Molly; Seifert, Ashley W.

2015-01-01

Abstract We investigated cellular contributions to intercalary regenerates and 180o supernumerary limbs during axolotl limb regeneration using the cell autonomous green fluorescent protein marker and exchanged blastemas between white and green fluorescent protein animals. After distal blastemas were grafted to proximal levels tissues of the intercalary regenerate behaved independently with regard to the law of distal transformation; graft epidermis was replaced by stump epidermis, muscle‐derived cells, blood vessels, and Schwann cells of the distal blastema moved proximally to the stylopodium and cartilage and dermal cells conformed to the law. After 180o rotation, blastemas showed contributions from stump tissues which failed to alter patterning of the blastema. Supernumerary limbs were composed of stump and graft tissues and extensive contributions of stump tissues generated inversions or duplications of polarity to produce limbs of mixed handedness. Tail skeletal muscle and cardiac muscle broke the law with cells derived from these tissues exhibiting an apparent anteroposterior polarity as they migrated to the anterior side of the blastema. We attribute this behavior to the possible presence of a chemotactic factor from the wound epidermis. PMID:26755943

Simultaneous cellular-resolution optical perturbation and imaging of place cell firing fields

PubMed Central

Rickgauer, John Peter; Deisseroth, Karl; Tank, David W.

2015-01-01

Linking neural microcircuit function to emergent properties of the mammalian brain requires fine-scale manipulation and measurement of neural activity during behavior, where each neuron’s coding and dynamics can be characterized. We developed an optical method for simultaneous cellular-resolution stimulation and large-scale recording of neuronal activity in behaving mice. Dual-wavelength two-photon excitation allowed largely independent functional imaging with a green fluorescent calcium sensor (GCaMP3, λ = 920 ± 6 nm) and single-neuron photostimulation with a red-shifted optogenetic probe (C1V1, λ = 1,064 ± 6 nm) in neurons coexpressing the two proteins. We manipulated task-modulated activity in individual hippocampal CA1 place cells during spatial navigation in a virtual reality environment, mimicking natural place-field activity, or ‘biasing’, to reveal subthreshold dynamics. Notably, manipulating single place-cell activity also affected activity in small groups of other place cells that were active around the same time in the task, suggesting a functional role for local place cell interactions in shaping firing fields. PMID:25402854