Stochastic Individual-Based Modeling of Bacterial Growth and Division Using Flow Cytometry.

PubMed

García, Míriam R; Vázquez, José A; Teixeira, Isabel G; Alonso, Antonio A

2017-01-01

A realistic description of the variability in bacterial growth and division is critical to produce reliable predictions of safety risks along the food chain. Individual-based modeling of bacteria provides the theoretical framework to deal with this variability, but it requires information about the individual behavior of bacteria inside populations. In this work, we overcome this problem by estimating the individual behavior of bacteria from population statistics obtained with flow cytometry. For this objective, a stochastic individual-based modeling framework is defined based on standard assumptions during division and exponential growth. The unknown single-cell parameters required for running the individual-based modeling simulations, such as cell size growth rate, are estimated from the flow cytometry data. Instead of using directly the individual-based model, we make use of a modified Fokker-Plank equation. This only equation simulates the population statistics in function of the unknown single-cell parameters. We test the validity of the approach by modeling the growth and division of Pediococcus acidilactici within the exponential phase. Estimations reveal the statistics of cell growth and division using only data from flow cytometry at a given time. From the relationship between the mother and daughter volumes, we also predict that P. acidilactici divide into two successive parallel planes.

Polymer models of interphase chromosomes

PubMed Central

Vasquez, Paula A; Bloom, Kerry

2014-01-01

Clear organizational patterns on the genome have emerged from the statistics of population studies of fixed cells. However, how these results translate into the dynamics of individual living cells remains unexplored. We use statistical mechanics models derived from polymer physics to inquire into the effects that chromosome properties and dynamics have in the temporal and spatial behavior of the genome. Overall, changes in the properties of individual chains affect the behavior of all other chains in the domain. We explore two modifications of chain behavior: single chain motion and chain-chain interactions. We show that there is not a direct relation between these effects, as increase in motion, doesn’t necessarily translate into an increase on chain interaction. PMID:25482191

Classification of human natural killer cells based on migration behavior and cytotoxic response.

PubMed

Vanherberghen, Bruno; Olofsson, Per E; Forslund, Elin; Sternberg-Simon, Michal; Khorshidi, Mohammad Ali; Pacouret, Simon; Guldevall, Karolin; Enqvist, Monika; Malmberg, Karl-Johan; Mehr, Ramit; Önfelt, Björn

2013-02-21

Despite intense scrutiny of the molecular interactions between natural killer (NK) and target cells, few studies have been devoted to dissection of the basic functional heterogeneity in individual NK cell behavior. Using a microchip-based, time-lapse imaging approach allowing the entire contact history of each NK cell to be recorded, in the present study, we were able to quantify how the cytotoxic response varied between individual NK cells. Strikingly, approximately half of the NK cells did not kill any target cells at all, whereas a minority of NK cells was responsible for a majority of the target cell deaths. These dynamic cytotoxicity data allowed categorization of NK cells into 5 distinct classes. A small but particularly active subclass of NK cells killed several target cells in a consecutive fashion. These "serial killers" delivered their lytic hits faster and induced faster target cell death than other NK cells. Fast, necrotic target cell death was correlated with the amount of perforin released by the NK cells. Our data are consistent with a model in which a small fraction of NK cells drives tumor elimination and inflammation.

Modeling oscillations and spiral waves in Dictyostelium populations

NASA Astrophysics Data System (ADS)

Noorbakhsh, Javad; Schwab, David J.; Sgro, Allyson E.; Gregor, Thomas; Mehta, Pankaj

2015-06-01

Unicellular organisms exhibit elaborate collective behaviors in response to environmental cues. These behaviors are controlled by complex biochemical networks within individual cells and coordinated through cell-to-cell communication. Describing these behaviors requires new mathematical models that can bridge scales—from biochemical networks within individual cells to spatially structured cellular populations. Here we present a family of "multiscale" models for the emergence of spiral waves in the social amoeba Dictyostelium discoideum. Our models exploit new experimental advances that allow for the direct measurement and manipulation of the small signaling molecule cyclic adenosine monophosphate (cAMP) used by Dictyostelium cells to coordinate behavior in cellular populations. Inspired by recent experiments, we model the Dictyostelium signaling network as an excitable system coupled to various preprocessing modules. We use this family of models to study spatially unstructured populations of "fixed" cells by constructing phase diagrams that relate the properties of population-level oscillations to parameters in the underlying biochemical network. We then briefly discuss an extension of our model that includes spatial structure and show how this naturally gives rise to spiral waves. Our models exhibit a wide range of novel phenomena. including a density-dependent frequency change, bistability, and dynamic death due to slow cAMP dynamics. Our modeling approach provides a powerful tool for bridging scales in modeling of Dictyostelium populations.

Agent-Based Modeling of Cancer Stem Cell Driven Solid Tumor Growth.

PubMed

Poleszczuk, Jan; Macklin, Paul; Enderling, Heiko

2016-01-01

Computational modeling of tumor growth has become an invaluable tool to simulate complex cell-cell interactions and emerging population-level dynamics. Agent-based models are commonly used to describe the behavior and interaction of individual cells in different environments. Behavioral rules can be informed and calibrated by in vitro assays, and emerging population-level dynamics may be validated with both in vitro and in vivo experiments. Here, we describe the design and implementation of a lattice-based agent-based model of cancer stem cell driven tumor growth.

Planar Cell Polarity Pathway – Coordinating morphogenetic cell behaviors with embryonic polarity

PubMed Central

Gray, Ryan S.; Roszko, Isabelle; Solnica-Krezel, Lilianna

2011-01-01

Planar cell polarization entails establishment of cellular asymmetries within the tissue plane. An evolutionarily conserved Planar Cell Polarity (PCP) signaling system employs intra- and intercellular feedback interactions between its core components, including Frizzled, Van Gogh, Flamingo, Prickle and Dishevelled, to establish their characteristic asymmetric intracellular distributions and coordinate planar polarity of cell populations. By translating global patterning information into asymmetries of cell membranes and intracellular organelles, PCP signaling coordinates morphogenetic behaviors of individual cells and cell populations with the embryonic polarity. In vertebrates, by polarizing cilia in the node/Kupffer’s vesicle, PCP signaling links the anteroposterior to left-right embryonic polarity. PMID:21763613

Migration of cells in a social context

PubMed Central

Vedel, Søren; Tay, Savaş; Johnston, Darius M.; Bruus, Henrik; Quake, Stephen R.

2013-01-01

In multicellular organisms and complex ecosystems, cells migrate in a social context. Whereas this is essential for the basic processes of life, the influence of neighboring cells on the individual remains poorly understood. Previous work on isolated cells has observed a stereotypical migratory behavior characterized by short-time directional persistence with long-time random movement. We discovered a much richer dynamic in the social context, with significant variations in directionality, displacement, and speed, which are all modulated by local cell density. We developed a mathematical model based on the experimentally identified “cellular traffic rules” and basic physics that revealed that these emergent behaviors are caused by the interplay of single-cell properties and intercellular interactions, the latter being dominated by a pseudopod formation bias mediated by secreted chemicals and pseudopod collapse following collisions. The model demonstrates how aspects of complex biology can be explained by simple rules of physics and constitutes a rapid test bed for future studies of collective migration of individual cells. PMID:23251032

Migration of cells in a social context.

PubMed

Vedel, Søren; Tay, Savaş; Johnston, Darius M; Bruus, Henrik; Quake, Stephen R

2013-01-02

In multicellular organisms and complex ecosystems, cells migrate in a social context. Whereas this is essential for the basic processes of life, the influence of neighboring cells on the individual remains poorly understood. Previous work on isolated cells has observed a stereotypical migratory behavior characterized by short-time directional persistence with long-time random movement. We discovered a much richer dynamic in the social context, with significant variations in directionality, displacement, and speed, which are all modulated by local cell density. We developed a mathematical model based on the experimentally identified "cellular traffic rules" and basic physics that revealed that these emergent behaviors are caused by the interplay of single-cell properties and intercellular interactions, the latter being dominated by a pseudopod formation bias mediated by secreted chemicals and pseudopod collapse following collisions. The model demonstrates how aspects of complex biology can be explained by simple rules of physics and constitutes a rapid test bed for future studies of collective migration of individual cells.

Differentiated cell behavior: a multiscale approach using measure theory.

PubMed

Colombi, Annachiara; Scianna, Marco; Tosin, Andrea

2015-11-01

This paper deals with the derivation of a collective model of cell populations out of an individual-based description of the underlying physical particle system. By looking at the spatial distribution of cells in terms of time-evolving measures, rather than at individual cell paths, we obtain an ensemble representation stemming from the phenomenological behavior of the single component cells. In particular, as a key advantage of our approach, the scale of representation of the system, i.e., microscopic/discrete vs. macroscopic/continuous, can be chosen a posteriori according only to the spatial structure given to the aforesaid measures. The paper focuses in particular on the use of different scales based on the specific functions performed by cells. A two-population hybrid system is considered, where cells with a specialized/differentiated phenotype are treated as a discrete population of point masses while unspecialized/undifferentiated cell aggregates are represented by a continuous approximation. Numerical simulations and analytical investigations emphasize the role of some biologically relevant parameters in determining the specific evolution of such a hybrid cell system.

Collective interaction of microscale matters in natural analogy: human cancer cells vs. microspheres

NASA Astrophysics Data System (ADS)

Ahn, Sungsook; Lee, Sang Joon; Postech Team

2014-11-01

Collective behaviors have been considered both in living and lifeless things as a natural phenomenon. During the ordering process, a sudden and spontaneous transition is typically generated between an order and a disorder according to the population density of interacting elements. In a cellular level collective behavior, the cells are distributed in the characteristic patterns according to the population density and the mutual interaction of the individual cells undergo density-dependent diffusive motion. On the other hand, density-controlled surface-modified hollow microsphere suspension induces an overpopulation via buoyancy which provides a driving force to induce an assembly. The collective behaviors of the cells and microspheres in a designed liquid medium are explained in terms of the deviation from the interparticle distance distribution and the induced strength to organize the particle position in a specific distance range. as a result, microscale particulate matters exhibit high resemblance in their pair correlation and dynamical heterogeneity in the intermediate range between a single individual and an agglomerate. Therefore, it is suggested that biological systems are analogically explained to be dominated by physically interactive aspects.

Reconstructing the in vivo dynamics of hematopoietic stem cells from telomere length distributions

PubMed Central

Werner, Benjamin; Beier, Fabian; Hummel, Sebastian; Balabanov, Stefan; Lassay, Lisa; Orlikowsky, Thorsten; Dingli, David; Brümmendorf, Tim H; Traulsen, Arne

2015-01-01

We investigate the in vivo patterns of stem cell divisions in the human hematopoietic system throughout life. In particular, we analyze the shape of telomere length distributions underlying stem cell behavior within individuals. Our mathematical model shows that these distributions contain a fingerprint of the progressive telomere loss and the fraction of symmetric cell proliferations. Our predictions are tested against measured telomere length distributions in humans across all ages, collected from lymphocyte and granulocyte sorted telomere length data of 356 healthy individuals, including 47 cord blood and 28 bone marrow samples. We find an increasing stem cell pool during childhood and adolescence and an approximately maintained stem cell population in adults. Furthermore, our method is able to detect individual differences from a single tissue sample, i.e. a single snapshot. Prospectively, this allows us to compare cell proliferation between individuals and identify abnormal stem cell dynamics, which affects the risk of stem cell related diseases. DOI: http://dx.doi.org/10.7554/eLife.08687.001 PMID:26468615

Microtubule catastrophe and rescue.

PubMed

Gardner, Melissa K; Zanic, Marija; Howard, Jonathon

2013-02-01

Microtubules are long cylindrical polymers composed of tubulin subunits. In cells, microtubules play an essential role in architecture and motility. For example, microtubules give shape to cells, serve as intracellular transport tracks, and act as key elements in important cellular structures such as axonemes and mitotic spindles. To accomplish these varied functions, networks of microtubules in cells are very dynamic, continuously remodeling through stochastic length fluctuations at the ends of individual microtubules. The dynamic behavior at the end of an individual microtubule is termed 'dynamic instability'. This behavior manifests itself by periods of persistent microtubule growth interrupted by occasional switching to rapid shrinkage (called microtubule 'catastrophe'), and then by switching back from shrinkage to growth (called microtubule 'rescue'). In this review, we summarize recent findings which provide new insights into the mechanisms of microtubule catastrophe and rescue, and discuss the impact of these findings in regards to the role of microtubule dynamics inside of cells. Copyright © 2012 Elsevier Ltd. All rights reserved.

Engineering Sensorial Delay to Control Phototaxis and Emergent Collective Behaviors

NASA Astrophysics Data System (ADS)

Mijalkov, Mite; McDaniel, Austin; Wehr, Jan; Volpe, Giovanni

2016-01-01

Collective motions emerging from the interaction of autonomous mobile individuals play a key role in many phenomena, from the growth of bacterial colonies to the coordination of robotic swarms. For these collective behaviors to take hold, the individuals must be able to emit, sense, and react to signals. When dealing with simple organisms and robots, these signals are necessarily very elementary; e.g., a cell might signal its presence by releasing chemicals and a robot by shining light. An additional challenge arises because the motion of the individuals is often noisy; e.g., the orientation of cells can be altered by Brownian motion and that of robots by an uneven terrain. Therefore, the emphasis is on achieving complex and tunable behaviors from simple autonomous agents communicating with each other in robust ways. Here, we show that the delay between sensing and reacting to a signal can determine the individual and collective long-term behavior of autonomous agents whose motion is intrinsically noisy. We experimentally demonstrate that the collective behavior of a group of phototactic robots capable of emitting a radially decaying light field can be tuned from segregation to aggregation and clustering by controlling the delay with which they change their propulsion speed in response to the light intensity they measure. We track this transition to the underlying dynamics of this system, in particular, to the ratio between the robots' sensorial delay time and the characteristic time of the robots' random reorientation. Supported by numerics, we discuss how the same mechanism can be applied to control active agents, e.g., airborne drones, moving in a three-dimensional space. Given the simplicity of this mechanism, the engineering of sensorial delay provides a potentially powerful tool to engineer and dynamically tune the behavior of large ensembles of autonomous mobile agents; furthermore, this mechanism might already be at work within living organisms such as chemotactic cells.

Universal Approach to Estimate Perfluorocarbons Emissions During Individual High-Voltage Anode Effect for Prebaked Cell Technologies

NASA Astrophysics Data System (ADS)

Dion, Lukas; Gaboury, Simon; Picard, Frédéric; Kiss, Laszlo I.; Poncsak, Sandor; Morais, Nadia

2018-04-01

Recent investigations on aluminum electrolysis cell demonstrated limitations to the commonly used tier-3 slope methodology to estimate perfluorocarbon (PFC) emissions from high-voltage anode effects (HVAEs). These limitations are greater for smelters with a reduced HVAE frequency. A novel approach is proposed to estimate the specific emissions using a tier 2 model resulting from individual HVAE instead of estimating monthly emissions for pot lines with the slope methodology. This approach considers the nonlinear behavior of PFC emissions as a function of the polarized anode effect duration but also integrates the change in behavior attributed to cell productivity. Validation was performed by comparing the new approach and the slope methodology with measurement campaigns from different smelters. The results demonstrate a good agreement between measured and estimated emissions as well as more accurately reflect individual HVAE dynamics occurring over time. Finally, the possible impact of this approach for the aluminum industry is discussed.

Quantification of mammalian tumor cell state plasticity with digital holographic cytometry

NASA Astrophysics Data System (ADS)

Hejna, Miroslav; Jorapur, Aparna; Zhang, Yuntian; Song, Jun S.; Judson, Robert L.

2018-02-01

Individual cells within isogenic tumor populations can exhibit distinct cellular morphologies, behaviors, and molecular profiles. Cell state plasticity refers to the propensity of a cell to transition between these different morphologies and behaviors. Elevation of cell state plasticity is thought to contribute to critical stages in tumor evolution, including metastatic dissemination and acquisition of therapeutic resistance. However, methods for quantifying general plasticity in mammalian cells remain limited. Working with a HoloMonitor M4 digital holographic cytometry platform, we have established a machine learning-based pipeline for high accuracy and label-free classification of adherent cells. We use twenty-six morphological and optical density-derived features for label-free identification of cell state in heterogeneous cultures. The system is housed completely within a mammalian cell incubator, permitting the monitoring of changes in cell state over time. Here we present an application of our approach for studying cell state plasticity. Human melanoma cell lines of known metastatic potential were monitored in standard growth conditions. The rate of feature change was quantified for each individual cell in the populations. We observed that cells of higher metastatic potential exhibited more rapid fluctuation of cell state in homeostatic conditions. The approach we demonstrate will be advantageous for further investigations into the factors that influence cell state plasticity.

Deconstructing (and reconstructing) cell migration.

PubMed

Maheshwari, G; Lauffenburger, D A

1998-12-01

An overriding objective in cell biology is to be able to relate properties of particular molecular components to cell behavioral functions and even physiology. In the "traditional" mode of molecular cell biology, this objective has been tackled on a molecule-by-molecule basis, and in the "future" mode sometimes termed "functional genomics," it might be attacked in a high-throughput, parallel manner. Regardless of the manner of approach, the relationship between molecular-level properties and cell-level function is exceedingly difficult to elucidate because of the large number of relevant components involved, their high degree of interconnectedness, and the inescapable fact that they operate as physico-chemical entities-according to the laws of kinetics and mechanics-in space and time within the cell. Cell migration is a prominent representative example of such a cell behavioral function that requires increased understanding for both scientific and technological advance. This article presents a framework, derived from an engineering perspective regarding complex systems, intended to aid in developing improved understanding of how properties of molecular components influence the function of cell migration. That is, cell population migration behavior can be deconstructed as follows: first in terms of a mathematical model comprising cell population parameters (random motility, chemotaxis/haptotaxis, and chemokinesis/haptokinesis coefficients), which in turn depend on characteristics of individual cell paths that can be analyzed in terms of a mathematical model comprising individual cell parameters (translocation speed, directional persistence time, chemotactic/haptotactic index), which in turn depend on cell-level physical processes underlying motility (membrane extension and retraction, cell/substratum adhesion, cell contractile force, front-vs.-rear asymmetry), which in turn depend on molecular-level properties of the plethora of components involved in governance and regulation of these processes. Hence, the influence of any molecular component on cell population migration can be understood by reconstructing these relationships from the molecular level to the physical process level to the individual cell path level to the cell population distribution level. This approach requires combining experimental, theoretical, and computational methodologies from molecular biology, biochemistry, biophysics, and bioengineering.

Multiscale Modeling of Cell Interaction in Angiogenesis: From the Micro- to Macro-scale

NASA Astrophysics Data System (ADS)

Pillay, Samara; Maini, Philip; Byrne, Helen

Solid tumors require a supply of nutrients to grow in size. To this end, tumors induce the growth of new blood vessels from existing vasculature through the process of angiogenesis. In this work, we use a discrete agent-based approach to model the behavior of individual endothelial cells during angiogenesis. We incorporate crowding effects through volume exclusion, motility of cells through biased random walks, and include birth and death processes. We use the transition probabilities associated with the discrete models to determine collective cell behavior, in terms of partial differential equations, using a Markov chain and master equation framework. We find that the cell-level dynamics gives rise to a migrating cell front in the form of a traveling wave on the macro-scale. The behavior of this front depends on the cell interactions that are included and the extent to which volume exclusion is taken into account in the discrete micro-scale model. We also find that well-established continuum models of angiogenesis cannot distinguish between certain types of cell behavior on the micro-scale. This may impact drug development strategies based on these models.

Silk Film Topography Directs Collective Epithelial Cell Migration

PubMed Central

Rosenblatt, Mark I.

2012-01-01

The following study provides new insight into how surface topography dictates directed collective epithelial cell sheet growth through the guidance of individual cell movement. Collective cell behavior of migrating human corneal limbal-epithelial cell sheets were studied on highly biocompatible flat and micro-patterned silk film surfaces. The silk film edge topography guided the migratory direction of individual cells making up the collective epithelial sheet, which resulted in a 75% increase in total culture elongation. This was due to a 3-fold decrease in cell sheet migration rate efficiency for movement perpendicular to the topography edge. Individual cell migration direction is preferred in the parallel approach to the edge topography where localization of cytoskeletal proteins to the topography’s edge region is reduced, which results in the directed growth of the collective epithelial sheet. Findings indicate customized biomaterial surfaces may be created to direct both the migration rate and direction of tissue epithelialization. PMID:23185573

Multiscale Characterization of Bacterial Swarming Illuminates Principles Governing Directed Surface Motility

NASA Astrophysics Data System (ADS)

Strickland, Ben; Hoeger, Kentaro; Ursell, Tristan

In many systems, individual characteristics interact, leading to the spontaneous emergence of order and complexity. In biological settings like microbes, such collective behaviors can imbue a variety of benefits to constituent individuals, including increased spatial range, improved access to nutrients, and enhanced resistance to antibiotic threats. To untangle the biophysical underpinnings of collective motility, we use passive tracers and a curated genetic library of Bacillus subtilis, including motile, non-motile, biofilm-deficient, and non-chemotactic mutants. We characterize and connect individual behavior on the microscopic scale to macroscopic colony morphology and motility of dendritic swarming. We analyze the persistence and dynamics of coordinated movement on length scales up to 4 orders of magnitude larger than that of individual cells, revealing rapid and directed responses of microbial groups to external stimuli, such as avoidance dynamics across chemical gradients. Our observations uncover the biophysical interplay between individual motility, surface wetness, phenotypic diversity, and external physical forces that robustly precipitate coordinated group behavior in microbes, and suggest general principles that govern the transition from individual to group behavior.

Social Competition in Rats: Cell Proliferation and Behavior

PubMed Central

Hoshaw, Brian A.; Evans, Jennifer C.; Mueller, Bridget; Valentino, Rita J.; Lucki, Irwin

2007-01-01

Behavioral and physiological changes were studied following prolonged exposure to social competition in pairs of non food-deprived rats competing daily for a limited supply of graham cracker crumbs. Stable dominant-subordinate relationships developed in most pairs, as measured by feeding time, which were maintained over a 5–6-week study period. In other behavioral tests, subordinates demonstrated a decreased latency to immobility in the forced swim test compared with dominants, but no difference in locomotor activity. Subordinates had increased bladder size, decreased adrenal gland size, and a 35% reduction of hippocampus cell proliferation compared with the dominant member. Therefore, prolonged social competition, based on restricted access to palatable substances, produced hierarchies among individuals that were associated with differences in behavior, physiology and hippocampal cell proliferation. PMID:17045347

Feasibility and acceptability of cell phone diaries to measure HIV risk behavior among female sex workers.

PubMed

Roth, Alexis M; Hensel, Devon J; Fortenberry, J Dennis; Garfein, Richard S; Gunn, Jayleen K L; Wiehe, Sarah E

2014-12-01

Individual, social, and structural factors affecting HIV risk behaviors among female sex workers (FSWs) are difficult to assess using retrospective surveys methods. To test the feasibility and acceptability of cell phone diaries to collect information about sexual events, we recruited 26 FSWs in Indianapolis, Indiana (US). Over 4 weeks, FSWs completed twice daily digital diaries about their mood, drug use, sexual interactions, and daily activities. Feasibility was assessed using repeated measures general linear modeling and descriptive statistics examined event-level contextual information and acceptability. Of 1,420 diaries expected, 90.3 % were completed by participants and compliance was stable over time (p > .05 for linear trend). Sexual behavior was captured in 22 % of diaries and participant satisfaction with diary data collection was high. These data provide insight into event-level factors impacting HIV risk among FSWs. We discuss implications for models of sexual behavior and individually tailored interventions to prevent HIV in this high-risk group.

A Fully Automated High-Throughput Zebrafish Behavioral Ototoxicity Assay.

PubMed

Todd, Douglas W; Philip, Rohit C; Niihori, Maki; Ringle, Ryan A; Coyle, Kelsey R; Zehri, Sobia F; Zabala, Leanne; Mudery, Jordan A; Francis, Ross H; Rodriguez, Jeffrey J; Jacob, Abraham

2017-08-01

Zebrafish animal models lend themselves to behavioral assays that can facilitate rapid screening of ototoxic, otoprotective, and otoregenerative drugs. Structurally similar to human inner ear hair cells, the mechanosensory hair cells on their lateral line allow the zebrafish to sense water flow and orient head-to-current in a behavior called rheotaxis. This rheotaxis behavior deteriorates in a dose-dependent manner with increased exposure to the ototoxin cisplatin, thereby establishing itself as an excellent biomarker for anatomic damage to lateral line hair cells. Building on work by our group and others, we have built a new, fully automated high-throughput behavioral assay system that uses automated image analysis techniques to quantify rheotaxis behavior. This novel system consists of a custom-designed swimming apparatus and imaging system consisting of network-controlled Raspberry Pi microcomputers capturing infrared video. Automated analysis techniques detect individual zebrafish, compute their orientation, and quantify the rheotaxis behavior of a zebrafish test population, producing a powerful, high-throughput behavioral assay. Using our fully automated biological assay to test a standardized ototoxic dose of cisplatin against varying doses of compounds that protect or regenerate hair cells may facilitate rapid translation of candidate drugs into preclinical mammalian models of hearing loss.

Role of Proteome Physical Chemistry in Cell Behavior.

PubMed

Ghosh, Kingshuk; de Graff, Adam M R; Sawle, Lucas; Dill, Ken A

2016-09-15

We review how major cell behaviors, such as bacterial growth laws, are derived from the physical chemistry of the cell's proteins. On one hand, cell actions depend on the individual biological functionalities of their many genes and proteins. On the other hand, the common physics among proteins can be as important as the unique biology that distinguishes them. For example, bacterial growth rates depend strongly on temperature. This dependence can be explained by the folding stabilities across a cell's proteome. Such modeling explains how thermophilic and mesophilic organisms differ, and how oxidative damage of highly charged proteins can lead to unfolding and aggregation in aging cells. Cells have characteristic time scales. For example, E. coli can duplicate as fast as 2-3 times per hour. These time scales can be explained by protein dynamics (the rates of synthesis and degradation, folding, and diffusional transport). It rationalizes how bacterial growth is slowed down by added salt. In the same way that the behaviors of inanimate materials can be expressed in terms of the statistical distributions of atoms and molecules, some cell behaviors can be expressed in terms of distributions of protein properties, giving insights into the microscopic basis of growth laws in simple cells.

Historical Overview of Nonstandard Treatments.

ERIC Educational Resources Information Center

Hulme, Pamela

This review of nonstandard treatments as they relate to individuals with mental retardation reveals attempts to increase intelligence and make individuals "normal." Covering the early 1930s through the present, the review addresses: cell therapy, electric shock, behavior modification, vitamin B-6 therapy, Doman-Delacato treatment,…

Timing the start of division in E. coli: a single-cell study

NASA Astrophysics Data System (ADS)

Reshes, G.; Vanounou, S.; Fishov, I.; Feingold, M.

2008-12-01

We monitor the shape dynamics of individual E. coli cells using time-lapse microscopy together with accurate image analysis. This allows measuring the dynamics of single-cell parameters throughout the cell cycle. In previous work, we have used this approach to characterize the main features of single-cell morphogenesis between successive divisions. Here, we focus on the behavior of the parameters that are related to cell division and study their variation over a population of 30 cells. In particular, we show that the single-cell data for the constriction width dynamics collapse onto a unique curve following appropriate rescaling of the corresponding variables. This suggests the presence of an underlying time scale that determines the rate at which the cell cycle advances in each individual cell. For the case of cell length dynamics a similar rescaling of variables emphasizes the presence of a breakpoint in the growth rate at the time when division starts, τc. We also find that the τc of individual cells is correlated with their generation time, τg, and inversely correlated with the corresponding length at birth, L0. Moreover, the extent of the T-period, τg - τc, is apparently independent of τg. The relations between τc, τg and L0 indicate possible compensation mechanisms that maintain cell length variability at about 10%. Similar behavior was observed for both fast-growing cells in a rich medium (LB) and for slower growth in a minimal medium (M9-glucose). To reveal the molecular mechanisms that lead to the observed organization of the cell cycle, we should further extend our approach to monitor the formation of the divisome.

Behavior of HepG2 liver cancer cells using microfluidic-microscopy: a preliminary study

NASA Astrophysics Data System (ADS)

Karamahmutoglu, Hande; ćetin, Metin; Yaǧcı, Tamer; Elitaş, Meltem

2018-02-01

Hepatocellular carcinoma is one of the most common types of liver cancer causing death all over the world. Although early-stage liver cancer can sometimes be treated with partial hepatectomy, liver transplantation, ablation, and embolization, sorafenib treatment is the only approved systemic therapy for advanced HCC. The aim of this research is to develop tools and methods to understand the individuality of hepatocellular carcinoma. Microfluidic cell-culture platform has been developed to observe behavior of single-cells; fluorescence microscopy has been implemented to investigate phenotypic changes of cells. Our preliminary data proved high-level heterogeneity of hepatocellular carcinoma while verifying limited growth of liver cancer cell lines on the silicon wafer.

Autonomy and Non-autonomy of Angiogenic Cell Movements Revealed by Experiment-Driven Mathematical Modeling.

PubMed

Sugihara, Kei; Nishiyama, Koichi; Fukuhara, Shigetomo; Uemura, Akiyoshi; Arima, Satoshi; Kobayashi, Ryo; Köhn-Luque, Alvaro; Mochizuki, Naoki; Suda, Toshio; Ogawa, Hisao; Kurihara, Hiroki

2015-12-01

Angiogenesis is a multicellular phenomenon driven by morphogenetic cell movements. We recently reported morphogenetic vascular endothelial cell (EC) behaviors to be dynamic and complex. However, the principal mechanisms orchestrating individual EC movements in angiogenic morphogenesis remain largely unknown. Here we present an experiment-driven mathematical model that enables us to systematically dissect cellular mechanisms in branch elongation. We found that cell-autonomous and coordinated actions governed these multicellular behaviors, and a cell-autonomous process sufficiently illustrated essential features of the morphogenetic EC dynamics at both the single-cell and cell-population levels. Through refining our model and experimental verification, we further identified a coordinated mode of tip EC behaviors regulated via a spatial relationship between tip and follower ECs, which facilitates the forward motility of tip ECs. These findings provide insights that enhance our mechanistic understanding of not only angiogenic morphogenesis, but also other types of multicellular phenomenon. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Possession attachment predicts cell phone use while driving.

PubMed

Weller, Joshua A; Shackleford, Crystal; Dieckmann, Nathan; Slovic, Paul

2013-04-01

Distracted driving has become an important public health concern. However, little is known about the predictors of this health-risking behavior. One overlooked risk factor for distracted driving is the perceived attachment that one feels toward his or her phone. Prior research has suggested that individuals develop bonds toward objects, and qualitative research suggests that the bond between young drivers and their phones can be strong. It follows that individuals who perceive a strong attachment to their phone would be more likely to use it, even when driving. In a nationally representative sample of young drivers (17-28 years), participants (n = 1,006) completed a survey about driving behaviors and phone use. Risk perception surrounding cell phone use while driving and perceived attachment to one's phone were assessed by administering factor-analytically derived scales that were created as part of a larger project. Attachment toward one's phone predicted the proportion of trips in which a participant reported using their cell phone while driving, beyond that accounted for by risk perception and overall phone use. Further, attachment predicted self-reported distracted driving behaviors, such as the use of social media while driving. Attachment to one's phone may be an important but overlooked risk factor for the engagement of potentially health-risking driving behaviors. Understanding that phone attachment may adversely affect driving behaviors has the potential to inform prevention and intervention efforts designed to reduce distracted driving behaviors, especially in young drivers. 2013 APA, all rights reserved

Tools for Genomic and Transcriptomic Analysis of Microbes at Single-Cell Level

PubMed Central

Chen, Zixi; Chen, Lei; Zhang, Weiwen

2017-01-01

Microbiologists traditionally study population rather than individual cells, as it is generally assumed that the status of individual cells will be similar to that observed in the population. However, the recent studies have shown that the individual behavior of each single cell could be quite different from that of the whole population, suggesting the importance of extending traditional microbiology studies to single-cell level. With recent technological advances, such as flow cytometry, next-generation sequencing (NGS), and microspectroscopy, single-cell microbiology has greatly enhanced the understanding of individuality and heterogeneity of microbes in many biological systems. Notably, the application of multiple ‘omics’ in single-cell analysis has shed light on how individual cells perceive, respond, and adapt to the environment, how heterogeneity arises under external stress and finally determines the fate of the whole population, and how microbes survive under natural conditions. As single-cell analysis involves no axenic cultivation of target microorganism, it has also been demonstrated as a valuable tool for dissecting the microbial ‘dark matter.’ In this review, current state-of-the-art tools and methods for genomic and transcriptomic analysis of microbes at single-cell level were critically summarized, including single-cell isolation methods and experimental strategies of single-cell analysis with NGS. In addition, perspectives on the future trends of technology development in the field of single-cell analysis was also presented. PMID:28979258

Tracking flow of leukocytes in blood for drug analysis

NASA Astrophysics Data System (ADS)

Basharat, Arslan; Turner, Wesley; Stephens, Gillian; Badillo, Benjamin; Lumpkin, Rick; Andre, Patrick; Perera, Amitha

2011-03-01

Modern microscopy techniques allow imaging of circulating blood components under vascular flow conditions. The resulting video sequences provide unique insights into the behavior of blood cells within the vasculature and can be used as a method to monitor and quantitate the recruitment of inflammatory cells at sites of vascular injury/ inflammation and potentially serve as a pharmacodynamic biomarker, helping screen new therapies and individualize dose and combinations of drugs. However, manual analysis of these video sequences is intractable, requiring hours per 400 second video clip. In this paper, we present an automated technique to analyze the behavior and recruitment of human leukocytes in whole blood under physiological conditions of shear through a simple multi-channel fluorescence microscope in real-time. This technique detects and tracks the recruitment of leukocytes to a bioactive surface coated on a flow chamber. Rolling cells (cells which partially bind to the bioactive matrix) are detected counted, and have their velocity measured and graphed. The challenges here include: high cell density, appearance similarity, and low (1Hz) frame rate. Our approach performs frame differencing based motion segmentation, track initialization and online tracking of individual leukocytes.

Can you hear me now?

PubMed Central

Shacham, Enbal; Stamm, Kate E.; Overton, Edgar T.

2013-01-01

Recent studies support technology-based behavioral interventions for individuals with HIV. This study focused on the use of cell phone and internet technologies among a cohort of 515 HIV-infected individuals. Socio-demographic and clinic data were collected among individuals presenting at an urban Midwestern university HIV clinic in 2007. Regular internet usage occurred more often with males, Caucasians, those who were employed, had higher salaries, and were more educated. Higher levels of education and salary >$10,000 predicted regular usage when controlling for race, employment, and gender. Cell phone ownership was associated with being Caucasian, employed, more educated, and salary > $10,000. Employment was the only predictor of owning a cell phone when controlling for income, race, and education. Individuals who were <40 years of age, employed, and more educated were more likely to know how to text message. Employment and post-high school education predicted knowledge of text messaging, when controlling for age. Disparities among internet, cell phone, and text messaging usage exist among HIV-infected individuals. PMID:20024756

Cell-to-cell variation and specialization in sugar metabolism in clonal bacterial populations

PubMed Central

Schreiber, Frank; Dal Co, Alma; Kiviet, Daniel J.; Littmann, Sten

2017-01-01

While we have good understanding of bacterial metabolism at the population level, we know little about the metabolic behavior of individual cells: do single cells in clonal populations sometimes specialize on different metabolic pathways? Such metabolic specialization could be driven by stochastic gene expression and could provide individual cells with growth benefits of specialization. We measured the degree of phenotypic specialization in two parallel metabolic pathways, the assimilation of glucose and arabinose. We grew Escherichia coli in chemostats, and used isotope-labeled sugars in combination with nanometer-scale secondary ion mass spectrometry and mathematical modeling to quantify sugar assimilation at the single-cell level. We found large variation in metabolic activities between single cells, both in absolute assimilation and in the degree to which individual cells specialize in the assimilation of different sugars. Analysis of transcriptional reporters indicated that this variation was at least partially based on cell-to-cell variation in gene expression. Metabolic differences between cells in clonal populations could potentially reduce metabolic incompatibilities between different pathways, and increase the rate at which parallel reactions can be performed. PMID:29253903

An Observation-Driven Agent-Based Modeling and Analysis Framework for C. elegans Embryogenesis.

PubMed

Wang, Zi; Ramsey, Benjamin J; Wang, Dali; Wong, Kwai; Li, Husheng; Wang, Eric; Bao, Zhirong

2016-01-01

With cutting-edge live microscopy and image analysis, biologists can now systematically track individual cells in complex tissues and quantify cellular behavior over extended time windows. Computational approaches that utilize the systematic and quantitative data are needed to understand how cells interact in vivo to give rise to the different cell types and 3D morphology of tissues. An agent-based, minimum descriptive modeling and analysis framework is presented in this paper to study C. elegans embryogenesis. The framework is designed to incorporate the large amounts of experimental observations on cellular behavior and reserve data structures/interfaces that allow regulatory mechanisms to be added as more insights are gained. Observed cellular behaviors are organized into lineage identity, timing and direction of cell division, and path of cell movement. The framework also includes global parameters such as the eggshell and a clock. Division and movement behaviors are driven by statistical models of the observations. Data structures/interfaces are reserved for gene list, cell-cell interaction, cell fate and landscape, and other global parameters until the descriptive model is replaced by a regulatory mechanism. This approach provides a framework to handle the ongoing experiments of single-cell analysis of complex tissues where mechanistic insights lag data collection and need to be validated on complex observations.

An Ultrasensitive Bacterial Motor Revealed by Monitoring Signaling Proteins in Single Cells

NASA Astrophysics Data System (ADS)

Cluzel, Philippe; Surette, Michael; Leibler, Stanislas

2000-03-01

Understanding biology at the single-cell level requires simultaneous measurements of biochemical parameters and behavioral characteristics in individual cells. Here, the output of individual flagellar motors in Escherichia coli was measured as a function of the intracellular concentration of the chemotactic signaling protein. The concentration of this molecule, fused to green fluorescent protein, was monitored with fluorescence correlation spectroscopy. Motors from different bacteria exhibited an identical steep input-output relation, suggesting that they actively contribute to signal amplification in chemotaxis. This experimental approach can be extended to quantitative in vivo studies of other biochemical networks.

Nanoscale monitoring of drug actions on cell membrane using atomic force microscopy

PubMed Central

Li, Mi; Liu, Lian-qing; Xi, Ning; Wang, Yue-chao

2015-01-01

Knowledge of the nanoscale changes that take place in individual cells in response to a drug is useful for understanding the drug action. However, due to the lack of adequate techniques, such knowledge was scarce until the advent of atomic force microscopy (AFM), which is a multifunctional tool for investigating cellular behavior with nanometer resolution under near-physiological conditions. In the past decade, researchers have applied AFM to monitor the morphological and mechanical dynamics of individual cells following drug stimulation, yielding considerable novel insight into how the drug molecules affect an individual cell at the nanoscale. In this article we summarize the representative applications of AFM in characterization of drug actions on cell membrane, including topographic imaging, elasticity measurements, molecular interaction quantification, native membrane protein imaging and manipulation, etc. The challenges that are hampering the further development of AFM for studies of cellular activities are aslo discussed. PMID:26027658

Engineered extracellular microenvironment with a tunable mechanical property for controlling cell behavior and cardiomyogenic fate of cardiac stem cells.

PubMed

Choi, Min-Young; Kim, Jong-Tae; Lee, Won-Jin; Lee, Yunki; Park, Kyung Min; Yang, Young-Il; Park, Ki Dong

2017-03-01

Endogenous cardiac stem cells (CSCs) are known to play a certain role in the myocardial homeostasis of the adult heart. The extracellular matrix (ECM) surrounding CSCs provides mechanical signals to regulate a variety of cell behaviors, yet the impact in the adult heart of these mechanical properties of ECM on CSC renewal and fate decisions is mostly unknown. To elucidate CSC mechanoresponses at the individual cell and myocardial level, we used the sol-to-gel transitional gelatin-poly(ethylene glycol)-tyramine (GPT) hydrogel with a tunable mechanical property to construct a three-dimensional (3D) matrix for culturing native myocardium and CSCs. The elastic modulus of the GPT hydrogel was controlled by adjusting cross-linking density using hydrogen peroxide. The GPT hydrogel showed an ability to transduce integrin-mediated signals into the myocardium and to permit myocardial homeostatic processes in vitro, including CSC migration and proliferation into the hydrogel from the myocardium. Decreasing the elastic modulus of the hydrogel resulted in upregulation of phosphorylated integrin-mediated signaling molecules in CSCs, which were associated with significant increases in cell spreading, migration, and proliferation of CSCs in a modulus-dependent manner. However, increasing the elastic modulus of hydrogel induced the arrest of cell growth but led to upregulation of cardiomyocyte-associated mRNAs in CSCs. This work demonstrates that tunable 3D-engineered microenvironments created by GPT hydrogel are able to control CSC behavior and to direct cardiomyogenic fate. Our system may also be appropriate for studying the mechanoresponse of CSCs in a 3D context as well as for developing therapeutic strategies for in situ myocardial regeneration. The extracellular matrix (ECM) provides a physical framework of myocardial niches in which endogenous cardiac stem cells (CSCs) reside, renew, differentiate, and replace cardiac cells. Interactions between ECM and CSCs might be critical for the maintenance of myocardial homeostasis in the adult heart. Yet most studies done so far have used irrelevant cell types and have been performed at the individual cell level, none able to reflect the in vivo situation. By the use of a chemically defined hydrogel to create a tunable 3D microenvironment, we succeeded in controlling CSC behavior at the myocardial and individual cell level and directing the cardiomyogenic fate. Our work may provide insight into the design of biomaterials for in situ myocardial regeneration as well as for tissue engineering. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Housing conditions and sacrifice protocol affect neural activity and vocal behavior in a songbird species, the zebra finch (Taeniopygia guttata).

PubMed

Elie, Julie Estelle; Soula, Hédi Antoine; Trouvé, Colette; Mathevon, Nicolas; Vignal, Clémentine

2015-12-01

Individual cages represent a widely used housing condition in laboratories. This isolation represents an impoverished physical and social environment in gregarious animals. It prevents animals from socializing, even when auditory and visual contact is maintained. Zebra finches are colonial songbirds that are widely used as laboratory animals for the study of vocal communication from brain to behavior. In this study, we investigated the effect of single housing on the vocal behavior and the brain activity of male zebra finches (Taeniopygia guttata): male birds housed in individual cages were compared to freely interacting male birds housed as a social group in a communal cage. We focused on the activity of septo-hypothalamic regions of the "social behavior network" (SBN), a set of limbic regions involved in several social behaviors in vertebrates. The activity of four structures of the SBN (BSTm, medial bed nucleus of the stria terminalis; POM, medial preoptic area; lateral septum; ventromedial hypothalamus) and one associated region (paraventricular nucleus of the hypothalamus) was assessed using immunoreactive nuclei density of the immediate early gene Zenk (egr-1). We further assessed the identity of active cell populations by labeling vasotocin (VT). Brain activity was related to behavioral activities of birds like physical and vocal interactions. We showed that individual housing modifies vocal exchanges between birds compared to communal housing. This is of particular importance in the zebra finch, a model species for the study of vocal communication. In addition, a protocol that daily removes one or two birds from the group affects differently male zebra finches depending of their housing conditions: while communally-housed males changed their vocal output, brains of individually housed males show increased Zenk labeling in non-VT cells of the BSTm and enhanced correlation of Zenk-revealed activity between the studied structures. These results show that housing conditions must gain some attention in behavioral neuroscience protocols. Copyright © 2015. Published by Elsevier SAS.

Bursting synchronization dynamics of pancreatic β-cells with electrical and chemical coupling.

PubMed

Meng, Pan; Wang, Qingyun; Lu, Qishao

2013-06-01

Based on bifurcation analysis, the synchronization behaviors of two identical pancreatic β-cells connected by electrical and chemical coupling are investigated, respectively. Various firing patterns are produced in coupled cells when a single cell exhibits tonic spiking or square-wave bursting individually, irrespectively of what the cells are connected by electrical or chemical coupling. On the one hand, cells can burst synchronously for both weak electrical and chemical coupling when an isolated cell exhibits tonic spiking itself. In particular, for electrically coupled cells, under the variation of the coupling strength there exist complex transition processes of synchronous firing patterns such as "fold/limit cycle" type of bursting, then anti-phase continuous spiking, followed by the "fold/torus" type of bursting, and finally in-phase tonic spiking. On the other hand, it is shown that when the individual cell exhibits square-wave bursting, suitable coupling strength can make the electrically coupled system generate "fold/Hopf" bursting via "fold/fold" hysteresis loop; whereas, the chemically coupled cells generate "fold/subHopf" bursting. Especially, chemically coupled bursters can exhibit inverse period-adding bursting sequence. Fast-slow dynamics analysis is applied to explore the generation mechanism of these bursting oscillations. The above analysis of bursting types and the transition may provide us with better insight into understanding the role of coupling in the dynamic behaviors of pancreatic β-cells.

Single cell multiplexed assay for proteolytic activity using droplet microfluidics.

PubMed

Ng, Ee Xien; Miller, Miles A; Jing, Tengyang; Chen, Chia-Hung

2016-07-15

Cellular enzymes interact in a post-translationally regulated fashion to govern individual cell behaviors, yet current platform technologies are limited in their ability to measure multiple enzyme activities simultaneously in single cells. Here, we developed multi-color Förster resonance energy transfer (FRET)-based enzymatic substrates and use them in a microfluidics platform to simultaneously measure multiple specific protease activities from water-in-oil droplets that contain single cells. By integrating the microfluidic platform with a computational analytical method, Proteolytic Activity Matrix Analysis (PrAMA), we are able to infer six different protease activity signals from individual cells in a high throughput manner (~100 cells/experimental run). We characterized protease activity profiles at single cell resolution for several cancer cell lines including breast cancer cell line MDA-MB-231, lung cancer cell line PC-9, and leukemia cell line K-562 using both live-cell and in-situ cell lysis assay formats, with special focus on metalloproteinases important in metastasis. The ability to measure multiple proteases secreted from or expressed in individual cells allows us to characterize cell heterogeneity and has potential applications including systems biology, pharmacology, cancer diagnosis and stem cell biology. Copyright © 2016 Elsevier B.V. All rights reserved.

Integrated Micro/nanoengineered Functional Biomaterials for Cell Mechanics and Mechanobiology: A Materials Perspective

PubMed Central

Shao, Yue

2014-01-01

The rapid development of micro/nanoengineered functional biomaterials in the last two decades has empowered materials scientists and bioengineers to precisely control different aspects of the in vitro cell microenvironment. Following a philosophy of reductionism, many studies using synthetic functional biomaterials have revealed instructive roles of individual extracellular biophysical and biochemical cues in regulating cellular behaviors. Development of integrated micro/nanoengineered functional biomaterials to study complex and emergent biological phenomena has also thrived rapidly in recent years, revealing adaptive and integrated cellular behaviors closely relevant to human physiological and pathological conditions. Working at the interface between materials science and engineering, biology, and medicine, we are now at the beginning of a great exploration using micro/nanoengineered functional biomaterials for both fundamental biology study and clinical and biomedical applications such as regenerative medicine and drug screening. In this review, we present an overview of state of the art micro/nanoengineered functional biomaterials that can control precisely individual aspects of cell-microenvironment interactions and highlight them as well-controlled platforms for mechanistic studies of mechano-sensitive and -responsive cellular behaviors and integrative biology research. We also discuss the recent exciting trend where micro/nanoengineered biomaterials are integrated into miniaturized biological and biomimetic systems for dynamic multiparametric microenvironmental control of emergent and integrated cellular behaviors. The impact of integrated micro/nanoengineered functional biomaterials for future in vitro studies of regenerative medicine, cell biology, as well as human development and disease models are discussed. PMID:24339188

The impact of spatial and temporal patterns on multi-cellular behavior

NASA Astrophysics Data System (ADS)

Nikolic, Djordje L.

What makes a fruit fly a fruit fly? Essentially this question stems from one of the most fascinating problems in biology: how a single cell (fertilized egg) can give rise to a fully grown animal. To be able to answer this question, the importance to how spatial and temporal patterns of gene and protein expression influence the development of an organism must be understood. After all, fruit fly larvae are segmented, while fertilized eggs are not. Pattern formation is fundamental to establishing this organization of the developing embryo with the ultimate goal being the precise arrangements of specialized cells and tissues within each organ in an adult organism. The research presented here showcases the examples of studies that assess the impact spatial and temporal protein patterns have on the behavior of a collection of cells. By introducing new experimental, non-traditional techniques we developed model systems that allowed us to examine the dependence of the strength of adhesion of cells on the protein organization on sub-cellular, micron length scales, and to investigate how epithelial cell sheets coordinate their migration incorporating individual cell locomotion, molecular signal propagation and different boundary conditions. The first part of this dissertation presents a photolithography-based silanization patterning technique that allowed us to homogeneously pattern large areas with high precision. This method is then applied to organizing cell adhesion-promoting proteins on surfaces for the purposes of studying and manipulating cell behavior. We show how the strength of adhesion is dependent on high local density of an adhesive extracellular matrix protein fibronectin. The varied appeal of this technique is exhibited by showing its applicability to pattern stretched DNA, too. The second part of this dissertation focuses on the impact of spatial and temporal propagation of a molecular signal (ERK 1/2 MAPK) in migrating epithelial sheets during wound healing. By tracking the motion of individual cells within the sheet under the three constructed conditions, we show how the dynamics of the individual cells' motion is responsible for the coordinated migration of the sheet in accordance with the activation of ERK 1/2 MAPK.

Maternal cell phone use during pregnancy and child behavioral problems in five birth cohorts.

PubMed

Birks, Laura; Guxens, Mònica; Papadopoulou, Eleni; Alexander, Jan; Ballester, Ferran; Estarlich, Marisa; Gallastegi, Mara; Ha, Mina; Haugen, Margaretha; Huss, Anke; Kheifets, Leeka; Lim, Hyungryul; Olsen, Jørn; Santa-Marina, Loreto; Sudan, Madhuri; Vermeulen, Roel; Vrijkotte, Tanja; Cardis, Elisabeth; Vrijheid, Martine

2017-07-01

Previous studies have reported associations between prenatal cell phone use and child behavioral problems, but findings have been inconsistent and based on retrospective assessment of cell phone use. This study aimed to assess this association in a multi-national analysis, using data from three cohorts with prospective data on prenatal cell phone use, together with previously published data from two cohorts with retrospectively collected cell phone use data. We used individual participant data from 83,884 mother-child pairs in the five cohorts from Denmark (1996-2002), Korea (2006-2011), the Netherlands (2003-2004), Norway (2004-2008), and Spain (2003-2008). We categorized cell phone use into none, low, medium, and high, based on frequency of calls during pregnancy reported by the mothers. Child behavioral problems (reported by mothers using the Strengths and Difficulties Questionnaire or Child Behavior Checklist) were classified in the borderline/clinical and clinical ranges using validated cut-offs in children aged 5-7years. Cohort specific risk estimates were meta-analyzed. Overall, 38.8% of mothers, mostly from the Danish cohort, reported no cell phone use during pregnancy and these mothers were less likely to have a child with overall behavioral, hyperactivity/inattention or emotional problems. Evidence for a trend of increasing risk of child behavioral problems through the maternal cell phone use categories was observed for hyperactivity/inattention problems (OR for problems in the clinical range: 1.11, 95%CI 1.01, 1.22; 1.28, 95%CI 1.12, 1.48, among children of medium and high users, respectively). This association was fairly consistent across cohorts and between cohorts with retrospectively and prospectively collected cell phone use data. Maternal cell phone use during pregnancy may be associated with an increased risk for behavioral problems, particularly hyperactivity/inattention problems, in the offspring. The interpretation of these results is unclear as uncontrolled confounding may influence both maternal cell phone use and child behavioral problems. Copyright © 2017 Elsevier Ltd. All rights reserved.

In vitro motility of cells from human epidermoid carcinomas. A study by phase-contrast and reflection-contrast cinematography.

PubMed

Haemmerli, G; Sträuli, P

1981-05-15

The motile behavior of six cell lines derived from human squamous carcinomas (two from the larynx, four from the tongue) was studied by cinematography under phase- and reflection-contrast illumination. The recorded cell activities consist in spreading, stationary and translocation motility, and aggregate formation. Within this common pattern, quantitative modifications ("sub-pattern") are stable properties of the individual cells lines. Such modifications are particularly evident with regard to the dynamic texture of the aggregates which ranges from loose, netlike structures to compact islands with smooth borders. Accordingly, the intensity of cell traffic within and around the aggregates varies considerably. It is discussed to what extent the in vitro motility of the carcinoma cell populations reflects their behavior in the organism and thus the significance of cell movements for invasion.

Revelation of Different Nanoparticle-Uptake Behavior in Two Standard Cell Lines NIH/3T3 and A549 by Flow Cytometry and Time-Lapse Imaging

PubMed Central

Jochums, André; Friehs, Elsa; Sambale, Franziska; Lavrentieva, Antonina; Bahnemann, Detlef; Scheper, Thomas

2017-01-01

The uptake of nanomaterials into different cell types is a central pharmacological issue for the determination of nanotoxicity as well as for the development of drug delivery strategies. Most responses of the cells depend on their intracellular interactions with nanoparticles (NPs). Uptake behavior can be precisely investigated in vitro, with sensitive high throughput methods such as flow cytometry. In this study, we investigated two different standard cell lines, human lung carcinoma (A549) and mouse fibroblast (NIH/3T3) cells, regarding their uptake behavior of titanium dioxide NPs. Cells were incubated with different concentrations of TiO2 NPs and samples were taken at certain time points to compare the uptake kinetics of both cell lines. Samples were analyzed with the help of flow cytometry by studying changes in the side and forward scattering signal. To additionally enable a detection via fluorescence, NPs were labeled with the fluorescent dye fluorescein isothiocyanate (FITC) and propidium iodide (PI). We found that NIH/3T3 cells take up the studied NPs more efficiently than A549 cells. These findings were supported by time-lapse microscopic imaging of the cells incubated with TiO2 NPs. Our results confirm that the uptake behavior of individual cell types has to be considered before interpreting any results of nanomaterial studies. PMID:29051447

Collective ordering of microscale matters in natural analogy

PubMed Central

Ahn, Sungsook; Joon Lee, Sang

2015-01-01

Collective interaction occurs in many natural and artificial matters in broad scales. In a biological system, collective spatial organization of live individuals in a colony is important for their viability determination. Interactive motions between a single individual and an agglomerate are critical for whole procedure of the collective behaviors, but few has been clarified for these intermediate range behaviors. Here, collective interactions of microscale matters are investigated with human cells, plant seeds and artificial microspheres in terms of commonly occurring spatial arrangements. Human cancer cells are inherently attractive to form an agglomerate by cohesive motion, while plant chia seeds are repulsive by excreting mucilage. Microsphere model is employed to investigate the dynamic assembly equilibrated by an attraction and repulsion. There is a fundamental analogy in terms of an onset of regular pattern formation even without physical contact of individuals. The collective interactions are suggested to start before the individual components become physically agglomerated. This study contributes to fundamental understanding on the microscale particulate matters and natural pattern formation which are further useful for various applications both in academic and industrial areas. PMID:26027819

Human development VIII: a theory of "deep" quantum chemistry and cell consciousness: quantum chemistry controls genes and biochemistry to give cells and higher organisms consciousness and complex behavior.

PubMed

Ventegodt, Søren; Hermansen, Tyge Dahl; Flensborg-Madsen, Trine; Nielsen, Maj Lyck; Merrick, Joav

2006-11-14

Deep quantum chemistry is a theory of deeply structured quantum fields carrying the biological information of the cell, making it able to remember, intend, represent the inner and outer world for comparison, understand what it "sees", and make choices on its structure, form, behavior and division. We suggest that deep quantum chemistry gives the cell consciousness and all the qualities and abilities related to consciousness. We use geometric symbolism, which is a pre-mathematical and philosophical approach to problems that cannot yet be handled mathematically. Using Occam's razor we have started with the simplest model that works; we presume this to be a many-dimensional, spiral fractal. We suggest that all the electrons of the large biological molecules' orbitals make one huge "cell-orbital", which is structured according to the spiral fractal nature of quantum fields. Consciousness of single cells, multi cellular structures as e.g. organs, multi-cellular organisms and multi-individual colonies (like ants) and human societies can thus be explained by deep quantum chemistry. When biochemical activity is strictly controlled by the quantum-mechanical super-orbital of the cell, this orbital can deliver energetic quanta as biological information, distributed through many fractal levels of the cell to guide form and behavior of an individual single or a multi-cellular organism. The top level of information is the consciousness of the cell or organism, which controls all the biochemical processes. By this speculative work inspired by Penrose and Hameroff we hope to inspire other researchers to formulate more strict and mathematically correct hypothesis on the complex and coherence nature of matter, life and consciousness.

Human Development VIII: A Theory of “Deep” Quantum Chemistry and Cell Consciousness: Quantum Chemistry Controls Genes and Biochemistry to Give Cells and Higher Organisms Consciousness and Complex Behavior

PubMed Central

Ventegodt, Søren; Hermansen, Tyge Dahl; Flensborg-Madsen, Trine; Nielsen, Maj Lyck; Merrick, Joav

2006-01-01

Deep quantum chemistry is a theory of deeply structured quantum fields carrying the biological information of the cell, making it able to remember, intend, represent the inner and outer world for comparison, understand what it “sees”, and make choices on its structure, form, behavior and division. We suggest that deep quantum chemistry gives the cell consciousness and all the qualities and abilities related to consciousness. We use geometric symbolism, which is a pre-mathematical and philosophical approach to problems that cannot yet be handled mathematically. Using Occams razor we have started with the simplest model that works; we presume this to be a many-dimensional, spiral fractal. We suggest that all the electrons of the large biological molecules orbitals make one huge “cell-orbital”, which is structured according to the spiral fractal nature of quantum fields. Consciousness of single cells, multi cellular structures as e.g. organs, multi-cellular organisms and multi-individual colonies (like ants) and human societies can thus be explained by deep quantum chemistry. When biochemical activity is strictly controlled by the quantum-mechanical super-orbital of the cell, this orbital can deliver energetic quanta as biological information, distributed through many fractal levels of the cell to guide form and behavior of an individual single or a multi-cellular organism. The top level of information is the consciousness of the cell or organism, which controls all the biochemical processes. By this speculative work inspired by Penrose and Hameroff we hope to inspire other researchers to formulate more strict and mathematically correct hypothesis on the complex and coherence nature of matter, life and consciousness. PMID:17115084

Comprehensive neuropsychological evaluation of children and adolescents with sickle cell anemia: a hospital-based sample.

PubMed

Nunes, Samantha; Argollo, Nayara; Mota, Marivania; Vieira, Camilo; Sena, Eduardo Pondé de

Individuals with sickle cell anemia may suffer symptomatic or silent cerebral infarcts leading to neurocognitive complications. This study investigated the cognitive and intellectual performance of children and adolescents with sickle cell anemia. The socioeconomic status, clinical aspects and behavioral profile of 15 young individuals with sickle cell anemia were evaluated. The Wechsler Intelligence Scale for Children, the Developmental Neuropsychological Assessment Test, and the Child Behavior Checklist were applied. Participants with a history of stroke had lower intelligence quotient (IQ) scores. Alterations were found in attention and executive functioning, language, verbal and visual memory, visuospatial processing and sensorimotor skills. These alterations were found both in the children and adolescents who had had a cerebral infarction and in those who apparently had not. In the majority of cases, there were learning difficulties, a history of repeating school years and a need for specialist educational support. The most common additional diagnoses in accordance with the Diagnostic and Statistical Manual of Mental Disorders IV were depressive disorder, anxiety disorder and somatic disorder, as well as conditions associated with physical and psychosocial repercussions of sickle cell anemia. As sickle cell anemia is considered a progressive cerebral vasculopathy, it is a potential risk factor for neurocognitive and psychosocial development. Therefore, periodic neuropsychological and behavioral evaluations of children and adolescents with sickle cell anemia may represent a useful measure to reduce long-term biopsychosocial repercussions. Copyright © 2016 Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular. Published by Elsevier Editora Ltda. All rights reserved.

Cell-cell recognition and social networking in bacteria

PubMed Central

Troselj, Vera; Cao, Pengbo; Wall, Daniel

2018-01-01

SUMMARY The ability to recognize self and to recognize partnering cells allows microorganisms to build social networks that perform functions beyond the capabilities of the individual. In bacteria, recognition typically involves genetic determinants that provide cell surface receptors or diffusible signaling chemicals to identify proximal cells at the molecular level that can participate in cooperative processes. Social networks also rely on discriminating mechanisms to exclude competing cells from joining and exploiting their groups. In addition to their appropriate genotypes, cell-cell recognition also requires compatible phenotypes, which vary according to environmental cues or exposures as well as stochastic processes that leads to heterogeneity and potential disharmony in the population. Understanding how bacteria identify their social partners and how they synchronize their behaviors to conduct multicellular functions is an expanding field of research. Here we review recent progress in the field and contrast the various strategies used in recognition and behavioral networking. PMID:29194914

Convective exosome-tracing microfluidics for analysis of cell-non-autonomous neurogenesis.

PubMed

Oh, Hyun Jeong; Shin, Yoojin; Chung, Seok; Hwang, Do Won; Lee, Dong Soo

2017-01-01

The effective role of exosome delivering neurogenic microRNA (miRNA) enables to induce efficient differentiation process during neurogenesis. The microfludic system capable of visualizing the exosomal behavior such as secretion, migration, and uptake of individual exosomes can be used as a robust technique to understand the exosome-mediated change of cellular behavior. Here, we developed the exosome-tracing microfluidic system to visualize exosomal transport carrying the neurogenic miRNA from leading to neighboring cells, and found a new mode of exosome-mediated cell-non-autonomous neurogenesis. The miR-193a facilitated neurogenesis in F11 cells by blocking proliferation-related target genes. In addition to time-lapse live-cell imaging using microfluidics visualized the convective transport of exosomes from differentiated to undifferentiated cells. Individual exosomes containing miR-193a from differentiated donor cells were taken up by undifferentiated cells to lead them to neurogenesis. Induction of anti-miR-193a was sufficient to block neurogenesis in F11 cells. Inhibition of the exosomal production by manumycin-A and treatment of anti-miR-193a in the differentiated donor cells failed to induce neurogenesis in undifferentiated recipient cells. These findings indicate that exosomes of neural progenitors and neurogenic miRNA within these exosomes propagate cell-non-autonomous differentiation to neighboring progenitors, to delineate the roles of exosome mediating neurogenesis of population of homologous neural progenitor cells. Copyright © 2016 Elsevier Ltd. All rights reserved.

Psychological Adjustment of Children with Sickle Cell Disease: Stability and Change over a 10-Month Period.

ERIC Educational Resources Information Center

Thompson, Robert J.; And Others

1994-01-01

Describes investigation utilizing sickle cell disease subjects from a stress and coping project. Found little stability in classification of individuals' adjustment, low congruence in behavior problem patterns and diagnoses, and less stability in adjustment by child report than mother report. Suggests children's coping strategies are intervention…

Core Principles of Bacterial Autoinducer Systems

PubMed Central

2015-01-01

SUMMARY Autoinduction (AI), the response to self-produced chemical signals, is widespread in the bacterial world. This process controls vastly different target functions, such as luminescence, nutrient acquisition, and biofilm formation, in different ways and integrates additional environmental and physiological cues. This diversity raises questions about unifying principles that underlie all AI systems. Here, we suggest that such core principles exist. We argue that the general purpose of AI systems is the homeostatic control of costly cooperative behaviors, including, but not limited to, secreted public goods. First, costly behaviors require preassessment of their efficiency by cheaper AI signals, which we encapsulate in a hybrid “push-pull” model. The “push” factors cell density, diffusion, and spatial clustering determine when a behavior becomes effective. The relative importance of each factor depends on each species' individual ecological context and life history. In turn, “pull” factors, often stress cues that reduce the activation threshold, determine the cellular demand for the target behavior. Second, control is homeostatic because AI systems, either themselves or through accessory mechanisms, not only initiate but also maintain the efficiency of target behaviors. Third, AI-controlled behaviors, even seemingly noncooperative ones, are generally cooperative in nature, when interpreted in the appropriate ecological context. The escape of individual cells from biofilms, for example, may be viewed as an altruistic behavior that increases the fitness of the resident population by reducing starvation stress. The framework proposed here helps appropriately categorize AI-controlled behaviors and allows for a deeper understanding of their ecological and evolutionary functions. PMID:25694124

Can you hear me now? Limited use of technology among an urban HIV-infected cohort.

PubMed

Shacham, E; Stamm, K; Overton, E T

2009-08-01

Recent studies support technology-based behavioral interventions for individuals with HIV. This study focused on the use of cell phone and internet technologies among a cohort of 515 HIV-infected individuals. Socio-demographic and clinic data were collected among individuals presenting at an urban Midwestern university HIV clinic in 2007. Regular internet usage occurred more often with males, Caucasians, those who were employed, had higher income, and were more educated. Higher levels of education and income >$10,000 predicted regular usage when controlling for race, employment, and gender. Cell phone ownership was associated with being Caucasian, employed, more educated, and salary >$10,000. Employment was the only predictor of owning a cell phone when controlling for income, race, and education. Individuals who were <40 years of age, employed, and more educated were more likely to know how to text message. Employment and post-high school education predicted knowledge of text messaging, when controlling for age. Disparities among internet, cell phone, and text messaging usage exist among HIV-infected individuals.

Role of Proteome Physical Chemistry in Cell Behavior

PubMed Central

2016-01-01

We review how major cell behaviors, such as bacterial growth laws, are derived from the physical chemistry of the cell’s proteins. On one hand, cell actions depend on the individual biological functionalities of their many genes and proteins. On the other hand, the common physics among proteins can be as important as the unique biology that distinguishes them. For example, bacterial growth rates depend strongly on temperature. This dependence can be explained by the folding stabilities across a cell’s proteome. Such modeling explains how thermophilic and mesophilic organisms differ, and how oxidative damage of highly charged proteins can lead to unfolding and aggregation in aging cells. Cells have characteristic time scales. For example, E. coli can duplicate as fast as 2–3 times per hour. These time scales can be explained by protein dynamics (the rates of synthesis and degradation, folding, and diffusional transport). It rationalizes how bacterial growth is slowed down by added salt. In the same way that the behaviors of inanimate materials can be expressed in terms of the statistical distributions of atoms and molecules, some cell behaviors can be expressed in terms of distributions of protein properties, giving insights into the microscopic basis of growth laws in simple cells. PMID:27513457

Emergence of tissue mechanics from cellular processes: shaping a fly wing

NASA Astrophysics Data System (ADS)

Merkel, Matthias; Etournay, Raphael; Popovic, Marko; Nandi, Amitabha; Brandl, Holger; Salbreux, Guillaume; Eaton, Suzanne; Jülicher, Frank

Nowadays, biologistsare able to image biological tissueswith up to 10,000 cells in vivowhere the behavior of each individual cell can be followed in detail.However, how precisely large-scale tissue deformation and stresses emerge from cellular behavior remains elusive. Here, we study this question in the developing wing of the fruit fly. To this end, we first establish a geometrical framework that exactly decomposes tissue deformation into contributions by different kinds of cellular processes. These processes comprise cell shape changes, cell neighbor exchanges, cell divisions, and cell extrusions. As the key idea, we introduce a tiling of the cellular network into triangles. This approach also reveals that tissue deformation can also be created by correlated cellular motion. Based on quantifications using these concepts, we developed a novel continuum mechanical model for the fly wing. In particular, our model includes active anisotropic stresses and a delay in the response of cell rearrangements to material stresses. A different approach to study the emergence of tissue mechanics from cellular behavior are cell-based models. We characterize the properties of a cell-based model for 3D tissues that is a hybrid between single particle models and the so-called vertex models.

Hippocampal awake replay in fear memory retrieval

PubMed Central

Wu, Chun-Ting; Haggerty, Daniel; Kemere, Caleb; Ji, Daoyun

2017-01-01

Hippocampal place cells are key to episodic memories. How these cells participate in memory retrieval remains unclear. Here, after rats acquired a fear memory by receiving mild foot-shocks at a shock zone of a track, we analyzed place cells when the animals were placed back to the track and displayed an apparent memory retrieval behavior: avoidance of the shock zone. We found that place cells representing the shock zone were reactivated, despite the fact that the animals did not enter the shock zone. This reactivation occurred in ripple-associated awake replay of place cell sequences encoding the paths from the animal’s current positions to the shock zone, but not in place cell sequences within individual cycles of theta oscillation. The result reveals a specific place cell pattern underlying the inhibitory avoidance behavior and provides strong evidence for the involvement of awake replay in fear memory retrieval. PMID:28218916

An Off-Lattice Hybrid Discrete-Continuum Model of Tumor Growth and Invasion

PubMed Central

Jeon, Junhwan; Quaranta, Vito; Cummings, Peter T.

2010-01-01

Abstract We have developed an off-lattice hybrid discrete-continuum (OLHDC) model of tumor growth and invasion. The continuum part of the OLHDC model describes microenvironmental components such as matrix-degrading enzymes, nutrients or oxygen, and extracellular matrix (ECM) concentrations, whereas the discrete portion represents individual cell behavior such as cell cycle, cell-cell, and cell-ECM interactions and cell motility by the often-used persistent random walk, which can be depicted by the Langevin equation. Using this framework of the OLHDC model, we develop a phenomenologically realistic and bio/physically relevant model that encompasses the experimentally observed superdiffusive behavior (at short times) of mammalian cells. When systemic simulations based on the OLHDC model are performed, tumor growth and its morphology are found to be strongly affected by cell-cell adhesion and haptotaxis. There is a combination of the strength of cell-cell adhesion and haptotaxis in which fingerlike shapes, characteristic of invasive tumor, are observed. PMID:20074513

Keratinocyte Motility Is Affected by UVA Radiation-A Comparison between Normal and Dysplastic Cells.

PubMed

Niculiţe, Cristina M; Nechifor, Marina T; Urs, Andreea O; Olariu, Laura; Ceafalan, Laura C; Leabu, Mircea

2018-06-07

UVA radiation induces multiple and complex changes in the skin, affecting epidermal cell behavior. This study reports the effects of UVA exposure on normal (HaCaT) and dysplastic (DOK) keratinocytes. The adherence, spreading and proliferation were investigated by time-lapse measurement of cell layer impedance on different matrix proteins. Prior to UVA exposure, the time required for adherence and spreading did not differ significantly for HaCaT and DOK cells, while spreading areas were larger for HaCaT cells. Under UVA exposure, HaCaT and DOK cells behavior differed in terms of movement and proliferation. The cells' ability to cover the denuded surface and individual cell trajectories were recorded by time-lapse videomicroscopy, during wound healing experiments. Dysplastic keratinocytes showed more sensitivity to UVA, exhibiting transient deficiencies in directionality of movement and a delay in re-coating the denuded area. The actin cytoskeleton displayed a cortical organization immediately after irradiation, in both cell lines, similar to mock-irradiated cells. Post-irradiation, DOK cells displayed a better organization of stress fibers, persistent filopodia, and new, stronger focal contacts. In conclusion, after UVA exposure HaCaT and DOK cells showed a different behavior in terms of adherence, spreading, motility, proliferation, and actin cytoskeleton dynamics, with the dyplastic keratinocytes being more sensitive.

Integrated micro/nanoengineered functional biomaterials for cell mechanics and mechanobiology: a materials perspective.

PubMed

Shao, Yue; Fu, Jianping

2014-03-12

The rapid development of micro/nanoengineered functional biomaterials in the last two decades has empowered materials scientists and bioengineers to precisely control different aspects of the in vitro cell microenvironment. Following a philosophy of reductionism, many studies using synthetic functional biomaterials have revealed instructive roles of individual extracellular biophysical and biochemical cues in regulating cellular behaviors. Development of integrated micro/nanoengineered functional biomaterials to study complex and emergent biological phenomena has also thrived rapidly in recent years, revealing adaptive and integrated cellular behaviors closely relevant to human physiological and pathological conditions. Working at the interface between materials science and engineering, biology, and medicine, we are now at the beginning of a great exploration using micro/nanoengineered functional biomaterials for both fundamental biology study and clinical and biomedical applications such as regenerative medicine and drug screening. In this review, an overview of state of the art micro/nanoengineered functional biomaterials that can control precisely individual aspects of cell-microenvironment interactions is presented and they are highlighted them as well-controlled platforms for mechanistic studies of mechano-sensitive and -responsive cellular behaviors and integrative biology research. The recent exciting trend where micro/nanoengineered biomaterials are integrated into miniaturized biological and biomimetic systems for dynamic multiparametric microenvironmental control of emergent and integrated cellular behaviors is also discussed. The impact of integrated micro/nanoengineered functional biomaterials for future in vitro studies of regenerative medicine, cell biology, as well as human development and disease models are discussed. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

The swimming behavior of flagellated bacteria in viscous and viscoelastic media

NASA Astrophysics Data System (ADS)

Qu, Zijie; Henderikx, Rene; Breuer, Kenneth

2016-11-01

The motility of bacteria E.coli in viscous and viscoelastic fluids has been widely studied although full understanding remains elusive. The swimming mode of wild-type E.coli is well-described by a run-and-tumble sequence in which periods of straight swimming at a constant speed are randomly interrupted by a tumble, defined as a sudden change of direction with a very low speed. Using a tracking microscope, we follow cells for extended periods of time and find that the swimming behavior can be more complex, and can include a wider variety of behaviors including a "slow random walk" in which the cells move at relatively low speed without the characteristic run. Significant variation between individual cells is observed, and furthermore, a single cell can change its motility during the course of a tracking event. Changing the viscosity and viscoelasticy of the swimming media also has profound effects on the average swimming speed and run-tumble nature of the cell motility, including changing the distribution, duration of tumbling and slow random walk events. The reasons for these changes are explained using a Purcell-style resistive force model for the cell and flagellar behavior as well as model for the changes in flagellar bundling in different fluid viscosities. National Science Foundation.

Cognitive behavioral therapy in patients with sickle cell disease.

PubMed

Daniels, Sheena

2015-01-01

Sickle cell disease (SCD) is an inherited autosomal recessive disorder. In the United States, most individuals with SCD are African Americans, withan incidence of 1 in 400 to 1 in 500 live births. SCD is a lifelong disorder with no known cure. SCD causes anemia, frequent painful episodes, and reduced life ex- pectancy. The most disturbing clinical problem associated with SCD is severe pain episodes, the most common reason for hospitalization. Pharmacological interventions have been the mainstream for treatment; however, psychological interventions such as cognitive behavioral therapy (CBT) may complement current medical treatment, lead- ing to better coping and overall improved quality of life. In a quasi-experimental one-group pretest-posttest study, 9 African American individuals with SCD completed 3 weekly educational sessions learning CBT methods. Participants demonstrated increased frequency of use of CBT methods post-intervention, including diverting attention, coping self-statements, and behavioral activities, leading to better pain control. However, quality of life and role limitation did not show significant improvement. CBT may be beneficial to those suffering from SCD when combined with conventional treatment options; however, there are still barriers to incorporating psychological interventions into practice. CBT shows promise for individuals with chronic conditions such as SCD, but more investigation into its efficacy is needed with larger sample sizes over longer periods of time.

Noise and Epigenetic Inheritance of Single-Cell Division Times Influence Population Fitness.

PubMed

Cerulus, Bram; New, Aaron M; Pougach, Ksenia; Verstrepen, Kevin J

2016-05-09

The fitness effect of biological noise remains unclear. For example, even within clonal microbial populations, individual cells grow at different speeds. Although it is known that the individuals' mean growth speed can affect population-level fitness, it is unclear how or whether growth speed heterogeneity itself is subject to natural selection. Here, we show that noisy single-cell division times can significantly affect population-level growth rate. Using time-lapse microscopy to measure the division times of thousands of individual S. cerevisiae cells across different genetic and environmental backgrounds, we find that the length of individual cells' division times can vary substantially between clonal individuals and that sublineages often show epigenetic inheritance of division times. By combining these experimental measurements with mathematical modeling, we find that, for a given mean division time, increasing heterogeneity and epigenetic inheritance of division times increases the population growth rate. Furthermore, we demonstrate that the heterogeneity and epigenetic inheritance of single-cell division times can be linked with variation in the expression of catabolic genes. Taken together, our results reveal how a change in noisy single-cell behaviors can directly influence fitness through dynamics that operate independently of effects caused by changes to the mean. These results not only allow a better understanding of microbial fitness but also help to more accurately predict fitness in other clonal populations, such as tumors. Copyright © 2016 Elsevier Ltd. All rights reserved.

Physical activity measured using global positioning system tracking in non-small cell lung cancer: an observational study.

PubMed

Granger, Catherine L; Denehy, Linda; McDonald, Christine F; Irving, Louis; Clark, Ross A

2014-11-01

Increasingly physical activity (PA) is being recognized as an important outcome in non-small cell lung cancer (NSCLC). We investigated PA using novel global positioning system (GPS) tracking individuals with NSCLC and a group of similar-aged healthy individuals. A prospective cross-sectional multicenter study. Fifty individuals with NSCLC from 3 Australian tertiary hospitals and 35 similar-aged healthy individuals without cancer were included. Individuals with NSCLC were assessed pretreatment. Primary measures were triaxial accelerometery (steps/day) and GPS tracking (outdoor PA behavior). Secondary measures were questionnaires assessing depression, motivation to exercise, and environmental barriers to PA. Between-group comparisons were analyzed using analysis of covariance. Individuals with NSCLC engaged in significantly less PA than similar-aged healthy individuals (mean difference 2363 steps/day, P = .007) and had higher levels of depression (P = .027) and lower motivation to exercise (P = .001). Daily outdoor walking time (P = .874) and distance travelled away from home (P = .883) were not different between groups. Individuals with NSCLC spent less time outdoors in their local neighborhood area (P < .001). A greater number of steps per day was seen in patients who were less depressed (r = .39) or had better access to nonresidential destinations such as shopping centers (r = .25). Global positioning system tracking appears to be a feasible methodology for adult cancer patients and holds promise for use in future studies investigating PA and or lifestyle behaviors. © The Author(s) 2014.

The pharmacogenetics of body odor: as easy as ABCC?

PubMed

Brown, Sara

2013-07-01

ABCC11 genotype affects apocrine secretory cell function and determines individual body odor phenotype. Rodriguez et al. have applied genetic epidemiology using predetermined phenotype data to demonstrate an association between a single-nucleotide polymorphism (rs17822931) and the human behavior of deodorant application. Individuals with the ABCC11 genotype predicting a nonodorous phenotype report a significantly lower frequency of deodorant use.

Nanolithographic control of the spatial organization of cellular adhesion receptors at the single-molecule level

PubMed Central

Schvartzman, Mark; Palma, Matteo; Sable, Julia; Abramson, Justin; Hu, Xian; Sheetz, Michael P.; Wind, Shalom J.

2011-01-01

The ability to control the placement of individual molecules promises to enable a wide range of applications and is a key challenge in nanoscience and nanotechnology. Many biological interactions, in particular, are sensitive to the precise geometric arrangement of proteins. We have developed a technique which combines molecular-scale nanolithography with site-selective biochemistry to create biomimetic arrays of individual protein binding sites. The binding sites can be arranged in heterogeneous patterns of virtually any possible geometry with a nearly unlimited number of degrees of freedom. We have used these arrays to explore how the geometric organization of the extracellular matrix (ECM) binding ligand RGD (Arg-Gly-Asp) affects cell adhesion and spreading. Systematic variation of spacing, density and cluster size of individual integrin binding sites was used to elicit different cell behavior. Cell spreading assays on arrays of different geometric arrangements revealed a dramatic increase in spreading efficiency when at least 4 liganded sites were spaced within 60 nm or less, with no dependence on global density. This points to the existence of a minimal matrix adhesion unit for fibronectin defined in space and stoichiometry. Developing an understanding of the ECM geometries that activate specific cellular functional complexes is a critical step toward controlling cell behavior. Potential practical applications range from new therapeutic treatments to the rational design of tissue scaffolds that can optimize healing without scarring. More broadly, spatial control at the single-molecule level can elucidate factors controlling individual molecular interactions and can enable synthesis of new systems based on molecular-scale architectures. PMID:21319842

Multiscale Modeling of Angiogenesis and Predictive Capacity

NASA Astrophysics Data System (ADS)

Pillay, Samara; Byrne, Helen; Maini, Philip

Tumors induce the growth of new blood vessels from existing vasculature through angiogenesis. Using an agent-based approach, we model the behavior of individual endothelial cells during angiogenesis. We incorporate crowding effects through volume exclusion, motility of cells through biased random walks, and include birth and death-like processes. We use the transition probabilities associated with the discrete model and a discrete conservation equation for cell occupancy to determine collective cell behavior, in terms of partial differential equations (PDEs). We derive three PDE models incorporating single, multi-species and no volume exclusion. By fitting the parameters in our PDE models and other well-established continuum models to agent-based simulations during a specific time period, and then comparing the outputs from the PDE models and agent-based model at later times, we aim to determine how well the PDE models predict the future behavior of the agent-based model. We also determine whether predictions differ across PDE models and the significance of those differences. This may impact drug development strategies based on PDE models.

Origins of heterogeneity in Streptococcus mutans competence: interpreting an environment-sensitive signaling pathway

NASA Astrophysics Data System (ADS)

Hagen, Stephen J.; Son, Minjun

2017-02-01

Bacterial pathogens rely on chemical signaling and environmental cues to regulate disease-causing behavior in complex microenvironments. The human pathogen Streptococcus mutans employs a particularly complex signaling and sensing scheme to regulate genetic competence and other virulence behaviors in the oral biofilms it inhabits. Individual S. mutans cells make the decision to enter the competent state by integrating chemical and physical cues received from their microenvironment along with endogenously produced peptide signals. Studies at the single-cell level, using microfluidics to control the extracellular environment, provide physical insight into how the cells process these inputs to generate complex and often heterogeneous outputs. Fine changes in environmental stimuli can dramatically alter the behavior of the competence circuit. Small shifts in pH can switch the quorum sensing response on or off, while peptide-rich media appear to switch the output from a unimodal to a bimodal behavior. Therefore, depending on environmental cues, the quorum sensing circuitry can either synchronize virulence across the population, or initiate and amplify heterogeneity in that behavior. Much of this complex behavior can be understood within the framework of a quorum sensing system that can operate both as an intercellular signaling mechanism and intracellularly as a noisy bimodal switch.

Hydrogel design of experiments methodology to optimize hydrogel for iPSC-NPC culture.

PubMed

Lam, Jonathan; Carmichael, S Thomas; Lowry, William E; Segura, Tatiana

2015-03-11

Bioactive signals can be incorporated in hydrogels to direct encapsulated cell behavior. Design of experiments methodology methodically varies the signals systematically to determine the individual and combinatorial effects of each factor on cell activity. Using this approach enables the optimization of three ligands concentrations (RGD, YIGSR, IKVAV) for the survival and differentiation of neural progenitor cells. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Observing the conformation of individual SNARE proteins inside live cells

NASA Astrophysics Data System (ADS)

Weninger, Keith

2010-10-01

Protein conformational dynamics are directly linked to function in many instances. Within living cells, protein dynamics are rarely synchronized so observing ensemble-averaged behaviors can hide details of signaling pathways. Here we present an approach using single molecule fluorescence resonance energy transfer (FRET) to observe the conformation of individual SNARE proteins as they fold to enter the SNARE complex in living cells. Proteins were recombinantly expressed, labeled with small-molecule fluorescent dyes and microinjected for in vivo imaging and tracking using total internal reflection microscopy. Observing single molecules avoids the difficulties of averaging over unsynchronized ensembles. Our approach is easily generalized to a wide variety of proteins in many cellular signaling pathways.

An animated landscape representation of CD4+ T-cell differentiation, variability, and plasticity: Insights into the behavior of populations versus cells

PubMed Central

Rebhahn, Jonathan A; Deng, Nan; Sharma, Gaurav; Livingstone, Alexandra M; Huang, Sui; Mosmann, Tim R

2014-01-01

Recent advances in understanding CD4+ T-cell differentiation suggest that previous models of a few distinct, stable effector phenotypes were too simplistic. Although several well-characterized phenotypes are still recognized, some states display plasticity, and intermediate phenotypes exist. As a framework for reexamining these concepts, we use Waddington's landscape paradigm, augmented with explicit consideration of stochastic variations. Our animation program “LAVA” visualizes T-cell differentiation as cells moving across a landscape of hills and valleys, leading to attractor basins representing stable or semistable differentiation states. The model illustrates several principles, including: (i) cell populations may behave more predictably than individual cells; (ii) analogous to reticulate evolution, differentiation may proceed through a network of interconnected states, rather than a single well-defined pathway; (iii) relatively minor changes in the barriers between attractor basins can change the stability or plasticity of a population; (iv) intrapopulation variability of gene expression may be an important regulator of differentiation, rather than inconsequential noise; (v) the behavior of some populations may be defined mainly by the behavior of outlier cells. While not a quantitative representation of actual differentiation, our model is intended to provoke discussion of T-cell differentiation pathways, particularly highlighting a probabilistic view of transitions between states. PMID:24945794

Rotation is the primary motion of paired human epidermal keratinocytes.

PubMed

Tate, Sota; Imai, Matome; Matsushita, Natsuki; Nishimura, Emi K; Higashiyama, Shigeki; Nanba, Daisuke

2015-09-01

Collective motion of keratinocytes is involved in morphogenesis, homeostasis, and wound healing of the epidermis. Yet how the collective motion of keratinocytes emerges from the behavior of individual cells is still largely unknown. The aim of this study was to find the cellular behavior that links single and collective motion of keratinocytes. We investigated the behavior of two-cell colonies of HaCaT keratinocytes by a combination of time-lapse imaging and image processing. The two-cell colonies of HaCaT cells were formed as a contacted pair of keratinocyte clones. Image analysis and cell culture experiments revealed that the rotational speed of two-cell colonies was positively associated with their proliferative capacity. α6 integrin was required for the rotational motion of two-cell keratinocyte colonies. We also confirmed that two-cell colonies of keratinocytes predominantly exhibited the rotational, but not translational, motion, two modes of motion in a contact pair of rotating objects. The rotational motion is the primary motion of two-cell keratinocyte colonies and its speed is positively associated with their proliferative capacity. This study suggests that the assembly of rotating keratinocytes generates the collective motion of proliferative keratinocytes during morphogenesis and wound healing of the epidermis. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Embryonic cell-cell adhesion: a key player in collective neural crest migration.

PubMed

Barriga, Elias H; Mayor, Roberto

2015-01-01

Cell migration is essential for morphogenesis, adult tissue remodeling, wound healing, and cancer cell migration. Cells can migrate as individuals or groups. When cells migrate in groups, cell-cell interactions are crucial in order to promote the coordinated behavior, essential for collective migration. Interestingly, recent evidence has shown that cell-cell interactions are also important for establishing and maintaining the directionality of these migratory events. We focus on neural crest cells, as they possess extraordinary migratory capabilities that allow them to migrate and colonize tissues all over the embryo. Neural crest cells undergo an epithelial-to-mesenchymal transition at the same time than perform directional collective migration. Cell-cell adhesion has been shown to be an important source of planar cell polarity and cell coordination during collective movement. We also review molecular mechanisms underlying cadherin turnover, showing how the modulation and dynamics of cell-cell adhesions are crucial in order to maintain tissue integrity and collective migration in vivo. We conclude that cell-cell adhesion during embryo development cannot be considered as simple passive resistance to force, but rather participates in signaling events that determine important cell behaviors required for cell migration. © 2015 Elsevier Inc. All rights reserved.

Encoding of Tactile Stimuli by Mechanoreceptors and Interneurons of the Medicinal Leech

PubMed Central

Kretzberg, Jutta; Pirschel, Friederice; Fathiazar, Elham; Hilgen, Gerrit

2016-01-01

For many animals processing of tactile information is a crucial task in behavioral contexts like exploration, foraging, and stimulus avoidance. The leech, having infrequent access to food, developed an energy efficient reaction to tactile stimuli, avoiding unnecessary muscle movements: The local bend behavior moves only a small part of the body wall away from an object touching the skin, while the rest of the animal remains stationary. Amazingly, the precision of this localized behavioral response is similar to the spatial discrimination threshold of the human fingertip, although the leech skin is innervated by an order of magnitude fewer mechanoreceptors and each midbody ganglion contains only 400 individually identified neurons in total. Prior studies suggested that this behavior is controlled by a three-layered feed-forward network, consisting of four mechanoreceptors (P cells), approximately 20 interneurons and 10 individually characterized motor neurons, all of which encode tactile stimulus location by overlapping, symmetrical tuning curves. Additionally, encoding of mechanical force was attributed to three types of mechanoreceptors reacting to distinct intensity ranges: T cells for touch, P cells for pressure, and N cells for strong, noxious skin stimulation. In this study, we provide evidences that tactile stimulus encoding in the leech is more complex than previously thought. Combined electrophysiological, anatomical, and voltage sensitive dye approaches indicate that P and T cells both play a major role in tactile information processing resulting in local bending. Our results indicate that tactile encoding neither relies on distinct force intensity ranges of different cell types, nor location encoding is restricted to spike count tuning. Instead, we propose that P and T cells form a mixed type population, which simultaneously employs temporal response features and spike counts for multiplexed encoding of touch location and force intensity. This hypothesis is supported by our finding that previously identified local bend interneurons receive input from both P and T cells. Some of these interneurons seem to integrate mechanoreceptor inputs, while others appear to use temporal response cues, presumably acting as coincidence detectors. Further voltage sensitive dye studies can test these hypotheses how a tiny nervous system performs highly precise stimulus processing. PMID:27840612

Cooperative control of blood compatibility and re-endothelialization by immobilized heparin and substrate topography.

PubMed

Ding, Yonghui; Yang, Meng; Yang, Zhilu; Luo, Rifang; Lu, Xiong; Huang, Nan; Huang, Pingbo; Leng, Yang

2015-03-01

A wide variety of environmental cues provided by the extracellular matrix, including biophysical and biochemical cues, are responsible for vascular cell behavior and function. In particular, substrate topography and surface chemistry have been shown to regulate blood and vascular compatibility individually. The combined impact of chemical and topographic cues on blood and vascular compatibility, and the interplay between these two types of cues, are subjects that are currently being explored. In the present study, a facile polydopamine-mediated approach is introduced for immobilization of heparin on topographically patterned substrates, and the combined effects of these cues on blood compatibility and re-endothelialization are systematically investigated. The results show that immobilized heparin and substrate topography cooperatively modulate anti-coagulation activity, endothelial cell (EC) attachment, proliferation, focal adhesion formation and endothelial marker expression. Meanwhile, the substrate topography is the primary determinant of cell alignment and elongation, driving in vivo-like endothelial organization. Importantly, combining immobilized heparin with substrate topography empowers substantially greater competitive ability of ECs over smooth muscle cells than each cue individually. Moreover, a model is proposed to elucidate the cooperative interplay between immobilized heparin and substrate topography in regulating cell behavior. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Blood-gene expression reveals reduced circadian rhythmicity in individuals resistant to sleep deprivation.

PubMed

Arnardottir, Erna S; Nikonova, Elena V; Shockley, Keith R; Podtelezhnikov, Alexei A; Anafi, Ron C; Tanis, Keith Q; Maislin, Greg; Stone, David J; Renger, John J; Winrow, Christopher J; Pack, Allan I

2014-10-01

To address whether changes in gene expression in blood cells with sleep loss are different in individuals resistant and sensitive to sleep deprivation. Blood draws every 4 h during a 3-day study: 24-h normal baseline, 38 h of continuous wakefulness and subsequent recovery sleep, for a total of 19 time-points per subject, with every 2-h psychomotor vigilance task (PVT) assessment when awake. Sleep laboratory. Fourteen subjects who were previously identified as behaviorally resistant (n = 7) or sensitive (n = 7) to sleep deprivation by PVT. Thirty-eight hours of continuous wakefulness. We found 4,481 unique genes with a significant 24-h diurnal rhythm during a normal sleep-wake cycle in blood (false discovery rate [FDR] < 5%). Biological pathways were enriched for biosynthetic processes during sleep. After accounting for circadian effects, two genes (SREBF1 and CPT1A, both involved in lipid metabolism) exhibited small, but significant, linear changes in expression with the duration of sleep deprivation (FDR < 5%). The main change with sleep deprivation was a reduction in the amplitude of the diurnal rhythm of expression of normally cycling probe sets. This reduction was noticeably higher in behaviorally resistant subjects than sensitive subjects, at any given P value. Furthermore, blood cell type enrichment analysis showed that the expression pattern difference between sensitive and resistant subjects is mainly found in cells of myeloid origin, such as monocytes. Individual differences in behavioral effects of sleep deprivation are associated with differences in diurnal amplitude of gene expression for genes that show circadian rhythmicity. © 2014 Associated Professional Sleep Societies, LLC.

Multi-Scale Spatio-Temporal Modeling: Lifelines of Microorganisms in Bioreactors and Tracking Molecules in Cells

NASA Astrophysics Data System (ADS)

Lapin, Alexei; Klann, Michael; Reuss, Matthias

Agent-based models are rigorous tools for simulating the interactions of individual entities, such as organisms or molecules within cells and assessing their effects on the dynamic behavior of the system as a whole. In context with bioprocess and biosystems engineering there are several interesting and important applications. This contribution aims at introducing this strategy with the aid of two examples characterized by striking distinctions in the scale of the individual entities and the mode of their interactions. In the first example a structured-segregated model is applied to travel along the lifelines of single cells in the environment of a three-dimensional turbulent field of a stirred bioreactor. The modeling approach is based on an Euler-Lagrange formulation of the system. The strategy permits one to account for the heterogeneity present in real reactors in both the fluid and cellular phases, respectively. The individual response of the cells to local variations in the extracellular concentrations is pictured by a dynamically structured model of the key reactions of the central metabolism. The approach permits analysis of the lifelines of individual cells in space and time.

Dissection of Drosophila Visual Circuits Implicative in Figure Motion

NASA Astrophysics Data System (ADS)

Kelley, Ross G.

The Drosophila visual system offers a model to study the foundations of how motion signals are computed from raw visual input and transformed into behavioral output. My studies focus on how specific cells in the Drosophila nervous system implement this input-output transformation. The individual cell types are known from classical studies using Golgi impregnations, but the assembly of motion processing circuits and the behavioral outputs remain poorly understood. Using an electronic flight simulator for flies and a white-noise analysis developed by Aptekar et al., I screen specific neurons in the optic lobes for behavioral ramifications. This approach produces wing responses to both the spatial and temporal dynamics of motion signals. The results of these experiments give Spatiotemporal Action Fields (STAFs) across the entire visual panorama. Genetically inactivating a distinct grouping of cells in the third optic ganglion, the Lobula Plate, the Horizontal System (HS) cell group, produced a robust phenotype through STAF analysis. Using the Gal4-UAS transgene expression system, we selectively inactivated the HS cells by expressing in their membrane inward rectifying potassium channels (Kir2.1) to hyperpolarize these cells, preventing their role in synaptic signaling. The results of the experiments show mutants lose steering responses to several distinct categories of figure motion and reduced behavioral responses to figure motion set against a contrasting moving background, highlighting their role in figure tracking behavior. Finally, a synapse inactivating protein, tetanus toxin (TNT), expressed in the HS cell group, produces a different behavioral phenotype than overexpressing inward rectifier. TNT, a bacterial neurotoxin, cleaves SNARE proteins resulting in loss of synaptic output of the cell, but the dendrites are intact and signal normally, preserving dendro-dendritic interactions known to sculpt the visual receptive fields of these cells. The two distinct phenotypes to each genetically targeted silencer differentiate the functional role of dendritic integration versus axonal output in this important cell group.

Power-law creep behavior of a semiflexible chain.

PubMed

Majumdar, Arnab; Suki, Béla; Rosenblatt, Noah; Alencar, Adriano M; Stamenović, Dimitrije

2008-10-01

Rheological properties of adherent cells are essential for their physiological functions, and microrheological measurements on living cells have shown that their viscoelastic responses follow a weak power law over a wide range of time scales. This power law is also influenced by mechanical prestress borne by the cytoskeleton, suggesting that cytoskeletal prestress determines the cell's viscoelasticity, but the biophysical origins of this behavior are largely unknown. We have recently developed a stochastic two-dimensional model of an elastically joined chain that links the power-law rheology to the prestress. Here we use a similar approach to study the creep response of a prestressed three-dimensional elastically jointed chain as a viscoelastic model of semiflexible polymers that comprise the prestressed cytoskeletal lattice. Using a Monte Carlo based algorithm, we show that numerical simulations of the chain's creep behavior closely correspond to the behavior observed experimentally in living cells. The power-law creep behavior results from a finite-speed propagation of free energy from the chain's end points toward the center of the chain in response to an externally applied stretching force. The property that links the power law to the prestress is the chain's stiffening with increasing prestress, which originates from entropic and enthalpic contributions. These results indicate that the essential features of cellular rheology can be explained by the viscoelastic behaviors of individual semiflexible polymers of the cytoskeleton.

The feasibility of cell phone based electronic diaries for STI/HIV research.

PubMed

Hensel, Devon J; Fortenberry, James D; Harezlak, Jaroslaw; Craig, Dorothy

2012-06-12

Self-reports of sensitive, socially stigmatized or illegal behavior are common in STI/HIV research, but can raise challenges in terms of data reliability and validity. The use of electronic data collection tools, including ecological momentary assessment (EMA), can increase the accuracy of this information by allowing a participant to self-administer a survey or diary entry, in their own environment, as close to the occurrence of the behavior as possible. In this paper, we evaluate the feasibility of using cell phone-based EMA as a tool for understanding sexual risk and STI among adult men and women. As part of a larger prospective clinical study on sexual risk behavior and incident STI in clinically recruited adult men and women, using study-provided cell phones, participants (N = 243) completed thrice-daily EMA diaries monitoring individual and partner-specific emotional attributes, non-sexual activities, non-coital or coital sexual behaviors, and contraceptive behaviors. Using these data, we assess feasibility in terms of participant compliance, behavior reactivity, general method acceptability and method efficacy for capturing behaviors. Participants were highly compliant with diary entry protocol and schedule: over the entire 12 study weeks, participants submitted 89.7% (54,914/61,236) of the expected diary entries, with an average of 18.86 of the 21 expected diaries (85.7%) each week. Submission did not differ substantially across gender, race/ethnicity and baseline sexually transmitted infection status. A sufficient volume and range of sexual behaviors were captured, with reporting trends in different legal and illegal behaviors showing small variation over time. Participants found the methodology to be acceptable, enjoyed and felt comfortable participating in the study. Achieving the correct medium of data collection can drastically improve, or degrade, the timeliness and quality of an individual's self-reported sexual risk behavior, which in turn, is a key factor in the success of intervention or education programs relying on this information. Our findings demonstrate that completion of electronic diaries via cellular phone is feasible way to describe STI/HIV risk among clinically recruited adult men and women.

Intracellular pH Response to Weak Acid Stress in Individual Vegetative Bacillus subtilis Cells

PubMed Central

Pandey, Rachna; Vischer, Norbert O. E.; Smelt, Jan P. P. M.; van Beilen, Johan W. A.; Ter Beek, Alexander; De Vos, Winnok H.; Manders, Erik M. M.

2016-01-01

ABSTRACT Intracellular pH (pHi) critically affects bacterial cell physiology. Hence, a variety of food preservation strategies are aimed at perturbing pHi homeostasis. Unfortunately, accurate pHi quantification with existing methods is suboptimal, since measurements are averages across populations of cells, not taking into account interindividual heterogeneity. Yet, physiological heterogeneity in isogenic populations is well known to be responsible for differences in growth and division kinetics of cells in response to external stressors. To assess in this context the behavior of intracellular acidity, we have developed a robust method to quantify pHi at single-cell levels in Bacillus subtilis. Bacilli spoil food, cause disease, and are well known for their ability to form highly stress-resistant spores. Using an improved version of the genetically encoded ratiometric pHluorin (IpHluorin), we have quantified pHi in individual B. subtilis cells, cultured at an external pH of 6.4, in the absence or presence of weak acid stresses. In the presence of 3 mM potassium sorbate, a decrease in pHi and an increase in the generation time of growing cells were observed. Similar effects were observed when cells were stressed with 25 mM potassium acetate. Time-resolved analysis of individual bacteria in growing colonies shows that after a transient pH decrease, long-term pH evolution is highly cell dependent. The heterogeneity at the single-cell level shows the existence of subpopulations that might be more resistant and contribute to population survival. Our approach contributes to an understanding of pHi regulation in individual bacteria and may help scrutinizing effects of existing and novel food preservation strategies. IMPORTANCE This study shows how the physiological response to commonly used weak organic acid food preservatives, such as sorbic and acetic acids, can be measured at the single-cell level. These data are key to coupling often-observed single-cell heterogeneous growth behavior upon the addition of weak organic acid food preservatives. Generally, these data are gathered in the form of plate counting of samples incubated with the acids. Here, we visualize the underlying heterogeneity in cellular pH homeostasis, opening up avenues for mechanistic analyses of the heterogeneity in the weak acid stress response. Thus, microbial risk assessment can become more robust, widening the scope of use of these well-known weak organic acid food preservatives. PMID:27565617

Measuring In Vivo Protein Dynamics Throughout the Cell Cycle Using Microfluidics.

PubMed

de Leeuw, Roy; Brazda, Peter; Charl Moolman, M; Kerssemakers, J W J; Solano, Belen; Dekker, Nynke H

2017-01-01

Studying the dynamics of intracellular processes and investigating the interaction of individual macromolecules in live cells is one of the main objectives of cell biology. These macromolecules move, assemble, disassemble, and reorganize themselves in distinct manners under specific physiological conditions throughout the cell cycle. Therefore, in vivo experimental methods that enable the study of individual molecules inside cells at controlled culturing conditions have proved to be powerful tools to obtain insights into the molecular roles of these macromolecules and how their individual behavior influence cell physiology. The importance of controlled experimental conditions is enhanced when the investigated phenomenon covers long time periods, or perhaps multiple cell cycles. An example is the detection and quantification of proteins during bacterial DNA replication. Wide-field microscopy combined with microfluidics is a suitable technique for this. During fluorescence experiments, microfluidics offer well-defined cellular orientation and immobilization, flow and medium interchangeability, and high-throughput long-term experimentation of cells. Here we present a protocol for the combined use of wide-field microscopy and microfluidics for the study of proteins of the Escherichia coli DNA replication process. We discuss the preparation and application of a microfluidic device, data acquisition steps, and image analysis procedures to determine the stoichiometry and dynamics of a replisome component throughout the cell cycle of live bacterial cells.

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

Apical constriction drives tissue-scale hydrodynamic flow to mediate cell elongation

PubMed Central

He, Bing; Doubrovinski, Konstantin; Polyakov, Oleg; Wieschaus, Eric

2014-01-01

Epithelial folding mediated by apical constriction converts flat epithelial sheets into multilayered, complex tissue structures and is employed throughout the development in most animals1. Little is known, however, how forces produced near the apical surface of the tissue are transmitted within individual cells to generate the global changes in cell shape that characterize tissue deformation. Here we apply particle tracking velocimetry in gastrulating Drosophila embryos to measure the movement of cytoplasm and plasma membrane during ventral furrow (VF) formation2, 3. We find that cytoplasmic redistribution during the lengthening phase of VF formation can be precisely described by viscous flows that quantitatively match the predictions of hydrodynamics. Cell membranes move with the ambient cytoplasm, with little resistance to or driving force on the flow. Strikingly, apical constriction produces similar flow patterns in mutant embryos that fail to form cells prior to gastrulation (“acellular” embryos), such that the global redistribution of cytoplasm mirrors the summed redistribution occurring in individual cells of wild type embryos. Our results suggest that during the lengthening phase of VF formation, hydrodynamic behavior of the cytoplasm provides the predominant mechanism transmitting apically generated forces deep into the tissue and that cell individualization is dispensable. PMID:24590071

Proinflammatory T Cell Status Associated with Early Life Adversity.

PubMed

Elwenspoek, Martha M C; Hengesch, Xenia; Leenen, Fleur A D; Schritz, Anna; Sias, Krystel; Schaan, Violetta K; Mériaux, Sophie B; Schmitz, Stephanie; Bonnemberger, Fanny; Schächinger, Hartmut; Vögele, Claus; Turner, Jonathan D; Muller, Claude P

2017-12-15

Early life adversity (ELA) has been associated with an increased risk for diseases in which the immune system plays a critical role. The ELA immune phenotype is characterized by inflammation, impaired cellular immunity, and immunosenescence. However, data on cell-specific immune effects are largely absent. Additionally, stress systems and health behaviors are altered in ELA, which may contribute to the generation of the ELA immune phenotype. The present investigation tested cell-specific immune differences in relationship to the ELA immune phenotype, altered stress parameters, and health behaviors in individuals with ELA ( n = 42) and those without a history of ELA (control, n = 73). Relative number and activation status (CD25, CD69, HLA-DR, CD11a, CD11b) of monocytes, NK cells, B cells, T cells, and their main subsets were assessed by flow cytometry. ELA was associated with significantly reduced numbers of CD69 + CD8 + T cells ( p = 0.022), increased numbers of HLA-DR + CD4 and HLA-DR + CD8 T cells ( p < 0.001), as well as increased numbers of CD25 + CD8 + T cells ( p = 0.036). ELA also showed a trend toward higher numbers of CCR4 + CXCR3 - CCR6 + CD4 T cells. Taken together, our data suggest an elevated state of immune activation in ELA, in which particularly T cells are affected. Although several aspects of the ELA immune phenotype were related to increased activation markers, neither stress nor health-risk behaviors explained the observed group differences. Thus, the state of immune activation in ELA does not seem to be secondary to alterations in the stress system or health-risk behaviors, but rather a primary effect of early life programming on immune cells. Copyright © 2017 by The American Association of Immunologists, Inc.

Clonal analysis of stem cells in differentiation and disease.

PubMed

Colom, Bartomeu; Jones, Philip H

2016-12-01

Tracking the fate of individual cells and their progeny by clonal analysis has redefined the concept of stem cells and their role in health and disease. The maintenance of cell turnover in adult tissues is achieved by the collective action of populations of stem cells with an equal likelihood of self-renewal or differentiation. Following injury stem cells exhibit striking plasticity, switching from homeostatic behavior in order to repair damaged tissues. The effects of disease states on stem cells are also being uncovered, with new insights into how somatic mutations trigger clonal expansion in early neoplasia. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Distinct learning-induced changes in stimulus selectivity and interactions of GABAergic interneuron classes in visual cortex.

PubMed

Khan, Adil G; Poort, Jasper; Chadwick, Angus; Blot, Antonin; Sahani, Maneesh; Mrsic-Flogel, Thomas D; Hofer, Sonja B

2018-06-01

How learning enhances neural representations for behaviorally relevant stimuli via activity changes of cortical cell types remains unclear. We simultaneously imaged responses of pyramidal cells (PYR) along with parvalbumin (PV), somatostatin (SOM), and vasoactive intestinal peptide (VIP) inhibitory interneurons in primary visual cortex while mice learned to discriminate visual patterns. Learning increased selectivity for task-relevant stimuli of PYR, PV and SOM subsets but not VIP cells. Strikingly, PV neurons became as selective as PYR cells, and their functional interactions reorganized, leading to the emergence of stimulus-selective PYR-PV ensembles. Conversely, SOM activity became strongly decorrelated from the network, and PYR-SOM coupling before learning predicted selectivity increases in individual PYR cells. Thus, learning differentially shapes the activity and interactions of multiple cell classes: while SOM inhibition may gate selectivity changes, PV interneurons become recruited into stimulus-specific ensembles and provide more selective inhibition as the network becomes better at discriminating behaviorally relevant stimuli.

What is a stem cell?

PubMed

Slack, Jonathan M W

2018-05-15

The historical roots of the stem cell concept are traced with respect to its usage in embryology and in hematology. The modern consensus definition of stem cells, comprising both pluripotent stem cells in culture and tissue-specific stem cells in vivo, is explained and explored. Methods for identifying stem cells are discussed with respect to cell surface markers, telomerase, label retention and transplantability, and properties of the stem cell niche are explored. The CreER method for identifying stem cells in vivo is explained, as is evidence in favor of a stochastic rather than an obligate asymmetric form of cell division. In conclusion, it is found that stem cells do not possess any unique and specific molecular markers; and stem cell behavior depends on the environment of the cell as well as the stem cell's intrinsic qualities. Furthermore, the stochastic mode of division implies that stem cell behavior is a property of a cell population not of an individual cell. In this sense, stem cells do not exist in isolation but only as a part of multicellular system. This article is categorized under: Adult Stem Cells, Tissue Renewal, and Regeneration > Tissue Stem Cells and Niches Adult Stem Cells, Tissue Renewal, and Regeneration > Methods and Principles Adult Stem Cells, Tissue Renewal, and Regeneration > Environmental Control of Stem Cells. © 2018 Wiley Periodicals, Inc.

Blood-Gene Expression Reveals Reduced Circadian Rhythmicity in Individuals Resistant to Sleep Deprivation

PubMed Central

Arnardottir, Erna S.; Nikonova, Elena V.; Shockley, Keith R.; Podtelezhnikov, Alexei A.; Anafi, Ron C.; Tanis, Keith Q.; Maislin, Greg; Stone, David J.; Renger, John J.; Winrow, Christopher J.; Pack, Allan I.

2014-01-01

Study Objectives: To address whether changes in gene expression in blood cells with sleep loss are different in individuals resistant and sensitive to sleep deprivation. Design: Blood draws every 4 h during a 3-day study: 24-h normal baseline, 38 h of continuous wakefulness and subsequent recovery sleep, for a total of 19 time-points per subject, with every 2-h psychomotor vigilance task (PVT) assessment when awake. Setting: Sleep laboratory. Participants: Fourteen subjects who were previously identified as behaviorally resistant (n = 7) or sensitive (n = 7) to sleep deprivation by PVT. Intervention: Thirty-eight hours of continuous wakefulness. Measurements and Results: We found 4,481 unique genes with a significant 24-h diurnal rhythm during a normal sleep-wake cycle in blood (false discovery rate [FDR] < 5%). Biological pathways were enriched for biosynthetic processes during sleep. After accounting for circadian effects, two genes (SREBF1 and CPT1A, both involved in lipid metabolism) exhibited small, but significant, linear changes in expression with the duration of sleep deprivation (FDR < 5%). The main change with sleep deprivation was a reduction in the amplitude of the diurnal rhythm of expression of normally cycling probe sets. This reduction was noticeably higher in behaviorally resistant subjects than sensitive subjects, at any given P value. Furthermore, blood cell type enrichment analysis showed that the expression pattern difference between sensitive and resistant subjects is mainly found in cells of myeloid origin, such as monocytes. Conclusion: Individual differences in behavioral effects of sleep deprivation are associated with differences in diurnal amplitude of gene expression for genes that show circadian rhythmicity. Citation: Arnardottir ES, Nikonova EV, Shockley KR, Podtelezhnikov AA, Anafi RC, Tanis KQ, Maislin G, Stone DJ, Renger JJ, Winrow CJ, Pack AI. Blood-gene expression reveals reduced circadian rhythmicity in individuals resistant to sleep deprivation. SLEEP 2014;37(10):1589-1600. PMID:25197809

Stable long-term blood formation by stem cells in murine steady-state hematopoiesis.

PubMed

Zavidij, Oksana; Ball, Claudia R; Herbst, Friederike; Oppel, Felix; Fessler, Sylvia; Schmidt, Manfred; von Kalle, Christof; Glimm, Hanno

2012-09-01

Hematopoietic stem cells (HSCs) generate all mature blood cells during the whole lifespan of an individual. However, the clonal contribution of individual HSC and progenitor cells in steady-state hematopoiesis is poorly understood. To investigate the activity of HSCs under steady-state conditions, murine HSC and progenitor cells were genetically marked in vivo by integrating lentiviral vectors (LVs) encoding green fluorescent protein (GFP). Hematopoietic contribution of individual marked clones was monitored by determination of lentiviral integration sites using highly sensitive linear amplification-mediated-polymerase chain reaction. A remarkably stable small proportion of hematopoietic cells expressed GFP in LV-injected animals for up to 24 months, indicating stable marking of murine steady-state hematopoiesis. Analysis of the lentiviral integration sites revealed that multiple hematopoietic clones with both myeloid and lymphoid differentiation potential contributed to long-term hematopoiesis. In contrast to intrafemoral vector injection, intravenous administration of LV preferentially targeted short-lived progenitor cells. Myelosuppressive treatment of mice prior to LV-injection did not affect the marking efficiency. Our study represents the first continuous analysis of clonal behavior of genetically marked hematopoietic cells in an unmanipulated system, providing evidence that multiple clones are simultaneously active in murine steady-state hematopoiesis. Copyright © 2012 AlphaMed Press.

Individually ventilated cages cause chronic low-grade hypoxia impacting mice hematologically and behaviorally

PubMed Central

York, Jason M.; McDaniel, Allison W.; Blevins, Neil A.; Guillet, Riley R.; Allison, Sarah O.; Cengel, Keith A.; Freund, Gregory G.

2012-01-01

Use of individually ventilated caging (IVC) systems for mouse-based laboratory investigation has dramatically increased. We found that without mice present, intra-cage oxygen concentration was comparable (21%) between IVC housing and ambient environment caging (AEC) that used wire top lids. However, when mice were housed 4-to-a-cage for 1 week, intra-cage oxygen dropped to 20.5% in IVC housing as compared to 21% for AEC housing. IVC intra-cage humidity was also elevated relative to AEC housing. Mice raised in IVC housing as compared to mice raised in AEC housing had higher RBC mass, hematocrit and hemoglobin concentrations. They also had elevated platelet counts but lower white blood cell counts. IVC mice relative to AEC mice had increased saccharin preference and increased fluid consumption but similar locomotion, food intake, social exploration and novel object recognition when tested in an AEC environment. Taken together, these data indicate that ventilated caging systems can have a 0.5% reduction from ambient oxygen concentration that is coupled to mouse red blood cell indices indicative of chronic exposure to a hypoxia. Importantly, IVC housing can impact behavioral testing for depressive-like behavior. PMID:22561683

A critical-like collective state leads to long-range cell communication in Dictyostelium discoideum aggregation

PubMed Central

De Palo, Giovanna; Yi, Darvin; Endres, Robert G.

2017-01-01

The transition from single-cell to multicellular behavior is important in early development but rarely studied. The starvation-induced aggregation of the social amoeba Dictyostelium discoideum into a multicellular slug is known to result from single-cell chemotaxis towards emitted pulses of cyclic adenosine monophosphate (cAMP). However, how exactly do transient, short-range chemical gradients lead to coherent collective movement at a macroscopic scale? Here, we developed a multiscale model verified by quantitative microscopy to describe behaviors ranging widely from chemotaxis and excitability of individual cells to aggregation of thousands of cells. To better understand the mechanism of long-range cell—cell communication and hence aggregation, we analyzed cell—cell correlations, showing evidence of self-organization at the onset of aggregation (as opposed to following a leader cell). Surprisingly, cell collectives, despite their finite size, show features of criticality known from phase transitions in physical systems. By comparing wild-type and mutant cells with impaired aggregation, we found the longest cell—cell communication distance in wild-type cells, suggesting that criticality provides an adaptive advantage and optimally sized aggregates for the dispersal of spores. PMID:28422986

From cells to tissue: A continuum model of epithelial mechanics

NASA Astrophysics Data System (ADS)

Ishihara, Shuji; Marcq, Philippe; Sugimura, Kaoru

2017-08-01

A two-dimensional continuum model of epithelial tissue mechanics was formulated using cellular-level mechanical ingredients and cell morphogenetic processes, including cellular shape changes and cellular rearrangements. This model incorporates stress and deformation tensors, which can be compared with experimental data. Focusing on the interplay between cell shape changes and cell rearrangements, we elucidated dynamical behavior underlying passive relaxation, active contraction-elongation, and tissue shear flow, including a mechanism for contraction-elongation, whereby tissue flows perpendicularly to the axis of cell elongation. This study provides an integrated scheme for the understanding of the orchestration of morphogenetic processes in individual cells to achieve epithelial tissue morphogenesis.

Acquisition of neural learning in cerebellum and cerebral cortex for smooth pursuit eye movements

PubMed Central

Li, Jennifer X.; Medina, Javier F.; Frank, Loren M.; Lisberger, Stephen G.

2011-01-01

We have evaluated the emergence of neural learning in the frontal eye fields (FEFSEM) and the floccular complex of the cerebellum while monkeys learned a precisely-timed change in the direction of pursuit eye movement. For each neuron, we measured the time course of changes in neural response across a learning session that comprised at least 100 repetitions of an instructive change in target direction. In both areas, the average population learning curves tracked the behavioral changes with high fidelity, consistent with possible roles in driving learning. However, the learning curves of individual neurons sometimes bore little relation to the smooth, monotonic progression of behavioral learning. In the FEFSEM, neural learning was episodic. For individual neurons, learning appeared at different times during the learning session and sometimes disappeared by the end of the session. Different FEFSEM neurons expressed maximal learning at different times relative to the acquisition of behavioral learning. In the floccular complex, many Purkinje cells acquired learned simple-spike responses according to the same time course as behavioral learning and retained their learned responses throughout the learning session. A minority of Purkinje cells acquired learned responses late in the learning session, after behavioral learning had reached an asymptote. We conclude that learning in single neurons can follow a very different time course from behavioral learning. Both the FEFSEM and the floccular complex contain representations of multiple temporal components of learning, with different neurons contributing to learning at different times during the acquisition of a learned movement. PMID:21900551

Imaging viscoelastic properties of live cells by AFM: power-law rheology on the nanoscale.

PubMed

Hecht, Fabian M; Rheinlaender, Johannes; Schierbaum, Nicolas; Goldmann, Wolfgang H; Fabry, Ben; Schäffer, Tilman E

2015-06-21

We developed force clamp force mapping (FCFM), an atomic force microscopy (AFM) technique for measuring the viscoelastic creep behavior of live cells with sub-micrometer spatial resolution. FCFM combines force-distance curves with an added force clamp phase during tip-sample contact. From the creep behavior measured during the force clamp phase, quantitative viscoelastic sample properties are extracted. We validate FCFM on soft polyacrylamide gels. We find that the creep behavior of living cells conforms to a power-law material model. By recording short (50-60 ms) force clamp measurements in rapid succession, we generate, for the first time, two-dimensional maps of power-law exponent and modulus scaling parameter. Although these maps reveal large spatial variations of both parameters across the cell surface, we obtain robust mean values from the several hundreds of measurements performed on each cell. Measurements on mouse embryonic fibroblasts show that the mean power-law exponents and the mean modulus scaling parameters differ greatly among individual cells, but both parameters are highly correlated: stiffer cells consistently show a smaller power-law exponent. This correlation allows us to distinguish between wild-type cells and cells that lack vinculin, a dominant protein of the focal adhesion complex, even though the mean values of viscoelastic properties between wildtype and knockout cells did not differ significantly. Therefore, FCFM spatially resolves viscoelastic sample properties and can uncover subtle mechanical signatures of proteins in living cells.

Modeling mechanical inhomogeneities in small populations of proliferating monolayers and spheroids.

PubMed

Lejeune, Emma; Linder, Christian

2018-06-01

Understanding the mechanical behavior of multicellular monolayers and spheroids is fundamental to tissue culture, organism development, and the early stages of tumor growth. Proliferating cells in monolayers and spheroids experience mechanical forces as they grow and divide and local inhomogeneities in the mechanical microenvironment can cause individual cells within the multicellular system to grow and divide at different rates. This differential growth, combined with cell division and reorganization, leads to residual stress. Multiple different modeling approaches have been taken to understand and predict the residual stresses that arise in growing multicellular systems, particularly tumor spheroids. Here, we show that by using a mechanically robust agent-based model constructed with the peridynamic framework, we gain a better understanding of residual stresses in multicellular systems as they grow from a single cell. In particular, we focus on small populations of cells (1-100 s) where population behavior is highly stochastic and prior investigation has been limited. We compare the average strain energy density of cells in monolayers and spheroids using different growth and division rules and find that, on average, cells in spheroids have a higher strain energy density than cells in monolayers. We also find that cells in the interior of a growing spheroid are, on average, in compression. Finally, we demonstrate the importance of accounting for stochastic fluctuations in the mechanical environment, particularly when the cellular response to mechanical cues is nonlinear. The results presented here serve as a starting point for both further investigation with agent-based models, and for the incorporation of major findings from agent-based models into continuum scale models when explicit representation of individual cells is not computationally feasible.

Optogenetic dissection of neural circuits underlying emotional valence and motivated behaviors

PubMed Central

Nieh, Edward H.; Kim, Sung-Yon; Namburi, Praneeth; Tye, Kay M.

2014-01-01

The neural circuits underlying emotional valence and motivated behaviors are several synapses away from both defined sensory inputs and quantifiable motor outputs. Electrophysiology has provided us with a suitable means for observing neural activity during behavior, but methods for controlling activity for the purpose of studying motivated behaviors have been inadequate: electrical stimulation lacks cellular specificity and pharmacological manipulation lacks temporal resolution. The recent emergence of optogenetic tools provides a new means for establishing causal relationships between neural activity and behavior. Optogenetics, the use of genetically-encodable light-activated proteins, permits the modulation of specific neural circuit elements with millisecond precision. The ability to control individual cell types, and even projections between distal regions, allows us to investigate functional connectivity in a causal manner. The greatest consequence of controlling neural activity with finer precision has been the characterization of individual neural circuits within anatomical brain regions as defined functional units. Within the mesolimbic dopamine system, optogenetics has helped separate subsets of dopamine neurons with distinct functions for reward, aversion and salience processing, elucidated GABA neuronal effects on behavior, and characterized connectivity with forebrain and cortical structures. Within the striatum, optogenetics has confirmed the opposing relationship between direct and indirect pathway medium spiny neurons (MSNs), in addition to characterizing the inhibition of MSNs by cholinergic interneurons. Within the hypothalamus, optogenetics has helped overcome the heterogeneity in neuronal cell-type and revealed distinct circuits mediating aggression and feeding. Within the amygdala, optogenetics has allowed the study of intra-amygdala microcircuitry as well as interconnections with distal regions involved in fear and anxiety. In this review, we will present the body of optogenetic studies that has significantly enhanced our understanding of emotional valence and motivated behaviors. PMID:23142759

Changes in the flagellar bundling time account for variations in swimming behavior of flagellated bacteria in viscous media

NASA Astrophysics Data System (ADS)

Qu, Zijie; Temel, Fatma; Henderikx, Rene; Breuer, Kenneth

2017-11-01

The motility of bacteria E.coli in viscous fluids has been widely studied, although conflicting results on the effect of viscosity on swimming speed abound. The swimming mode of wild-type E.coli is idealized as a run-and-tumble sequence in which periods of straight swimming at a constant speed are randomly interrupted by a tumble, defined as a sudden change of direction with a very low speed. Using a tracking microscope, we follow cells for extended time and find that the swimming behavior of a single cell can exhibit a variety of behaviors including run-and-tumble and ``slow-random-walk'' in which the cells move at relatively low speed without the characteristic run. Although the characteristic swimming speed varies between individuals and in different polymer solutions, we find that the skewness of the speed distribution is solely a function of viscosity, and uniquely determines the ratio of the average speed to the characteristic run speed. Using Resistive Force Theory and the cell-specific measured characteristic run speed, we show that differences in the swimming behavior observed in solutions of different viscosity are due to changes in the flagellar bundling time, which increases as the viscosity rises, due to lower rotation rate of the flagellar motor. National Science Foundation.

Viruses Roll the Dice: The Stochastic Behavior of Viral Genome Molecules Accelerates Viral Adaptation at the Cell and Tissue Levels

PubMed Central

Miyashita, Shuhei; Ishibashi, Kazuhiro; Kishino, Hirohisa; Ishikawa, Masayuki

2015-01-01

Recent studies on evolutionarily distant viral groups have shown that the number of viral genomes that establish cell infection after cell-to-cell transmission is unexpectedly small (1–20 genomes). This aspect of viral infection appears to be important for the adaptation and survival of viruses. To clarify how the number of viral genomes that establish cell infection is determined, we developed a simulation model of cell infection for tomato mosaic virus (ToMV), a positive-strand RNA virus. The model showed that stochastic processes that govern the replication or degradation of individual genomes result in the infection by a small number of genomes, while a large number of infectious genomes are introduced in the cell. It also predicted two interesting characteristics regarding cell infection patterns: stochastic variation among cells in the number of viral genomes that establish infection and stochastic inequality in the accumulation of their progenies in each cell. Both characteristics were validated experimentally by inoculating tobacco cells with a library of nucleotide sequence–tagged ToMV and analyzing the viral genomes that accumulated in each cell using a high-throughput sequencer. An additional simulation model revealed that these two characteristics enhance selection during tissue infection. The cell infection model also predicted a mechanism that enhances selection at the cellular level: a small difference in the replication abilities of coinfected variants results in a large difference in individual accumulation via the multiple-round formation of the replication complex (i.e., the replication machinery). Importantly, this predicted effect was observed in vivo. The cell infection model was robust to changes in the parameter values, suggesting that other viruses could adopt similar adaptation mechanisms. Taken together, these data reveal a comprehensive picture of viral infection processes including replication, cell-to-cell transmission, and evolution, which are based on the stochastic behavior of the viral genome molecules in each cell. PMID:25781391

Aluminum and temperature alteration of cell membrane permeability of Quercus rubra

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

Junping Chen; Sucoff, E.I.; Stadelmann, E.J.

1991-06-01

Al toxicity is the major factor limiting plant growth in acid soils. This report extends research on Al-induced changes in membrane behavior of intact root cortex cells of Northern red oak (Quercus rubra). Membrane permeability was determined by the plasmometric method for individual intact cells at temperatures from 2 or 4 to 35 C. Al (0.37 millimolar) significantly increased membrane permeability to urea and monoethyl urea and decreased permeability to water. Al significantly altered the activation energy required to transport water (+ 32%), urea (+ 9%), and monoethyl urea ({minus}7%) across cell membranes. Above 9 C, Al increased the lipidmore » partiality of the cell membranes; below 7 C, Al decreased it. Al narrowed by 6 C the temperature range over which plasmolysis occurred without membrane damage. These changes in membrane behavior are explainable if Al reduced membrane lipid fluidity and kink frequency and increases packing density and the occurrence of straight lipid chains.« less

Intracellular pH Response to Weak Acid Stress in Individual Vegetative Bacillus subtilis Cells.

PubMed

Pandey, Rachna; Vischer, Norbert O E; Smelt, Jan P P M; van Beilen, Johan W A; Ter Beek, Alexander; De Vos, Winnok H; Brul, Stanley; Manders, Erik M M

2016-11-01

Intracellular pH (pH i ) critically affects bacterial cell physiology. Hence, a variety of food preservation strategies are aimed at perturbing pH i homeostasis. Unfortunately, accurate pH i quantification with existing methods is suboptimal, since measurements are averages across populations of cells, not taking into account interindividual heterogeneity. Yet, physiological heterogeneity in isogenic populations is well known to be responsible for differences in growth and division kinetics of cells in response to external stressors. To assess in this context the behavior of intracellular acidity, we have developed a robust method to quantify pH i at single-cell levels in Bacillus subtilis Bacilli spoil food, cause disease, and are well known for their ability to form highly stress-resistant spores. Using an improved version of the genetically encoded ratiometric pHluorin (IpHluorin), we have quantified pH i in individual B. subtilis cells, cultured at an external pH of 6.4, in the absence or presence of weak acid stresses. In the presence of 3 mM potassium sorbate, a decrease in pH i and an increase in the generation time of growing cells were observed. Similar effects were observed when cells were stressed with 25 mM potassium acetate. Time-resolved analysis of individual bacteria in growing colonies shows that after a transient pH decrease, long-term pH evolution is highly cell dependent. The heterogeneity at the single-cell level shows the existence of subpopulations that might be more resistant and contribute to population survival. Our approach contributes to an understanding of pH i regulation in individual bacteria and may help scrutinizing effects of existing and novel food preservation strategies. This study shows how the physiological response to commonly used weak organic acid food preservatives, such as sorbic and acetic acids, can be measured at the single-cell level. These data are key to coupling often-observed single-cell heterogeneous growth behavior upon the addition of weak organic acid food preservatives. Generally, these data are gathered in the form of plate counting of samples incubated with the acids. Here, we visualize the underlying heterogeneity in cellular pH homeostasis, opening up avenues for mechanistic analyses of the heterogeneity in the weak acid stress response. Thus, microbial risk assessment can become more robust, widening the scope of use of these well-known weak organic acid food preservatives. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Universal behavior of the osmotically compressed cell and its analogy to the colloidal glass transition

PubMed Central

Zhou, E. H.; Trepat, X.; Park, C. Y.; Lenormand, G.; Oliver, M. N.; Mijailovich, S. M.; Hardin, C.; Weitz, D. A.; Butler, J. P.; Fredberg, J. J.

2009-01-01

Mechanical robustness of the cell under different modes of stress and deformation is essential to its survival and function. Under tension, mechanical rigidity is provided by the cytoskeletal network; with increasing stress, this network stiffens, providing increased resistance to deformation. However, a cell must also resist compression, which will inevitably occur whenever cell volume is decreased during such biologically important processes as anhydrobiosis and apoptosis. Under compression, individual filaments can buckle, thereby reducing the stiffness and weakening the cytoskeletal network. However, the intracellular space is crowded with macromolecules and organelles that can resist compression. A simple picture describing their behavior is that of colloidal particles; colloids exhibit a sharp increase in viscosity with increasing volume fraction, ultimately undergoing a glass transition and becoming a solid. We investigate the consequences of these 2 competing effects and show that as a cell is compressed by hyperosmotic stress it becomes progressively more rigid. Although this stiffening behavior depends somewhat on cell type, starting conditions, molecular motors, and cytoskeletal contributions, its dependence on solid volume fraction is exponential in every instance. This universal behavior suggests that compression-induced weakening of the network is overwhelmed by crowding-induced stiffening of the cytoplasm. We also show that compression dramatically slows intracellular relaxation processes. The increase in stiffness, combined with the slowing of relaxation processes, is reminiscent of a glass transition of colloidal suspensions, but only when comprised of deformable particles. Our work provides a means to probe the physical nature of the cytoplasm under compression, and leads to results that are universal across cell type. PMID:19520830

The role of the interaction network in the emergence of diversity of behavior

PubMed Central

Tabacof, Pedro; Von Zuben, Fernando J.

2017-01-01

How can systems in which individuals’ inner workings are very similar to each other, as neural networks or ant colonies, produce so many qualitatively different behaviors, giving rise to roles and specialization? In this work, we bring new perspectives to this question by focusing on the underlying network that defines how individuals in these systems interact. We applied a genetic algorithm to optimize rules and connections of cellular automata in order to solve the density classification task, a classical problem used to study emergent behaviors in decentralized computational systems. The networks used were all generated by the introduction of shortcuts in an originally regular topology, following the small-world model. Even though all cells follow the exact same rules, we observed the existence of different classes of cells’ behaviors in the best cellular automata found—most cells were responsible for memory and others for integration of information. Through the analysis of structural measures and patterns of connections (motifs) in successful cellular automata, we observed that the distribution of shortcuts between distant regions and the speed in which a cell can gather information from different parts of the system seem to be the main factors for the specialization we observed, demonstrating how heterogeneity in a network can create heterogeneity of behavior. PMID:28234962

Workflow for high-content, individual cell quantification of fluorescent markers from universal microscope data, supported by open source software.

PubMed

Stockwell, Simon R; Mittnacht, Sibylle

2014-12-16

Advances in understanding the control mechanisms governing the behavior of cells in adherent mammalian tissue culture models are becoming increasingly dependent on modes of single-cell analysis. Methods which deliver composite data reflecting the mean values of biomarkers from cell populations risk losing subpopulation dynamics that reflect the heterogeneity of the studied biological system. In keeping with this, traditional approaches are being replaced by, or supported with, more sophisticated forms of cellular assay developed to allow assessment by high-content microscopy. These assays potentially generate large numbers of images of fluorescent biomarkers, which enabled by accompanying proprietary software packages, allows for multi-parametric measurements per cell. However, the relatively high capital costs and overspecialization of many of these devices have prevented their accessibility to many investigators. Described here is a universally applicable workflow for the quantification of multiple fluorescent marker intensities from specific subcellular regions of individual cells suitable for use with images from most fluorescent microscopes. Key to this workflow is the implementation of the freely available Cell Profiler software(1) to distinguish individual cells in these images, segment them into defined subcellular regions and deliver fluorescence marker intensity values specific to these regions. The extraction of individual cell intensity values from image data is the central purpose of this workflow and will be illustrated with the analysis of control data from a siRNA screen for G1 checkpoint regulators in adherent human cells. However, the workflow presented here can be applied to analysis of data from other means of cell perturbation (e.g., compound screens) and other forms of fluorescence based cellular markers and thus should be useful for a wide range of laboratories.

Mapping cell surface adhesion by rotation tracking and adhesion footprinting

NASA Astrophysics Data System (ADS)

Li, Isaac T. S.; Ha, Taekjip; Chemla, Yann R.

2017-03-01

Rolling adhesion, in which cells passively roll along surfaces under shear flow, is a critical process involved in inflammatory responses and cancer metastasis. Surface adhesion properties regulated by adhesion receptors and membrane tethers are critical in understanding cell rolling behavior. Locally, adhesion molecules are distributed at the tips of membrane tethers. However, how functional adhesion properties are globally distributed on the individual cell’s surface is unknown. Here, we developed a label-free technique to determine the spatial distribution of adhesive properties on rolling cell surfaces. Using dark-field imaging and particle tracking, we extract the rotational motion of individual rolling cells. The rotational information allows us to construct an adhesion map along the contact circumference of a single cell. To complement this approach, we also developed a fluorescent adhesion footprint assay to record the molecular adhesion events from cell rolling. Applying the combination of the two methods on human promyelocytic leukemia cells, our results surprisingly reveal that adhesion is non-uniformly distributed in patches on the cell surfaces. Our label-free adhesion mapping methods are applicable to the variety of cell types that undergo rolling adhesion and provide a quantitative picture of cell surface adhesion at the functional and molecular level.

Videomicroscopic extraction of specific information on cell proliferation and migration in vitro

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

Debeir, Olivier; Megalizzi, Veronique; Warzee, Nadine

2008-10-01

In vitro cell imaging is a useful exploratory tool for cell behavior monitoring with a wide range of applications in cell biology and pharmacology. Combined with appropriate image analysis techniques, this approach has been shown to provide useful information on the detection and dynamic analysis of cell events. In this context, numerous efforts have been focused on cell migration analysis. In contrast, the cell division process has been the subject of fewer investigations. The present work focuses on this latter aspect and shows that, in complement to cell migration data, interesting information related to cell division can be extracted frommore » phase-contrast time-lapse image series, in particular cell division duration, which is not provided by standard cell assays using endpoint analyses. We illustrate our approach by analyzing the effects induced by two sigma-1 receptor ligands (haloperidol and 4-IBP) on the behavior of two glioma cell lines using two in vitro cell models, i.e., the low-density individual cell model and the high-density scratch wound model. This illustration also shows that the data provided by our approach are suggestive as to the mechanism of action of compounds, and are thus capable of informing the appropriate selection of further time-consuming and more expensive biological evaluations required to elucidate a mechanism.« less

Sexting, substance use, and sexual risk behavior in young adults

PubMed Central

Benotsch, Eric G.; Snipes, Daniel J.; Martin, Aaron M.; Bull, Sheana S.

2012-01-01

Purpose Cell phone use has become more widespread over the past decade. Young adults are frequently early adopters of new technologies, including cell phones. Most prior research examining sexting, the act of sending sexually explicit or suggestive images via text message, has focused on the legal or social consequences of this behavior. The current study focused on the public health implications of sexting by examining associations between sexting, substance use, and sexual risk behavior in youth. Methods Young adults (N=763) completed online questionnaires assessing demographics, cell phone use (e.g., texting, sexting), substance use, and sexual risk behaviors. Results Sexting was reported by a substantial minority of participants (44%). Compared to their non-sexting counterparts, participants who engaged in sexting were more likely to report recent substance use and high-risk sexual behaviors, including unprotected sex and sex with multiple partners. Of those who engaged in sexting, a considerable percentage (31.8%) reported having sex with a new partner for the first time after sexting with that person. In multivariate analyses, sexting was associated with high-risk sexual behavior after accounting for demographic factors, total texting behaviors, and substance use. Conclusions Results suggest that sexting is robustly associated with high-risk sexual behavior. Many individuals exchange explicit or provocative photos with long-term sexual partners, but at least some participants in this study were incurring new sexual risks subsequent to sexting. Additional research is needed to understand the contexts in which sexting occurs, motivations for sexting, and relationship of sexting to risk behavior. PMID:23299017

Sexting, substance use, and sexual risk behavior in young adults.

PubMed

Benotsch, Eric G; Snipes, Daniel J; Martin, Aaron M; Bull, Sheana S

2013-03-01

Cell phone use has become more widespread over the past decade. Young adults are frequently early adopters of new technologies, including cell phones. Most previous research examining sexting, the act of sending sexually explicit or suggestive images via text message, has focused on the legal or social consequences of this behavior. The current study focused on the public health implications of sexting by examining associations between sexting, substance use, and sexual risk behavior in youth. Young adults (N = 763) completed online questionnaires assessing demographics, cell phone use (e.g., texting, sexting), substance use, and sexual risk behaviors. Sexting was reported by a substantial minority of participants (44%). Compared with their nonsexting counterparts, participants who engaged in sexting were more likely to report recent substance use and high-risk sexual behaviors, including unprotected sex and sex with multiple partners. Of those who engaged in sexting, a considerable percentage (31.8%) reported having sex with a new partner for the first time after sexting with that person. In multivariate analyses, sexting was associated with high-risk sexual behavior, after accounting for demographic factors, total texting behaviors, and substance use. Results suggest that sexting is robustly associated with high-risk sexual behavior. Many individuals exchange explicit or provocative photos with long-term sexual partners, but at least some participants in this study were incurring new sexual risks after sexting. Additional research is needed to understand the contexts in which sexting occurs, motivations for sexting, and relationship of sexting to risk behavior. Copyright © 2013 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

Synthetic battery cycling techniques

NASA Technical Reports Server (NTRS)

Leibecki, H. F.; Thaller, L. H.

1982-01-01

Synthetic battery cycling makes use of the fast growing capability of computer graphics to illustrate some of the basic characteristics of operation of individual electrodes within an operating electrochemical cell. It can also simulate the operation of an entire string of cells that are used as the energy storage subsystem of a power system. The group of techniques that as a class have been referred to as Synthetic Battery Cycling is developed in part to try to bridge the gap of understanding that exists between single cell characteristics and battery system behavior.

Collective Motion in Behaviorally Heterogeneous Systems

NASA Astrophysics Data System (ADS)

Copenhagen, Katherine

Collective motion is a widespread phenomenon in nature where individuals actively propel themselves, gather together and move as a group. Some examples of collective motion are bird flocks, fish schools, bacteria swarms, cell clusters, and crowds of people. Many models seek to understand the effects of activity in collective systems including things such as environmental disorder, density, and interaction details primarily at infinite size limits and with uniform populations. In this dissertation I investigate the effects of finite sizes and behavioral heterogeneity as it exists in nature. Behavioral heterogeneity can originate from several different sources. Mixed populations of individuals can have inherently different behaviors such as mutant bacteria, injured fish, or agents that prefer individualistic behavior over coordinated motion. Alternatively, agents may modify their own behavior based on some local environmental dependency, such as local substrate, or density. In cases such as mutant cheaters in bacteria or malfunctioning drones in swarms, mixed populations of behaviorally heterogeneous agents can be modelled as arising in the form of aligning and non-aligning agents. When this kind of heterogeneity is introduced, there is a critical carrying capacity of non-aligners above which the system is unable to form a cohesive ordered group. However, if the cohesion of the group is relaxed to allow for fracture, the system will actively sort out non-aligning agents the system will exist at a critical non-aligner fraction. A similar heterogeneity could result in a mixture of high and low noise individuals. In this case there is also a critical carry capacity beyond which the system is unable to reach an ordered state, however the nature of this transition depends on the model details. Agents which are part of an ordered collective may vary their behavior as the group changes environments such as a flock of birds flying into a cloud. Using a unique model of a flock where the group behaves as a rigid disk reveals interesting behaviors as the system crosses a boundary between interfaces. The collective rotates and reorients or becomes stuck on the boundary as it crosses. I also investigate the effects of variable behavior depending on local density, and find that a frustration driven transient rotational phase arises in clusters where agents with low local density move faster than those with high local density as in cell clusters. All together I have shown that behavioral heterogeneity in collective motion can lead to unique phases and behaviors that are not seen in their homogeneous counterparts.

Stigmergy

PubMed Central

Gloag, Erin S; Javed, Muhammad A; Wang, Huabin; Gee, Michelle L; Wade, Scott A; Turnbull, Lynne; Whitchurch, Cynthia B

2013-01-01

Bacterial biofilms are complex multicellular communities that are often associated with the emergence of large-scale patterns across the biofilm. How bacteria self-organize to form these structured communities is an area of active research. We have recently determined that the emergence of an intricate network of trails that forms during the twitching motility mediated expansion of Pseudomonas aeruginosa biofilms is attributed to an interconnected furrow system that is forged in the solidified nutrient media by aggregates of cells as they migrate across the media surface. This network acts as a means for self-organization of collective behavior during biofilm expansion as the cells following these vanguard aggregates were preferentially confined within the furrow network resulting in the formation of an intricate network of trails of cells. Here we further explore the process by which the intricate network of trails emerges. We have determined that the formation of the intricate network of furrows is associated with significant remodeling of the sub-stratum underlying the biofilm. The concept of stigmergy has been used to describe a variety of self-organization processes observed in higher organisms and abiotic systems that involve indirect communication via persistent cues in the environment left by individuals that influence the behavior of other individuals of the group at a later point in time. We propose that the concept of stigmergy can also be applied to describe self-organization of bacterial biofilms and can be included in the repertoire of systems used by bacteria to coordinate complex multicellular behaviors. PMID:24753789

Mechanism for Collective Cell Alignment in Myxococcus xanthus Bacteria

PubMed Central

Balagam, Rajesh; Igoshin, Oleg A.

2015-01-01

Myxococcus xanthus cells self-organize into aligned groups, clusters, at various stages of their lifecycle. Formation of these clusters is crucial for the complex dynamic multi-cellular behavior of these bacteria. However, the mechanism underlying the cell alignment and clustering is not fully understood. Motivated by studies of clustering in self-propelled rods, we hypothesized that M. xanthus cells can align and form clusters through pure mechanical interactions among cells and between cells and substrate. We test this hypothesis using an agent-based simulation framework in which each agent is based on the biophysical model of an individual M. xanthus cell. We show that model agents, under realistic cell flexibility values, can align and form cell clusters but only when periodic reversals of cell directions are suppressed. However, by extending our model to introduce the observed ability of cells to deposit and follow slime trails, we show that effective trail-following leads to clusters in reversing cells. Furthermore, we conclude that mechanical cell alignment combined with slime-trail-following is sufficient to explain the distinct clustering behaviors observed for wild-type and non-reversing M. xanthus mutants in recent experiments. Our results are robust to variation in model parameters, match the experimentally observed trends and can be applied to understand surface motility patterns of other bacterial species. PMID:26308508

Tailoring Mathematical Models to Stem-Cell Derived Cardiomyocyte Lines Can Improve Predictions of Drug-Induced Changes to Their Electrophysiology.

PubMed

Lei, Chon Lok; Wang, Ken; Clerx, Michael; Johnstone, Ross H; Hortigon-Vinagre, Maria P; Zamora, Victor; Allan, Andrew; Smith, Godfrey L; Gavaghan, David J; Mirams, Gary R; Polonchuk, Liudmila

2017-01-01

Human induced pluripotent stem cell derived cardiomyocytes (iPSC-CMs) have applications in disease modeling, cell therapy, drug screening and personalized medicine. Computational models can be used to interpret experimental findings in iPSC-CMs, provide mechanistic insights, and translate these findings to adult cardiomyocyte (CM) electrophysiology. However, different cell lines display different expression of ion channels, pumps and receptors, and show differences in electrophysiology. In this exploratory study, we use a mathematical model based on iPSC-CMs from Cellular Dynamic International (CDI, iCell), and compare its predictions to novel experimental recordings made with the Axiogenesis Cor.4U line. We show that tailoring this model to the specific cell line, even using limited data and a relatively simple approach, leads to improved predictions of baseline behavior and response to drugs. This demonstrates the need and the feasibility to tailor models to individual cell lines, although a more refined approach will be needed to characterize individual currents, address differences in ion current kinetics, and further improve these results.

Hybrid multiscale modeling and prediction of cancer cell behavior

PubMed Central

Habibi, Jafar

2017-01-01

Background Understanding cancer development crossing several spatial-temporal scales is of great practical significance to better understand and treat cancers. It is difficult to tackle this challenge with pure biological means. Moreover, hybrid modeling techniques have been proposed that combine the advantages of the continuum and the discrete methods to model multiscale problems. Methods In light of these problems, we have proposed a new hybrid vascular model to facilitate the multiscale modeling and simulation of cancer development with respect to the agent-based, cellular automata and machine learning methods. The purpose of this simulation is to create a dataset that can be used for prediction of cell phenotypes. By using a proposed Q-learning based on SVR-NSGA-II method, the cells have the capability to predict their phenotypes autonomously that is, to act on its own without external direction in response to situations it encounters. Results Computational simulations of the model were performed in order to analyze its performance. The most striking feature of our results is that each cell can select its phenotype at each time step according to its condition. We provide evidence that the prediction of cell phenotypes is reliable. Conclusion Our proposed model, which we term a hybrid multiscale modeling of cancer cell behavior, has the potential to combine the best features of both continuum and discrete models. The in silico results indicate that the 3D model can represent key features of cancer growth, angiogenesis, and its related micro-environment and show that the findings are in good agreement with biological tumor behavior. To the best of our knowledge, this paper is the first hybrid vascular multiscale modeling of cancer cell behavior that has the capability to predict cell phenotypes individually by a self-generated dataset. PMID:28846712

Hybrid multiscale modeling and prediction of cancer cell behavior.

PubMed

Zangooei, Mohammad Hossein; Habibi, Jafar

2017-01-01

Understanding cancer development crossing several spatial-temporal scales is of great practical significance to better understand and treat cancers. It is difficult to tackle this challenge with pure biological means. Moreover, hybrid modeling techniques have been proposed that combine the advantages of the continuum and the discrete methods to model multiscale problems. In light of these problems, we have proposed a new hybrid vascular model to facilitate the multiscale modeling and simulation of cancer development with respect to the agent-based, cellular automata and machine learning methods. The purpose of this simulation is to create a dataset that can be used for prediction of cell phenotypes. By using a proposed Q-learning based on SVR-NSGA-II method, the cells have the capability to predict their phenotypes autonomously that is, to act on its own without external direction in response to situations it encounters. Computational simulations of the model were performed in order to analyze its performance. The most striking feature of our results is that each cell can select its phenotype at each time step according to its condition. We provide evidence that the prediction of cell phenotypes is reliable. Our proposed model, which we term a hybrid multiscale modeling of cancer cell behavior, has the potential to combine the best features of both continuum and discrete models. The in silico results indicate that the 3D model can represent key features of cancer growth, angiogenesis, and its related micro-environment and show that the findings are in good agreement with biological tumor behavior. To the best of our knowledge, this paper is the first hybrid vascular multiscale modeling of cancer cell behavior that has the capability to predict cell phenotypes individually by a self-generated dataset.

Multiaxial Polarity Determines Individual Cellular and Nuclear Chirality

PubMed Central

Raymond, Michael J.; Ray, Poulomi; Kaur, Gurleen; Fredericks, Michael; Singh, Ajay V.; Wan, Leo Q.

2016-01-01

Intrinsic cell chirality has been implicated in the left-right (LR) asymmetry of embryonic development. Impaired cell chirality could lead to severe birth defects in laterality. Previously, we detected cell chirality with an in vitro micropatterning system. Here, we demonstrate for the first time that chirality can be quantified as the coordination of multiaxial polarization of individual cells and nuclei. Using an object labeling, connected component based method, we characterized cell chirality based on cell and nuclear shape polarization and nuclear positioning of each cell in multicellular patterns of epithelial cells. We found that the cells adopted a LR bias the boundaries by positioning the sharp end towards the leading edge and leaving the nucleus at the rear. This behavior is consistent with the directional migration observed previously on the boundary of micropatterns. Although the nucleus is chirally aligned, it is not strongly biased towards or away from the boundary. As the result of the rear positioning of nuclei, the nuclear positioning has an opposite chirality to that of cell alignment. Overall, our results have revealed deep insights of chiral morphogenesis as the coordination of multiaxial polarization at the cellular and subcellular levels. PMID:28360944

Multiaxial Polarity Determines Individual Cellular and Nuclear Chirality.

PubMed

Raymond, Michael J; Ray, Poulomi; Kaur, Gurleen; Fredericks, Michael; Singh, Ajay V; Wan, Leo Q

2017-02-01

Intrinsic cell chirality has been implicated in the left-right (LR) asymmetry of embryonic development. Impaired cell chirality could lead to severe birth defects in laterality. Previously, we detected cell chirality with an in vitro micropatterning system. Here, we demonstrate for the first time that chirality can be quantified as the coordination of multiaxial polarization of individual cells and nuclei. Using an object labeling, connected component based method, we characterized cell chirality based on cell and nuclear shape polarization and nuclear positioning of each cell in multicellular patterns of epithelial cells. We found that the cells adopted a LR bias the boundaries by positioning the sharp end towards the leading edge and leaving the nucleus at the rear. This behavior is consistent with the directional migration observed previously on the boundary of micropatterns. Although the nucleus is chirally aligned, it is not strongly biased towards or away from the boundary. As the result of the rear positioning of nuclei, the nuclear positioning has an opposite chirality to that of cell alignment. Overall, our results have revealed deep insights of chiral morphogenesis as the coordination of multiaxial polarization at the cellular and subcellular levels.

Cell Migration in Tissues: Explant Culture and Live Imaging.

PubMed

Staneva, Ralitza; Barbazan, Jorge; Simon, Anthony; Vignjevic, Danijela Matic; Krndija, Denis

2018-01-01

Cell migration is a process that ensures correct cell localization and function in development and homeostasis. In disease such as cancer, cells acquire an upregulated migratory capacity that leads to their dissemination throughout the body. Live imaging of cell migration allows for better understanding of cell behaviors in development, adult tissue homeostasis and disease. We have optimized live imaging procedures to track cell migration in adult murine tissue explants derived from: (1) healthy gut; (2) primary intestinal carcinoma; and (3) the liver, a common metastatic site. To track epithelial cell migration in the gut, we generated an inducible fluorescent reporter mouse, enabling us to visualize and track individual cells in unperturbed gut epithelium. To image intratumoral cancer cells, we use a spontaneous intestinal cancer model based on the activation of Notch1 and deletion of p53 in the mouse intestinal epithelium, which gives rise to aggressive carcinoma. Interaction of cancer cells with a metastatic niche, the mouse liver, is addressed using a liver colonization model. In summary, we describe a method for long-term 3D imaging of tissue explants by two-photon excitation microscopy. Explant culturing and imaging can help understand dynamic behavior of cells in homeostasis and disease, and would be applicable to various tissues.

Platelet-mediated transformation of mtDNA-less human cells: Analysis of phenotypic variability among clones from normal individuals-and complementation behavior of the tRNA[sup Lys] mutation causing myoclonic epilepsy and ragged red fibers

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

Chomyn, A.; Lai, S.T.; Shakeley, R.

1994-06-01

In the present work, the authors demonstrate the possibility of using human blood platelets as mitochondrial donors for the repopulation of mtDNA-less ([rho][sup o]) cells. The noninvasive nature of platelet isolation, combined with the prolonged viability of platelet mitochondria and the simplicity and efficiency of the mitochondria-transfer procedure, has substantially increased the applicability of the [rho][sup o] cell transformation approach for mitochondrial genetic analysis and for the study of mtDNA-linked diseases. This approach has been applied to platelets from several normal human individuals and one individual affected by the myoclonic-epilepsy-and-ragged-red-fibers (MERRF) encephalomyopathy. A certain variability in respiratory capacity was observedmore » among the platelet-derived [rho][sup o] cell transformants from a given normal subject, and it was shown to be unrelated to their mtDNA content. The results of sequential transfer of mitochondria from selected transformants into a [rho][sup o] cell line different from the first [rho][sup o] acceptor strongly suggest that this variability reflected, at least in part, differences in nuclear gene content and/or activity among the original recipient cells. A much greater variability in respiratory capacity was observed among the transformants derived from the MERRF patient and was found to be related to the presence and amount of the mitochondrial tRNA[sup Lys] mutation associated with the MERRF syndrome. An analysis of the relationship between proportion of mtDNA carrying the MERRF mutation and degree of respiratory activity in various transformations derived from the MERRF patient revealed an unusual complementation behavior of the tRNA[sup Lys] mutation, possibly reflecting the distribution of mutant mtDNA among the platelet mitochondria. 29 refs., 4 figs., 1 tab.« less

Insulin, Central Dopamine D2 Receptors, and Monetary Reward Discounting in Obesity

PubMed Central

Eisenstein, Sarah A.; Gredysa, Danuta M.; Antenor–Dorsey, Jo Ann; Green, Leonard; Arbeláez, Ana Maria; Koller, Jonathan M.; Black, Kevin J.; Perlmutter, Joel S.; Moerlein, Stephen M.; Hershey, Tamara

2015-01-01

Animal research finds that insulin regulates dopamine signaling and reward behavior, but similar research in humans is lacking. We investigated whether individual differences in body mass index, percent body fat, pancreatic β-cell function, and dopamine D2 receptor binding were related to reward discounting in obese and non-obese adult men and women. Obese (n = 27; body mass index>30) and non-obese (n = 20; body mass index<30) adults were assessed for percent body fat with dual-energy X-ray absorptiometry and for β-cell function using disposition index. Choice of larger, but delayed or less certain, monetary rewards relative to immediate, certain smaller monetary rewards was measured using delayed and probabilistic reward discounting tasks. Positron emission tomography using a non-displaceable D2-specific radioligand, [11C](N-methyl)benperidol quantified striatal D2 receptor binding. Groups differed in body mass index, percent body fat, and disposition index, but not in striatal D2 receptor specific binding or reward discounting. Higher percent body fat in non-obese women related to preference for a smaller, certain reward over a larger, less likely one (greater probabilistic discounting). Lower β-cell function in the total sample and lower insulin sensitivity in obese related to stronger preference for an immediate and smaller monetary reward over delayed receipt of a larger one (greater delay discounting). In obese adults, higher striatal D2 receptor binding related to greater delay discounting. Interestingly, striatal D2 receptor binding was not significantly related to body mass index, percent body fat, or β-cell function in either group. Our findings indicate that individual differences in percent body fat, β-cell function, and striatal D2 receptor binding may each contribute to altered reward discounting behavior in non-obese and obese individuals. These results raise interesting questions about whether and how striatal D2 receptor binding and metabolic factors, including β-cell function, interact to affect reward discounting in humans. PMID:26192187

Insulin, Central Dopamine D2 Receptors, and Monetary Reward Discounting in Obesity.

PubMed

Eisenstein, Sarah A; Gredysa, Danuta M; Antenor-Dorsey, Jo Ann; Green, Leonard; Arbeláez, Ana Maria; Koller, Jonathan M; Black, Kevin J; Perlmutter, Joel S; Moerlein, Stephen M; Hershey, Tamara

2015-01-01

Animal research finds that insulin regulates dopamine signaling and reward behavior, but similar research in humans is lacking. We investigated whether individual differences in body mass index, percent body fat, pancreatic β-cell function, and dopamine D2 receptor binding were related to reward discounting in obese and non-obese adult men and women. Obese (n = 27; body mass index>30) and non-obese (n = 20; body mass index<30) adults were assessed for percent body fat with dual-energy X-ray absorptiometry and for β-cell function using disposition index. Choice of larger, but delayed or less certain, monetary rewards relative to immediate, certain smaller monetary rewards was measured using delayed and probabilistic reward discounting tasks. Positron emission tomography using a non-displaceable D2-specific radioligand, [11C](N-methyl)benperidol quantified striatal D2 receptor binding. Groups differed in body mass index, percent body fat, and disposition index, but not in striatal D2 receptor specific binding or reward discounting. Higher percent body fat in non-obese women related to preference for a smaller, certain reward over a larger, less likely one (greater probabilistic discounting). Lower β-cell function in the total sample and lower insulin sensitivity in obese related to stronger preference for an immediate and smaller monetary reward over delayed receipt of a larger one (greater delay discounting). In obese adults, higher striatal D2 receptor binding related to greater delay discounting. Interestingly, striatal D2 receptor binding was not significantly related to body mass index, percent body fat, or β-cell function in either group. Our findings indicate that individual differences in percent body fat, β-cell function, and striatal D2 receptor binding may each contribute to altered reward discounting behavior in non-obese and obese individuals. These results raise interesting questions about whether and how striatal D2 receptor binding and metabolic factors, including β-cell function, interact to affect reward discounting in humans.

Single-Cell Microfluidics to Study the Effects of Genome Deletion on Bacterial Growth Behavior.

PubMed

Yuan, Xiaofei; Couto, Jillian M; Glidle, Andrew; Song, Yanqing; Sloan, William; Yin, Huabing

2017-12-15

By directly monitoring single cell growth in a microfluidic platform, we interrogated genome-deletion effects in Escherichia coli strains. We compared the growth dynamics of a wild type strain with a clean genome strain, and their derived mutants at the single-cell level. A decreased average growth rate and extended average lag time were found for the clean genome strain, compared to those of the wild type strain. Direct correlation between the growth rate and lag time of individual cells showed that the clean genome population was more heterogeneous. Cell culturability (the ratio of growing cells to the sum of growing and nongrowing cells) of the clean genome population was also lower. Interestingly, after the random mutations induced by a glucose starvation treatment, for the clean genome population mutants that had survived the competition of chemostat culture, each parameter markedly improved (i.e., the average growth rate and cell culturability increased, and the lag time and heterogeneity decreased). However, this effect was not seen in the wild type strain; the wild type mutants cultured in a chemostat retained a high diversity of growth phenotypes. These results suggest that quasi-essential genes that were deleted in the clean genome might be required to retain a diversity of growth characteristics at the individual cell level under environmental stress. These observations highlight that single-cell microfluidics can reveal subtle individual cellular responses, enabling in-depth understanding of the population.

Feeding the beast: can microglia in the senescent brain be regulated by diet?

PubMed

Johnson, Rodney W

2015-01-01

Microglial cells, resident macrophages in the central nervous system (CNS), are relatively quiescent but can respond to signals from the peripheral immune system and induce neuroinflammation. In aging, microglia tend to transition to the M1 pro-inflammatory state and become hypersensitive to messages emerging from immune-to-brain signaling pathways. Thus, whereas in younger individuals where microglia respond to signals from the peripheral immune system and induce a well-controlled neuroinflammatory response that is adaptive (e.g., when well controlled, fever and sickness behavior facilitate recovery from infection), in older individuals with an infection, microglia overreact and produce excessive levels of inflammatory cytokines causing behavioral pathology including cognitive dysfunction. Importantly, recent studies indicate a number of naturally occurring bioactive compounds present in certain foods have anti-inflammatory properties and are capable of mitigating brain microglial cells. These include, e.g., flavonoid and non-flavonoid compounds in fruits and vegetables, and n-3 polyunsaturated fatty acids (PUFA) in oily fish. Thus, dietary bioactives have potential to restore the population of microglial cells in the senescent brain to a more quiescent state. The pragmatic concept to constrain microglia through dietary intervention is significant because neuroinflammation and cognitive deficits are co-morbid factors in many chronic inflammatory diseases. Controlling microglial cell reactivity has important consequences for preserving adult neurogenesis, neuronal structure and function, and cognition. Copyright © 2014 Elsevier Inc. All rights reserved.

Mouse and human HSPC immobilization in liquid culture by CD43- or CD44-antibody coating.

PubMed

Loeffler, Dirk; Wang, Weijia; Hopf, Alois; Hilsenbeck, Oliver; Bourgine, Paul E; Rudolf, Fabian; Martin, Ivan; Schroeder, Timm

2018-03-29

Keeping track of individual cell identifications is imperative to the study of dynamic single-cell behavior over time. Highly motile hematopoietic stem and progenitor cells (HSPCs) migrate quickly and do not adhere, and thus must be imaged very frequently to keep cell identifications. Even worse, they are also flushed away during medium exchange. To overcome these limitations, we tested antibody coating for reducing HSPC motility in vitro. Anti-CD43- and anti-CD44-antibody coating reduced the cell motility of mouse and human HSPCs in a concentration-dependent manner. This enables 2-dimensional (2D) colony formation without cell mixing in liquid cultures, massively increases time-lapse imaging throughput, and also maintains cell positions during media exchange. Anti-CD43 but not anti-CD44 coating reduces mouse HSPC proliferation with increasing concentrations. No relevant effects on cell survival or myeloid and megakaryocyte differentiation of hematopoietic stem cells and multipotent progenitors 1-5 were detected. Human umbilical cord hematopoietic CD34 + cell survival, proliferation, and differentiation were not affected by either coating. This approach both massively simplifies and accelerates continuous analysis of suspension cells, and enables the study of their behavior in dynamic rather than static culture conditions over time. © 2018 by The American Society of Hematology.

Multidimensional Single-Cell Analysis of BCR Signaling Reveals Proximal Activation Defect As a Hallmark of Chronic Lymphocytic Leukemia B Cells

PubMed Central

Palomba, M. Lia; Piersanti, Kelly; Ziegler, Carly G. K.; Decker, Hugo; Cotari, Jesse W.; Bantilan, Kurt; Rijo, Ivelise; Gardner, Jeff R.; Heaney, Mark; Bemis, Debra; Balderas, Robert; Malek, Sami N.; Seymour, Erlene; Zelenetz, Andrew D.

2014-01-01

Purpose Chronic Lymphocytic Leukemia (CLL) is defined by a perturbed B-cell receptor-mediated signaling machinery. We aimed to model differential signaling behavior between B cells from CLL and healthy individuals to pinpoint modes of dysregulation. Experimental Design We developed an experimental methodology combining immunophenotyping, multiplexed phosphospecific flow cytometry, and multifactorial statistical modeling. Utilizing patterns of signaling network covariance, we modeled BCR signaling in 67 CLL patients using Partial Least Squares Regression (PLSR). Results from multidimensional modeling were validated using an independent test cohort of 38 patients. Results We identified a dynamic and variable imbalance between proximal (pSYK, pBTK) and distal (pPLCγ2, pBLNK, ppERK) phosphoresponses. PLSR identified the relationship between upstream tyrosine kinase SYK and its target, PLCγ2, as maximally predictive and sufficient to distinguish CLL from healthy samples, pointing to this juncture in the signaling pathway as a hallmark of CLL B cells. Specific BCR pathway signaling signatures that correlate with the disease and its degree of aggressiveness were identified. Heterogeneity in the PLSR response variable within the B cell population is both a characteristic mark of healthy samples and predictive of disease aggressiveness. Conclusion Single-cell multidimensional analysis of BCR signaling permitted focused analysis of the variability and heterogeneity of signaling behavior from patient-to-patient, and from cell-to-cell. Disruption of the pSYK/pPLCγ2 relationship is uncovered as a robust hallmark of CLL B cell signaling behavior. Together, these observations implicate novel elements of the BCR signal transduction as potential therapeutic targets. PMID:24489640

Intracellular dynamics and fate of polystyrene nanoparticles in A549 Lung epithelial cells monitored by image (cross-) correlation spectroscopy and single particle tracking.

PubMed

Deville, Sarah; Penjweini, Rozhin; Smisdom, Nick; Notelaers, Kristof; Nelissen, Inge; Hooyberghs, Jef; Ameloot, Marcel

2015-10-01

Novel insights in nanoparticle (NP) uptake routes of cells, their intracellular trafficking and subcellular targeting can be obtained through the investigation of their temporal and spatial behavior. In this work, we present the application of image (cross-) correlation spectroscopy (IC(C)S) and single particle tracking (SPT) to monitor the intracellular dynamics of polystyrene (PS) NPs in the human lung carcinoma A549 cell line. The ensemble kinetic behavior of NPs inside the cell was characterized by temporal and spatiotemporal image correlation spectroscopy (TICS and STICS). Moreover, a more direct interpretation of the diffusion and flow detected in the NP motion was obtained by SPT by monitoring individual NPs. Both techniques demonstrate that the PS NP transport in A549 cells is mainly dependent on microtubule-assisted transport. By applying spatiotemporal image cross-correlation spectroscopy (STICCS), the correlated motions of NPs with the early endosomes, late endosomes and lysosomes are identified. PS NPs were equally distributed among the endolysosomal compartment during the time interval of the experiments. The cotransport of the NPs with the lysosomes is significantly larger compared to the other cell organelles. In the present study we show that the complementarity of ICS-based techniques and SPT enables a consistent elaborate model of the complex behavior of NPs inside biological systems. Copyright © 2015 Elsevier B.V. All rights reserved.

Dynamic Partitioning of a GPI-Anchored Protein in Glycosphingolipid-Rich Microdomains Imaged by Single-Quantum Dot Tracking

PubMed Central

Pinaud, Fabien; Michalet, Xavier; Iyer, Gopal; Margeat, Emmanuel; Moore, Hsiao-Ping; Weiss, Shimon

2009-01-01

Recent experimental developments have led to a revision of the classical fluid mosaic model proposed by Singer and Nicholson 35 years ago. In particular, it is now well established that lipids and proteins diffuse heterogeneously in cell plasma membranes. Their complex motion patterns reflect the dynamic structure and composition of the membrane itself, as well as the presence of the underlying cytoskeleton scaffold and that of the extracellular matrix. How the structural organization of plasma membranes influences the diffusion of individual proteins remains a challenging, yet central question for cell signaling and its regulation. Here we have developed a raft-associated glycosylphosphatidyl Inositol-anchored avidin test probe (Av-GPI), whose diffusion patterns indirectly reports on the structure and dynamics of putative raft microdomains in the membrane of HeLa cells. Labeling with quantum dots (qdots) allowed high-resolution and long-term tracking of individual Av-GPI and the classification of their various diffusive behaviors. Using dual-color total internal reflection fluorescence (TIRF) microscopy, we studied the correlation between the diffusion of individual Av-GPI and the location of glycosphingolipid GM1-rich microdomains and caveolae. We show that Av-GPI exhibit a fast and a slow diffusion regime in different membrane regions, and that slowing down of their diffusion is correlated with entry in GM1-rich microdomains located in close proximity to, but distinct, from caveolae. We further show that Av-GPI dynamically partition in and out of these microdomains in a cholesterol-dependent manner. Our results provide direct evidence that cholesterol/sphingolipid-rich microdomains can compartmentalize the diffusion of GPI-anchored proteins in living cells and that the dynamic partitioning raft model appropriately describes the diffusive behavior of some raft-associated proteins across the plasma membrane. PMID:19416475

Dynamic partitioning of a glycosyl-phosphatidylinositol-anchored protein in glycosphingolipid-rich microdomains imaged by single-quantum dot tracking.

PubMed

Pinaud, Fabien; Michalet, Xavier; Iyer, Gopal; Margeat, Emmanuel; Moore, Hsiao-Ping; Weiss, Shimon

2009-06-01

Recent experimental developments have led to a revision of the classical fluid mosaic model proposed by Singer and Nicholson more than 35 years ago. In particular, it is now well established that lipids and proteins diffuse heterogeneously in cell plasma membranes. Their complex motion patterns reflect the dynamic structure and composition of the membrane itself, as well as the presence of the underlying cytoskeleton scaffold and that of the extracellular matrix. How the structural organization of plasma membranes influences the diffusion of individual proteins remains a challenging, yet central, question for cell signaling and its regulation. Here we have developed a raft-associated glycosyl-phosphatidyl-inositol-anchored avidin test probe (Av-GPI), whose diffusion patterns indirectly report on the structure and dynamics of putative raft microdomains in the membrane of HeLa cells. Labeling with quantum dots (qdots) allowed high-resolution and long-term tracking of individual Av-GPI and the classification of their various diffusive behaviors. Using dual-color total internal reflection fluorescence (TIRF) microscopy, we studied the correlation between the diffusion of individual Av-GPI and the location of glycosphingolipid GM1-rich microdomains and caveolae. We show that Av-GPI exhibit a fast and a slow diffusion regime in different membrane regions, and that slowing down of their diffusion is correlated with entry in GM1-rich microdomains located in close proximity to, but distinct, from caveolae. We further show that Av-GPI dynamically partition in and out of these microdomains in a cholesterol-dependent manner. Our results provide direct evidence that cholesterol-/sphingolipid-rich microdomains can compartmentalize the diffusion of GPI-anchored proteins in living cells and that the dynamic partitioning raft model appropriately describes the diffusive behavior of some raft-associated proteins across the plasma membrane.

T Lymphocyte Activation Threshold and Membrane Reorganization Perturbations in Unique Culture Model

NASA Technical Reports Server (NTRS)

Adams, C. L.; Sams, C. F.

2000-01-01

Quantitative activation thresholds and cellular membrane reorganization are mechanisms by which resting T cells modulate their response to activating stimuli. Here we demonstrate perturbations of these cellular processes in a unique culture system that non-invasively inhibits T lymphocyte activation. During clinorotation, the T cell activation threshold is increased 5-fold. This increased threshold involves a mechanism independent of TCR triggering. Recruitment of lipid rafts to the activation site is impaired during clinorotation but does occur with increased stimulation. This study describes a situation in which an individual cell senses a change in its physical environment and alters its cell biological behavior.

Do endothelial cells dream of eclectic shape?

PubMed

Bentley, Katie; Philippides, Andrew; Ravasz Regan, Erzsébet

2014-04-28

Endothelial cells (ECs) exhibit dramatic plasticity of form at the single- and collective-cell level during new vessel growth, adult vascular homeostasis, and pathology. Understanding how, when, and why individual ECs coordinate decisions to change shape, in relation to the myriad of dynamic environmental signals, is key to understanding normal and pathological blood vessel behavior. However, this is a complex spatial and temporal problem. In this review we show that the multidisciplinary field of Adaptive Systems offers a refreshing perspective, common biological language, and straightforward toolkit that cell biologists can use to untangle the complexity of dynamic, morphogenetic systems. Copyright © 2014 Elsevier Inc. All rights reserved.

A hybrid agent-based approach for modeling microbiological systems.

PubMed

Guo, Zaiyi; Sloot, Peter M A; Tay, Joc Cing

2008-11-21

Models for systems biology commonly adopt Differential Equations or Agent-Based modeling approaches for simulating the processes as a whole. Models based on differential equations presuppose phenomenological intracellular behavioral mechanisms, while models based on Multi-Agent approach often use directly translated, and quantitatively less precise if-then logical rule constructs. We propose an extendible systems model based on a hybrid agent-based approach where biological cells are modeled as individuals (agents) while molecules are represented by quantities. This hybridization in entity representation entails a combined modeling strategy with agent-based behavioral rules and differential equations, thereby balancing the requirements of extendible model granularity with computational tractability. We demonstrate the efficacy of this approach with models of chemotaxis involving an assay of 10(3) cells and 1.2x10(6) molecules. The model produces cell migration patterns that are comparable to laboratory observations.

Modeling of combined capacity fade with thermal effects for a cycled LixC6-LiyMn2O4 cell

NASA Astrophysics Data System (ADS)

Vazquez-Arenas, Jorge; Fowler, Michael; Mao, Xiaofeng; Chen, Shih-ken

2012-10-01

Li-ion batteries are the most promising technology for use in electric vehicles in the near future, and as such it is critical to understand their performance at both beginning of life (BOL) and end of life (EOL). In this work different thermal and capacity fade effects (e.g. SEI formation, dissolution of LiyMn2O4 particles) are modeled to account comprehensively for the behavior of a LixC6-LiyMn2O4 cell. The comparison between baseline and complex models is systematically used to analyze individual contributions and perform a deeper evaluation of the variables affecting the capacity fade with thermal inputs during typical cycle life tests. Some modifications in the original model are proposed to better describe the behavior of the cell and speed up the calculations.

Photomixing of chlamydomonas rheinhardtii suspensions

NASA Astrophysics Data System (ADS)

Dervaux, Julien; Capellazzi Resta, Marina; Abou, Bérengère; Brunet, Philippe

2014-11-01

Chlamydomonas rheinhardtii is a fast swimming unicellular alga able to bias its swimming direction in gradients of light intensity, an ability know as phototaxis. We have investigated experimentally both the swimming behavior of individual cells and the macroscopic response of shallow suspensions of these micro-organisms in response to a localized light source. At low light intensity, algae exhibit positive phototaxis and accumulate beneath the excitation light. In weakly concentrated thin layers, the balance between phototaxis and cell motility results in steady symmetrical patterns compatible with a purely diffusive model using effective diffusion coefficients extracted from the analysis of individual cell trajectories. However, at higher cell density and layer depth, collective effects induce convective flows around the light source. These flows disturb the cell concentration patterns which spread and may then becomes unstable. Using large passive tracer particles, we have characterized the velocity fields associated with this forced bioconvection and their dependence on the cell density and layer depth. By tuning the light distribution, this mechanism of photo-bioconvection allows a fine control over the local fluid flows, and thus the mixing efficiency, in algal suspensions.

Characterizing the mechanical behavior of the zebrafish germ layers

NASA Astrophysics Data System (ADS)

Kealhofer, David; Serwane, Friedhelm; Mongera, Alessandro; Rowghanian, Payam; Lucio, Adam; Campàs, Otger

Organ morphogenesis and the development of the animal body plan involve complex spatial and temporal control of tissue- and cell-level mechanics. A prime example is the generation of stresses by individual cells to reorganize the tissue. These processes have remained poorly understood due to a lack of techniques to characterize the local constitutive law of the material, which relates local cellular forces to the resulting tissue flows. We have developed a method for quantitative, local in vivo study of material properties in living tissue using magnetic droplet probes. We use this technique to study the material properties of the different zebrafish germ layers using aggregates of zebrafish mesendodermal and ectodermal cells as a model system. These aggregates are ideal for controlled studies of the mechanics of individual germ layers because of the homogeneity of the cell type and the simple spherical geometry. Furthermore, the numerous molecular tools and transgenic lines already developed for this model organism can be applied to these aggregates, allowing us to characterize the contributions of cell cortex tension and cell adhesion to the mechanical properties of the zebrafish germ layers.

Investigation of acoustic metasurfaces with constituent material properties considered

NASA Astrophysics Data System (ADS)

Gerard, Nikhil JRK; Li, Yong; Jing, Yun

2018-03-01

This paper examines the transmission behavior of two acoustic metasurfaces and their constituent structural units while including the various material properties that could affect their functionality. The unit cells and the metasurfaces are modeled numerically, and the impact of the structural interaction and thermoviscosity on sound transmission and phase modulation is studied. Each of these effects is viewed individually in order to better understand their influence. Various cases are presented, and the change in the behavior of the metasurfaces is investigated. The deviations from the ideal desired results are examined and highlighted to show that it is important to incorporate these effects to better predict the behavior of acoustic metasurfaces.

Spatiotemporal relationships between growth and microtubule orientation as revealed in living root cells of Arabidopsis thaliana transformed with green-fluorescent-protein gene construct GFP-MBD

NASA Technical Reports Server (NTRS)

Granger, C. L.; Cyr, R. J.

2001-01-01

Arabidopsis thaliana plants were transformed with GFP-MBD (J. Marc et al., Plant Cell 10: 1927-1939, 1998) under the control of a constitutive (35S) or copper-inducible promoter. GFP-specific fluorescence distributions, levels, and persistence were determined and found to vary with age, tissue type, transgenic line, and individual plant. With the exception of an increased frequency of abnormal roots of 35S GFP-MBD plants grown on kanamycin-containing media, expression of GFP-MBD does not appear to affect plant phenotype. The number of leaves, branches, bolts, and siliques as well as overall height, leaf size, and seed set are similar between wild-type and transgenic plants as is the rate of root growth. Thus, we conclude that the transgenic plants can serve as a living model system in which the dynamic behavior of microtubules can be visualized. Confocal microscopy was used to simultaneously monitor growth and microtubule behavior within individual cells as they passed through the elongation zone of the Arabidopsis root. Generally, microtubules reoriented from transverse to oblique or longitudinal orientations as growth declined. Microtubule reorientation initiated at the ends of the cell did not necessarily occur simultaneously in adjacent neighboring cells and did not involve complete disintegration and repolymerization of microtubule arrays. Although growth rates correlated with microtubule reorientation, the two processes were not tightly coupled in terms of their temporal relationships, suggesting that other factor(s) may be involved in regulating both events. Additionally, microtubule orientation was more defined in cells whose growth was accelerating and less stringent in cells whose growth was decelerating, indicating that microtubule-orienting factor(s) may be sensitive to growth acceleration, rather than growth per se.

Stem cell responses to plasma surface modified electrospun polyurethane scaffolds.

PubMed

Zandén, Carl; Hellström Erkenstam, Nina; Padel, Thomas; Wittgenstein, Julia; Liu, Johan; Kuhn, H Georg

2014-07-01

The topographical effects from functional materials on stem cell behavior are currently of interest in tissue engineering and regenerative medicine. Here we investigate the influence of argon, oxygen, and hydrogen plasma surface modification of electrospun polyurethane fibers on human embryonic stem cell (hESC) and rat postnatal neural stem cell (NSC) responses. The plasma gases were found to induce three combinations of fiber surface functionalities and roughness textures. On randomly oriented fibers, plasma treatments lead to substantially increased hESC attachment and proliferation as compared to native fibers. Argon plasma was found to induce the most optimal combination of surface functionality and roughness for cell expansion. Contact guided migration of cells and alignment of cell processes were observed on aligned fibers. Neuronal differentiation around 5% was found for all samples and was not significantly affected by the induced variations of surface functional group distribution or individual fiber topography. In this study the influence of argon, oxygen, and hydrogen plasma surface modification of electrospun polyurethane fibers on human embryonic stem cell and rat postnatal neural stem cell (NSC) responses is studied with the goal of clarifying the potential effects of functional materials on stem cell behavior, a topic of substantial interest in tissue engineering and regenerative medicine. Copyright © 2014 Elsevier Inc. All rights reserved.

Size and competitive mating success in the yeast Saccharomyces cerevisiae.

PubMed

Smith, Carl; Pomiankowski, Andrew; Greig, Duncan

2014-03-01

In unicellular organisms like yeast, mating with the right partner is critical to future fitness because each individual can only mate once. Because cell size is important for viability, mating with a partner of the right size could be a significant advantage. To investigate this idea, we manipulated the size of unmated yeast cells and showed that their viability depended on environmental conditions; large cells do better on rich medium and small cells do better on poor medium. We also found that the fitness of offspring is determined by the size of their parents. Finally, we demonstrated that when a focal cell of one mating type was placed with a large and a small cell of the opposite mating type, it was more likely to mate with the cell that was closer to the optimum size for growth in a given environment. This pattern was not generated by differences in passive mating efficiency of large and small cells across environments but by competitive mating behavior, mate preference, or both. We conclude that the most likely mechanism underlying this interesting behavior is that yeast cells compete for mates by producing pheromone signals advertising their viability, and cells with the opportunity to choose prefer to mate with stronger signalers because such matings produce more viable offspring.

A Method for Detecting Circulating Tumor Cells Based on the Measurement of Single-Cell Metabolism in Droplet-Based Microfluidics.

PubMed

Del Ben, Fabio; Turetta, Matteo; Celetti, Giorgia; Piruska, Aigars; Bulfoni, Michela; Cesselli, Daniela; Huck, Wilhelm T S; Scoles, Giacinto

2016-07-18

The number of circulating tumor cells (CTCs) in blood is strongly correlated with the progress of metastatic cancer. Current methods to detect CTCs are based on immunostaining or discrimination of physical properties. Herein, a label-free method is presented exploiting the abnormal metabolic behavior of cancer cells. A single-cell analysis technique is used to measure the secretion of acid from individual living tumor cells compartmentalized in microfluidically prepared, monodisperse, picoliter (pL) droplets. As few as 10 tumor cells can be detected in a background of 200 000 white blood cells and proof-of-concept data is shown on the detection of CTCs in the blood of metastatic patients. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

About the Nutritional Science Research Group | Division of Cancer Prevention

Cancer.gov

The Nutritional Science Research Group (NSRG) promotes and supports studies establishing a comprehensive understanding of the precise role of diet and food components in modulating cancer risk and tumor cell behavior. This focus includes approaches to characterize molecular targets and variability in individual responses to nutrients and dietary patterns. |

Chemokine (c-c motif) receptor 2 mediates mechanical and cold hypersensitivity in sickle cell disease mice.

PubMed

Sadler, Katelyn E; Zappia, Katherine J; O'Hara, Crystal L; Langer, Sarah N; Weyer, Andy D; Hillery, Cheryl A; Stucky, Cheryl L

2018-04-23

Approximately one third of individuals with sickle cell disease (SCD) develop chronic pain. This debilitating pain is inadequately treated because the underlying mechanisms driving the pain are poorly understood. In addition to persistent pain, SCD patients are also in a tonically pro-inflammatory state. Previous studies have revealed that there are elevated plasma levels of many inflammatory mediators including chemokine (c-c motif) ligand 2 (CCL2) in individuals with SCD. Using a transgenic mouse model of SCD, we investigated the contributions of CCL2 signaling to SCD-related pain. Inhibition of the chemokine receptor 2 (CCR2), but not CCR4, alleviated the behavioral mechanical and cold hypersensitivity in SCD. Further, acute CCR2 blockade reversed both the behavioral and the in vitro responsiveness of sensory neurons to an agonist of TRPV1, a neuronal ion channel previously implicated in SCD pain. These results provide insight into the immune-mediated regulation of hypersensitivity in SCD and could inform future development of analgesics or therapeutic measures to prevent chronic pain.

Recognition of mite-infested brood by honeybee (Apis mellifera) workers may involve thermal sensing.

PubMed

Bauer, Daniel; Wegener, Jakob; Bienefeld, Kaspar

2018-05-01

Hygienic behavior, i.e. the removal of diseased or damaged brood by worker honey bees (Apis mellifera), is seen as one of the principal behavioral elements of this species' social immunity. Identification of the stimuli that trigger it would be helpful in searching for biochemical and molecular markers of this important breeding trait. While many studies at the genomic, transcriptomic, and behavioral level have pointed to the implication of chemical cues, we here hypothesized that thermal cues are alternatively/additionally involved. To test this hypothesis, we first measured whether infestation by the mite Varroa destructor (a condition known to induce hygienic behavior) leads to a thermal gradient between affected and unaffected brood. We found that infested brood cells were between 0.03 and 0.19 °C warmer than uninfested controls. Next, we tested whether artificially heating an area of a brood comb would increase the removal of infested or uninfested brood as compared to an unheated control area, and found that this was not the case. Finally, we investigated whether the heating of individual brood cells, as opposed to comb areas, would influence brood removal from cells adjacent to the heated one. This was the case for uninfested, though not for infested cells. We conclude that infestation by V. destructor leads to a heating of brood cells that should be perceivable by bees, and that small-scale temperature gradients can influence brood removal. This makes it appear possible that thermal cues play a role in triggering hygienic behavior of honey bees directed at varroa-infested larvae/pupae, although our results are insufficient to prove such an involvement. Copyright © 2018. Published by Elsevier Ltd.

An investigation of Hebbian phase sequences as assembly graphs

PubMed Central

Almeida-Filho, Daniel G.; Lopes-dos-Santos, Vitor; Vasconcelos, Nivaldo A. P.; Miranda, José G. V.; Tort, Adriano B. L.; Ribeiro, Sidarta

2014-01-01

Hebb proposed that synapses between neurons that fire synchronously are strengthened, forming cell assemblies and phase sequences. The former, on a shorter scale, are ensembles of synchronized cells that function transiently as a closed processing system; the latter, on a larger scale, correspond to the sequential activation of cell assemblies able to represent percepts and behaviors. Nowadays, the recording of large neuronal populations allows for the detection of multiple cell assemblies. Within Hebb's theory, the next logical step is the analysis of phase sequences. Here we detected phase sequences as consecutive assembly activation patterns, and then analyzed their graph attributes in relation to behavior. We investigated action potentials recorded from the adult rat hippocampus and neocortex before, during and after novel object exploration (experimental periods). Within assembly graphs, each assembly corresponded to a node, and each edge corresponded to the temporal sequence of consecutive node activations. The sum of all assembly activations was proportional to firing rates, but the activity of individual assemblies was not. Assembly repertoire was stable across experimental periods, suggesting that novel experience does not create new assemblies in the adult rat. Assembly graph attributes, on the other hand, varied significantly across behavioral states and experimental periods, and were separable enough to correctly classify experimental periods (Naïve Bayes classifier; maximum AUROCs ranging from 0.55 to 0.99) and behavioral states (waking, slow wave sleep, and rapid eye movement sleep; maximum AUROCs ranging from 0.64 to 0.98). Our findings agree with Hebb's view that assemblies correspond to primitive building blocks of representation, nearly unchanged in the adult, while phase sequences are labile across behavioral states and change after novel experience. The results are compatible with a role for phase sequences in behavior and cognition. PMID:24782715

Modeling heterogeneous responsiveness of intrinsic apoptosis pathway

PubMed Central

2013-01-01

Background Apoptosis is a cell suicide mechanism that enables multicellular organisms to maintain homeostasis and to eliminate individual cells that threaten the organism’s survival. Dependent on the type of stimulus, apoptosis can be propagated by extrinsic pathway or intrinsic pathway. The comprehensive understanding of the molecular mechanism of apoptotic signaling allows for development of mathematical models, aiming to elucidate dynamical and systems properties of apoptotic signaling networks. There have been extensive efforts in modeling deterministic apoptosis network accounting for average behavior of a population of cells. Cellular networks, however, are inherently stochastic and significant cell-to-cell variability in apoptosis response has been observed at single cell level. Results To address the inevitable randomness in the intrinsic apoptosis mechanism, we develop a theoretical and computational modeling framework of intrinsic apoptosis pathway at single-cell level, accounting for both deterministic and stochastic behavior. Our deterministic model, adapted from the well-accepted Fussenegger model, shows that an additional positive feedback between the executioner caspase and the initiator caspase plays a fundamental role in yielding the desired property of bistability. We then examine the impact of intrinsic fluctuations of biochemical reactions, viewed as intrinsic noise, and natural variation of protein concentrations, viewed as extrinsic noise, on behavior of the intrinsic apoptosis network. Histograms of the steady-state output at varying input levels show that the intrinsic noise could elicit a wider region of bistability over that of the deterministic model. However, the system stochasticity due to intrinsic fluctuations, such as the noise of steady-state response and the randomness of response delay, shows that the intrinsic noise in general is insufficient to produce significant cell-to-cell variations at physiologically relevant level of molecular numbers. Furthermore, the extrinsic noise represented by random variations of two key apoptotic proteins, namely Cytochrome C and inhibitor of apoptosis proteins (IAP), is modeled separately or in combination with intrinsic noise. The resultant stochasticity in the timing of intrinsic apoptosis response shows that the fluctuating protein variations can induce cell-to-cell stochastic variability at a quantitative level agreeing with experiments. Finally, simulations illustrate that the mean abundance of fluctuating IAP protein is positively correlated with the degree of cellular stochasticity of the intrinsic apoptosis pathway. Conclusions Our theoretical and computational study shows that the pronounced non-genetic heterogeneity in intrinsic apoptosis responses among individual cells plausibly arises from extrinsic rather than intrinsic origin of fluctuations. In addition, it predicts that the IAP protein could serve as a potential therapeutic target for suppression of the cell-to-cell variation in the intrinsic apoptosis responsiveness. PMID:23875784

"Active" drops as phantom models for living cells: a mesoscopic particle-based approach.

PubMed

Dallavalle, Marco; Lugli, Francesca; Rapino, Stefania; Zerbetto, Francesco

2016-04-21

Drops and biological cells share some morphological features and visco-elastic properties. The modelling of drops by mesoscopic non-atomistic models has been carried out to a high degree of success in recent years. We extend such treatment and discuss a simple, drop-like model to describe the interactions of the outer layer of cells with the surfaces of materials. Cells are treated as active mechanical objects that are able to generate adhesion forces. They appear with their true size and are made of "parcels of fluids" or beads. The beads are described by (very) few quantities/parameters related to fundamental chemical forces such as hydrophilicity and lipophilicity that represent an average of the properties of a patch of material or an area of the cell(s) surface. The investigation of adhesion dynamics, motion of individual cells, and the collective behavior of clusters of cells on materials is possible. In the simulations, the drops become active soft matter objects and different from regular droplets they do not fuse when in contact, their trajectories are not Brownian, and they can be forced "to secrete" molecules, to name some of the properties targeted by the modeling. The behavior that emerges from the simulations allows ascribing some cell properties to their mechanics, which are related to their biological features.

Single Cell Assay for Analyzing Single Cell Exosome and Endocrine Secretion and Cancer Markers

NASA Astrophysics Data System (ADS)

Chiu, Yu-Jui

To understand the inhomogeneity of cells in biological systems, there is a growing demand for the capability to characterize the properties of individual single cells. Since single cell studies require continuous monitoring of the cell behaviors instead of a snapshot test at a single time point, an effective single-cell assay that can support time lapsed studies in a high throughput manner is desired. Most currently available single-cell technologies cannot provide proper environments to sustain cell growth and cannot provide, for appropriate cell types, proliferation of single cells and convenient, non-invasive tests of single cell behaviors from molecular markers. In this dissertation, I present a highly versatile single-cell assay that can accommodate different cellular types, enable easy and efficient single cell loading and culturing, and be suitable for the study of effects of in-vitro environmental factors in combination with drug screening. The salient features of the assay are the non-invasive collection and surveying of single cell secretions at different time points and massively parallel translocation of single cells by user defined criteria, producing very high compatibility to the downstream process such as single cell qPCR and sequencing. Above all, the acquired information is quantitative -- for example, one of the studies is measured by the number of exosomes each single cell secretes for a given time period. Therefore, our single-cell assay provides a convenient, low-cost, and enabling tool for quantitative, time lapsed studies of single cell properties.

Early cytoplasmic uncoating is associated with infectivity of HIV-1

PubMed Central

Cianci, Gianguido C.; Anderson, Meegan R.; Hope, Thomas J.

2017-01-01

After fusion, HIV delivers its conical capsid into the cytoplasm. To release the contained reverse-transcribing viral genome, the capsid must disassemble in a process termed uncoating. Defining the kinetics, dynamics, and cellular location of uncoating of virions leading to infection has been confounded by defective, noninfectious particles and the stochastic minefield blocking access to host DNA. We used live-cell fluorescent imaging of intravirion fluid phase markers to monitor HIV-1 uncoating at the individual particle level. We find that HIV-1 uncoating of particles leading to infection is a cytoplasmic process that occurs ∼30 min postfusion. Most, but not all, of the capsid protein is rapidly shed in tissue culture and primary target cells, independent of entry pathway. Extended time-lapse imaging with less than one virion per cell allows identification of infected cells by Gag-GFP expression and directly links individual particle behavior to infectivity, providing unprecedented insights into the biology of HIV infection. PMID:28784755

Dynamic Properties of Electrotonic Coupling between Cells of Early Xenopus Embryos

PubMed Central

DiCaprio, R. A.; French, A. S.; Sanders, E. J.

1974-01-01

Frequency response functions were measured between the cells of Xenopus laevis embryos during the first two cleavage stages. Linear systems theory was then used to produce electronic models which account for the electrical behavior of the systems. Coupling between the cells may be explained by models which have simple resistive elements joining each cell to its neighbors. The vitelline, or fertilization, membrane which surrounds the embryos has no detectable resistance to the passage of electric current. The electrical properties of the four-cell embryo can only be explained by the existence of individual junctions linking each pair of cells. This arrangement suggests that electrotonic coupling is important in the development of the embryos, at least until the four-cell stage. ImagesFIGURE 5FIGURE 14FIGURE 15 PMID:19431351

Prospects for neural stem cell-based therapies for neurological diseases.

PubMed

Imitola, Jaime

2007-10-01

Neural stem and progenitor cells have great potential for the treatment of neurological disorders. However, many obstacles remain to translate this field to the patient's bedside, including rationales for using neural stem cells in individual neurological disorders; the challenges of neural stem cell biology; and the caveats of current strategies of isolation and culturing neural precursors. Addressing these challenges is critical for the translation of neural stem cell biology to the clinic. Recent work using neural stem cells has yielded novel biologic concepts such as the importance of the reciprocal interaction between neural stem cells and the neurodegenerative environment. The prospect of using transplants of neural stem cells and progenitors to treat neurological diseases requires a better understanding of the molecular mechanisms of both neural stem cell behavior in experimental models and the intrinsic repair capacity of the injured brain.

A Microfluidic Technique to Probe Cell Deformability

PubMed Central

Hoelzle, David J.; Varghese, Bino A.; Chan, Clara K.; Rowat, Amy C.

2014-01-01

Here we detail the design, fabrication, and use of a microfluidic device to evaluate the deformability of a large number of individual cells in an efficient manner. Typically, data for ~102 cells can be acquired within a 1 hr experiment. An automated image analysis program enables efficient post-experiment analysis of image data, enabling processing to be complete within a few hours. Our device geometry is unique in that cells must deform through a series of micron-scale constrictions, thereby enabling the initial deformation and time-dependent relaxation of individual cells to be assayed. The applicability of this method to human promyelocytic leukemia (HL-60) cells is demonstrated. Driving cells to deform through micron-scale constrictions using pressure-driven flow, we observe that human promyelocytic (HL-60) cells momentarily occlude the first constriction for a median time of 9.3 msec before passaging more quickly through the subsequent constrictions with a median transit time of 4.0 msec per constriction. By contrast, all-trans retinoic acid-treated (neutrophil-type) HL-60 cells occlude the first constriction for only 4.3 msec before passaging through the subsequent constrictions with a median transit time of 3.3 msec. This method can provide insight into the viscoelastic nature of cells, and ultimately reveal the molecular origins of this behavior. PMID:25226269

A Novel Ex Vivo Method for Visualizing Live-Cell Calcium Response Behavior in Intact Human Tumors.

PubMed

Koh, James; Hogue, Joyce A; Sosa, Julie A

2016-01-01

The functional impact of intratumoral heterogeneity has been difficult to assess in the absence of a means to interrogate dynamic, live-cell biochemical events in the native tissue context of a human tumor. Conventional histological methods can reveal morphology and static biomarker expression patterns but do not provide a means to probe and evaluate tumor functional behavior and live-cell responsiveness to experimentally controlled stimuli. Here, we describe an approach that couples vibratome-mediated viable tissue sectioning with live-cell confocal microscopy imaging to visualize human parathyroid adenoma tumor cell responsiveness to extracellular calcium challenge. Tumor sections prepared as 300 micron-thick tissue slices retain viability throughout a >24 hour observation period and retain the native architecture of the parental tumor. Live-cell observation of biochemical signaling in response to extracellular calcium challenge in the intact tissue slices reveals discrete, heterogeneous kinetic waveform categories of calcium agonist reactivity within each tumor. Plotting the proportion of maximally responsive tumor cells as a function of calcium concentration yields a sigmoid dose-response curve with a calculated calcium EC50 value significantly elevated above published reference values for wild-type calcium-sensing receptor (CASR) sensitivity. Subsequent fixation and immunofluorescence analysis of the functionally evaluated tissue specimens allows alignment and mapping of the physical characteristics of individual cells within the tumor to specific calcium response behaviors. Evaluation of the relative abundance of intracellular PTH in tissue slices challenged with variable calcium concentrations demonstrates that production of the hormone can be dynamically manipulated ex vivo. The capability of visualizing live human tumor tissue behavior in response to experimentally controlled conditions opens a wide range of possibilities for personalized ex vivo therapeutic testing. This highly adaptable system provides a unique platform for live-cell ex vivo provocative testing of human tumor responsiveness to a range of physiological agonists or candidate therapeutic compounds.

Behavioral and Pharmacological Adherence in Pediatric Sickle Cell Disease: Parent-Child Agreement and Family Factors Associated With Adherence.

PubMed

Klitzman, Page H; Carmody, Julia K; Belkin, Mary H; Janicke, David M

2018-01-01

This study aimed to evaluate agreement between children and parents on a measure of behavioral and pharmacological adherence in children with sickle cell disease (SCD), and the associations among family factors (i.e., problem-solving skills, routines, communication) and adherence behaviors. In all, 85 children (aged 8-18 years) with SCD and their parents completed questionnaires assessing individual and family factors. Overall parent-child agreement on an adherence measure was poor, particularly for boys and older children. Greater use of child routines was associated with better overall child-reported adherence. Open family communication was associated with higher overall parent-reported adherence. While further research is needed before definitive conclusions can be drawn, results suggest the need to assess child adherence behaviors via both child and parent reports. Findings also suggest that more daily family routines and open family communication may be protective factors for better disease management. © The Author 2017. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Watching cellular machinery in action, one molecule at a time.

PubMed

Monachino, Enrico; Spenkelink, Lisanne M; van Oijen, Antoine M

2017-01-02

Single-molecule manipulation and imaging techniques have become important elements of the biologist's toolkit to gain mechanistic insights into cellular processes. By removing ensemble averaging, single-molecule methods provide unique access to the dynamic behavior of biomolecules. Recently, the use of these approaches has expanded to the study of complex multiprotein systems and has enabled detailed characterization of the behavior of individual molecules inside living cells. In this review, we provide an overview of the various force- and fluorescence-based single-molecule methods with applications both in vitro and in vivo, highlighting these advances by describing their applications in studies on cytoskeletal motors and DNA replication. We also discuss how single-molecule approaches have increased our understanding of the dynamic behavior of complex multiprotein systems. These methods have shown that the behavior of multicomponent protein complexes is highly stochastic and less linear and deterministic than previously thought. Further development of single-molecule tools will help to elucidate the molecular dynamics of these complex systems both inside the cell and in solutions with purified components. © 2017 Monachino et al.

Decoupling Polymer Properties to Elucidate Mechanisms Governing Cell Behavior

PubMed Central

Wang, Xintong; Boire, Timothy C.; Bronikowski, Christine; Zachman, Angela L.; Crowder, Spencer W.

2012-01-01

Determining how a biomaterial interacts with cells (“structure-function relationship”) reflects its eventual clinical applicability. Therefore, a fundamental understanding of how individual material properties modulate cell-biomaterial interactions is pivotal to improving the efficacy and safety of clinically translatable biomaterial systems. However, due to the coupled nature of material properties, their individual effects on cellular responses are difficult to understand. Structure-function relationships can be more clearly understood by the effective decoupling of each individual parameter. In this article, we discuss three basic decoupling strategies: (1) surface modification, (2) cross-linking, and (3) combinatorial approaches (i.e., copolymerization and polymer blending). Relevant examples of coupled material properties are briefly reviewed in each section to highlight the need for improved decoupling methods. This follows with examples of more effective decoupling techniques, mainly from the perspective of three primary classes of synthetic materials: polyesters, polyethylene glycol, and polyacrylamide. Recent strides in decoupling methodologies, especially surface-patterning and combinatorial techniques, offer much promise in further understanding the structure-function relationships that largely govern the success of future advancements in biomaterials, tissue engineering, and drug delivery. PMID:22536977

Regulation of bacteria population behaviors by AI-2 "consumer cells" and "supplier cells".

PubMed

Quan, Yufen; Meng, Fankang; Ma, Xinyu; Song, Xinhao; Liu, Xiao; Gao, Weixia; Dang, Yulei; Meng, Yao; Cao, Mingfeng; Song, Cunjiang

2017-09-19

Autoinducer-2 (AI-2) is a universal signal molecule and enables an individual bacteria to communicate with each other and ultimately control behaviors of the population. Harnessing the character of AI-2, two kinds of AI-2 "controller cells" ("consumer cells" and "supplier cells") were designed to "reprogram" the behaviors of entire population. For the consumer cells, genes associated with the uptake and processing of AI-2, which includes LsrACDB, LsrFG, LsrK, were overexpressed in varying combinations. Four consumer cell strains were constructed: Escherichia coli MG1655 pLsrACDB (NK-C1), MG1655 pLsrACDBK (NK-C2), MG1655 pLsrACDBFG (NK-C3) and MG1655 pLsrACDBFGK (NK-C4). The key enzymes responsible for production of AI-2, LuxS and Mtn, were also overexpressed, yielding strains MG1655 pLuxS (NK-SU1), and MG1655 pLuxS-Mtn (NK-SU2). All the consumer cells could decrease the environmental AI-2 concentration. NK-C2 and NK-C4 were most effective in AI-2 uptake and inhibited biofilm formation. While suppliers can increase the environmental AI-2 concentration and NK-SU2 was most effective in supplying AI-2 and facilitated biofilm formation. Further, reporter strain, MG1655 pLGFP was constructed. The expression of green fluorescent protein (GFP) in reporter cells was initiated and guided by AI-2. Mixture of consumer cells and reporter cells suggest that consumer cells can decrease the AI-2 concentration. And the supplier cells were co-cultured with reporter cells, indicating that supplier cells can provide more AI-2 compared to the control. The consumer cells and supplier cells could be used to regulate environmental AI-2 concentration and the biofilm formation. They can also modulate the AI-2 concentration when they were co-cultured with reporter cells. It can be envisioned that this system will become useful tools in synthetic biology and researching new antimicrobials.

Self-report measures of distractibility as correlates of simulated driving performance.

PubMed

Kass, Steven J; Beede, Kristen E; Vodanovich, Stephen J

2010-05-01

The present study investigated the relationship between self-reported measures pertaining to attention difficulties and simulated driving performance while distracted. Thirty-six licensed drivers participated in a simulator driving task while engaged in a cell phone conversation. The participants completed questionnaires assessing their tendency toward boredom, cognitive failures, and behaviors associated with attention deficit and hyperactivity. Scores on these measures were significantly correlated with various driving outcomes (e.g., speed, lane maintenance, reaction time). Significant relationships were also found between one aspect of boredom proneness (i.e., inability to generate interest or concentrate) and self-reports of past driving behavior (moving violations). The current study may aid in the understanding of how individual differences in driver distractibility may contribute to unsafe driving behaviors and accident involvement. Additionally, such measures may assist in the identification of individuals at risk for committing driving errors due to being easily distracted. The benefits and limitations of conducting and interpreting simulation research are discussed. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

Differential behavioral sensitivity to carbon dioxide (CO2) inhalation in rats

PubMed Central

Winter, Andrew; Ahlbrand, Rebecca; Naik, Devanshi; Sah, Renu

2017-01-01

Inhalation of carbon dioxide (CO2) is frequently employed as a biological challenge to evoke intense fear and anxiety. In individuals with panic disorder, CO2 reliably evokes panic attacks. Sensitivity to CO2 is highly heterogeneous among individuals, and although a genetic component is implicated, underlying mechanisms are not clear. Preclinical models that can simulate differential responsivity to CO2 are therefore relevant. In the current study we investigated CO2-evoked behavioral responses in four different rat strains: Sprague-Dawley (SD), Wistar (W), Long Evans (LE) and Wistar-Kyoto, (WK) rats. We also assessed tryptophan hydroxylase 2 (TPH-2)-positive serotonergic neurons in anxiety/panic regulatory subdivisions of the dorsal raphe nucleus (DR), as well as dopamine β hydroxylase (DβH)-positive noradrenergic neurons in the locus coeruleus, implicated in central CO2-chemosensitivity. Behavioral responsivity to CO2 inhalation varied between strains. CO2-evoked immobility was significantly higher in LE and WK rats as compared with W and SD cohorts. Differences were also observed in CO2-evoked rearing and grooming behaviors. Exposure to CO2 did not produce conditioned behavioral responses upon re-exposure to CO2 context in any strain. Reduced TPH-2 positive cell counts were observed specifically in the panic-regulatory dorsal raphe ventrolateral (DRVL)-ventrolateral periaqueductal grey (VLPAG) subdivision in CO2-sensitive strains. Conversely, DβH positive cell counts within the LC were significantly higher in CO2-sensitive strains. Collectively, our data provide evidence for strain dependent, differential CO2-sensitivity and potential differences in monoaminergic systems regulating panic and anxiety. Comparative studies between CO2-vulnerable and resistant strains may facilitate the mechanistic understanding of differential CO2-sensitivity in the development of panic and anxiety disorders. PMID:28087339

Learning, memory and exploratory similarities in genetically identical cloned dogs.

PubMed

Shin, Chi Won; Kim, Geon A; Park, Won Jun; Park, Kwan Yong; Jeon, Jeong Min; Oh, Hyun Ju; Kim, Min Jung; Lee, Byeong Chun

2016-12-30

Somatic cell nuclear transfer allows generation of genetically identical animals using donor cells derived from animals with particular traits. To date, few studies have investigated whether or not these cloned dogs will show identical behavior patterns. To address this question, learning, memory and exploratory patterns were examined using six cloned dogs with identical nuclear genomes. The variance of total incorrect choice number in the Y-maze test among cloned dogs was significantly lower than that of the control dogs. There was also a significant decrease in variance in the level of exploratory activity in the open fields test compared to age-matched control dogs. These results indicate that cloned dogs show similar cognitive and exploratory patterns, suggesting that these behavioral phenotypes are related to the genotypes of the individuals.

Influence of the ionophore A23187 on the plastic behavior of normal erythrocytes.

PubMed

Kuettner, J F; Dreher, K L; Rao, G H; Eaton, J W; Blackshear, P L; White, J G

1977-07-01

Previous studies have demonstrated that A23187, an ionophore which selectively transports divalent cations across cell membranes, has profound effects on human erythrocytes: it causes red cells to take up calcium; lose potassium, water, and ATP; convert from biconcave discs to echinocytes and spheroechinocytes; and become more rigid. The present study has explored the influence of calcium uptake induced by the ionophore on the behavior of individual erythrocyte membranes by the micropipette aspiration technique. Exposure of erythrocytes to calcium and A23187 for intervals of up to 30 minutes resulted in marked changes in membrane viscoelastic properties, including the development of increased resistance to aspiration. The most striking manifestation of altered membrane mechanics was apparent after 10 minutes on incubation. Cells pulled into the pipette for a few seconds and the extruded back into the medium retained the deformity imposed by the pipette for several seconds to a few minutes before regaining the form they manifested prior to initial aspiration. The calcium-induced changes in erythrocyte behavior observed in this study strongly support the concept that extrinsic proteins located inside the membrane provide mechanical support to the cell wall, and that increased levels of calcium cause precipitation or cross-linking of the proteins responsible for the increased resistence to deformation and recoil observed after aspiration into micropipettes.

Prefrontal Recruitment Mitigates Risk-Taking Behavior in Human Immunodeficiency Virus-Infected Young Adults.

PubMed

Smith, Robert X; Guha, Anika; Vaida, Florin; Paul, Robert H; Ances, Beau

2018-05-02

Human immunodeficiency virus (HIV)-infected (HIV+) young adults often engage in risk-taking behavior. However, the disruptive effects of HIV on the neurobiological underpinnings of risky decision making are not well understood. Risky decision making, measured via the Iowa Gambling Task (IGT), was compared voxel-wise to resting cerebral blood flow (rCBF) acquired via arterial spin labeling. Separate topographical maps were obtained for HIV-uninfected (HIV-; n = 62) and HIV+ (n = 41) young adults (18-24 years old) and were compared to the full cohort of participants. For the HIV+ group, rCBF was compared to recent and nadir CD4. IGT performance was supported by rCBF in 3 distinct brain regions: regions I, II, and III. The relationship between IGT performance and rCBF in HIV+ individuals was most robust in region I, the ventromedial prefrontal and insular cortices. Region II contained strong relationships for both HIV- and HIV+. Region III, dorsolateral prefrontal and posterior cingulate cortices, contained relationships that were strongest for HIV- controls. IGT performance was intact among HIV+ participants with higher rCBF in either region I or region III. By contrast, performance was worse among HIV+ individuals with lower rCBF in both regions I and III when compared to HIV- controls (P = .01). rCBF in region III was reduced in HIV+ compared with HIV- individuals (P = .04), and positively associated with nadir CD4 cell count (P = .02). Recruitment of executive systems (region III) mitigates risk-taking behavior in HIV+ and HIV- individuals. Recruitment of reward systems (region I) mitigates risk-taking behavior when region III is disrupted due to immunological compromise. Identifying individual recruitment patterns may aid anatomically directed therapeutics or psychosocial interventions.

Towards comprehensive cell lineage reconstructions in complex organisms using light-sheet microscopy.

PubMed

Amat, Fernando; Keller, Philipp J

2013-05-01

Understanding the development of complex multicellular organisms as a function of the underlying cell behavior is one of the most fundamental goals of developmental biology. The ability to quantitatively follow cell dynamics in entire developing embryos is an indispensable step towards such a system-level understanding. In recent years, light-sheet fluorescence microscopy has emerged as a particularly promising strategy for recording the in vivo data required to realize this goal. Using light-sheet fluorescence microscopy, entire complex organisms can be rapidly imaged in three dimensions at sub-cellular resolution, achieving high temporal sampling and excellent signal-to-noise ratio without damaging the living specimen or bleaching fluorescent markers. The resulting datasets allow following individual cells in vertebrate and higher invertebrate embryos over up to several days of development. However, the complexity and size of these multi-terabyte recordings typically preclude comprehensive manual analyses. Thus, new computational approaches are required to automatically segment cell morphologies, accurately track cell identities and systematically analyze cell behavior throughout embryonic development. We review current efforts in light-sheet microscopy and bioimage informatics towards this goal, and argue that comprehensive cell lineage reconstructions are finally within reach for many key model organisms, including fruit fly, zebrafish and mouse. © 2013 The Authors Development, Growth & Differentiation © 2013 Japanese Society of Developmental Biologists.

Efficient coarse simulation of a growing avascular tumor

PubMed Central

Kavousanakis, Michail E.; Liu, Ping; Boudouvis, Andreas G.; Lowengrub, John; Kevrekidis, Ioannis G.

2013-01-01

The subject of this work is the development and implementation of algorithms which accelerate the simulation of early stage tumor growth models. Among the different computational approaches used for the simulation of tumor progression, discrete stochastic models (e.g., cellular automata) have been widely used to describe processes occurring at the cell and subcell scales (e.g., cell-cell interactions and signaling processes). To describe macroscopic characteristics (e.g., morphology) of growing tumors, large numbers of interacting cells must be simulated. However, the high computational demands of stochastic models make the simulation of large-scale systems impractical. Alternatively, continuum models, which can describe behavior at the tumor scale, often rely on phenomenological assumptions in place of rigorous upscaling of microscopic models. This limits their predictive power. In this work, we circumvent the derivation of closed macroscopic equations for the growing cancer cell populations; instead, we construct, based on the so-called “equation-free” framework, a computational superstructure, which wraps around the individual-based cell-level simulator and accelerates the computations required for the study of the long-time behavior of systems involving many interacting cells. The microscopic model, e.g., a cellular automaton, which simulates the evolution of cancer cell populations, is executed for relatively short time intervals, at the end of which coarse-scale information is obtained. These coarse variables evolve on slower time scales than each individual cell in the population, enabling the application of forward projection schemes, which extrapolate their values at later times. This technique is referred to as coarse projective integration. Increasing the ratio of projection times to microscopic simulator execution times enhances the computational savings. Crucial accuracy issues arising for growing tumors with radial symmetry are addressed by applying the coarse projective integration scheme in a cotraveling (cogrowing) frame. As a proof of principle, we demonstrate that the application of this scheme yields highly accurate solutions, while preserving the computational savings of coarse projective integration. PMID:22587128

High-throughput separation of cells by dielectrophoresis enhanced with 3D gradient AC electric field.

PubMed

Tada, Shigeru; Hayashi, Masako; Eguchi, Masanori; Tsukamoto, Akira

2017-11-01

We propose a novel, high-performance dielectrophoretic (DEP) cell-separation flow chamber with a parallel-plate channel geometry. The flow chamber, consisting of a planar electrode on the top and an interdigitated-pair electrode array at the bottom, was developed to facilitate the separation of cells by creating a nonuniform AC electric field throughout the volume of the flow chamber. The operation and performance of the device were evaluated using live and dead human epithermal breast (MCF10A) cells. The separation dynamics of the cell suspension in the flow chamber was also investigated by numerically simulating the trajectories of individual cells. A theoretical model to describe the dynamic cell behavior under the action of DEP, including dipole-dipole interparticle, viscous, and gravitational forces, was developed. The results demonstrated that the live cells traveling through the flow chamber congregated into sites where the electric field gradient was minimal, in the middle of the flow stream slightly above the centerlines of the grounded electrodes at the bottom. Meanwhile, the dead cells were trapped on the edges of the high-voltage electrodes at the bottom. Cells were thus successfully separated with a remarkably high separation ratio (∼98%) at the appropriately tuned field frequency and applied voltage. The numerically predicted behavior and spatial distribution of the cells during separation also showed good agreement with those observed experimentally.

Environmentally induced amplitude death and firing provocation in large-scale networks of neuronal systems

NASA Astrophysics Data System (ADS)

Pankratova, Evgeniya V.; Kalyakulina, Alena I.

2016-12-01

We study the dynamics of multielement neuronal systems taking into account both the direct interaction between the cells via linear coupling and nondiffusive cell-to-cell communication via common environment. For the cells exhibiting individual bursting behavior, we have revealed the dependence of the network activity on its scale. Particularly, we show that small-scale networks demonstrate the inability to maintain complicated oscillations: for a small number of elements in an ensemble, the phenomenon of amplitude death is observed. The existence of threshold network scales and mechanisms causing firing in artificial and real multielement neural networks, as well as their significance for biological applications, are discussed.

Cell density-dependent differential proliferation of neural stem cells on omnidirectional nanopore-arrayed surface.

PubMed

Cha, Kyoung Je; Kong, Sun-Young; Lee, Ji Soo; Kim, Hyung Woo; Shin, Jae-Yeon; La, Moonwoo; Han, Byung Woo; Kim, Dong Sung; Kim, Hyun-Jung

2017-10-12

Recently, the importance of surface nanotopography in the determination of stem cell fate and behavior has been revealed. In the current study, we generated polystyrene cell-culture dishes with an omnidirectional nanopore arrayed surface (ONAS) (diameter: 200 nm, depth: 500 nm, center-to-center distance: 500 nm) and investigated the effects of nanotopography on rat neural stem cells (NSCs). NSCs cultured on ONAS proliferated better than those on the flat surface when cell density was low and showed less spontaneous differentiation during proliferation in the presence of mitogens. Interestingly, NSCs cultured on ONAS at clonal density demonstrated a propensity to generate neurospheres, whereas those on the flat surface migrated out, proliferated as individuals, and spread out to attach to the surface. However, the differential patterns of proliferation were cell density-dependent since the distinct phenomena were lost when cell density was increased. ONAS modulated cytoskeletal reorganization and inhibited formation of focal adhesion, which is generally observed in NSCs grown on flat surfaces. ONAS appeared to reinforce NSC-NSC interaction, restricted individual cell migration and prohibited NSC attachment to the nanopore surface. These data demonstrate that ONAS maintains NSCs as undifferentiated while retaining multipotency and is a better topography for culturing low density NSCs.

Within-individual correlations reveal link between a behavioral syndrome, condition and cortisol in free-ranging Belding's ground squirrels

PubMed Central

Brooks, Katherine C.; Mateo, Jill. M.

2014-01-01

Animals often exhibit consistent individual differences in behavior (i.e. animal personality) and correlations between behaviors (i.e. behavioral syndromes), yet the causes of those patterns of behavioral variation remain insufficiently understood. Many authors hypothesize that state-dependent behavior produces animal personality and behavioral syndromes. However, empirical studies assessing patterns of covariation among behavioral traits and state variables have produced mixed results. New statistical methods that partition correlations into between-individual and residual within-individual correlations offer an opportunity to more sufficiently quantify relationships among behaviors and state variables to assess hypotheses of animal personality and behavioral syndromes. In a population of wild Belding's ground squirrels (Urocitellus beldingi) we repeatedly measured activity, exploration, and response to restraint behaviors alongside glucocorticoids and nutritional condition. We used multivariate mixed models to determine whether between-individual or within-individual correlations drive phenotypic relationships among traits. Squirrels had consistent individual differences for all five traits. At the between-individual level, activity and exploration were positively correlated whereas both traits negatively correlated with response to restraint, demonstrating a behavioral syndrome. At the within-individual level, condition negatively correlated with cortisol, activity and exploration. Importantly, this indicates that although behavior is state-dependent, which may play a role in animal personality and behavioral syndromes, feedback mechanisms between condition and behavior appear not to produce consistent individual differences in behavior and correlations between them. PMID:25598565

Modelling the collective response of heterogeneous cell populations to stationary gradients and chemical signal relay

NASA Astrophysics Data System (ADS)

Pineda, M.; Eftimie, R.

2017-12-01

The directed motion of cell aggregates toward a chemical source occurs in many relevant biological processes. Understanding the mechanisms that control this complex behavior is of great relevance for our understanding of developmental biological processes and many diseases. In this paper, we consider a self-propelled particle model for the movement of heterogeneous subpopulations of chemically interacting cells towards an imposed stable chemical gradient. Our simulations show explicitly how self-organisation of cell populations (which could lead to engulfment or complete cell segregation) can arise from the heterogeneity of chemotactic responses alone. This new result complements current theoretical and experimental studies that emphasise the role of differential cell-cell adhesion on self-organisation and spatial structure of cellular aggregates. We also investigate how the speed of individual cell aggregations increases with the chemotactic sensitivity of the cells, and decreases with the number of cells inside the aggregates

Collective Signal Processing in Cluster Chemotaxis: Roles of Adaptation, Amplification, and Co-attraction in Collective Guidance

PubMed Central

Camley, Brian A.; Zimmermann, Juliane; Levine, Herbert; Rappel, Wouter-Jan

2016-01-01

Single eukaryotic cells commonly sense and follow chemical gradients, performing chemotaxis. Recent experiments and theories, however, show that even when single cells do not chemotax, clusters of cells may, if their interactions are regulated by the chemoattractant. We study this general mechanism of “collective guidance” computationally with models that integrate stochastic dynamics for individual cells with biochemical reactions within the cells, and diffusion of chemical signals between the cells. We show that if clusters of cells use the well-known local excitation, global inhibition (LEGI) mechanism to sense chemoattractant gradients, the speed of the cell cluster becomes non-monotonic in the cluster’s size—clusters either larger or smaller than an optimal size will have lower speed. We argue that the cell cluster speed is a crucial readout of how the cluster processes chemotactic signals; both amplification and adaptation will alter the behavior of cluster speed as a function of size. We also show that, contrary to the assumptions of earlier theories, collective guidance does not require persistent cell-cell contacts and strong short range adhesion. If cell-cell adhesion is absent, and the cluster cohesion is instead provided by a co-attraction mechanism, e.g. chemotaxis toward a secreted molecule, collective guidance may still function. However, new behaviors, such as cluster rotation, may also appear in this case. Co-attraction and adaptation allow for collective guidance that is robust to varying chemoattractant concentrations while not requiring strong cell-cell adhesion. PMID:27367541

Imaging and Force Recognition of Single Molecular Behaviors Using Atomic Force Microscopy

PubMed Central

Li, Mi; Dang, Dan; Liu, Lianqing; Xi, Ning; Wang, Yuechao

2017-01-01

The advent of atomic force microscopy (AFM) has provided a powerful tool for investigating the behaviors of single native biological molecules under physiological conditions. AFM can not only image the conformational changes of single biological molecules at work with sub-nanometer resolution, but also sense the specific interactions of individual molecular pair with piconewton force sensitivity. In the past decade, the performance of AFM has been greatly improved, which makes it widely used in biology to address diverse biomedical issues. Characterizing the behaviors of single molecules by AFM provides considerable novel insights into the underlying mechanisms guiding life activities, contributing much to cell and molecular biology. In this article, we review the recent developments of AFM studies in single-molecule assay. The related techniques involved in AFM single-molecule assay were firstly presented, and then the progress in several aspects (including molecular imaging, molecular mechanics, molecular recognition, and molecular activities on cell surface) was summarized. The challenges and future directions were also discussed. PMID:28117741

Culture on 3D Chitosan-Hyaluronic Acid Scaffolds Enhances Stem Cell Marker Expression and Drug Resistance in Human Glioblastoma Cancer Stem Cells.

PubMed

Wang, Kui; Kievit, Forrest M; Erickson, Ariane E; Silber, John R; Ellenbogen, Richard G; Zhang, Miqin

2016-12-01

The lack of in vitro models that support the growth of glioblastoma (GBM) stem cells (GSCs) that underlie clinical aggressiveness hinders developing new, effective therapies for GBM. While orthotopic patient-derived xenograft models of GBM best reflect in vivo tumor behavior, establishing xenografts is a time consuming, costly, and frequently unsuccessful endeavor. To address these limitations, a 3D porous scaffold composed of chitosan and hyaluronic acid (CHA) is synthesized. Growth and expression of the cancer stem cell (CSC) phenotype of the GSC GBM6 taken directly from fresh xenogratfs grown on scaffolds or as adherent monolayers is compared. While 2D adherent cultures grow as monolayers of flat epitheliod cells, GBM6 cells proliferate within pores of CHA scaffolds as clusters of self-adherent ovoid cells. Growth on scaffolds is accompanied by greater expression of genes that mediate epithelial-mesenchymal transition and maintain a primitive, undifferentiated phenotype, hallmarks of CSCs. Scaffold-grown cells also display higher expression of genes that promote resistance to hypoxia-induced oxidative stress. In accord, scaffold-grown cells show markedly greater resistance to clinically utilized alkylating agents compared to adherent cells. These findings suggest that our CHA scaffolds better mimic in vivo biological and clinical behavior and provide insights for developing novel individualized treatments. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Cell-type-specific role of ΔFosB in nucleus accumbens in modulating inter-male aggression.

PubMed

Aleyasin, Hossein; Flanigan, Meghan E; Golden, Sam A; Takahashi, Aki; Menard, Caroline; Pfau, Madeline L; Multer, Jacob; Pina, Jacqueline; McCabe, Kathryn A; Bhatti, Naemal; Hodes, Georgia E; Heshmati, Mitra; Neve, Rachael L; Nestler, Eric J; Heller, Elizabeth A; Russo, Scott J

2018-06-11

A growing number of studies implicate the brain's reward circuitry in aggressive behavior. However, the cellular and molecular mechanisms within brain reward regions that modulate the intensity of aggression as well as motivation for it have been underexplored. Here, we investigate the cell-type-specific influence of ΔFosB, a transcription factor known to regulate a range of reward and motivated behaviors, acting in the nucleus accumbens (NAc)-a key reward region-in male aggression in mice. We show that ΔFosB is specifically increased in dopamine D1 receptor (Drd1) expressing medium spiny neurons (D1-MSNs) in NAc after repeated aggressive encounters. Viral-mediated induction of ΔFosB selectively in D1-MSNs of NAc intensifies aggressive behavior, without affecting the preference for the aggression-paired context in a conditioned place preference (CPP) assay. In contrast, ΔFosB induction selectively in D2-MSNs reduces the time spent exploring the aggression-paired context during CPP without affecting the intensity of aggression per se. These data strongly support a dissociable cell-type-specific role for ΔFosB in the NAc in modulating aggression and aggression reward. Significance Statement: Aggressive behavior is associated with several neuropsychiatric disorders and can be disruptive for the individuals as well as their victims. Studies have shown a positive reinforcement mechanism underlying aggressive behavior that shares many common features with drug addiction. Here, we explore the cell-type-specific role of the addiction-associated transcription factor ΔFosB in the nucleus accumbens (NAc) in aggression. We found that ΔFosB expression promotes aggressive behavior, effects that are dissociable from its effects on aggression reward. This finding is a significant first step in identifying therapeutic targets for the reduction of aggressive behavior across a range of neuropsychiatric illnesses. Copyright © 2018 the authors.

From global to local: exploring the relationship between parameters and behaviors in models of electrical excitability.

PubMed

Fletcher, Patrick; Bertram, Richard; Tabak, Joel

2016-06-01

Models of electrical activity in excitable cells involve nonlinear interactions between many ionic currents. Changing parameters in these models can produce a variety of activity patterns with sometimes unexpected effects. Further more, introducing new currents will have different effects depending on the initial parameter set. In this study we combined global sampling of parameter space and local analysis of representative parameter sets in a pituitary cell model to understand the effects of adding K (+) conductances, which mediate some effects of hormone action on these cells. Global sampling ensured that the effects of introducing K (+) conductances were captured across a wide variety of contexts of model parameters. For each type of K (+) conductance we determined the types of behavioral transition that it evoked. Some transitions were counterintuitive, and may have been missed without the use of global sampling. In general, the wide range of transitions that occurred when the same current was applied to the model cell at different locations in parameter space highlight the challenge of making accurate model predictions in light of cell-to-cell heterogeneity. Finally, we used bifurcation analysis and fast/slow analysis to investigate why specific transitions occur in representative individual models. This approach relies on the use of a graphics processing unit (GPU) to quickly map parameter space to model behavior and identify parameter sets for further analysis. Acceleration with modern low-cost GPUs is particularly well suited to exploring the moderate-sized (5-20) parameter spaces of excitable cell and signaling models.

Ergodicity, hidden bias and the growth rate gain

NASA Astrophysics Data System (ADS)

Rochman, Nash D.; Popescu, Dan M.; Sun, Sean X.

2018-05-01

Many single-cell observables are highly heterogeneous. A part of this heterogeneity stems from age-related phenomena: the fact that there is a nonuniform distribution of cells with different ages. This has led to a renewed interest in analytic methodologies including use of the ‘von Foerster equation’ for predicting population growth and cell age distributions. Here we discuss how some of the most popular implementations of this machinery assume a strong condition on the ergodicity of the cell cycle duration ensemble. We show that one common definition for the term ergodicity, ‘a single individual observed over many generations recapitulates the behavior of the entire ensemble’ is implied by the other, ‘the probability of observing any state is conserved across time and over all individuals’ in an ensemble with a fixed number of individuals but that this is not true when the ensemble is growing. We further explore the impact of generational correlations between cell cycle durations on the population growth rate. Finally, we explore the ‘growth rate gain’—the phenomenon that variations in the cell cycle duration leads to an improved population-level growth rate—in this context. We highlight that, fundamentally, this effect is due to asymmetric division.

Synthesis and characterization of lithium ion nanobatteries and lithium battery nanoelectrode arrays

NASA Astrophysics Data System (ADS)

Vullum, Fride

2005-07-01

Arrays of individual nanobatteries were constructed by confining V 2O5 ambigel and a PEO wax electrolyte containing lithium triflate in the porous structure of an alumina membrane. The pores had an average diameter of 200 nm. Cyclic voltammetry data indicated that this configuration could be described by a nanoelectrode array model. A.C. impedance data of the macro cell coupled with a lithium anode showed that there was little or no unstable passivation behavior of the lithium anode in contact with the PEO wax electrolyte. This was attributed to a self-assembled hydrocarbon layer that formed at the surface of the wax preventing the lithium metal from chemically reacting with oxygen atoms in the PEO backbone. Individual nanobatteries were characterized by charge/discharge analysis. Electrical contact with individual nanocathodes was achieved using the cantilever tip of an atomic force microscope. Of the three different anode materials that were investigated SnO2 seemed to perform better than either graphite or lithium metal. This was attributed to SnO2 being able to accept more lithium ions into its structure than graphite. The favorable capacity values compared to the lithium anode batteries were attributed to better contact between the electrolyte and the anode. Average volumetric capacities for the SnO2 system were found to be around 45 muAh/cm2mum, which compare favorably to similar systems reported in literature. These nanobatteries also exhibited capacitor-like behavior, having capacitances around 300-400 F/g, which is in the range of what is expected for a supercapacitor. An electrochemical cell combining battery-like and capacitor-like behavior is a very promising power supply for applications such as electric vehicle propulsion systems.

Combining Individual-Based Modeling and Food Microenvironment Descriptions To Predict the Growth of Listeria monocytogenes on Smear Soft Cheese

PubMed Central

Ferrier, Rachel; Hezard, Bernard; Lintz, Adrienne; Stahl, Valérie

2013-01-01

An individual-based modeling (IBM) approach was developed to describe the behavior of a few Listeria monocytogenes cells contaminating smear soft cheese surface. The IBM approach consisted of assessing the stochastic individual behaviors of cells on cheese surfaces and knowing the characteristics of their surrounding microenvironments. We used a microelectrode for pH measurements and micro-osmolality to assess the water activity of cheese microsamples. These measurements revealed a high variability of microscale pH compared to that of macroscale pH. A model describing the increase in pH from approximately 5.0 to more than 7.0 during ripening was developed. The spatial variability of the cheese surface characterized by an increasing pH with radius and higher pH on crests compared to that of hollows on cheese rind was also modeled. The microscale water activity ranged from approximately 0.96 to 0.98 and was stable during ripening. The spatial variability on cheese surfaces was low compared to between-cheese variability. Models describing the microscale variability of cheese characteristics were combined with the IBM approach to simulate the stochastic growth of L. monocytogenes on cheese, and these simulations were compared to bacterial counts obtained from irradiated cheeses artificially contaminated at different ripening stages. The simulated variability of L. monocytogenes counts with the IBM/microenvironmental approach was consistent with the observed one. Contrasting situations corresponding to no growth or highly contaminated foods could be deduced from these models. Moreover, the IBM approach was more effective than the traditional population/macroenvironmental approach to describe the actual bacterial behavior variability. PMID:23872572

Alkali vapor pressure modulation on the 100 ms scale in a single-cell vacuum system for cold atom experiments

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

Dugrain, Vincent; Reichel, Jakob; Rosenbusch, Peter

2014-08-15

We describe and characterize a device for alkali vapor pressure modulation on the 100 ms timescale in a single-cell cold atom experiment. Its mechanism is based on optimized heat conduction between a current-modulated alkali dispenser and a heat sink at room temperature. We have studied both the short-term behavior during individual pulses and the long-term pressure evolution in the cell. The device combines fast trap loading and relatively long trap lifetime, enabling high repetition rates in a very simple setup. These features make it particularly suitable for portable atomic sensors.

Methods for Studying Ciliary-Mediated Chemoresponse in Paramecium.

PubMed

Valentine, Megan Smith; Van Houten, Judith L

2016-01-01

Paramecium is a useful model organism for the study of ciliary-mediated chemical sensing and response. Here we describe ways to take advantage of Paramecium to study chemoresponse.Unicellular organisms like the ciliated protozoan Paramecium sense and respond to chemicals in their environment (Van Houten, Ann Rev Physiol 54:639-663, 1992; Van Houten, Trends Neurosci 17:62-71, 1994). A thousand or more cilia that cover Paramecium cells serve as antennae for chemical signals, similar to ciliary function in a large variety of metazoan cell types that have primary or motile cilia (Berbari et al., Curr Biol 19(13):R526-R535, 2009; Singla V, Reiter J, Science 313:629-633, 2006). The Paramecium cilia also produce the motor output of the detection of chemical cues by controlling swimming behavior. Therefore, in Paramecium the cilia serve multiple roles of detection and response.We present this chapter in three sections to describe the methods for (1) assaying populations of cells for their behavioral responses to chemicals (attraction and repulsion), (2) characterization of the chemoreceptors and associated channels of the cilia using proteomics and binding assays, and (3) electrophysiological analysis of individual cells' responses to chemicals. These methods are applied to wild type cells, mutants, transformed cells that express tagged proteins, and cells depleted of gene products by RNA Interference (RNAi).

Quantitative 4D analyses of epithelial folding during Drosophila gastrulation.

PubMed

Khan, Zia; Wang, Yu-Chiun; Wieschaus, Eric F; Kaschube, Matthias

2014-07-01

Understanding the cellular and mechanical processes that underlie the shape changes of individual cells and their collective behaviors in a tissue during dynamic and complex morphogenetic events is currently one of the major frontiers in developmental biology. The advent of high-speed time-lapse microscopy and its use in monitoring the cellular events in fluorescently labeled developing organisms demonstrate tremendous promise in establishing detailed descriptions of these events and could potentially provide a foundation for subsequent hypothesis-driven research strategies. However, obtaining quantitative measurements of dynamic shapes and behaviors of cells and tissues in a rapidly developing metazoan embryo using time-lapse 3D microscopy remains technically challenging, with the main hurdle being the shortage of robust imaging processing and analysis tools. We have developed EDGE4D, a software tool for segmenting and tracking membrane-labeled cells using multi-photon microscopy data. Our results demonstrate that EDGE4D enables quantification of the dynamics of cell shape changes, cell interfaces and neighbor relations at single-cell resolution during a complex epithelial folding event in the early Drosophila embryo. We expect this tool to be broadly useful for the analysis of epithelial cell geometries and movements in a wide variety of developmental contexts. © 2014. Published by The Company of Biologists Ltd.

Behavioral characterization of the alarm reaction and anxiolytic-like effect of acute treatment with fluoxetine in piauçu fish.

PubMed

Barbosa Júnior, Augusto; Alves, Fabiana Luca; Pereira, Aparecida de Sousa Fim; Ide, Liliam Midori; Hoffmann, Anette

2012-02-01

In Ostariophysan fish, the detection of the alarm substance liberated into the water as a consequence of an attack by a predator elicits an alarm reaction or anti-predatory behavior. In this study, experiments were performed to: (i) describe and quantitatively characterize the behavioral and ventilatory responses in piauçu fish (Leporinus macrocephalus), individually and as part of a school, to conspecific alarm substance (CAS) and; (ii) test the effect of acute fluoxetine treatment on alarm reaction. Histological analysis revealed the presence of club cells in the intermediate and superficial layers of the epidermis. The predominant behavioral response to CAS was freezing for fish held individually, characterized by the cessation of the swimming activity as the animal settles to a bottom corner of the aquarium. Fish exposed to CAS showed decrease in the mean ventilatory frequency (approximately 13%) relative to control. In schools, CAS elicited a biphasic response that was characterized by erratic movements followed by increased school cohesion and immobility, reflected as an increased school cohesion (65.5% vs. -5.8% for controls) and in the number of animals near the bottom of the aquarium (42.0% vs. 6.5% for controls). Animals treated with single i.p. injections of fluoxetine (10 μg/g b.w.) did not exhibit alarm behavior following CAS stimulation. These results show that an alarm pheromone system is present in piauçu fish, evidenced by the presence of epidermal club cells and an alarm reaction induced by CAS and consequently of a chemosensory system to transmit the appropriate information to neural structures responsible for initiating anti-predator behavioral responses. In addition, fluoxetine treatment caused an anxiolytic-like effect following CAS exposure. Thus, the alarm reaction in piauçu can be a useful model for neuroethological and pharmacological studies of anxiety-related states. Copyright © 2011 Elsevier Inc. All rights reserved.

Amoeba-based computing for traveling salesman problem: long-term correlations between spatially separated individual cells of Physarum polycephalum.

PubMed

Zhu, Liping; Aono, Masashi; Kim, Song-Ju; Hara, Masahiko

2013-04-01

A single-celled, multi-nucleated amoeboid organism, a plasmodium of the true slime mold Physarum polycephalum, can perform sophisticated computing by exhibiting complex spatiotemporal oscillatory dynamics while deforming its amorphous body. We previously devised an "amoeba-based computer (ABC)" to quantitatively evaluate the optimization capability of the amoeboid organism in searching for a solution to the traveling salesman problem (TSP) under optical feedback control. In ABC, the organism changes its shape to find a high quality solution (a relatively shorter TSP route) by alternately expanding and contracting its pseudopod-like branches that exhibit local photoavoidance behavior. The quality of the solution serves as a measure of the optimality of which the organism maximizes its global body area (nutrient absorption) while minimizing the risk of being illuminated (exposure to aversive stimuli). ABC found a high quality solution for the 8-city TSP with a high probability. However, it remains unclear whether intracellular communication among the branches of the organism is essential for computing. In this study, we conducted a series of control experiments using two individual cells (two single-celled organisms) to perform parallel searches in the absence of intercellular communication. We found that ABC drastically lost its ability to find a solution when it used two independent individuals. However, interestingly, when two individuals were prepared by dividing one individual, they found a solution for a few tens of minutes. That is, the two divided individuals remained correlated even though they were spatially separated. These results suggest the presence of a long-term memory in the intrinsic dynamics of this organism and its significance in performing sophisticated computing. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

A combination therapy of neural and glial restricted precursor cells and chronic quipazine treatment paired with passive cycling promotes quipazine-induced stepping in adult spinalized rats.

PubMed

Dugan, Elizabeth A; Shumsky, Jed S

2015-11-01

In order to develop optimal treatments to promote recovery from complete spinal cord injury (SCI), we examined the combination of: (1) a cellular graft of neural and glial restricted precursor (NRP/GRP) cells, (2) passive exercise, and (3) chronic quipazine treatment on behavioral outcomes and compared them with the individual treatment elements. NRP/GRP cells were transplanted at the time of spinalization. Daily passive exercise began 1 week after injury to give sufficient time for the animals to recover. Chronic quipazine administration began 2 weeks after spinalization to allow for sufficient receptor upregulation permitting the expression of its behavioral effects. Behavioral measures consisted of the Basso, Beattie, and Bresnahan (BBB) locomotor score and percent of weight-supported steps and hops on a treadmill. Rats displayed an increased response to quipazine (BBB ≥ 9) beginning at 8 weeks post-injury in all the animals that received the combination therapy. This increase in BBB score was persistent through the end of the study (12 weeks post-injury). Unlike the individual treatment groups which never achieved weight support, the combination therapy animals were able to perform uncoordinated weight-supported stepping without a body weight support system while on a moving treadmill (6.5 m per minute) and were capable of supporting their own weight in stance during open field locomotion testing. No regeneration of descending serotonergic projections into and through the lesion cavity was observed. Furthermore, these results are a testament to the capacity of the lumbar spinal cord, when properly stimulated, to sustain functioning locomotor circuitry following complete SCI.

Applying image quality in cell phone cameras: lens distortion

NASA Astrophysics Data System (ADS)

Baxter, Donald; Goma, Sergio R.; Aleksic, Milivoje

2009-01-01

This paper describes the framework used in one of the pilot studies run under the I3A CPIQ initiative to quantify overall image quality in cell-phone cameras. The framework is based on a multivariate formalism which tries to predict overall image quality from individual image quality attributes and was validated in a CPIQ pilot program. The pilot study focuses on image quality distortions introduced in the optical path of a cell-phone camera, which may or may not be corrected in the image processing path. The assumption is that the captured image used is JPEG compressed and the cellphone camera is set to 'auto' mode. As the used framework requires that the individual attributes to be relatively perceptually orthogonal, in the pilot study, the attributes used are lens geometric distortion (LGD) and lateral chromatic aberrations (LCA). The goal of this paper is to present the framework of this pilot project starting with the definition of the individual attributes, up to their quantification in JNDs of quality, a requirement of the multivariate formalism, therefore both objective and subjective evaluations were used. A major distinction in the objective part from the 'DSC imaging world' is that the LCA/LGD distortions found in cell-phone cameras, rarely exhibit radial behavior, therefore a radial mapping/modeling cannot be used in this case.

Toward the reconstitution of synthetic cell motility

PubMed Central

Siton-Mendelson, Orit; Bernheim-Groswasser, Anne

2016-01-01

ABSTRACT Cellular motility is a fundamental process essential for embryonic development, wound healing, immune responses, and tissues development. Cells are mostly moving by crawling on external, or inside, substrates which can differ in their surface composition, geometry, and dimensionality. Cells can adopt different migration phenotypes, e.g., bleb-based and protrusion-based, depending on myosin contractility, surface adhesion, and cell confinement. In the few past decades, research on cell motility has focused on uncovering the major molecular players and their order of events. Despite major progresses, our ability to infer on the collective behavior from the molecular properties remains a major challenge, especially because cell migration integrates numerous chemical and mechanical processes that are coupled via feedbacks that span over large range of time and length scales. For this reason, reconstituted model systems were developed. These systems allow for full control of the molecular constituents and various system parameters, thereby providing insight into their individual roles and functions. In this review we describe the various reconstituted model systems that were developed in the past decades. Because of the multiple steps involved in cell motility and the complexity of the overall process, most of the model systems focus on very specific aspects of the individual steps of cell motility. Here we describe the main advancement in cell motility reconstitution and discuss the main challenges toward the realization of a synthetic motile cell. PMID:27019160

Multi-scale lung modeling.

PubMed

Tawhai, Merryn H; Bates, Jason H T

2011-05-01

Multi-scale modeling of biological systems has recently become fashionable due to the growing power of digital computers as well as to the growing realization that integrative systems behavior is as important to life as is the genome. While it is true that the behavior of a living organism must ultimately be traceable to all its components and their myriad interactions, attempting to codify this in its entirety in a model misses the insights gained from understanding how collections of system components at one level of scale conspire to produce qualitatively different behavior at higher levels. The essence of multi-scale modeling thus lies not in the inclusion of every conceivable biological detail, but rather in the judicious selection of emergent phenomena appropriate to the level of scale being modeled. These principles are exemplified in recent computational models of the lung. Airways responsiveness, for example, is an organ-level manifestation of events that begin at the molecular level within airway smooth muscle cells, yet it is not necessary to invoke all these molecular events to accurately describe the contraction dynamics of a cell, nor is it necessary to invoke all phenomena observable at the level of the cell to account for the changes in overall lung function that occur following methacholine challenge. Similarly, the regulation of pulmonary vascular tone has complex origins within the individual smooth muscle cells that line the blood vessels but, again, many of the fine details of cell behavior average out at the level of the organ to produce an effect on pulmonary vascular pressure that can be described in much simpler terms. The art of multi-scale lung modeling thus reduces not to being limitlessly inclusive, but rather to knowing what biological details to leave out.

INDIVIDUAL DIFFERENCES IN IMPULSIVE CHOICE AND TIMING IN RATS

PubMed Central

Galtress, Tiffany; Garcia, Ana; Kirkpatrick, Kimberly

2012-01-01

Individual differences in impulsive choice behavior have been linked to a variety of behavioral problems including substance abuse, smoking, gambling, and poor financial decision-making. Given the potential importance of individual differences in impulsive choice as a predictor of behavioral problems, the present study sought to measure the extent of individual differences in a normal sample of hooded Lister rats. Three experiments utilized variations of a delay discounting task to measure the degree of variation in impulsive choice behavior across individual rats. The individual differences accounted for 22–55% of the variance in choice behavior across the three experiments. In Experiments 2 and 3, the individual differences were still apparent when behavior was measured across multiple choice points. Large individual differences in the rate of responding, and modest individual differences in timing of responding were also observed during occasional peak trials. The individual differences in timing and rate, however, did not correlate consistently with individual differences in choice behavior. This suggests that a variety of factors may affect choice behavior, response rate, and response timing. PMID:22851792

Cooperative synchronized assemblies enhance orientation discrimination.

PubMed

Samonds, Jason M; Allison, John D; Brown, Heather A; Bonds, A B

2004-04-27

There is no clear link between the broad tuning of single neurons and the fine behavioral capabilities of orientation discrimination. We recorded from populations of cells in the cat visual cortex (area 17) to examine whether the joint activity of cells can support finer discrimination than found in individual responses. Analysis of joint firing yields a substantial advantage (i.e., cooperation) in fine-angle discrimination. This cooperation increases to more considerable levels as the population of an assembly is increased. The cooperation in a population of six cells provides encoding of orientation with an information advantage that is at least 2-fold in terms of requiring either fewer cells or less time than independent coding. This cooperation suggests that correlated or synchronized activity can increase information.

Patients' Illness Perception as a Tool to Improve Individual Disease Management in Primary Cutaneous Lymphomas.

PubMed

Porkert, Stefanie; Lehner-Baumgartner, Eva; Valencak, Julia; Knobler, Robert; Riedl, Elisabeth; Jonak, Constanze

2018-02-07

The Revised Illness Perception Questionnaire (IPQ-R) has been shown to assess illness perception reproducibly in primary cutaneous T-cell lymphomas (CTCL). Illness perception reflects patients' individual concepts of understanding and interpretation of the disease, influencing illness behaviour and health-related quality of life (HRQOL). This study investigated the clinical relevance of the relationships between illness perception, illness behaviour, and HRQOL in CTCL and cutaneous B-cell lymphomas (CBCL). A total of 92 patients completed the IPQ-R, the Scale for the Assessment of Illness Behavior (SAIB), and a skin-specific HRQOL tool (Skindex-29). Data on illness behaviour were not evidently related to illness perception, whereas illness perception was significantly associated with HRQOL. Both, IPQ-R and HRQOL results correlated with disease entity, stage, and socio-demographics. Only IPQ-R results provided practical information on patients' needs to train personal coping strategies. IPQ-R assessment in CTCL and CBCL might be a useful instrument to improve individual disease management.

Effects of membrane properties on the binding activities of the HN and HC heavy-chain domains of botulinum neurotoxin A.

PubMed

Ayyar, B Vijayalakshmi; Atassi, M Zouhair

2016-12-01

Binding behaviors of the H N and the H C domains of BoNT/A were investigated individually to identify if there exist any differences in their interaction with the cell membrane. Recombinant fragments corresponding to both BoNT/A H N and H C regions were prepared (H N 519-845 and H C 967-1296) and their binding to synaptic proteins was verified. The binding behaviors of these heavy-chain domains were analyzed by treating the Neuro 2a, a murine neuroblastoma cell line, with compounds known to alter membrane properties. Cholesterol depletion and lipid raft inhibition increased the binding of H N 519-845 to Neuro 2a cells without affecting H C 967-1296-cell interaction. Sphingolipid depletion decreased the binding of cells to both H C 967-1296 and H N 519-845 whereas, loading exogenous GD1a, on to the Neuro 2a cells, increased the binding of both the peptides to cells. Microtubule disruption of the Neuro 2a cells by nocodazole decreased the binding of both H C 967-1296 and H N 519-845 to the treated cells. Inhibition of the clathrin-mediated endocytosis using dynasore, chlorpromazine or potassium (K + ) depletion buffer lowered the binding of both H C 967-1296 and H N 519-845 to the cells, but seemed to exert a more pronounced effect on the binding of H C 967-1296 than on the binding of H N 519-845. Results indicate that while both the H N and H C domains are involved in the binding of the toxin to neuronal cells there are differences in their behavior which probably stem from their respective amino acid composition and structural location in the toxin three-dimensional structure along with their intended role in translocation and internalization into the cells. Copyright © 2016 Elsevier B.V. All rights reserved.

Collective Cellular Decision-Making Gives Developmental Plasticity: A Model of Signaling in Branching Roots

NASA Astrophysics Data System (ADS)

McCleery, W. Tyler; Mohd-Radzman, Nadiatul A.; Grieneisen, Veronica A.

Cells within tissues can be regarded as autonomous entities that respond to their local environment and signaling from neighbors. Cell coordination is particularly important in plants, where root architecture must strategically invest resources for growth to optimize nutrient acquisition. Thus, root cells are constantly adapting to environmental cues and neighbor communication in a non-linear manner. To explain such plasticity, we view the root as a swarm of coupled multi-cellular structures, ''metamers'', rather than as a continuum of identical cells. These metamers are individually programmed to achieve a local objective - developing a lateral root primordia, which aids in local foraging of nutrients. Collectively, such individual attempts may be halted, structuring root architecture as an emergent behavior. Each metamer's decision to branch is coordinated locally and globally through hormone signaling, including processes of controlled diffusion, active polar transport, and dynamic feedback. We present a physical model of the signaling mechanism that coordinates branching decisions in response to the environment. This work was funded by the European Commission 7th Framework Program, Project No. 601062, SWARM-ORGAN.

A Nonlinear Mixed Effects Approach for Modeling the Cell-To-Cell Variability of Mig1 Dynamics in Yeast

PubMed Central

Almquist, Joachim; Bendrioua, Loubna; Adiels, Caroline Beck; Goksör, Mattias; Hohmann, Stefan; Jirstrand, Mats

2015-01-01

The last decade has seen a rapid development of experimental techniques that allow data collection from individual cells. These techniques have enabled the discovery and characterization of variability within a population of genetically identical cells. Nonlinear mixed effects (NLME) modeling is an established framework for studying variability between individuals in a population, frequently used in pharmacokinetics and pharmacodynamics, but its potential for studies of cell-to-cell variability in molecular cell biology is yet to be exploited. Here we take advantage of this novel application of NLME modeling to study cell-to-cell variability in the dynamic behavior of the yeast transcription repressor Mig1. In particular, we investigate a recently discovered phenomenon where Mig1 during a short and transient period exits the nucleus when cells experience a shift from high to intermediate levels of extracellular glucose. A phenomenological model based on ordinary differential equations describing the transient dynamics of nuclear Mig1 is introduced, and according to the NLME methodology the parameters of this model are in turn modeled by a multivariate probability distribution. Using time-lapse microscopy data from nearly 200 cells, we estimate this parameter distribution according to the approach of maximizing the population likelihood. Based on the estimated distribution, parameter values for individual cells are furthermore characterized and the resulting Mig1 dynamics are compared to the single cell times-series data. The proposed NLME framework is also compared to the intuitive but limited standard two-stage (STS) approach. We demonstrate that the latter may overestimate variabilities by up to almost five fold. Finally, Monte Carlo simulations of the inferred population model are used to predict the distribution of key characteristics of the Mig1 transient response. We find that with decreasing levels of post-shift glucose, the transient response of Mig1 tend to be faster, more extended, and displays an increased cell-to-cell variability. PMID:25893847

Lateral diffusion and retrograde movements of individual cell surface components on single motile cells observed with Nanovid microscopy

PubMed Central

1991-01-01

A recently introduced extension of video-enhanced light microscopy, called Nanovid microscopy, documents the dynamic reorganization of individual cell surface components on living cells. 40-microns colloidal gold probes coupled to different types of poly-L-lysine label negative cell surface components of PTK2 cells. Evidence is provided that they bind to negative sialic acid residues of glycoproteins, probably through nonspecific electrostatic interactions. The gold probes, coupled to short poly-L-lysine molecules (4 kD) displayed Brownian motion, with a diffusion coefficient in the range 0.1-0.2 micron2/s. A diffusion coefficient in the 0.1 micron2/s range was also observed with 40-nm gold probes coupled to an antibody against the lipid-linked Thy-1 antigen on 3T3 fibroblasts. Diffusion of these probes is largely confined to apparent microdomains of 1-2 microns in size. On the other hand, the gold probes, coupled to long poly-L-lysine molecules (240 kD) molecules and bound to the leading lamella, were driven rearward, toward the boundary between lamelloplasm and perinuclear cytoplasm at a velocity of 0.5-1 micron/min by a directed ATP-dependent mechanism. This uniform motion was inhibited by cytochalasin, suggesting actin microfilament involvement. A similar behavior on MO cells was observed when the antibody-labeled gold served as a marker for the PGP-1 (GP-80) antigen. These results show that Nanovid microscopy, offering the possibility to observe the motion of individual specific cell surface components, provides a new and powerful tool to study the dynamic reorganization of the cell membrane during locomotion and in other biological contexts as well. PMID:1670778

Live cell imaging reveals marked variability in myoblast proliferation and fate

PubMed Central

2013-01-01

Background During the process of muscle regeneration, activated stem cells termed satellite cells proliferate, and then differentiate to form new myofibers that restore the injured area. Yet not all satellite cells contribute to muscle repair. Some continue to proliferate, others die, and others become quiescent and are available for regeneration following subsequent injury. The mechanisms that regulate the adoption of different cell fates in a muscle cell precursor population remain unclear. Methods We have used live cell imaging and lineage tracing to study cell fate in the C2 myoblast line. Results Analyzing the behavior of individual myoblasts revealed marked variability in both cell cycle duration and viability, but similarities between cells derived from the same parental lineage. As a consequence, lineage sizes and outcomes differed dramatically, and individual lineages made uneven contributions toward the terminally differentiated population. Thus, the cohort of myoblasts undergoing differentiation at the end of an experiment differed dramatically from the lineages present at the beginning. Treatment with IGF-I increased myoblast number by maintaining viability and by stimulating a fraction of cells to complete one additional cell cycle in differentiation medium, and as a consequence reduced the variability of the terminal population compared with controls. Conclusion Our results reveal that heterogeneity of responses to external cues is an intrinsic property of cultured myoblasts that may be explained in part by parental lineage, and demonstrate the power of live cell imaging for understanding how muscle differentiation is regulated. PMID:23638706

Nascent RNA kinetics: Transient and steady state behavior of models of transcription

NASA Astrophysics Data System (ADS)

Choubey, Sandeep

2018-02-01

Regulation of transcription is a vital process in cells, but mechanistic details of this regulation still remain elusive. The dominant approach to unravel the dynamics of transcriptional regulation is to first develop mathematical models of transcription and then experimentally test the predictions these models make for the distribution of mRNA and protein molecules at the individual cell level. However, these measurements are affected by a multitude of downstream processes which make it difficult to interpret the measurements. Recent experimental advancements allow for counting the nascent mRNA number of a gene as a function of time at the single-inglr cell level. These measurements closely reflect the dynamics of transcription. In this paper, we consider a general mechanism of transcription with stochastic initiation and deterministic elongation and probe its impact on the temporal behavior of nascent RNA levels. Using techniques from queueing theory, we derive exact analytical expressions for the mean and variance of the nascent RNA distribution as functions of time. We apply these analytical results to obtain the mean and variance of nascent RNA distribution for specific models of transcription. These models of initiation exhibit qualitatively distinct transient behaviors for both the mean and variance which further allows us to discriminate between them. Stochastic simulations confirm these results. Overall the analytical results presented here provide the necessary tools to connect mechanisms of transcription initiation to single-cell measurements of nascent RNA.

Technology computer aided design of 29.5% efficient perovskite/interdigitated back contact silicon heterojunction mechanically stacked tandem solar cell for energy-efficient applications

NASA Astrophysics Data System (ADS)

Pandey, Rahul; Chaujar, Rishu

2017-04-01

A 29.5% efficient perovskite/SiC passivated interdigitated back contact silicon heterojunction (IBC-SiHJ) mechanically stacked tandem solar cell device has been designed and simulated. This is a substantial improvement of 40% and 15%, respectively, compared to the transparent perovskite solar cell (21.1%) and Si solar cell (25.6%) operated individually. The perovskite solar cell has been used as a top subcell, whereas 250- and 25-μm-thick IBC-SiHJ solar cells have been used as bottom subcells. The realistic technology computer aided design analysis has been performed to understand the physical processes in the device and to make reliable predictions of the behavior. The performance of the top subcell has been obtained for different acceptor densities and hole mobility in Spiro-MeOTAD along with the impact of counter electrode work function. To incorporate the effect of material quality, the influence of carrier lifetimes has also been studied for perovskite top and IBC-SiHJ bottom subcells. The optical and electrical behavior of the devices has been obtained for both standalone as well as tandem configuration. Results reported in this study reveal that the proposed four-terminal tandem device may open a new door for cost-effective and energy-efficient applications.

Entrainment and Control of Bacterial Populations: An in Silico Study over a Spatially Extended Agent Based Model.

PubMed

Mina, Petros; Tsaneva-Atanasova, Krasimira; Bernardo, Mario di

2016-07-15

We extend a spatially explicit agent based model (ABM) developed previously to investigate entrainment and control of the emergent behavior of a population of synchronized oscillating cells in a microfluidic chamber. Unlike most of the work in models of control of cellular systems which focus on temporal changes, we model individual cells with spatial dependencies which may contribute to certain behavioral responses. We use the model to investigate the response of both open loop and closed loop strategies, such as proportional control (P-control), proportional-integral control (PI-control) and proportional-integral-derivative control (PID-control), to heterogeinities and growth in the cell population, variations of the control parameters and spatial effects such as diffusion in the spatially explicit setting of a microfluidic chamber setup. We show that, as expected from the theory of phase locking in dynamical systems, open loop control can only entrain the cell population in a subset of forcing periods, with a wide variety of dynamical behaviors obtained outside these regions of entrainment. Closed-loop control is shown instead to guarantee entrainment in a much wider region of control parameter space although presenting limitations when the population size increases over a certain threshold. In silico tracking experiments are also performed to validate the ability of classical control approaches to achieve other reference behaviors such as a desired constant output or a linearly varying one. All simulations are carried out in BSim, an advanced agent-based simulator of microbial population which is here extended ad hoc to include the effects of control strategies acting onto the population.

Intersection of diverse neuronal genomes and neuropsychiatric disease: The Brain Somatic Mosaicism Network.

PubMed

McConnell, Michael J; Moran, John V; Abyzov, Alexej; Akbarian, Schahram; Bae, Taejeong; Cortes-Ciriano, Isidro; Erwin, Jennifer A; Fasching, Liana; Flasch, Diane A; Freed, Donald; Ganz, Javier; Jaffe, Andrew E; Kwan, Kenneth Y; Kwon, Minseok; Lodato, Michael A; Mills, Ryan E; Paquola, Apua C M; Rodin, Rachel E; Rosenbluh, Chaggai; Sestan, Nenad; Sherman, Maxwell A; Shin, Joo Heon; Song, Saera; Straub, Richard E; Thorpe, Jeremy; Weinberger, Daniel R; Urban, Alexander E; Zhou, Bo; Gage, Fred H; Lehner, Thomas; Senthil, Geetha; Walsh, Christopher A; Chess, Andrew; Courchesne, Eric; Gleeson, Joseph G; Kidd, Jeffrey M; Park, Peter J; Pevsner, Jonathan; Vaccarino, Flora M

2017-04-28

Neuropsychiatric disorders have a complex genetic architecture. Human genetic population-based studies have identified numerous heritable sequence and structural genomic variants associated with susceptibility to neuropsychiatric disease. However, these germline variants do not fully account for disease risk. During brain development, progenitor cells undergo billions of cell divisions to generate the ~80 billion neurons in the brain. The failure to accurately repair DNA damage arising during replication, transcription, and cellular metabolism amid this dramatic cellular expansion can lead to somatic mutations. Somatic mutations that alter subsets of neuronal transcriptomes and proteomes can, in turn, affect cell proliferation and survival and lead to neurodevelopmental disorders. The long life span of individual neurons and the direct relationship between neural circuits and behavior suggest that somatic mutations in small populations of neurons can significantly affect individual neurodevelopment. The Brain Somatic Mosaicism Network has been founded to study somatic mosaicism both in neurotypical human brains and in the context of complex neuropsychiatric disorders. Copyright © 2017, American Association for the Advancement of Science.

Estimating individual influences of behavioral intentions: an application of random-effects modeling to the theory of reasoned action.

PubMed

Hedeker, D; Flay, B R; Petraitis, J

1996-02-01

Methods are proposed and described for estimating the degree to which relations among variables vary at the individual level. As an example of the methods, M. Fishbein and I. Ajzen's (1975; I. Ajzen & M. Fishbein, 1980) theory of reasoned action is examined, which posits first that an individual's behavioral intentions are a function of 2 components: the individual's attitudes toward the behavior and the subjective norms as perceived by the individual. A second component of their theory is that individuals may weight these 2 components differently in assessing their behavioral intentions. This article illustrates the use of empirical Bayes methods based on a random-effects regression model to estimate these individual influences, estimating an individual's weighting of both of these components (attitudes toward the behavior and subjective norms) in relation to their behavioral intentions. This method can be used when an individual's behavioral intentions, subjective norms, and attitudes toward the behavior are all repeatedly measured. In this case, the empirical Bayes estimates are derived as a function of the data from the individual, strengthened by the overall sample data.

Analyzing cell fate control by cytokines through continuous single cell biochemistry.

PubMed

Rieger, Michael A; Schroeder, Timm

2009-10-01

Cytokines are important regulators of cell fates with high clinical and commercial relevance. However, despite decades of intense academic and industrial research, it proved surprisingly difficult to describe the biological functions of cytokines in a precise and comprehensive manner. The exact analysis of cytokine biology is complicated by the fact that individual cytokines control many different cell fates and activate a multitude of intracellular signaling pathways. Moreover, although activating different molecular programs, different cytokines can be redundant in their biological effects. In addition, cytokines with different biological effects can activate overlapping signaling pathways. This prospect article will outline the necessity of continuous single cell biochemistry to unravel the biological functions of molecular cytokine signaling. It focuses on potentials and limitations of recent technical developments in fluorescent time-lapse imaging and single cell tracking allowing constant long-term observation of molecules and behavior of single cells. (c) 2009 Wiley-Liss, Inc.

The effect of fibrin on cultured vascular endothelial cells.

PubMed

Kadish, J L; Butterfield, C E; Folkman, J

1979-01-01

The normal cobblestone monolayer architecture of cultured vascular endothelium becomes rapidly disorganized after contact of the cell layer with a fibrin clot. The cells of a confluent endothelial monolayer separate into individual migratory cells in 4--6 hr after contact with fibrin. The effect is reversible in that removal of the fibrin clot results in resumption of the normal morphology within about 2 hr. No other cell type tested exhibits the same change in organization when exposed to fibrin. A similar morphological change in endothelium does occur after the cell layer is overlaid with a collagen fibril gel but a gel of methylcellulose has no effect. It is proposed that the change in behavior of endothelial cells in response to contact with fibrin may represent a cellular component of fibrinolysis. The implications of this finding for the pathophysiology of disease states involving intravascular fibrin deposition are discussed.

De novo variants in EBF3 are associated with hypotonia, developmental delay, intellectual disability, and autism

PubMed Central

Tanaka, Akemi J.; Cho, Megan T.; Willaert, Rebecca; Retterer, Kyle; Zarate, Yuri A.; Bosanko, Katie; Stefans, Vikki; Oishi, Kimihiko; Williamson, Amy; Wilson, Golder N.; Basinger, Alice; Barbaro-Dieber, Tina; Ortega, Lucia; Sorrentino, Susanna; Gabriel, Melissa K.; Anderson, Ilse J.; Sacoto, Maria J. Guillen; Schnur, Rhonda E.; Chung, Wendy K.

2017-01-01

Using whole-exome sequencing, we identified seven unrelated individuals with global developmental delay, hypotonia, dysmorphic facial features, and an increased frequency of short stature, ataxia, and autism with de novo heterozygous frameshift, nonsense, splice, and missense variants in the Early B-cell Transcription Factor Family Member 3 (EBF3) gene. EBF3 is a member of the collier/olfactory-1/early B-cell factor (COE) family of proteins, which are required for central nervous system (CNS) development. COE proteins are highly evolutionarily conserved and regulate neuronal specification, migration, axon guidance, and dendritogenesis during development and are essential for maintaining neuronal identity in adult neurons. Haploinsufficiency of EBF3 may affect brain development and function, resulting in developmental delay, intellectual disability, and behavioral differences observed in individuals with a deleterious variant in EBF3. PMID:29162653

Viscoelastic Properties Measurement of Human Lymphocytes by Atomic Force Microscopy Based on Magnetic Beads Cell Isolation.

PubMed

Mi Li; Lianqing Liu; Xiubin Xiao; Ning Xi; Yuechao Wang

2016-07-01

Cell mechanics has been proved to be an effective biomarker for indicating cellular states. The advent of atomic force microscopy (AFM) provides an exciting instrument for measuring the mechanical properties of single cells. However, current AFM single-cell mechanical measurements are commonly performed on cell lines cultured in vitro which are quite different from the primary cells in the human body. Investigating the mechanical properties of primary cells from clinical environments can help us to better understand cell behaviors. Here, by combining AFM with magnetic beads cell isolation, the viscoelastic properties of human primary B lymphocytes were quantitatively measured. B lymphocytes were isolated from the peripheral blood of healthy volunteers by density gradient centrifugation and CD19 magnetic beads cell isolation. The activity and specificity of the isolated cells were confirmed by fluorescence microscopy. AFM imaging revealed the surface topography and geometric parameters of B lymphocytes. The instantaneous modulus and relaxation time of living B lymphocytes were measured by AFM indenting technique, showing that the instantaneous modulus of human normal B lymphocytes was 2-3 kPa and the relaxation times were 0.03-0.06 s and 0.35-0.55 s. The differences in cellular visocoelastic properties between primary B lymphocytes and cell lines cultured in vitro were analyzed. The study proves the capability of AFM in quantifying the viscoelastic properties of individual specific primary cells from the blood sample of clinical patients, which will improve our understanding of the behaviors of cells in the human body.

Cyberspace and Real-World Behavioral Relationships: Towards the Applications of Interest Search Queries to Identify Individuals At-Risk for Suicide

DTIC Science & Technology

2012-06-14

weight fat loss effects diet standard nutrition lose nfpa protein Topic 214: menu restaurant engineering restaurants jones wings seat wild buffalo...Selection ................................................................................... 30 3.5 Raw Data File Format...text mining to descriptions of biological activity and the target of the biological activity (i.e., gene, protein , cell, or microorganism) to predict

A Macro-to-Micro Interface for the Control of Cellular Organization

PubMed Central

Hui, Elliot E.; Li, Chun; Agrawal, Amit; Bhatia, Sangeeta N.

2015-01-01

The spatial organization of cellular communities plays a fundamental role in determining intercellular communication and emergent behavior. However, few tools exist to modulate tissue organization at the scale of individual cells, particularly in the case of dynamic manipulation. Micromechanical reconfigurable culture achieves dynamic control of tissue organization by culturing adherent cells on microfabricated plates that can be shifted to reorganize the arrangement of the cells. While biological studies utilizing this approach have been previously reported, this paper focuses on the engineering of the device, including the mechanism for translating manual manipulation to precise microscale position control, fault-tolerant design for manufacture, and the synthetic-to-living interface. PMID:26167106

Interrater Agreement of the Individualized Behavior Rating Scale Tool

ERIC Educational Resources Information Center

Iovannone, Rose; Greenbaum, Paul E.; Wang, Wei; Dunlap, Glen; Kincaid, Don

2014-01-01

Data assessment is critical for determining student behavior change in response to individualized behavior interventions in schools. This study examined the interrater agreement of the Individualized Behavior Rating Scale Tool (IBRST), a perceptual direct behavior rating tool that was used by typical school personnel to record behavior occurrence…

Individual differences in temperament and behavioral management practices for nonhuman primates

PubMed Central

Coleman, Kristine

2011-01-01

Effective behavioral management plans are tailored to unique behavioral patterns of each individual species. However, even within a species behavioral needs of individuals can vary. Factors such as age, sex, and temperament can affect behavioral needs of individuals. While some of these factors, such as age and sex, are taken into account, other factors, such as an individual’s temperament, are rarely specifically provided for in behavioral management plans. However, temperament may affect how animals respond to socialization, positive reinforcement training and other forms of enrichment. This review will examine how individual differences in temperament might affect, or be affected by, behavioral management practices for captive primates. Measuring temperament may help us predict outcome of social introductions. It can also predict which animals may be difficult to train using traditional methods. Further, knowledge of temperament may be able to help identify individuals at risk for development of behavioral problems. Taken together, understanding individual differences in temperament of captive primates can help guide behavioral management decisions. PMID:22518067

Regeneration of Sensory Hair Cells Requires Localized Interactions between the Notch and Wnt Pathways.

PubMed

Romero-Carvajal, Andrés; Navajas Acedo, Joaquín; Jiang, Linjia; Kozlovskaja-Gumbrienė, Agnė; Alexander, Richard; Li, Hua; Piotrowski, Tatjana

2015-08-10

In vertebrates, mechano-electrical transduction of sound is accomplished by sensory hair cells. Whereas mammalian hair cells are not replaced when lost, in fish they constantly renew and regenerate after injury. In vivo tracking and cell fate analyses of all dividing cells during lateral line hair cell regeneration revealed that support and hair cell progenitors localize to distinct tissue compartments. Importantly, we find that the balance between self-renewal and differentiation in these compartments is controlled by spatially restricted Notch signaling and its inhibition of Wnt-induced proliferation. The ability to simultaneously study and manipulate individual cell behaviors and multiple pathways in vivo transforms the lateral line into a powerful paradigm to mechanistically dissect sensory organ regeneration. The striking similarities to other vertebrate stem cell compartments uniquely place zebrafish to help elucidate why mammals possess such low capacity to regenerate hair cells. Copyright © 2015 Elsevier Inc. All rights reserved.

Mathematical analysis of antiretroviral therapy aimed at HIV-1 eradication or maintenance of low viral loads.

PubMed

Wein, L M; D'Amato, R M; Perelson, A S

1998-05-07

Motivated by the ability of combinations of antiretroviral agents to sustain viral suppression in HIV-1-infected individuals, we analyse the transient and steady-state behavior of a mathematical model of HIV-1 dynamics in vivo in order to predict whether these drug regimens can eradicate HIV-1 or maintain viral loads at low levels. The model incorporates two cell types (CD4+ T cells and a long-lived pool of cells), two strains of virus (drug-sensitive wild type and drug-resistant mutant) and two types of antiretroviral agents (reverse transcriptase and protease inhibitors). The transient behavior of the cells and virus and the eventual eradication of the virus are determined primarily by the strength of the combination therapy against the mutant strain and the maximum achievable increase in the uninfected CD4+ T cell concentration. We also predict, if the parameters of the model remain constant during therapy, that less intensive maintenance regimens will be unable to maintain low viral loads for extensive periods of time. However, if the reduction in viral load produced by therapy reduces the state of activation of the immune system, the number of cells susceptible for HIV-1 infection may decrease even though total CD4+ T cells increase. Our model predicts that if this occurs strong inductive therapy that reduces viral load followed by weaker maintenance regimes may succeed.

Recent Advances in Biosensing With Photonic Crystal Surfaces: A Review

PubMed Central

Cunningham, B.T.; Zhang, M.; Zhuo, Y.; Kwon, L.; Race, C.

2016-01-01

Photonic crystal surfaces that are designed to function as wavelength-selective optical resonators have become a widely adopted platform for label-free biosensing, and for enhancement of the output of photon-emitting tags used throughout life science research and in vitro diagnostics. While some applications, such as analysis of drug-protein interactions, require extremely high resolution and the ability to accurately correct for measurement artifacts, others require sensitivity that is high enough for detection of disease biomarkers in serum with concentrations less than 1 pg/ml. As the analysis of cells becomes increasingly important for studying the behavior of stem cells, cancer cells, and biofilms under a variety of conditions, approaches that enable high resolution imaging of live cells without cytotoxic stains or photobleachable fluorescent dyes are providing new tools to biologists who seek to observe individual cells over extended time periods. This paper will review several recent advances in photonic crystal biosensor detection instrumentation and device structures that are being applied towards direct detection of small molecules in the context of high throughput drug screening, photonic crystal fluorescence enhancement as utilized for high sensitivity multiplexed cancer biomarker detection, and label-free high resolution imaging of cells and individual nanoparticles as a new tool for life science research and single-molecule diagnostics. PMID:27642265

Effects of departing individuals on collective behaviors

NASA Astrophysics Data System (ADS)

Nishiyama, Yuta; Okuda, Shoma; Migita, Masao; Murakami, Hisashi; Tomaru, Takenori

2017-07-01

Utilizing living organisms' abilities is an effective approach to realize flexible and unconventional computing. One possible bio-inspired computer might be developed from animal collective research by clarifying collective behaviors. Therefore, it is important to reveal how collective animal behaviors emerge. In many studies, individuals departing from the other individualsare generally ignored. Is it not possible that such departing individuals contribute to the organization of such collectives? To investigate the effects of individuals departing from a collective against collective behaviors, we observed and analyzed the behaviors of 40 soldier crabs in four types of experimental arenas. The recorded behaviors demonstrate a temporally changing pattern and the existence of departing individuals. We analyzed the relationship between global activity and cohesion levels and verified the features of departing individuals. The results imply that departing individuals contribute to collective behaviors.

Real-time monitoring of quorum sensing in 3D-printed bacterial aggregates using scanning electrochemical microscopy.

PubMed

Connell, Jodi L; Kim, Jiyeon; Shear, Jason B; Bard, Allen J; Whiteley, Marvin

2014-12-23

Microbes frequently live in nature as small, densely packed aggregates containing ∼10(1)-10(5) cells. These aggregates not only display distinct phenotypes, including resistance to antibiotics, but also, serve as building blocks for larger biofilm communities. Aggregates within these larger communities display nonrandom spatial organization, and recent evidence indicates that this spatial organization is critical for fitness. Studying single aggregates as well as spatially organized aggregates remains challenging because of the technical difficulties associated with manipulating small populations. Micro-3D printing is a lithographic technique capable of creating aggregates in situ by printing protein-based walls around individual cells or small populations. This 3D-printing strategy can organize bacteria in complex arrangements to investigate how spatial and environmental parameters influence social behaviors. Here, we combined micro-3D printing and scanning electrochemical microscopy (SECM) to probe quorum sensing (QS)-mediated communication in the bacterium Pseudomonas aeruginosa. Our results reveal that QS-dependent behaviors are observed within aggregates as small as 500 cells; however, aggregates larger than 2,000 bacteria are required to stimulate QS in neighboring aggregates positioned 8 μm away. These studies provide a powerful system to analyze the impact of spatial organization and aggregate size on microbial behaviors.

Molecular insights into human daily behavior

PubMed Central

Brown, Steven A.; Kunz, Dieter; Dumas, Amelie; Westermark, Pål O.; Vanselow, Katja; Tilmann-Wahnschaffe, Amely; Herzel, Hanspeter; Kramer, Achim

2008-01-01

Human beings exhibit wide variation in their timing of daily behavior. We and others have suggested previously that such differences might arise because of alterations in the period length of the endogenous human circadian oscillator. Using dermal fibroblast cells from skin biopsies of 28 subjects of early and late chronotype (11 “larks” and 17 “owls”), we have studied the circadian period lengths of these two groups, as well as their ability to phase-shift and entrain to environmental and chemical signals. We find not only period length differences between the two classes, but also significant changes in the amplitude and phase-shifting properties of the circadian oscillator among individuals with identical “normal” period lengths. Mathematical modeling shows that these alterations could also account for the extreme behavioral phenotypes of these subjects. We conclude that human chronotype may be influenced not only by the period length of the circadian oscillator, but also by cellular components that affect its amplitude and phase. In many instances, these changes can be studied at the molecular level in primary dermal cells. PMID:18227513

Discrete modes of social information processing predict individual behavior of fish in a group

PubMed Central

Harpaz, Roy; Tkačik, Gašper

2017-01-01

Individual computations and social interactions underlying collective behavior in groups of animals are of great ethological, behavioral, and theoretical interest. While complex individual behaviors have successfully been parsed into small dictionaries of stereotyped behavioral modes, studies of collective behavior largely ignored these findings; instead, their focus was on inferring single, mode-independent social interaction rules that reproduced macroscopic and often qualitative features of group behavior. Here, we bring these two approaches together to predict individual swimming patterns of adult zebrafish in a group. We show that fish alternate between an “active” mode, in which they are sensitive to the swimming patterns of conspecifics, and a “passive” mode, where they ignore them. Using a model that accounts for these two modes explicitly, we predict behaviors of individual fish with high accuracy, outperforming previous approaches that assumed a single continuous computation by individuals and simple metric or topological weighing of neighbors’ behavior. At the group level, switching between active and passive modes is uncorrelated among fish, but correlated directional swimming behavior still emerges. Our quantitative approach for studying complex, multimodal individual behavior jointly with emergent group behavior is readily extensible to additional behavioral modes and their neural correlates as well as to other species. PMID:28874581

Individual and Combined Roles of the Master Regulators AphA and LuxR in Control of the Vibrio harveyi Quorum-Sensing Regulon

PubMed Central

van Kessel, Julia C.; Rutherford, Steven T.; Shao, Yi; Utria, Alan F.

2013-01-01

Bacteria use a chemical communication process called quorum sensing to control transitions between individual and group behaviors. In the Vibrio harveyi quorum-sensing circuit, two master transcription factors, AphA and LuxR, coordinate the quorum-sensing response. Here we show that AphA regulates 167 genes, LuxR regulates 625 genes, and they coregulate 77 genes. LuxR strongly controls genes at both low cell density and high cell density, suggesting that it is the major quorum-sensing regulator. In contrast, AphA is absent at high cell density and acts to fine-tune quorum-sensing gene expression at low cell density. We examined two loci as case studies of coregulation by AphA and LuxR. First, AphA and LuxR directly regulate expression of the genes encoding the quorum-regulatory small RNAs Qrr2, Qrr3, and Qrr4, the consequence of which is a specifically timed transition between the individual and the group life-styles. Second, AphA and LuxR repress type III secretion system genes but at different times and to different extents. The consequence of this regulation is that type III secretion is restricted to a peak at mid-cell density. Thus, the asymmetric production of AphA and LuxR coupled with differences in their strengths and timing of target gene regulation generate a precise temporal pattern of gene expression. PMID:23204455

The hippocampo-amygdala control of contextual fear expression is affected in a model of intellectual disability.

PubMed

Zhang, Chun-Lei; Houbaert, Xander; Lepleux, Marilyn; Deshors, Melissa; Normand, Elisabeth; Gambino, Frédéric; Herzog, Etienne; Humeau, Yann

2015-11-01

The process of learning mainly depends on the ability to store new information, while the ability to retrieve this information and express appropriate behaviors are also crucial for the adaptation of individuals to environmental cues. Thereby, all three components contribute to the cognitive fitness of an individual. While a lack of behavioral adaptation is a recurrent trait of intellectually disabled patients, discriminating between memory formation, memory retrieval or behavioral expression deficits is not easy to establish. Here, we report some deficits in contextual fear behavior in knockout mice for the intellectual disability gene Il1rapl1. Functional in vivo experiments revealed that the lack of conditioned response resulted from a local inhibitory to excitatory (I/E) imbalance in basolateral amygdala (BLA) consecutive to a loss of excitatory drive onto BLA principal cells by caudal hippocampus axonal projections. A normalization of the fear behavior was obtained in adult mutant mice following opsin-based in vivo synaptic priming of hippocampo-BLA synapses in adult il1rapl1 knockout mice, indicating that synaptic efficacy at hippocampo-BLA projections is crucial for contextual fear memory expression. Importantly, because this restoration was obtained after the learning phase, our results suggest that some of the genetically encoded cognitive deficits in humans may originate from a lack of restitution of genuinely formed memories rather than an exclusive inability to store new memories.

Social contact networks and disease eradicability under voluntary vaccination.

PubMed

Perisic, Ana; Bauch, Chris T

2009-02-01

Certain theories suggest that it should be difficult or impossible to eradicate a vaccine-preventable disease under voluntary vaccination: Herd immunity implies that the individual incentive to vaccinate disappears at high coverage levels. Historically, there have been examples of declining coverage for vaccines, such as MMR vaccine and whole-cell pertussis vaccine, that are consistent with this theory. On the other hand, smallpox was globally eradicated by 1980 despite voluntary vaccination policies in many jurisdictions. Previous modeling studies of the interplay between disease dynamics and individual vaccinating behavior have assumed that infection is transmitted in a homogeneously mixing population. By comparison, here we simulate transmission of a vaccine-preventable SEIR infection through a random, static contact network. Individuals choose whether to vaccinate based on infection risks from neighbors, and based on vaccine risks. When neighborhood size is small, rational vaccinating behavior results in rapid containment of the infection through voluntary ring vaccination. As neighborhood size increases (while the average force of infection is held constant), a threshold is reached beyond which the infection can break through partially vaccinated rings, percolating through the whole population and resulting in considerable epidemic final sizes and a large number vaccinated. The former outcome represents convergence between individually and socially optimal outcomes, whereas the latter represents their divergence, as observed in most models of individual vaccinating behavior that assume homogeneous mixing. Similar effects are observed in an extended model using smallpox-specific natural history and transmissibility assumptions. This work illustrates the significant qualitative differences between behavior-infection dynamics in discrete contact-structured populations versus continuous unstructured populations. This work also shows how disease eradicability in populations where voluntary vaccination is the primary control mechanism may depend partly on whether the disease is transmissible only to a few close social contacts or to a larger subset of the population.

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.

Beyond the Niche: Tissue-Level Coordination of Stem Cell Dynamics

PubMed Central

O’Brien, Lucy Erin; Bilder, David

2014-01-01

Adult animals rely on populations of stem cells to ensure organ function throughout their lifetime. Stem cells are governed by signals from stem cell niches, and much is known about how single niches promote stemness and direct stem cell behavior. However, most organs contain a multitude of stem cell–niche units, which are often distributed across the entire expanse of the tissue. Beyond the biology of individual stem cell–niche interactions, the next challenge is to uncover the tissue-level processes that orchestrate spatial control of stem-based renewal, repair, and remodeling throughout a whole organ. Here we examine what is known about higher order mechanisms for interniche coordination in epithelial organs, whose simple geometry offers a promising entry point for understanding the regulation of niche number, distribution, and activity. We also consider the potential existence of stem cell territories and how tissue architecture may influence niche coordination. PMID:23937350

Ecotoxicological effects of the insecticide fipronil in Brazilian native stingless bees Melipona scutellaris (Apidae: Meliponini).

PubMed

de Morais, Cássio Resende; Travençolo, Bruno Augusto Nassif; Carvalho, Stephan Malfitano; Beletti, Marcelo Emílio; Vieira Santos, Vanessa Santana; Campos, Carlos Fernando; de Campos Júnior, Edimar Olegário; Pereira, Boscolli Barbosa; Carvalho Naves, Maria Paula; de Rezende, Alexandre Azenha Alves; Spanó, Mário Antônio; Vieira, Carlos Ueira; Bonetti, Ana Maria

2018-09-01

Melipona scutellaris Latreille, 1811 (Hymenoptera, Apidae) is a pollinator of various native and cultivated plants. Because of the expansion of agriculture and the need to ensure pest control, the use of insecticides such as fipronil (FP) has increased. This study aimed to evaluate the effects of sublethal doses of FP insecticide on M. scutellaris at different time intervals (6, 12, and 24 h) after exposure, via individually analyzed behavioral biomarkers (locomotor activity, behavioral change) as well as the effect of FP on different brain structures of bees (mushroom bodies, antennal cells, and optic cells), using sub-individual cell biomarkers (heterochromatin dispersion, total nuclear and heterochromatic volume). Forager bees were collected when they were returning to the nest and were exposed to three different concentrations of FP (0.40, 0.040, and 0.0040 ng a.i/bee) by topical application. The results revealed a reduction in the mean velocity, lethargy, motor difficulty, paralysis, and hyperexcitation in all groups of bees treated with FP. A modification of the heterochromatic dispersion pattern and changes in the total volume of the nucleus and heterochromatin were also observed in the mushroom bodies (6, 12, and 24 h of exposure) and antennal lobes (6 and 12 h) of bees exposed to 0.0040 ng a.i/bee (LD 50/100 ). FP is toxic to M. scutellaris and impairs the essential functions required for the foraging activity. Copyright © 2018 Elsevier Ltd. All rights reserved.

Membrane potential bistability in nonexcitable cells as described by inward and outward voltage-gated ion channels.

PubMed

Cervera, Javier; Alcaraz, Antonio; Mafe, Salvador

2014-10-30

The membrane potential of nonexcitable cells, defined as the electrical potential difference between the cell cytoplasm and the extracellular environment when the current is zero, is controlled by the individual electrical conductance of different ion channels. In particular, inward- and outward-rectifying voltage-gated channels are crucial for cell hyperpolarization/depolarization processes, being amenable to direct physical study. High (in absolute value) negative membrane potentials are characteristic of terminally differentiated cells, while low membrane potentials are found in relatively depolarized, more plastic cells (e.g., stem, embryonic, and cancer cells). We study theoretically the hyperpolarized and depolarized values of the membrane potential, as well as the possibility to obtain a bistability behavior, using simplified models for the ion channels that regulate this potential. The bistability regions, which are defined in the multidimensional state space determining the cell state, can be relevant for the understanding of the different model cell states and the transitions between them, which are triggered by changes in the external environment.

A robust and tunable mitotic oscillator in artificial cells

PubMed Central

Wang, Shiyuan; Barnes, Patrick M; Liu, Xuwen; Xu, Haotian; Jin, Minjun; Liu, Allen P

2018-01-01

Single-cell analysis is pivotal to deciphering complex phenomena like heterogeneity, bistability, and asynchronous oscillations, where a population ensemble cannot represent individual behaviors. Bulk cell-free systems, despite having unique advantages of manipulation and characterization of biochemical networks, lack the essential single-cell information to understand a class of out-of-steady-state dynamics including cell cycles. Here, by encapsulating Xenopus egg extracts in water-in-oil microemulsions, we developed artificial cells that are adjustable in sizes and periods, sustain mitotic oscillations for over 30 cycles, and function in forms from the simplest cytoplasmic-only to the more complicated ones involving nuclear dynamics, mimicking real cells. Such innate flexibility and robustness make it key to studying clock properties like tunability and stochasticity. Our results also highlight energy as an important regulator of cell cycles. We demonstrate a simple, powerful, and likely generalizable strategy of integrating strengths of single-cell approaches into conventional in vitro systems to study complex clock functions. PMID:29620527

Quantitative phase imaging characterization of tumor-associated blood vessel formation on a chip

NASA Astrophysics Data System (ADS)

Guo, Peng; Huang, Jing; Moses, Marsha A.

2018-02-01

Angiogenesis, the formation of new blood vessels from existing ones, is a biological process that has an essential role in solid tumor growth, development, and progression. Recent advances in Lab-on-a-Chip technology has created an opportunity for scientists to observe endothelial cell (EC) behaviors during the dynamic process of angiogenesis using a simple and economical in vitro platform that recapitulates in vivo blood vessel formation. Here, we use quantitative phase imaging (QPI) microscopy to continuously and non-invasively characterize the dynamic process of tumor cell-induced angiogenic sprout formation on a microfluidic chip. The live tumor cell-induced angiogenic sprouts are generated by multicellular endothelial sprouting into 3 dimensional (3D) Matrigel using human umbilical vein endothelial cells (HUVECs). By using QPI, we quantitatively measure a panel of cellular morphological and behavioral parameters of each individual EC participating in this sprouting. In this proof-of-principle study, we demonstrate that QPI is a powerful tool that can provide real-time quantitative analysis of biological processes in in vitro 3D biomimetic devices, which, in turn, can improve our understanding of the biology underlying functional tissue engineering.

Social Motility in African Trypanosomes

PubMed Central

McLelland, Bryce T.; Hill, Kent L.

2010-01-01

African trypanosomes are devastating human and animal pathogens that cause significant human mortality and limit economic development in sub-Saharan Africa. Studies of trypanosome biology generally consider these protozoan parasites as individual cells in suspension cultures or in animal models of infection. Here we report that the procyclic form of the African trypanosome Trypanosoma brucei engages in social behavior when cultivated on semisolid agarose surfaces. This behavior is characterized by trypanosomes assembling into multicellular communities that engage in polarized migrations across the agarose surface and cooperate to divert their movements in response to external signals. These cooperative movements are flagellum-mediated, since they do not occur in trypanin knockdown parasites that lack normal flagellum motility. We term this behavior social motility based on features shared with social motility and other types of surface-induced social behavior in bacteria. Social motility represents a novel and unexpected aspect of trypanosome biology and offers new paradigms for considering host-parasite interactions. PMID:20126443

Nanofiber Orientation and Surface Functionalization Modulate Human Mesenchymal Stem Cell Behavior In Vitro

PubMed Central

Kolambkar, Yash M.; Bajin, Mehmet; Wojtowicz, Abigail; Hutmacher, Dietmar W.; García, Andrés J.

2014-01-01

Electrospun nanofiber meshes have emerged as a new generation of scaffold membranes possessing a number of features suitable for tissue regeneration. One of these features is the flexibility to modify their structure and composition to orchestrate specific cellular responses. In this study, we investigated the effects of nanofiber orientation and surface functionalization on human mesenchymal stem cell (hMSC) migration and osteogenic differentiation. We used an in vitro model to examine hMSC migration into a cell-free zone on nanofiber meshes and mitomycin C treatment to assess the contribution of proliferation to the observed migration. Poly (ɛ-caprolactone) meshes with oriented topography were created by electrospinning aligned nanofibers on a rotating mandrel, while randomly oriented controls were collected on a stationary collector. Both aligned and random meshes were coated with a triple-helical, type I collagen-mimetic peptide, containing the glycine-phenylalanine-hydroxyproline-glycine-glutamate-arginine (GFOGER) motif. Our results indicate that nanofiber GFOGER peptide functionalization and orientation modulate cellular behavior, individually, and in combination. GFOGER significantly enhanced the migration, proliferation, and osteogenic differentiation of hMSCs on nanofiber meshes. Aligned nanofiber meshes displayed increased cell migration along the direction of fiber orientation compared to random meshes; however, fiber alignment did not influence osteogenic differentiation. Compared to each other, GFOGER coating resulted in a higher proliferation-driven cell migration, whereas fiber orientation appeared to generate a larger direct migratory effect. This study demonstrates that peptide surface modification and topographical cues associated with fiber alignment can be used to direct cellular behavior on nanofiber mesh scaffolds, which may be exploited for tissue regeneration. PMID:24020454

Functional photoreceptor loss revealed with adaptive optics: an alternate cause of color blindness.

PubMed

Carroll, Joseph; Neitz, Maureen; Hofer, Heidi; Neitz, Jay; Williams, David R

2004-06-01

There is enormous variation in the X-linked L/M (long/middle wavelength sensitive) gene array underlying "normal" color vision in humans. This variability has been shown to underlie individual variation in color matching behavior. Recently, red-green color blindness has also been shown to be associated with distinctly different genotypes. This has opened the possibility that there may be important phenotypic differences within classically defined groups of color blind individuals. Here, adaptive optics retinal imaging has revealed a mechanism for producing dichromatic color vision in which the expression of a mutant cone photopigment gene leads to the loss of the entire corresponding class of cone photoreceptor cells. Previously, the theory that common forms of inherited color blindness could be caused by the loss of photoreceptor cells had been discounted. We confirm that remarkably, this loss of one-third of the cones does not impair any aspect of vision other than color.

De novo variants in EBF3 are associated with hypotonia, developmental delay, intellectual disability, and autism.

PubMed

Tanaka, Akemi J; Cho, Megan T; Willaert, Rebecca; Retterer, Kyle; Zarate, Yuri A; Bosanko, Katie; Stefans, Vikki; Oishi, Kimihiko; Williamson, Amy; Wilson, Golder N; Basinger, Alice; Barbaro-Dieber, Tina; Ortega, Lucia; Sorrentino, Susanna; Gabriel, Melissa K; Anderson, Ilse J; Sacoto, Maria J Guillen; Schnur, Rhonda E; Chung, Wendy K

2017-11-01

Using whole-exome sequencing, we identified seven unrelated individuals with global developmental delay, hypotonia, dysmorphic facial features, and an increased frequency of short stature, ataxia, and autism with de novo heterozygous frameshift, nonsense, splice, and missense variants in the Early B-cell Transcription Factor Family Member 3 ( EBF3 ) gene. EBF3 is a member of the collier/olfactory-1/early B-cell factor (COE) family of proteins, which are required for central nervous system (CNS) development. COE proteins are highly evolutionarily conserved and regulate neuronal specification, migration, axon guidance, and dendritogenesis during development and are essential for maintaining neuronal identity in adult neurons. Haploinsufficiency of EBF3 may affect brain development and function, resulting in developmental delay, intellectual disability, and behavioral differences observed in individuals with a deleterious variant in EBF3 . © 2017 Tanaka et al.; Published by Cold Spring Harbor Laboratory Press.

Sequential social experiences interact to modulate aggression but not brain gene expression in the honey bee (Apis mellifera).

PubMed

Rittschof, Clare C

2017-01-01

In highly structured societies, individuals behave flexibly and cooperatively in order to achieve a particular group-level outcome. However, even in social species, environmental inputs can have long lasting effects on individual behavior, and variable experiences can even result in consistent individual differences and constrained behavioral flexibility. Despite the fact that such constraints on behavior could have implications for behavioral optimization at the social group level, few studies have explored how social experiences accumulate over time, and the mechanistic basis of these effects. In the current study, I evaluate how sequential social experiences affect individual and group level aggressive phenotypes, and individual brain gene expression, in the highly social honey bee ( Apis mellifera ). To do this, I combine a whole colony chronic predator disturbance treatment with a lab-based manipulation of social group composition. Compared to the undisturbed control, chronically disturbed individuals show lower aggression levels overall, but also enhanced behavioral flexibility in the second, lab-based social context. Disturbed bees display aggression levels that decline with increasing numbers of more aggressive, undisturbed group members. However, group level aggressive phenotypes are similar regardless of the behavioral tendencies of the individuals that make up the group, suggesting a combination of underlying behavioral tendency and negative social feedback influences the aggressive behaviors displayed, particularly in the case of disturbed individuals. An analysis of brain gene expression showed that aggression related biomarker genes reflect an individual's disturbance history, but not subsequent social group experience or behavioral outcomes. In highly social animals with collective behavioral phenotypes, social context may mask underlying variation in individual behavioral tendencies. Moreover, gene expression patterns may reflect behavioral tendency, while behavioral outcomes are further regulated by social cues perceived in real-time.

The white gene of Drosophila melanogaster encodes a protein with a role in courtship behavior.

PubMed

Anaka, Matthew; MacDonald, C Danielle; Barkova, Eva; Simon, Karl; Rostom, Reem; Godoy, Ruth A; Haigh, Andrew J; Meinertzhagen, Ian A; Lloyd, Vett

2008-01-01

The white gene of Drosophila melanogaster has been extensively studied, yet it is still not understood how its ectopic overexpression induces male-male courtship. To investigate the cellular basis of this behavior, we examined the sexual behavior of several classes of mutants. We find that male-male courtship is seen not only in flies overexpressing the white gene, but also in mutants expected to have mislocalized White protein. This finding confirms that mislocalizing White transporter in the cells in which it is normally expressed will produce male-male courtship behaviors; the courtship behavior is not an indirect consequence of aberrant physiological changes elsewhere in the body. Male-male courtship is also seen in some mutants with altered monoamine metabolism and deficits in learning and memory, but can be distinguished from that produced by White mislocalization by its reduced intensity and locomotor activity. Double mutants overexpressing white and with mutations in genes for serotonergic neurons suggest that male-male courtship produced by mislocalizing White may not be mediated exclusively by serotonergic neurons. We also find decreased olfactory learning in white mutants and in individuals with mutations in the genes for White's binding partners, brown and scarlet. Finally, in cultured Drosophila and mammalian cells, the White transporter is found in the endosomal compartment. The additional genes identified here as being involved in male-male courtship increase the repertoire of mutations available to study sexual behavior in Drosophila.

Cerebellar Output in Zebrafish: An Analysis of Spatial Patterns and Topography in Eurydendroid Cell Projections

PubMed Central

Heap, Lucy A.; Goh, Chi Ching; Kassahn, Karin S.; Scott, Ethan K.

2013-01-01

The cerebellum is a brain region responsible for motor coordination and for refining motor programs. While a great deal is known about the structure and connectivity of the mammalian cerebellum, fundamental questions regarding its function in behavior remain unanswered. Recently, the zebrafish has emerged as a useful model organism for cerebellar studies, owing in part to the similarity in cerebellar circuits between zebrafish and mammals. While the cell types composing their cerebellar cortical circuits are generally conserved with mammals, zebrafish lack deep cerebellar nuclei, and instead a majority of cerebellar output comes from a single type of neuron: the eurydendroid cell. To describe spatial patterns of cerebellar output in zebrafish, we have used genetic techniques to label and trace eurydendroid cells individually and en masse. We have found that cerebellar output targets the thalamus and optic tectum, and have confirmed the presence of pre-synaptic terminals from eurydendroid cells in these structures using a synaptically targeted GFP. By observing individual eurydendroid cells, we have shown that different medial-lateral regions of the cerebellum have eurydendroid cells projecting to different targets. Finally, we found topographic organization in the connectivity between the cerebellum and the optic tectum, where more medial eurydendroid cells project to the rostral tectum while lateral cells project to the caudal tectum. These findings indicate that there is spatial logic underpinning cerebellar output in zebrafish with likely implications for cerebellar function. PMID:23554587

The availability of filament ends modulates actin stochastic dynamics in live plant cells

PubMed Central

Li, Jiejie; Staiger, Benjamin H.; Henty-Ridilla, Jessica L.; Abu-Abied, Mohamad; Sadot, Einat; Blanchoin, Laurent; Staiger, Christopher J.

2014-01-01

A network of individual filaments that undergoes incessant remodeling through a process known as stochastic dynamics comprises the cortical actin cytoskeleton in plant epidermal cells. From images at high spatial and temporal resolution, it has been inferred that the regulation of filament barbed ends plays a central role in choreographing actin organization and turnover. How this occurs at a molecular level, whether different populations of ends exist in the array, and how individual filament behavior correlates with the overall architecture of the array are unknown. Here we develop an experimental system to modulate the levels of heterodimeric capping protein (CP) and examine the consequences for actin dynamics, architecture, and cell expansion. Significantly, we find that all phenotypes are the opposite for CP-overexpression (OX) cells compared with a previously characterized cp-knockdown line. Specifically, CP OX lines have fewer filament–filament annealing events, as well as reduced filament lengths and lifetimes. Further, cp-knockdown and OX lines demonstrate the existence of a subpopulation of filament ends sensitive to CP concentration. Finally, CP levels correlate with the biological process of axial cell expansion; for example, epidermal cells from hypocotyls with reduced CP are longer than wild-type cells, whereas CP OX lines have shorter cells. On the basis of these and other genetic studies in this model system, we hypothesize that filament length and lifetime positively correlate with the extent of axial cell expansion in dark-grown hypocotyls. PMID:24523291

Significantly improved precision of cell migration analysis in time-lapse video microscopy through use of a fully automated tracking system

PubMed Central

2010-01-01

Background Cell motility is a critical parameter in many physiological as well as pathophysiological processes. In time-lapse video microscopy, manual cell tracking remains the most common method of analyzing migratory behavior of cell populations. In addition to being labor-intensive, this method is susceptible to user-dependent errors regarding the selection of "representative" subsets of cells and manual determination of precise cell positions. Results We have quantitatively analyzed these error sources, demonstrating that manual cell tracking of pancreatic cancer cells lead to mis-calculation of migration rates of up to 410%. In order to provide for objective measurements of cell migration rates, we have employed multi-target tracking technologies commonly used in radar applications to develop fully automated cell identification and tracking system suitable for high throughput screening of video sequences of unstained living cells. Conclusion We demonstrate that our automatic multi target tracking system identifies cell objects, follows individual cells and computes migration rates with high precision, clearly outperforming manual procedures. PMID:20377897

Toward single cell traction microscopy within 3D collagen matrices

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

Hall, Matthew S.; Long, Rong; Feng, Xinzeng

Mechanical interaction between the cell and its extracellular matrix (ECM) regulates cellular behaviors, including proliferation, differentiation, adhesion, and migration. Cells require the three-dimensional (3D) architectural support of the ECM to perform physiologically realistic functions. However, current understanding of cell–ECM and cell–cell mechanical interactions is largely derived from 2D cell traction force microscopy, in which cells are cultured on a flat substrate. 3D cell traction microscopy is emerging for mapping traction fields of single animal cells embedded in either synthetic or natively derived fibrous gels. We discuss here the development of 3D cell traction microscopy, its current limitations, and perspectives onmore » the future of this technology. Emphasis is placed on strategies for applying 3D cell traction microscopy to individual tumor cell migration within collagen gels. - Highlights: • Review of the current state of the art in 3D cell traction force microscopy. • Bulk and micro-characterization of remodelable fibrous collagen gels. • Strategies for performing 3D cell traction microscopy within collagen gels.« less

Physical Mechanisms Driving Cell Sorting in Hydra.

PubMed

Cochet-Escartin, Olivier; Locke, Tiffany T; Shi, Winnie H; Steele, Robert E; Collins, Eva-Maria S

2017-12-19

Cell sorting, whereby a heterogeneous cell mixture organizes into distinct tissues, is a fundamental patterning process in development. Hydra is a powerful model system for carrying out studies of cell sorting in three dimensions, because of its unique ability to regenerate after complete dissociation into individual cells. The physicists Alfred Gierer and Hans Meinhardt recognized Hydra's self-organizing properties more than 40 years ago. However, what drives cell sorting during regeneration of Hydra from cell aggregates is still debated. Differential motility and differential adhesion have been proposed as driving mechanisms, but the available experimental data are insufficient to distinguish between these two. Here, we answer this longstanding question by using transgenic Hydra expressing fluorescent proteins and a multiscale experimental and numerical approach. By quantifying the kinematics of single cell and whole aggregate behaviors, we show that no differences in cell motility exist among cell types and that sorting dynamics follow a power law with an exponent of ∼0.5. Additionally, we measure the physical properties of separated tissues and quantify their viscosities and surface tensions. Based on our experimental results and numerical simulations, we conclude that tissue interfacial tensions are sufficient to explain cell sorting in aggregates of Hydra cells. Furthermore, we demonstrate that the aggregate's geometry during sorting is key to understanding the sorting dynamics and explains the exponent of the power law behavior. Our results answer the long standing question of the physical mechanisms driving cell sorting in Hydra cell aggregates. In addition, they demonstrate how powerful this organism is for biophysical studies of self-organization and pattern formation. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Neutral competition of stem cells is skewed by proliferative changes downstream of Hh and Hpo.

PubMed

Amoyel, Marc; Simons, Benjamin D; Bach, Erika A

2014-10-16

Neutral competition, an emerging feature of stem cell homeostasis, posits that individual stem cells can be lost and replaced by their neighbors stochastically, resulting in chance dominance of a clone at the niche. A single stem cell with an oncogenic mutation could bias this process and clonally spread the mutation throughout the stem cell pool. The Drosophila testis provides an ideal system for testing this model. The niche supports two stem cell populations that compete for niche occupancy. Here, we show that cyst stem cells (CySCs) conform to the paradigm of neutral competition and that clonal deregulation of either the Hedgehog (Hh) or Hippo (Hpo) pathway allows a single CySC to colonize the niche. We find that the driving force behind such behavior is accelerated proliferation. Our results demonstrate that a single stem cell colonizes its niche through oncogenic mutation by co-opting an underlying homeostatic process. © 2014 The Authors.

Cell segmentation in phase contrast microscopy images via semi-supervised classification over optics-related features.

PubMed

Su, Hang; Yin, Zhaozheng; Huh, Seungil; Kanade, Takeo

2013-10-01

Phase-contrast microscopy is one of the most common and convenient imaging modalities to observe long-term multi-cellular processes, which generates images by the interference of lights passing through transparent specimens and background medium with different retarded phases. Despite many years of study, computer-aided phase contrast microscopy analysis on cell behavior is challenged by image qualities and artifacts caused by phase contrast optics. Addressing the unsolved challenges, the authors propose (1) a phase contrast microscopy image restoration method that produces phase retardation features, which are intrinsic features of phase contrast microscopy, and (2) a semi-supervised learning based algorithm for cell segmentation, which is a fundamental task for various cell behavior analysis. Specifically, the image formation process of phase contrast microscopy images is first computationally modeled with a dictionary of diffraction patterns; as a result, each pixel of a phase contrast microscopy image is represented by a linear combination of the bases, which we call phase retardation features. Images are then partitioned into phase-homogeneous atoms by clustering neighboring pixels with similar phase retardation features. Consequently, cell segmentation is performed via a semi-supervised classification technique over the phase-homogeneous atoms. Experiments demonstrate that the proposed approach produces quality segmentation of individual cells and outperforms previous approaches. Copyright © 2013 Elsevier B.V. All rights reserved.

Integrating the health and mental health needs of the chronically ill: a group for individuals with depression and sickle cell disease.

PubMed

Comer, Edna W

2004-01-01

Concerns about high rates of depression among persons with sickle cell disease and no effective interventions for treatment of this condition were the impetuses for the study described in this paper. A groupwork service using cognitive-behavioral and self-management techniques were integrated into health care services at a Comprehensive Sickle Cell Center to treat depression in a small group of patients. An interdisciplinary team that included health care and mental health providers from the Center and a social work researcher guided the endeavor. Principles of Intervention Research were applied in the development of the service and to evaluate its effectiveness. Among the findings were that study participants realized a decrease in depressive symptoms.

Weevil x Insecticide: Does 'Personality' Matter?

PubMed

Morales, Juliana A; Cardoso, Danúbia G; Della Lucia, Terezinha Maria C; Guedes, Raul Narciso C

2013-01-01

An insect's behavior is the expression of its integrated physiology in response to external and internal stimuli, turning insect behavior into a potential determinant of insecticide exposure. Behavioral traits may therefore influence insecticide efficacy against insects, compromising the validity of standard bioassays of insecticide activity, which are fundamentally based on lethality alone. By extension, insect 'personality' (i.e., an individual's integrated set of behavioral tendencies that is inferred from multiple empirical measures) may also be an important determinant of insecticide exposure and activity. This has yet to be considered because the behavioral studies involving insects and insecticides focus on populations rather than on individuals. Even among studies of animal 'personality', the relative contributions of individual and population variation are usually neglected. Here, we assessed behavioral traits (within the categories: activity, boldness/shyness, and exploration/avoidance) of individuals from 15 populations of the maize weevil (Sitophilus zeamais), an important stored-grain pest with serious problems of insecticide resistance, and correlated the behavioral responses with the activity of the insecticide deltamethrin. This analysis was performed at both the population and individual levels. There was significant variation in weevil 'personality' among individuals and populations, but variation among individuals within populations accounted for most of the observed variation (92.57%). This result emphasizes the importance of individual variation in behavioral and 'personality' studies. When the behavioral traits assessed were correlated with median lethal time (LT50) at the population level and with the survival time under insecticide exposure, activity traits, particularly the distance walked, significantly increased survival time. Therefore, behavioral traits are important components of insecticide efficacy, and individual variation should be considered in such studies. This is so because population differences provided only crude approximation of the individual personality in a restrained experimental setting likely to restrict individual behavior favoring the transposition of the individual variation to the population.

C. elegans Stress-Induced Sleep Emerges from the Collective Action of Multiple Neuropeptides.

PubMed

Nath, Ravi D; Chow, Elly S; Wang, Han; Schwarz, Erich M; Sternberg, Paul W

2016-09-26

The genetic basis of sleep regulation remains poorly understood. In C. elegans, cellular stress induces sleep through epidermal growth factor (EGF)-dependent activation of the EGF receptor in the ALA neuron. The downstream mechanism by which this neuron promotes sleep is unknown. Single-cell RNA sequencing of ALA reveals that the most highly expressed, ALA-enriched genes encode neuropeptides. Here we have systematically investigated the four most highly enriched neuropeptides: flp-7, nlp-8, flp-24, and flp-13. When individually removed by null mutation, these peptides had little or no effect on stress-induced sleep. However, stress-induced sleep was abolished in nlp-8; flp-24; flp-13 triple-mutant animals, indicating that these neuropeptides work collectively in controlling stress-induced sleep. We tested the effect of overexpression of these neuropeptide genes on five behaviors modulated during sleep-pharyngeal pumping, defecation, locomotion, head movement, and avoidance response to an aversive stimulus-and we found that, if individually overexpressed, each of three neuropeptides (nlp-8, flp-24, or flp-13) induced a different suite of sleep-associated behaviors. These overexpression results raise the possibility that individual components of sleep might be specified by individual neuropeptides or combinations of neuropeptides. Copyright © 2016 Elsevier Ltd. All rights reserved.

Questions about Behavioral Function in Mental Illness (QABF-MI): A Behavior Checklist for Functional Assessment of Maladaptive Behavior Exhibited by Individuals with Mental Illness

ERIC Educational Resources Information Center

Singh, Nirbhay N.; Matson, Johnny L.; Lancioni, Giulio E.; Singh, Ashvind N.; Adkins, Angela D.; McKeegan, Gerald F.; Brown, Stephen W.

2006-01-01

The Questions About Behavioral Function (QABF), a 25-item rating scale, was developed to identify the function(s) of maladaptive behavior in individuals with developmental disabilities. The authors adapted it for use with individuals with serious mental illness who engage in maladaptive behavior and assessed the psychometric characteristics of the…

Quarrelsome behavior in borderline personality disorder: influence of behavioral and affective reactivity to perceptions of others.

PubMed

Sadikaj, Gentiana; Moskowitz, D S; Russell, Jennifer J; Zuroff, David C; Paris, Joel

2013-02-01

We examined how the amplification of 3 within-person processes (behavioral reactivity to interpersonal perceptions, affect reactivity to interpersonal perceptions, and behavioral reactivity to a person's own affect) accounts for greater quarrelsome behavior among individuals with borderline personality disorder (BPD). Using an event-contingent recording (ECR) methodology, individuals with BPD (N = 38) and community controls (N = 31) reported on their negative affect, quarrelsome behavior, and perceptions of the interaction partner's agreeable-quarrelsome behavior in interpersonal events during a 20-day period. Behavioral reactivity to negative affect was similar in both groups. However, behavioral reactivity and affect reactivity to interpersonal perceptions were elevated in individuals with BPD relative to community controls; specifically, individuals with BPD reported more quarrelsome behavior and more negative affect during interactions in which they perceived others as more cold-quarrelsome. Greater negative affect reactivity to perceptions of other's cold-quarrelsome behavior partly accounted for the increased quarrelsome behavior reported by individuals with BPD during these interactions. This pattern of results suggests a cycle in which the perception of cold-quarrelsome behavior in others triggers elevated negative affect and quarrelsome behavior in individuals with BPD, which subsequently led to more quarrelsome behavior from their interaction partners, which leads to perceptions of others as cold-quarrelsomeness, which begins the cycle anew. 2013 APA, all rights reserved

Endocrine mechanisms, behavioral phenotypes and plasticity: known relationships and open questions.

PubMed

Hau, Michaela; Goymann, Wolfgang

2015-01-01

Behavior of wild vertebrate individuals can vary in response to environmental or social factors. Such within-individual behavioral variation is often mediated by hormonal mechanisms. Hormones also serve as a basis for among-individual variations in behavior including animal personalities and the degree of responsiveness to environmental and social stimuli. How do relationships between hormones and behavioral traits evolve to produce such behavioral diversity within and among individuals? Answering questions about evolutionary processes generating among-individual variation requires characterizing how specific hormones are related to variation in specific behavioral traits, whether observed hormonal variation is related to individual fitness and, whether hormonal traits are consistent (repeatable) aspects of an individual's phenotype. With respect to within-individual variation, we need to improve our insight into the nature of the quantitative relationships between hormones and the traits they regulate, which in turn will determine how they may mediate behavioral plasticity of individuals. To address these questions, we review the actions of two steroid hormones, corticosterone and testosterone, in mediating changes in vertebrate behavior, focusing primarily on birds. In the first part, we concentrate on among-individual variation and present examples for how variation in corticosterone concentrations can relate to behaviors such as exploration of novel environments and parental care. We then review studies on correlations between corticosterone variation and fitness, and on the repeatability over time of corticosterone concentrations. At the end of this section, we suggest that further progress in our understanding of evolutionary patterns in the hormonal regulation of behavior may require, as one major tool, reaction norm approaches to characterize hormonal phenotypes as well as their responses to environments. In the second part, we discuss types of quantitative relationships between hormones and behavioral traits within individuals, using testosterone as an example. We review conceptual models for testosterone-behavior relationships and discuss the relevance of these models for within-individual plasticity in behavior. Next, we discuss approaches for testing the nature of quantitative relationships between testosterone and behavior, concluding that again reaction norm approaches might be a fruitful way forward. We propose that an integration of new tools, especially of reaction norm approaches into the field of behavioral endocrinology will allow us to make significant progress in our understanding of the mechanisms, the functional implications and the evolution of hormone-behavior relationships that mediate variation both within and among individuals. This knowledge will be crucial in light of already ongoing habitat alterations due to global change, as it will allow us to evaluate the mechanisms as well as the capacity of wild populations to adjust hormonally-mediated behaviors to altered environmental conditions.

Does boldness explain vulnerability to angling in Eurasian perch Perca fluviatilis?

PubMed

Vainikka, Anssi; Tammela, Ilkka; Hyvärinen, Pekka

2016-04-01

Consistent individual differences (CIDs) in behavior are of interest to both basic and applied research, because any selection acting on them could induce evolution of animal behavior. It has been suggested that CIDs in the behavior of fish might explain individual differences in vulnerability to fishing. If so, fishing could impose selection on fish behavior. In this study, we assessed boldness-indicating behaviors of Eurasian perch Perca fluviatilis using individually conducted experiments measuring the time taken to explore a novel arena containing predator (burbot, Lota lota ) cues. We studied if individual differences in boldness would explain vulnerability of individually tagged perch to experimental angling in outdoor ponds, or if fishing would impose selection on boldness-indicating behavior. Perch expressed repeatable individual differences in boldness-indicating behavior but the individual boldness-score (the first principal component) obtained using principal component analysis combining all the measured behavioral responses did not explain vulnerability to experimental angling. Instead, large body size appeared as the only statistically significant predictor of capture probability. Our results suggest that angling is selective for large size, but not always selective for high boldness.

Does boldness explain vulnerability to angling in Eurasian perch Perca fluviatilis?

PubMed Central

Vainikka, Anssi; Tammela, Ilkka; Hyvärinen, Pekka

2016-01-01

Abstract Consistent individual differences (CIDs) in behavior are of interest to both basic and applied research, because any selection acting on them could induce evolution of animal behavior. It has been suggested that CIDs in the behavior of fish might explain individual differences in vulnerability to fishing. If so, fishing could impose selection on fish behavior. In this study, we assessed boldness-indicating behaviors of Eurasian perch Perca fluviatilis using individually conducted experiments measuring the time taken to explore a novel arena containing predator (burbot, Lota lota) cues. We studied if individual differences in boldness would explain vulnerability of individually tagged perch to experimental angling in outdoor ponds, or if fishing would impose selection on boldness-indicating behavior. Perch expressed repeatable individual differences in boldness-indicating behavior but the individual boldness-score (the first principal component) obtained using principal component analysis combining all the measured behavioral responses did not explain vulnerability to experimental angling. Instead, large body size appeared as the only statistically significant predictor of capture probability. Our results suggest that angling is selective for large size, but not always selective for high boldness. PMID:29491897

Changes in cancer incidence in teenagers and young adults (ages 13 to 24 years) in England 1979-2003.

PubMed

Alston, Robert D; Geraci, Marco; Eden, Tim O B; Moran, Anthony; Rowan, Steve; Birch, Jillian M

2008-11-15

Cancer for teenagers and young adults represents a major source of morbidity and mortality. Trends in cancer incidence can provide pointers concerning how changes in the environment and in personal behavior affect cancer risks. Data on 39,129 neoplasms in individuals ages 13 to 24 years who were diagnosed in England from 1979 to 2003 were analyzed. Variability in incidence by time period and differences in the time trends by age group, sex, and geographic region were analyzed using generalized linear models. Incidence rates of leukemias, lymphomas, central nervous system, bone, and germ cell tumors; melanoma; and carcinomas of the thyroid, ovary, cervix, and colon/rectum increased over time (all P < .01); whereas the incidence of carcinomas of the stomach and bladder decreased (both P < .01). These changes were consistent by age, sex, and region for most neoplasms. Melanoma incidence stabilized in southern England by 1993 but continued to increase in northern England (P = .001). The increase in non-Hodgkin lymphoma was greater in individuals ages 20 to 24 year than in younger individuals, but the increase in Hodgkin lymphoma was confined to individuals ages 13 to 14 years. The changes in incidence rates may have been caused in part by environmental changes and in part by behavioral changes in young individuals. Some of these results can be used to inform public health campaigns, which can be constructed to encourage better lifestyle choices by young individuals.

Arrays of microscopic organic LEDs for high-resolution optogenetics

PubMed Central

Steude, Anja; Witts, Emily C.; Miles, Gareth B.; Gather, Malte C.

2016-01-01

Optogenetics is a paradigm-changing new method to study and manipulate the behavior of cells with light. Following major advances of the used genetic constructs over the last decade, the light sources required for optogenetic control are now receiving increased attention. We report a novel optogenetic illumination platform based on high-density arrays of microscopic organic light-emitting diodes (OLEDs). Because of the small dimensions of each array element (6 × 9 μm2) and the use of ultrathin device encapsulation, these arrays enable illumination of cells with unprecedented spatiotemporal resolution. We show that adherent eukaryotic cells readily proliferate on these arrays, and we demonstrate specific light-induced control of the ionic current across the membrane of individual live cells expressing different optogenetic constructs. Our work paves the way for the use of OLEDs for cell-specific optogenetic control in cultured neuronal networks and for acute brain slices, or as implants in vivo. PMID:27386540

Thermodynamics of protein destabilization in live cells.

PubMed

Danielsson, Jens; Mu, Xin; Lang, Lisa; Wang, Huabing; Binolfi, Andres; Theillet, François-Xavier; Bekei, Beata; Logan, Derek T; Selenko, Philipp; Wennerström, Håkan; Oliveberg, Mikael

2015-10-06

Although protein folding and stability have been well explored under simplified conditions in vitro, it is yet unclear how these basic self-organization events are modulated by the crowded interior of live cells. To find out, we use here in-cell NMR to follow at atomic resolution the thermal unfolding of a β-barrel protein inside mammalian and bacterial cells. Challenging the view from in vitro crowding effects, we find that the cells destabilize the protein at 37 °C but with a conspicuous twist: While the melting temperature goes down the cold unfolding moves into the physiological regime, coupled to an augmented heat-capacity change. The effect seems induced by transient, sequence-specific, interactions with the cellular components, acting preferentially on the unfolded ensemble. This points to a model where the in vivo influence on protein behavior is case specific, determined by the individual protein's interplay with the functionally optimized "interaction landscape" of the cellular interior.

Cell Assembly Dynamics of Sparsely-Connected Inhibitory Networks: A Simple Model for the Collective Activity of Striatal Projection Neurons.

PubMed

Angulo-Garcia, David; Berke, Joshua D; Torcini, Alessandro

2016-02-01

Striatal projection neurons form a sparsely-connected inhibitory network, and this arrangement may be essential for the appropriate temporal organization of behavior. Here we show that a simplified, sparse inhibitory network of Leaky-Integrate-and-Fire neurons can reproduce some key features of striatal population activity, as observed in brain slices. In particular we develop a new metric to determine the conditions under which sparse inhibitory networks form anti-correlated cell assemblies with time-varying activity of individual cells. We find that under these conditions the network displays an input-specific sequence of cell assembly switching, that effectively discriminates similar inputs. Our results support the proposal that GABAergic connections between striatal projection neurons allow stimulus-selective, temporally-extended sequential activation of cell assemblies. Furthermore, we help to show how altered intrastriatal GABAergic signaling may produce aberrant network-level information processing in disorders such as Parkinson's and Huntington's diseases.

Cell adhesion and guidance by micropost-array chemical sensors

NASA Astrophysics Data System (ADS)

Pantano, Paul; Quah, Soo-Kim; Danowski, Kristine L.

2002-06-01

An array of ~50,000 individual polymeric micropost sensors was patterned across a glass coverslip by a photoimprint lithographic technique. Individual micropost sensors were ~3-micrometers tall and ~8-micrometers wide. The O2-sensitive micropost array sensors (MPASs) comprised a ruthenium complex encapsulated in a gas permeable photopolymerizable siloxane. The pH-sensitive MPASs comprised a fluorescein conjugate encapsulated in a photocrosslinkable poly(vinyl alcohol)-based polymer. PO2 and pH were quantitated by acquiring MPAS luminescence images with an epifluorescence microscope/charge coupled device imaging system. O2-sensitive MPASs displayed linear Stern-Volmer quenching behavior with a maximum Io/I of ~8.6. pH-sensitive MPASs displayed sigmoidal calibration curves with a pKa of ~5.8. The adhesion of undifferentiated rat pheochromocytoma (PC12) cells across these two polymeric surface types was investigated. The greatest PC12 cell proliferation and adhesion occurred across the poly(vinyl alcohol)-based micropost arrays relative to planar poly(vinyl alcohol)-based surfaces and both patterned and planar siloxane surfaces. An additional advantage of the patterned MPAS layers relative to planar sensing layers was the ability to direct the growth of biological cells. Preliminary data is presented whereby nerve growth factor-differentiated PC12 cells grew neurite-like processes that extended along paths defined by the micropost architecture.

Individual-Level Factors in Colorectal Cancer Screening: A Review of the Literature on the Relation of Individual-Level Health Behavior Constructs and Screening Behavior

PubMed Central

Kiviniemi, Marc T.; Bennett, Alyssa; Zaiter, Marie; Marshall, James R.

2010-01-01

Compliance with colorectal cancer screening recommendations requires considerable conscious effort on the part of the individual patient, making an individual's decisions about engagement in screening an important contributor to compliance or noncompliance. The objective of this paper was to examine the effectiveness of individual-level behavior theories and their associated constructs in accounting for engagement in colorectal cancer screening behavior. We reviewed the literature examining constructs from formal models of individual-level health behavior as factors associated with compliance with screening for colorectal cancer. All published studies examining one or more constructs from the health belief model, theory of planned behavior, transtheoretical model, or social cognitive theory and their relation to screening behavior or behavioral intentions were included in the analysis. By and large, results of studies supported the theory-based predictions for the influence of constructs on cancer screening behavior. However, the evidence base for many of these relations, especially for models other than the health belief model, is quite limited. Suggestions are made for future research on individual-level determinants of colorectal cancer screening. PMID:21954045

Individual Differences, Intelligence, and Behavior Analysis

PubMed Central

Williams, Ben; Myerson, Joel; Hale, Sandra

2008-01-01

Despite its avowed goal of understanding individual behavior, the field of behavior analysis has largely ignored the determinants of consistent differences in level of performance among individuals. The present article discusses major findings in the study of individual differences in intelligence from the conceptual framework of a functional analysis of behavior. In addition to general intelligence, we discuss three other major aspects of behavior in which individuals differ: speed of processing, working memory, and the learning of three-term contingencies. Despite recent progress in our understanding of the relations among these aspects of behavior, numerous issues remain unresolved. Researchers need to determine which learning tasks predict individual differences in intelligence and which do not, and then identify the specific characteristics of these tasks that make such prediction possible. PMID:18831127

Effects of nanopillar array diameter and spacing on cancer cell capture and cell behaviors

NASA Astrophysics Data System (ADS)

Wang, Shunqiang; Wan, Yuan; Liu, Yaling

2014-10-01

While substrates with nanopillars (NPs) have emerged as promising platforms for isolation of circulating tumor cells (CTCs), the influence of diameter and spacing of NPs on CTC capture is still unclear. In this paper, CTC-capture yield and cell behaviors have been investigated by using antibody functionalized NPs of various diameters (120-1100 nm) and spacings (35-800 nm). The results show a linear relationship between the cell capture yield and effective contact area of NP substrates where a NP array of small diameter and reasonable spacing is preferred; however, spacing that is too small or too large adversely impairs the capture efficiency and specificity, respectively. In addition, the formation of pseudopodia between captured cells and the substrate is found to be dependent not only on cell adhesion status but also on elution strength and shear direction. These findings provide essential guidance in designing NP substrates for more efficient capture of CTCs and manipulation of cytomorphology in future.While substrates with nanopillars (NPs) have emerged as promising platforms for isolation of circulating tumor cells (CTCs), the influence of diameter and spacing of NPs on CTC capture is still unclear. In this paper, CTC-capture yield and cell behaviors have been investigated by using antibody functionalized NPs of various diameters (120-1100 nm) and spacings (35-800 nm). The results show a linear relationship between the cell capture yield and effective contact area of NP substrates where a NP array of small diameter and reasonable spacing is preferred; however, spacing that is too small or too large adversely impairs the capture efficiency and specificity, respectively. In addition, the formation of pseudopodia between captured cells and the substrate is found to be dependent not only on cell adhesion status but also on elution strength and shear direction. These findings provide essential guidance in designing NP substrates for more efficient capture of CTCs and manipulation of cytomorphology in future. Electronic supplementary information (ESI) available: Additional details about calculation of maximal displacement of an individual NP; additional study of substrate wettability through Cassie's Law; additional details about selection of incubation time and shaking speeds. See DOI: 10.1039/c4nr02854f

Probing cooperative force generation in collective cancer invasion

NASA Astrophysics Data System (ADS)

Alobaidi, Amani A.; Xu, Yaopengxiao; Chen, Shaohua; Jiao, Yang; Sun, Bo

2017-08-01

Collective cellular dynamics in the three-dimensional extracellular matrix (ECM) plays a crucial role in many physiological processes such as cancer invasion. Both chemical and mechanical signaling support cell-cell communications on a variety of length scales, leading to collective migratory behaviors. Here we conduct experiments using 3D in vitro tumor models and develop a phenomenological model in order to probe the cooperativity of force generation in the collective invasion of breast cancer cells. In our model, cell-cell communication is characterized by a single parameter that quantifies the correlation length of cellular migration cycles. We devise a stochastic reconstruction method to generate realizations of cell colonies with specific contraction phase correlation functions and correlation length a. We find that as a increases, the characteristic size of regions containing cells with similar contraction phases grows. For small a values, the large fluctuations in individual cell contraction phases smooth out the temporal fluctuations in the time-dependent deformation field in the ECM. For large a values, the periodicity of an individual cell contraction cycle is clearly manifested in the temporal variation of the overall deformation field in the ECM. Through quantitative comparisons of the simulated and experimentally measured deformation fields, we find that the correlation length for collective force generation in the breast cancer diskoid in geometrically micropatterned ECM (DIGME) system is a≈ 25~μ \\text{m} , which is roughly twice the linear size of a single cell. One possible mechanism for this intermediate cell correlation length is the fiber-mediated stress propagation in the 3D ECM network in the DIGME system.

Influence of type-I fimbriae and fluid shear stress on bacterial behavior and multicellular architecture of early Escherichia coli biofilms at single-cell resolution.

PubMed

Wang, Liyun; Keatch, Robert; Zhao, Qi; Wright, John A; Bryant, Clare E; Redmann, Anna L; Terentjev, Eugene M

2018-01-12

Biofilm formation on abiotic surfaces in food and medical industry can cause severe contamination and infection, yet how biological and physical factors determine cellular architecture of early biofilms and bacterial behavior of the constituent cells remains largely unknown. In this study we examine the specific role of type-I fimbriae in nascent stages of biofilm formation and the response of micro-colonies to environmental flow shear at single-cell resolution. The results show that type-I fimbriae are not required for reversible adhesion from plankton, but critical for irreversible adhesion of Escherichia coli ( E.coli ) MG1655 forming biofilms on polyethylene terephthalate (PET) surfaces. Besides establishing a firm cell-surface contact, the irreversible adhesion seems necessary to initiate the proliferation of E.coli on the surface. After application of shear stress, bacterial retention is dominated by the 3D architecture of colonies independent of the population and the multi-layered structure could protect the embedded cells from being insulted by fluid shear, while cell membrane permeability mainly depends on the biofilm population and the duration time of the shear stress. Importance Bacterial biofilms could lead to severe contamination problems in medical devices and food processing equipment. However, biofilms are usually studied at a rough macroscopic level, thus little is known about how individual bacterial behavior within biofilms and multicellular architecture are influenced by bacterial appendages (e.g. pili/fimbriae) and environmental factors during early biofilm formation. We apply Confocal Laser Scanning Microscopy (CLSM) to visualize E.coli micro-colonies at single-cell resolution. Our findings suggest that type-I fimbriae are vital to the initiation of bacterial proliferation on surfaces and that the responses of biofilm architecture and cell membrane permeability of constituent bacteria to fluid shear stress are different, which are respectively regulated by the 3D morphology and the population of micro-colonies. Copyright © 2018 American Society for Microbiology.

Leadership, Knowledge Sharing, and Creativity: The Key Factors in Nurses' Innovative Behaviors.

PubMed

Kim, Sung-Jin; Park, Myonghwa

2015-12-01

This study identified the factors that affect the innovative behaviors of nurses at general hospitals based on their individual and organizational characteristics. The predictors of innovative nursing behaviors, such as self-leadership, individual knowledge sharing, creative self-efficacy, organizational knowledge sharing, and innovative organizational cultures, should be explored at individual and organizational level. This study administered a cross-sectional survey to 347 registered nurses working at 6 general hospitals (with >300 beds) in central South Korea. Data were collected using a self-report questionnaire and analyzed using structural equation modeling. Self-leadership, creative self-efficacy, and individual knowledge sharing directly affected individual innovative behaviors. Organizational knowledge sharing indirectly affected individual innovative behaviors, and this effect was mediated by an innovative organizational culture. This study contributes to the knowledge base regarding the effective management of individuals and organizations through innovative behavior; furthermore, it provides future directions for nursing interventions.

Comprehensive Behavior Management: Individualized, Classroom, and Schoolwide Approaches. Second Edition

ERIC Educational Resources Information Center

Martella, Ronald C.; Nelson, J. Ron; Marchand-Martella, Nancy E.; O'Reilly, Mark

2011-01-01

"Comprehensive Behavior Management: Schoolwide, Classroom, and Individualized Approaches" supports teachers in preventing management problems and responding to unwanted behavior when it occurs in classrooms. The text offers a comprehensive presentation of three levels of behavior management strategies: individual, classroom, and schoolwide, all…

Identified Serotonin-Releasing Neurons Induce Behavioral Quiescence and Suppress Mating in Drosophila.

PubMed

Pooryasin, Atefeh; Fiala, André

2015-09-16

Animals show different levels of activity that are reflected in sensory responsiveness and endogenously generated behaviors. Biogenic amines have been determined to be causal factors for these states of arousal. It is well established that, in Drosophila, dopamine and octopamine promote increased arousal. However, little is known about factors that regulate arousal negatively and induce states of quiescence. Moreover, it remains unclear whether global, diffuse modulatory systems comprehensively affecting brain activity determine general states of arousal. Alternatively, individual aminergic neurons might selectively modulate the animals' activity in a distinct behavioral context. Here, we show that artificially activating large populations of serotonin-releasing neurons induces behavioral quiescence and inhibits feeding and mating. We systematically narrowed down a role of serotonin in inhibiting endogenously generated locomotor activity to neurons located in the posterior medial protocerebrum. We identified neurons of this cell cluster that suppress mating, but not feeding behavior. These results suggest that serotonin does not uniformly act as global, negative modulator of general arousal. Rather, distinct serotoninergic neurons can act as inhibitory modulators of specific behaviors. An animal's responsiveness to external stimuli and its various types of endogenously generated, motivated behavior are highly dynamic and change between states of high activity and states of low activity. It remains unclear whether these states are mediated by unitary modulatory systems globally affecting brain activity, or whether distinct neurons modulate specific neuronal circuits underlying particular types of behavior. Using the model organism Drosophila melanogaster, we find that activating large proportions of serotonin-releasing neurons induces behavioral quiescence. Moreover, distinct serotonin-releasing neurons that we genetically isolated and identified negatively affect aspects of mating behavior, but not food uptake. This demonstrates that individual serotoninergic neurons can modulate distinct types of behavior selectively. Copyright © 2015 the authors 0270-6474/15/3512792-21$15.00/0.

Buckling instability in ordered bacterial colonies

NASA Astrophysics Data System (ADS)

Boyer, Denis; Mather, William; Mondragón-Palomino, Octavio; Orozco-Fuentes, Sirio; Danino, Tal; Hasty, Jeff; Tsimring, Lev S.

2011-04-01

Bacterial colonies often exhibit complex spatio-temporal organization. This collective behavior is affected by a multitude of factors ranging from the properties of individual cells (shape, motility, membrane structure) to chemotaxis and other means of cell-cell communication. One of the important but often overlooked mechanisms of spatio-temporal organization is direct mechanical contact among cells in dense colonies such as biofilms. While in natural habitats all these different mechanisms and factors act in concert, one can use laboratory cell cultures to study certain mechanisms in isolation. Recent work demonstrated that growth and ensuing expansion flow of rod-like bacteria Escherichia coli in confined environments leads to orientation of cells along the flow direction and thus to ordering of cells. However, the cell orientational ordering remained imperfect. In this paper we study one mechanism responsible for the persistence of disorder in growing cell populations. We demonstrate experimentally that a growing colony of nematically ordered cells is prone to the buckling instability. Our theoretical analysis and discrete-element simulations suggest that the nature of this instability is related to the anisotropy of the stress tensor in the ordered cell colony.

Rare Cell Detection by Single-Cell RNA Sequencing as Guided by Single-Molecule RNA FISH.

PubMed

Torre, Eduardo; Dueck, Hannah; Shaffer, Sydney; Gospocic, Janko; Gupte, Rohit; Bonasio, Roberto; Kim, Junhyong; Murray, John; Raj, Arjun

2018-02-28

Although single-cell RNA sequencing can reliably detect large-scale transcriptional programs, it is unclear whether it accurately captures the behavior of individual genes, especially those that express only in rare cells. Here, we use single-molecule RNA fluorescence in situ hybridization as a gold standard to assess trade-offs in single-cell RNA-sequencing data for detecting rare cell expression variability. We quantified the gene expression distribution for 26 genes that range from ubiquitous to rarely expressed and found that the correspondence between estimates across platforms improved with both transcriptome coverage and increased number of cells analyzed. Further, by characterizing the trade-off between transcriptome coverage and number of cells analyzed, we show that when the number of genes required to answer a given biological question is small, then greater transcriptome coverage is more important than analyzing large numbers of cells. More generally, our report provides guidelines for selecting quality thresholds for single-cell RNA-sequencing experiments aimed at rare cell analyses. Copyright © 2018 Elsevier Inc. All rights reserved.

A model for the kinetics of homotypic cellular aggregation under static conditions

NASA Technical Reports Server (NTRS)

Neelamegham, S.; Munn, L. L.; Zygourakis, K.; McIntire, L. V. (Principal Investigator)

1997-01-01

We present the formulation and testing of a mathematical model for the kinetics of homotypic cellular aggregation. The model considers cellular aggregation under no-flow conditions as a two-step process. Individual cells and cell aggregates 1) move on the tissue culture surface and 2) collide with other cells (or aggregates). These collisions lead to the formation of intercellular bonds. The aggregation kinetics are described by a system of coupled, nonlinear ordinary differential equations, and the collision frequency kernel is derived by extending Smoluchowski's colloidal flocculation theory to cell migration and aggregation on a two-dimensional surface. Our results indicate that aggregation rates strongly depend upon the motility of cells and cell aggregates, the frequency of cell-cell collisions, and the strength of intercellular bonds. Model predictions agree well with data from homotypic lymphocyte aggregation experiments using Jurkat cells activated by 33B6, an antibody to the beta 1 integrin. Since cell migration speeds and all the other model parameters can be independently measured, the aggregation model provides a quantitative methodology by which we can accurately evaluate the adhesivity and aggregation behavior of cells.

Order Matters: The Order of Somatic Mutations Influences Cancer Evolution.

PubMed

Kent, David G; Green, Anthony R

2017-04-03

Cancers evolve as a consequence of multiple somatic lesions, with competition between subclones and sequential subclonal evolution. Some driver mutations arise either early or late in the evolution of different individual tumors, suggesting that the final malignant properties of a subclone reflect the sum of mutations acquired rather than the order in which they arose. However, very little is known about the cellular consequences of altering the order in which mutations are acquired. Recent studies of human myeloproliferative neoplasms show that the order in which individual mutations are acquired has a dramatic impact on the cell biological and molecular properties of tumor-initiating cells. Differences in clinical presentation, complications, and response to targeted therapy were all observed and implicate mutation order as an important player in cancer biology. These observations represent the first demonstration that the order of mutation acquisition influences stem and progenitor cell behavior and clonal evolution in any cancer. Thus far, the impact of different mutation orders has only been studied in hematological malignancies, and analogous studies of solid cancers are now required. Copyright © 2017 Cold Spring Harbor Laboratory Press; all rights reserved.

Ventromedial Hypothalamus and the Generation of Aggression

PubMed Central

Hashikawa, Yoshiko; Hashikawa, Koichi; Falkner, Annegret L.; Lin, Dayu

2017-01-01

Aggression is a costly behavior, sometimes with severe consequences including death. Yet aggression is prevalent across animal species ranging from insects to humans, demonstrating its essential role in the survival of individuals and groups. The question of how the brain decides when to generate this costly behavior has intrigued neuroscientists for over a century and has led to the identification of relevant neural substrates. Various lesion and electric stimulation experiments have revealed that the hypothalamus, an ancient structure situated deep in the brain, is essential for expressing aggressive behaviors. More recently, studies using precise circuit manipulation tools have identified a small subnucleus in the medial hypothalamus, the ventrolateral part of the ventromedial hypothalamus (VMHvl), as a key structure for driving both aggression and aggression-seeking behaviors. Here, we provide an updated summary of the evidence that supports a role of the VMHvl in aggressive behaviors. We will consider our recent findings detailing the physiological response properties of populations of VMHvl cells during aggressive behaviors and provide new understanding regarding the role of the VMHvl embedded within the larger whole-brain circuit for social sensation and action. PMID:29375329

Individual-Based Compulsive Sexual Behavior Scale: Its Development and Importance in Examining Compulsive Sexual Behavior.

PubMed

Efrati, Yaniv; Mikulincer, Mario

2018-04-03

Compulsive sexual behavior comprises individual-based (e.g., sexual fantasies, compulsive sexual thoughts, masturbation) and partnered (e.g., interpersonal sexual conquests, repeated infidelity) facets. Most instruments for assessing compulsive sexual behavior, however, focus less on the individual-based facet and specifically on fantasies and compulsive thoughts. In the current research, we developed and validated an individual-based compulsive sexual behavior scale (I-CSB). In Study 1 (N = 492), the factorial structure of the I-CSB was examined. In Study 2 (N = 406), we assessed I-CSB's convergent validity. In Study 3 (N = 112), we examined whether the I-CSB differentiates between individuals who suffer from compulsive sexual behavior and those who do not. Results revealed a four-factor structure for individual-based compulsive sexual behavior that is associated with an intense inner conflict regarding sexuality (high arousal contrasting with high sexual anxiety), and that accounts for approximately 75% of the differences between people with compulsive sexual behavior and controls. Results are discussed in light of the need for a broader understanding of compulsive sexual behavior.

Coding of auditory temporal and pitch information by hippocampal individual cells and cell assemblies in the rat.

PubMed

Sakurai, Y

2002-01-01

This study reports how hippocampal individual cells and cell assemblies cooperate for neural coding of pitch and temporal information in memory processes for auditory stimuli. Each rat performed two tasks, one requiring discrimination of auditory pitch (high or low) and the other requiring discrimination of their duration (long or short). Some CA1 and CA3 complex-spike neurons showed task-related differential activity between the high and low tones in only the pitch-discrimination task. However, without exception, neurons which showed task-related differential activity between the long and short tones in the duration-discrimination task were always task-related neurons in the pitch-discrimination task. These results suggest that temporal information (long or short), in contrast to pitch information (high or low), cannot be coded independently by specific neurons. The results also indicate that the two different behavioral tasks cannot be fully differentiated by the task-related single neurons alone and suggest a model of cell-assembly coding of the tasks. Cross-correlation analysis among activities of simultaneously recorded multiple neurons supported the suggested cell-assembly model.Considering those results, this study concludes that dual coding by hippocampal single neurons and cell assemblies is working in memory processing of pitch and temporal information of auditory stimuli. The single neurons encode both auditory pitches and their temporal lengths and the cell assemblies encode types of tasks (contexts or situations) in which the pitch and the temporal information are processed.

MULTISCALE MODELS OF TAXIS-DRIVEN PATTERNING IN BACTERIAL POPULATIONS

PubMed Central

XUE, CHUAN; OTHMER, HANS G.

2009-01-01

Spatially-distributed populations of various types of bacteria often display intricate spatial patterns that are thought to result from the cellular response to gradients of nutrients or other attractants. In the past decade a great deal has been learned about signal transduction, metabolism and movement in E. coli and other bacteria, but translating the individual-level behavior into population-level dynamics is still a challenging problem. However, this is a necessary step because it is computationally impractical to use a strictly cell-based model to understand patterning in growing populations, since the total number of cells may reach 1012 - 1014 in some experiments. In the past phenomenological equations such as the Patlak-Keller-Segel equations have been used in modeling the cell movement that is involved in the formation of such patterns, but the question remains as to how the microscopic behavior can be correctly described by a macroscopic equation. Significant progress has been made for bacterial species that employ a “run-and-tumble” strategy of movement, in that macroscopic equations based on simplified schemes for signal transduction and turning behavior have been derived [14, 15]. Here we extend previous work in a number of directions: (i) we allow for time-dependent signals, which extends the applicability of the equations to natural environments, (ii) we use a more general turning rate function that better describes the biological behavior, and (iii) we incorporate the effect of hydrodynamic forces that arise when cells swim in close proximity to a surface. We also develop a new approach to solving the moment equations derived from the transport equation that does not involve closure assumptions. Numerical examples show that the solution of the lowest-order macroscopic equation agrees well with the solution obtained from a Monte Carlo simulation of cell movement under a variety of temporal protocols for the signal. We also apply the method to derive equations of chemotactic movement that are governed by multiple chemotactic signals. PMID:19784399

Zeolite inorganic scaffolds for novel biomedical application: Effect of physicochemical characteristic of zeolite membranes on cell adhesion and viability

NASA Astrophysics Data System (ADS)

Tavolaro, Palmira; Catalano, Silvia; Martino, Guglielmo; Tavolaro, Adalgisa

2016-09-01

The design, preparation and selection of inorganic materials useful as functional scaffolds for cell adhesion is a complex question based both on the understanding of the chemical behavior of the materials and individual cells, and on their interactions. Pure zeolite membranes formed from synthetic crystals offer chemically-capable being modulated silanolic surfaces that are amenable to adhesion and growth of fibroblasts. We report the facile preparation of reusable, very longlasting, biocompatible, easily sterilized synthetic scaffolds in a zeolite membrane configuration, which are very stable in aqueous media (apart from ionic strength and pH values), able to adsorb pollutant species and to confine undesired toxic ions (present in culture media). This may ultimately lead to the development of cell supports for economic antibiotic-free culture media.

Interplay of cell dynamics and epithelial tension during morphogenesis of the Drosophila pupal wing

PubMed Central

Etournay, Raphaël; Popović, Marko; Merkel, Matthias; Nandi, Amitabha; Blasse, Corinna; Aigouy, Benoît; Brandl, Holger; Myers, Gene; Salbreux, Guillaume; Jülicher, Frank; Eaton, Suzanne

2015-01-01

How tissue shape emerges from the collective mechanical properties and behavior of individual cells is not understood. We combine experiment and theory to study this problem in the developing wing epithelium of Drosophila. At pupal stages, the wing-hinge contraction contributes to anisotropic tissue flows that reshape the wing blade. Here, we quantitatively account for this wing-blade shape change on the basis of cell divisions, cell rearrangements and cell shape changes. We show that cells both generate and respond to epithelial stresses during this process, and that the nature of this interplay specifies the pattern of junctional network remodeling that changes wing shape. We show that patterned constraints exerted on the tissue by the extracellular matrix are key to force the tissue into the right shape. We present a continuum mechanical model that quantitatively describes the relationship between epithelial stresses and cell dynamics, and how their interplay reshapes the wing. DOI: http://dx.doi.org/10.7554/eLife.07090.001 PMID:26102528

Solar cell design for avoiding LILT degradation. [low intensity, low temperature

NASA Technical Reports Server (NTRS)

Stella, P. M.; Ctorry, G. T.

1987-01-01

Growing concerns about radioisotope thermoelectric generator (RTG) performance potential, cost, safety, and availability have renewed interest in utilizing photovoltaic energy conversion for future JPL interplanetary missions such as the Mariner Mark II set. Although lightweight solar array technology has advanced to the point where it would appear to provide an alternative power source, anomalous silicon cell curve shape degradation at conditions of low intensity and low temperature (LILT) severely restricts photovoltaic applications for missions beyond 3 AU solar distance. In order to extend photovoltaic applications to distances of 5 AU, ways to minimize the deleterious impact of LILT cell degradation were investigated. These investigations have ranged from consideration of individual cell selection for LILT behavior to the examination of methods for reducing or eliminating cell LILT degradation by modifying the cell processing. Use of a partial oxide barrier between the cell n+ contacts and the silicon has been shown to reduce significantly both the occurrence and magnitude of the LILT degradation.

Multi-Cellular Logistics of Collective Cell Migration

PubMed Central

Yamao, Masataka; Naoki, Honda; Ishii, Shin

2011-01-01

During development, the formation of biological networks (such as organs and neuronal networks) is controlled by multicellular transportation phenomena based on cell migration. In multi-cellular systems, cellular locomotion is restricted by physical interactions with other cells in a crowded space, similar to passengers pushing others out of their way on a packed train. The motion of individual cells is intrinsically stochastic and may be viewed as a type of random walk. However, this walk takes place in a noisy environment because the cell interacts with its randomly moving neighbors. Despite this randomness and complexity, development is highly orchestrated and precisely regulated, following genetic (and even epigenetic) blueprints. Although individual cell migration has long been studied, the manner in which stochasticity affects multi-cellular transportation within the precisely controlled process of development remains largely unknown. To explore the general principles underlying multicellular migration, we focus on the migration of neural crest cells, which migrate collectively and form streams. We introduce a mechanical model of multi-cellular migration. Simulations based on the model show that the migration mode depends on the relative strengths of the noise from migratory and non-migratory cells. Strong noise from migratory cells and weak noise from surrounding cells causes “collective migration,” whereas strong noise from non-migratory cells causes “dispersive migration.” Moreover, our theoretical analyses reveal that migratory cells attract each other over long distances, even without direct mechanical contacts. This effective interaction depends on the stochasticity of the migratory and non-migratory cells. On the basis of these findings, we propose that stochastic behavior at the single-cell level works effectively and precisely to achieve collective migration in multi-cellular systems. PMID:22205934

Type IV pili interactions promote intercellular association and moderate swarming of Pseudomonas aeruginosa

PubMed Central

Anyan, Morgen E.; Amiri, Aboutaleb; Harvey, Cameron W.; Tierra, Giordano; Morales-Soto, Nydia; Driscoll, Callan M.; Alber, Mark S.; Shrout, Joshua D.

2014-01-01

Pseudomonas aeruginosa is a ubiquitous bacterium that survives in many environments, including as an acute and chronic pathogen in humans. Substantial evidence shows that P. aeruginosa behavior is affected by its motility, and appendages known as flagella and type IV pili (TFP) are known to confer such motility. The role these appendages play when not facilitating motility or attachment, however, is unclear. Here we discern a passive intercellular role of TFP during flagellar-mediated swarming of P. aeruginosa that does not require TFP extension or retraction. We studied swarming at the cellular level using a combination of laboratory experiments and computational simulations to explain the resultant patterns of cells imaged from in vitro swarms. Namely, we used a computational model to simulate swarming and to probe for individual cell behavior that cannot currently be otherwise measured. Our simulations showed that TFP of swarming P. aeruginosa should be distributed all over the cell and that TFP−TFP interactions between cells should be a dominant mechanism that promotes cell−cell interaction, limits lone cell movement, and slows swarm expansion. This predicted physical mechanism involving TFP was confirmed in vitro using pairwise mixtures of strains with and without TFP where cells without TFP separate from cells with TFP. While TFP slow swarm expansion, we show in vitro that TFP help alter collective motion to avoid toxic compounds such as the antibiotic carbenicillin. Thus, TFP physically affect P. aeruginosa swarming by actively promoting cell−cell association and directional collective motion within motile groups to aid their survival. PMID:25468980

Cutaneous Squamous Cell Carcinoma.

PubMed

Parekh, Vishwas; Seykora, John T

2017-09-01

Cutaneous squamous cell carcinoma (cSCC) is a malignant neoplasm of the skin characterized by an aberrant proliferation of keratinocytes. Cutaneous SCC is the second most common malignancy globally, and usually arises in the chronically sun-damaged skin of elderly white individuals. From a pathologist's perspective, it is important to differentiate cSCC from the benign and reactive squamoproliferative lesions and identify the high-risk features associated with aggressive tumor behavior. In this article, we provide an up-to-date overview of cSCC along with its precursor lesions and important histologic variants, with a particular emphasis on the histopathologic features and molecular pathogenesis. Copyright © 2017 Elsevier Inc. All rights reserved.

Transgenic mouse models enabling photolabeling of individual neurons in vivo.

PubMed

Peter, Manuel; Bathellier, Brice; Fontinha, Bruno; Pliota, Pinelopi; Haubensak, Wulf; Rumpel, Simon

2013-01-01

One of the biggest tasks in neuroscience is to explain activity patterns of individual neurons during behavior by their cellular characteristics and their connectivity within the neuronal network. To greatly facilitate linking in vivo experiments with a more detailed molecular or physiological analysis in vitro, we have generated and characterized genetically modified mice expressing photoactivatable GFP (PA-GFP) that allow conditional photolabeling of individual neurons. Repeated photolabeling at the soma reveals basic morphological features due to diffusion of activated PA-GFP into the dendrites. Neurons photolabeled in vivo can be re-identified in acute brain slices and targeted for electrophysiological recordings. We demonstrate the advantages of PA-GFP expressing mice by the correlation of in vivo firing rates of individual neurons with their expression levels of the immediate early gene c-fos. Generally, the mouse models described in this study enable the combination of various analytical approaches to characterize living cells, also beyond the neurosciences.

Individual Differences, Intelligence, and Behavior Analysis

ERIC Educational Resources Information Center

Williams, Ben; Myerson, Joel; Hale, Sandra

2008-01-01

Despite its avowed goal of understanding individual behavior, the field of behavior analysis has largely ignored the determinants of consistent differences in level of performance among individuals. The present article discusses major findings in the study of individual differences in intelligence from the conceptual framework of a functional…

Behavior Change Outcomes of Marathon Group Treatment

ERIC Educational Resources Information Center

Uhlemann, Max R.; Weigel, Richard G.

1977-01-01

This study evaluated behavior change occurring after a marathon group experience, with a focus on individualized rather than shared behavioral change criteria. The individualization of behavior change criteria is based on the assertion that few, if any, single change criteria are appropriate or realistic for assessing change in all individuals.…

Emergence of Swarming Behavior: Foraging Agents Evolve Collective Motion Based on Signaling.

PubMed

Witkowski, Olaf; Ikegami, Takashi

2016-01-01

Swarming behavior is common in biology, from cell colonies to insect swarms and bird flocks. However, the conditions leading to the emergence of such behavior are still subject to research. Since Reynolds' boids, many artificial models have reproduced swarming behavior, focusing on details ranging from obstacle avoidance to the introduction of fixed leaders. This paper presents a model of evolved artificial agents, able to develop swarming using only their ability to listen to each other's signals. The model simulates a population of agents looking for a vital resource they cannot directly detect, in a 3D environment. Instead of a centralized algorithm, each agent is controlled by an artificial neural network, whose weights are encoded in a genotype and adapted by an original asynchronous genetic algorithm. The results demonstrate that agents progressively evolve the ability to use the information exchanged between each other via signaling to establish temporary leader-follower relations. These relations allow agents to form swarming patterns, emerging as a transient behavior that improves the agents' ability to forage for the resource. Once they have acquired the ability to swarm, the individuals are able to outperform the non-swarmers at finding the resource. The population hence reaches a neutral evolutionary space which leads to a genetic drift of the genotypes. This reductionist approach to signal-based swarming not only contributes to shed light on the minimal conditions for the evolution of a swarming behavior, but also more generally it exemplifies the effect communication can have on optimal search patterns in collective groups of individuals.

Elucidating Neuronal Mechanisms Using Intracellular Recordings during Behavior.

PubMed

Lee, Albert K; Brecht, Michael

2018-06-01

Intracellular recording allows measurement and perturbation of the membrane potential of identified neurons with sub-millisecond and sub-millivolt precision. This gives intracellular recordings a unique capacity to provide rich information about individual cells (e.g., high-resolution characterization of inputs, outputs, excitability, and structure). Hence, such recordings can elucidate the mechanisms that underlie fundamental phenomena, such as brain state, sparse coding, gating, gain modulation, and learning. Technical developments have increased the range of behaviors during which intracellular recording methods can be employed, such as in freely moving animals and head-fixed animals actively performing tasks, including in virtual environments. Such advances, and the combination of intracellular recordings with genetic and imaging techniques, have enabled investigation of the mechanisms that underlie neural computations during natural and trained behaviors. Copyright © 2018 Elsevier Ltd. All rights reserved.

Agent-Based Phytoplankton Models of Cellular and Population Processes: Fostering Individual-Based Learning in Undergraduate Research

NASA Astrophysics Data System (ADS)

Berges, J. A.; Raphael, T.; Rafa Todd, C. S.; Bate, T. C.; Hellweger, F. L.

2016-02-01

Engaging undergraduate students in research projects that require expertise in multiple disciplines (e.g. cell biology, population ecology, and mathematical modeling) can be challenging because they have often not developed the expertise that allows them to participate at a satisfying level. Use of agent-based modeling can allow exploration of concepts at more intuitive levels, and encourage experimentation that emphasizes processes over computational skills. Over the past several years, we have involved undergraduate students in projects examining both ecological and cell biological aspects of aquatic microbial biology, using the freely-downloadable, agent-based modeling environment NetLogo (https://ccl.northwestern.edu/netlogo/). In Netlogo, actions of large numbers of individuals can be simulated, leading to complex systems with emergent behavior. The interface features appealing graphics, monitors, and control structures. In one example, a group of sophomores in a BioMathematics program developed an agent-based model of phytoplankton population dynamics in a pond ecosystem, motivated by observed macroscopic changes in cell numbers (due to growth and death), and driven by responses to irradiance, temperature and a limiting nutrient. In a second example, junior and senior undergraduates conducting Independent Studies created a model of the intracellular processes governing stress and cell death for individual phytoplankton cells (based on parameters derived from experiments using single-cell culturing and flow cytometry), and then this model was embedded in the agents in the pond ecosystem model. In our experience, students with a range of mathematical abilities learned to code quickly and could use the software with varying degrees of sophistication, for example, creation of spatially-explicit two and three-dimensional models. Skills developed quickly and transferred readily to other platforms (e.g. Matlab).

Therapeutic Effect of a Synthetic RORα/γ Agonist in an Animal Model of Autism

PubMed Central

2015-01-01

Autism is a developmental disorder of the nervous system associated with impaired social communication and interactions as well excessive repetitive behaviors. There are no drug therapies that directly target the pathology of this disease. The retinoic acid receptor-related orphan receptor α (RORα) is a nuclear receptor that has been demonstrated to have reduced expression in many individuals with autism spectrum disorder (ASD). Several genes that have been shown to be downregulated in individuals with ASD have also been identified as putative RORα target genes. Utilizing a synthetic RORα/γ agonist, SR1078, that we identified previously, we demonstrate that treatment of BTBR mice (a model of autism) with SR1078 results in reduced repetitive behavior. Furthermore, these mice display increased expression of ASD-associated RORα target genes in both the brains of the BTBR mice and in a human neuroblastoma cell line treated with SR1078. These data suggest that pharmacological activation of RORα may be a method for treatment of autism. PMID:26625251

Therapeutic Effect of a Synthetic RORα/γ Agonist in an Animal Model of Autism.

PubMed

Wang, Yongjun; Billon, Cyrielle; Walker, John K; Burris, Thomas P

2016-02-17

Autism is a developmental disorder of the nervous system associated with impaired social communication and interactions as well excessive repetitive behaviors. There are no drug therapies that directly target the pathology of this disease. The retinoic acid receptor-related orphan receptor α (RORα) is a nuclear receptor that has been demonstrated to have reduced expression in many individuals with autism spectrum disorder (ASD). Several genes that have been shown to be downregulated in individuals with ASD have also been identified as putative RORα target genes. Utilizing a synthetic RORα/γ agonist, SR1078, that we identified previously, we demonstrate that treatment of BTBR mice (a model of autism) with SR1078 results in reduced repetitive behavior. Furthermore, these mice display increased expression of ASD-associated RORα target genes in both the brains of the BTBR mice and in a human neuroblastoma cell line treated with SR1078. These data suggest that pharmacological activation of RORα may be a method for treatment of autism.

In Situ Radiographic Investigation of (De)Lithiation Mechanisms in a Tin-Electrode Lithium-Ion Battery.

PubMed

Sun, Fu; Markötter, Henning; Zhou, Dong; Alrwashdeh, Saad Sabe Sulaiman; Hilger, Andre; Kardjilov, Nikolay; Manke, Ingo; Banhart, John

2016-05-10

The lithiation and delithiation mechanisms of multiple-Sn particles in a customized flat radiography cell were investigated by in situ synchrotron radiography. For the first time, four (de)lithiation phenomena in a Sn-electrode battery system are highlighted: 1) the (de)lithiation behavior varies between different Sn particles, 2) the time required to lithiate individual Sn particles is markedly different from the time needed to discharge the complete battery, 3) electrochemical deactivation of originally electrochemically active particles is reported, and 4) a change of electrochemical behavior of individual particles during cycling is found and explained by dynamic changes of (de)lithiation pathways amongst particles within the electrode. These unexpected findings fundamentaly expand the understanding of the underlying (de)lithiation mechanisms inside commercial lithium-ion batteries (LIBs) and would open new design principles for high-performance next-generation LIBs. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

2,3,7,8-TCDD effects on visual structure and function in swim-up rainbow trout

USGS Publications Warehouse

Carvalho, Paulo S. M.

2004-01-01

An understanding of mechanisms of contaminant effects across levels of biological organization is essential in ecotoxicology if we are to generate predictive models for population-level effects. We applied a suite of biochemical, histological, and behavioral end points related to visual structure and function and foraging behavior to evaluate effects of 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) on swim-up rainbow trout. We detected a dose-dependent decrease in densities of retinal ganglion cells (RGC), key retinal neurons that link the eye with the brain. These changes resulted in corresponding deficits in visual/motor function including reductions in visual acuity and in scotopic and photopic thresholds due to TCDD. The loss of RGCs suggests an increase in convergence of synapses from photoreceptors to RGCs as a cellular mechanism for the visual deficits. Dose-dependent increases in immunohistochemical detection of CYP1A protein in the vasculature of the brain and eye choroid was proportional with decreased ganglion cell densities in the retina. TCDD-induced AHR-regulated effects on these tissues might be involved in the detected decrease in ganglion cell densities. Prey capture rate decreased after TCDD exposure only at the highest treatment groups evaluated. Collectively, these results show that TCDD causes biochemical and structural changes in the eye and brain of rainbow trout that are associated with behavioral deficits leading to decreased individual fitness.

Intelligence, Cognition, and Language of Green Plants.

PubMed

Trewavas, Anthony

2016-01-01

A summary definition of some 70 descriptions of intelligence provides a definition for all other organisms including plants that stresses fitness. Barbara McClintock, a plant biologist, posed the notion of the 'thoughtful cell' in her Nobel prize address. The systems structure necessary for a thoughtful cell is revealed by comparison of the interactome and connectome. The plant root cap, a group of some 200 cells that act holistically in responding to numerous signals, likely possesses a similar systems structure agreeing with Darwin's description of acting like the brain of a lower organism. Intelligent behavior requires assessment of different choices and taking the beneficial one. Decisions are constantly required to optimize the plant phenotype to a dynamic environment and the cambium is the assessing tissue diverting more or removing resources from different shoot and root branches through manipulation of vascular elements. Environmental awareness likely indicates consciousness. Spontaneity in plant behavior, ability to count to five and error correction indicate intention. Volatile organic compounds are used as signals in plant interactions and being complex in composition may be the equivalent of language accounting for self and alien recognition by individual plants. Game theory describes competitive interactions. Interactive and intelligent outcomes emerge from application of various games between plants themselves and interactions with microbes. Behavior profiting from experience, another simple definition of intelligence, requires both learning and memory and is indicated in the priming of herbivory, disease and abiotic stresses.

Food limitation leads to behavioral diversification and dietary specialization in sea otters

USGS Publications Warehouse

Tinker, M.T.; Bentall, G.; Estes, J.A.

2008-01-01

Dietary diversity often varies inversely with prey resource abundance. This pattern, although typically measured at the population level, is usually assumed to also characterize the behavior of individual animals within the population. However, the pattern might also be produced by changes in the degree of variation among individuals. Here we report on dietary and associated behavioral changes that occurred with the experimental translocation of sea otters from a food-poor to a food-rich environment. Although the diets of all individuals were broadly similar in the food-rich environment, a behaviorally based dietary polymorphism existed in the food-poor environment. Higher dietary diversity under low resource abundance was largely driven by greater variation among individuals. We further show that the dietary polymorphism in the food-poor environment included a broad suite of correlated behavioral variables and that the individuals that comprised specific behavioral clusters benefited from improved foraging efficiency on their individually preferred prey. Our findings add to the growing list of examples of extreme individuality in behavior and prey choice within populations and suggest that this phenomenon can emerge as a behavioral manifestation of increased population density. Individuality in foraging behavior adds complexity to both the fitness consequences of prey selection and food web dynamics, and it may figure prominently as a diversifying process over evolutionary timescales. ?? 2008 by The National Academy of Sciences of the USA.

Dynamic interactions between cells and their extracellular matrix mediate embryonic development.

PubMed

Goody, Michelle F; Henry, Clarissa A

2010-06-01

Cells and their surrounding extracellular matrix microenvironment interact throughout all stages of life. Understanding the continuously changing scope of cell-matrix interactions in vivo is crucial to garner insights into both congenital birth defects and disease progression. A current challenge in the field of developmental biology is to adapt in vitro tools and rapidly evolving imaging technology to study cell-matrix interactions in a complex 4-D environment. In this review, we highlight the dynamic modulation of cell-matrix interactions during development. We propose that individual cell-matrix adhesion proteins are best considered as complex proteins that can play multiple, often seemingly contradictory roles, depending upon the context of the microenvironment. In addition, cell-matrix proteins can also exert different short versus long term effects. It is thus important to consider cell behavior in light of the microenvironment because of the constant and dynamic reciprocal interactions occurring between them. Finally, we suggest that analysis of cell-matrix interactions at multiple levels (molecules, cells, tissues) in vivo is critical for an integrated understanding because different information can be acquired from all size scales. Copyright 2010 Wiley-Liss, Inc.

Personality, foraging behavior and specialization: integrating behavioral and food web ecology at the individual level.

PubMed

Toscano, Benjamin J; Gownaris, Natasha J; Heerhartz, Sarah M; Monaco, Cristián J

2016-09-01

Behavioral traits and diet were traditionally thought to be highly plastic within individuals. This view was espoused in the widespread use of optimality models, which broadly predict that individuals can modify behavioral traits and diet across ecological contexts to maximize fitness. Yet, research conducted over the past 15 years supports an alternative view; fundamental behavioral traits (e.g., activity level, exploration, sociability, boldness and aggressiveness) and diet often vary among individuals and this variation persists over time and across contexts. This phenomenon has been termed animal personality with regard to behavioral traits and individual specialization with regard to diet. While these aspects of individual-level phenotypic variation have been thus far studied in isolation, emerging evidence suggests that personality and individual specialization may covary, or even be causally related. Building on this work, we present the overarching hypothesis that animal personality can drive specialization through individual differences in various aspects of consumer foraging behavior. Specifically, we suggest pathways by which consumer personality traits influence foraging activity, risk-dependent foraging, roles in social foraging groups, spatial aspects of foraging and physiological drivers of foraging, which in turn can lead to consistent individual differences in food resource use. These pathways provide a basis for generating testable hypotheses directly linking animal personality to ecological dynamics, a major goal in contemporary behavioral ecology.

Moderators of the Dynamic Link between Alcohol Use and Aggressive Behavior among Adolescent Males

PubMed Central

White, Helene Raskin; Fite, Paula; Pardini, Dustin; Mun, Eun-Young; Loeber, Rolf

2012-01-01

Although longitudinal evidence has linked alcohol use with aggressive behavior during adolescence, most studies have failed to adequately control for the numerous between-individual differences that may underlie this association. In addition, few studies of adolescents have examined whether the nature of the within-individual association between alcohol use and aggression depends on individual and contextual factors. To address these limitations, this study examined the association between within-individual changes in alcohol use and aggressive behavior across adolescence and determined whether impulsive behavior, positive attitudes toward violence, violent peers, neighborhood crime, and race moderated this association. Data from 971 adolescent males assessed annually from ages 13 to 18 were analyzed using a within-individual regression panel model that eliminated all stable between-individual factors as potential confounds. Findings indicated that within-individual increases in alcohol use quantity from one’s own typical levels of drinking were concurrently associated with within-individual increases in aggressive behavior, and vice versa. However, increases in alcohol were more strongly linked to increases in aggressive behavior among boys with attitudes favoring violence and those who lived in high-crime neighborhoods. The association between alcohol and aggressive behavior was similar for White and Black young men. Interventions designed to reduce aggressive behaviors should consider targeting not only alcohol use, but also individual and environmental risk factors that contribute to this link. PMID:22911129

[Caring for families of charcoal-burning suicide patients].

PubMed

Pien, Feng-Chen; Feng, Hsin-Pei; Tzeng, Wen-Chii

2013-12-01

Charcoal-burning is the second major cause of suicide death in Taiwan. Predicting the variable damage and sequelae in this suicide mode is difficult due to the rapid combination of carbon monoxide with red blood cells. Delayed neuropsychological sequelae (DNS) may result in significantly extended recovery times, causing additional stress to the family. Nurses may help increase family understanding and support and guide family members to more positive intra-family interactions, shared perspectives on the recovery process, and resource seeking behavior by depicting subsequent family life and helping the entire family develop coping strategies those allow all members to effect cognitive, emotional and behavioral change. This result may help families of attempted suicide individuals recover successfully.

Contrasting performance of donor-acceptor copolymer pairs in ternary blend solar cells and two-acceptor copolymers in binary blend solar cells.

PubMed

Khlyabich, Petr P; Rudenko, Andrey E; Burkhart, Beate; Thompson, Barry C

2015-02-04

Here two contrasting approaches to polymer-fullerene solar cells are compared. In the first approach, two distinct semi-random donor-acceptor copolymers are blended with phenyl-C61-butyric acid methyl ester (PC61BM) to form ternary blend solar cells. The two poly(3-hexylthiophene)-based polymers contain either the acceptor thienopyrroledione (TPD) or diketopyrrolopyrrole (DPP). In the second approach, semi-random donor-acceptor copolymers containing both TPD and DPP acceptors in the same polymer backbone, termed two-acceptor polymers, are blended with PC61BM to give binary blend solar cells. The two approaches result in bulk heterojunction solar cells that have the same molecular active-layer components but differ in the manner in which these molecular components are mixed, either by physical mixing (ternary blend) or chemical "mixing" in the two-acceptor (binary blend) case. Optical properties and photon-to-electron conversion efficiencies of the binary and ternary blends were found to have similar features and were described as a linear combination of the individual components. At the same time, significant differences were observed in the open-circuit voltage (Voc) behaviors of binary and ternary blend solar cells. While in case of two-acceptor polymers, the Voc was found to be in the range of 0.495-0.552 V, ternary blend solar cells showed behavior inherent to organic alloy formation, displaying an intermediate, composition-dependent and tunable Voc in the range from 0.582 to 0.684 V, significantly exceeding the values achieved in the two-acceptor containing binary blend solar cells. Despite the differences between the physical and chemical mixing approaches, both pathways provided solar cells with similar power conversion efficiencies, highlighting the advantages of both pathways toward highly efficient organic solar cells.

The Effect of Keystone Individuals on Collective Outcomes Can Be Mediated through Interactions or Behavioral Persistence

PubMed Central

Pinter-Wollman, Noa; Keiser, Carl N.; Wollman, Roy; Pruitt, Jonathan N.

2017-01-01

Collective behavior emerges from interactions among group members who often vary in their behavior. The presence of just one or a few keystone individuals, such as leaders or tutors, may have a large effect on collective outcomes. These individuals can catalyze behavioral changes in other group members, thus altering group composition and collective behavior. The influence of keystone individuals on group function may lead to trade-offs between ecological situations, because the behavioral composition they facilitate may be suitable in one situation but not another. We use computer simulations to examine various mechanisms that allow keystone individuals to exert their influence on group members. We further discuss a trade-off between two potentially conflicting collective outcomes, cooperative prey attack and disease dynamics. Our simulations match empirical data from a social spider system and produce testable predictions for the causes and consequences of the influence of keystone individuals on group composition and collective outcomes. We find that a group’s behavioral composition can be impacted by the keystone individual through changes to interaction patterns or behavioral persistence over time. Group behavioral composition and the mechanisms that drive the distribution of phenotypes influence collective outcomes and lead to trade-offs between disease dynamics and cooperative prey attack. PMID:27420788

Viral Aggregation: Impact on Virus Behavior in the Environment.

PubMed

Gerba, Charles P; Betancourt, Walter Q

2017-07-05

Aggregates of viruses can have a significant impact on quantification and behavior of viruses in the environment. Viral aggregates may be formed in numerous ways. Viruses may form crystal like structures and aggregates in the host cell during replication or may form due to changes in environmental conditions after virus particles are released from the host cells. Aggregates tend to form near the isoelectric point of the virus, under the influence of certain salts and salt concentrations in solution, cationic polymers, and suspended organic matter. The given conditions under which aggregates form in the environment are highly dependent on the type of virus, type of salts in solution (cation, anion. monovalent, divalent) and pH. However, virus type greatly influences the conditions when aggregation/disaggregation will occur, making predictions difficult under any given set of water quality conditions. Most studies have shown that viral aggregates increase the survival of viruses in the environment and resistance to disinfectants, especially with more reactive disinfectants. The presence of viral aggregates may also result in overestimation of removal by filtration processes. Virus aggregation-disaggregation is a complex process and predicting the behavior of any individual virus is difficult under a given set of environmental circumstances without actual experimental data.

On sexual behavior and sex-role reversal.

PubMed

Schuiling, Gerard A

2005-09-01

Sex is not about reproduction; sex is about (re-)combination of DNA. Sex, not reproduction, always involves physical contact between two individuals; to achieve this, strategies of sexual behavior evolved. Sexual behavior, therefore, did not evolve as part of a reproductive strategy, but evolved to enable exchange of genetic material. In multicellular organisms the situation is more complicated than in unicellular organisms, as it is impossible for each cell within a multicellular body to have sex with another cell. Hence, evolution selected a system in which the possibility to have sex was limited to only one cell-line: the germ cells. As a result, sex adopted the character of fertilization, and sex and reproduction became inseparably linked. Still, in some species, including humans, sexual behavior still exhibits features of its evolutionary past: in humans (like in bonobo's) most sexual activity and many sexual behavioral patterns have nothing to do with reproduction (masturbation, homosexual behavior, for example); in humans, sexual behavior also became associated with other strategic objectives, such as intensifying the pair bond, expression of love or power. Different genders - male and female - evolved, and each gender evolved typical gender-related sexual and reproductive strategies as well. In most multicellular species, these strategies became inextricably mixed, and sexual behavior increasingly more - and in most species even exclusively - 'served' the interests of reproduction: sexual behavior became more or less synonymous with reproductive behavior. In most species, the 'mix' of sexual and reproductive strategies evolved into typical gender-related patterns of behavior, that is, in typical 'sex-roles'. Often, males are bigger and more 'beautiful' (= more intensely ornamented) than females; males compete with each other for access to females; males court females, while females choose males ('female choice'). However, ecological circumstances may cause a reversal of sex-roles, resulting in a situation in which females are bigger and more intensely ornamented than males, females compete for access to males, females court males and only males invest in care for the young, provided they are relatively certain of their paternity. Also, as in the case of the spotted hyena, females may be highly virilized and be socially dominant. This 'sex-role reversal' is seen, e.g., when males are relatively rare due to high predation pressure, or when the process of reproduction is very risky for the same reason: then it is 'better' that males, with their plenty of sperm, are wasted, than females with their few, precious eggs. It can be argued, with women being the fair sex, exhibiting competitive behavior and with an actively displaying courtship, and with men investing heavily in their offspring, meanwhile taking all (cultural) kinds of measures to guarantee their paternity, that humans, too, exhibit some degree of sex-role reversal.

Hyaluronan (HA) interacting proteins RHAMM and hyaluronidase impact prostate cancer cell behavior and invadopodia formation in 3D HA-based hydrogels.

PubMed

Gurski, Lisa A; Xu, Xian; Labrada, Lyana N; Nguyen, Ngoc T; Xiao, Longxi; van Golen, Kenneth L; Jia, Xinqiao; Farach-Carson, Mary C

2012-01-01

To study the individual functions of hyaluronan interacting proteins in prostate cancer (PCa) motility through connective tissues, we developed a novel three-dimensional (3D) hyaluronic acid (HA) hydrogel assay that provides a flexible, quantifiable, and physiologically relevant alternative to current methods. Invasion in this system reflects the prevalence of HA in connective tissues and its role in the promotion of cancer cell motility and tissue invasion, making the system ideal to study invasion through bone marrow or other HA-rich connective tissues. The bio-compatible cross-linking process we used allows for direct encapsulation of cancer cells within the gel where they adopt a distinct, cluster-like morphology. Metastatic PCa cells in these hydrogels develop fingerlike structures, "invadopodia", consistent with their invasive properties. The number of invadopodia, as well as cluster size, shape, and convergence, can provide a quantifiable measure of invasive potential. Among candidate hyaluronan interacting proteins that could be responsible for the behavior we observed, we found that culture in the HA hydrogel triggers invasive PCa cells to differentially express and localize receptor for hyaluronan mediated motility (RHAMM)/CD168 which, in the absence of CD44, appears to contribute to PCa motility and invasion by interacting with the HA hydrogel components. PCa cell invasion through the HA hydrogel also was found to depend on the activity of hyaluronidases. Studies shown here reveal that while hyaluronidase activity is necessary for invadopodia and inter-connecting cluster formation, activity alone is not sufficient for acquisition of invasiveness to occur. We therefore suggest that development of invasive behavior in 3D HA-based systems requires development of additional cellular features, such as activation of motility associated pathways that regulate formation of invadopodia. Thus, we report development of a 3D system amenable to dissection of biological processes associated with cancer cell motility through HA-rich connective tissues.

Associations of herd- and cow-level factors, cow lying behavior, and risk of elevated somatic cell count in free-stall housed lactating dairy cows.

PubMed

Watters, M E Alexandrea; Meijer, Karin M A; Barkema, Herman W; Leslie, Kenneth E; von Keyserlingk, Marina A G; Devries, Trevor J

2013-09-01

Recent evidence suggests that the risk of intramammary infection in dairy cows is related to lying patterns. The objectives of this study were to quantify the standing and lying behavior of dairy cows milked 3×/d, determine the cow- and herd-level factors associated with these behaviors, and relate these findings to the risk of an elevated somatic cell count (SCC). Five commercial free-stall dairy herds in Eastern Ontario, milking 3×/d, were enrolled in a longitudinal study. Forty Holstein-Friesian cows/herd were randomly selected as focal animals based on days in milk (<200 d) and SCC (<100,000 cells/mL). Farms were followed for 4, 5-week periods. Individual-cow SCC was recorded at the beginning of each period and end of the final period. Elevated SCC (eSCC) was used as an indicator of subclinical mastitis. A new incident eSCC was defined as an individual cow that started the period with a SCC <100,000 cells/mL but whose next SCC exceeded 200,000 cells/mL. Lying behavior was recorded 5d after each milk sampling using data loggers. For these 5d, individual milking times and feeding times were also recorded. On d1 of each recording period 2 trained observers scored focal cows for hygiene and lameness. Throughout the course of the study, cows averaged 11.2h/d of lying time, split into 8.6 lying bouts/d that were on average 84.6 min in length. Later lactation cows had longer daily lying times that were split into fewer lying bouts of longer duration than cows earlier in lactation. Lame cows had longer daily lying times and lying bout durations than non-lame cows. Cows with greater milk yield had lower lying times than lower producing cows. Average post-milking standing time across the study herds was 103 min. Manipulation of feed (feed delivery or push-up) by the stockperson, in the hour before milking or shortly thereafter, resulted in the longest post-milking standing times. Over the study period, 48 new eSCC were detected, resulting in a mean herd incidence rate of 0.91 eSCC/cow-year at risk for all study herds. A non-linear relationship between post-milking standing time and eSCC incidence was found; compared to those cows that lie down <90 min after milking, cows that lie down for the first time >90 min after milking had a lower risk of acquiring a new eSCC. The risk of experiencing an eSCC was also increased in multiparous cows, and in those cows with a higher SCC at the beginning of the study. These results indicate that management practices that promote post-milking standing time, such as the manipulation of feed delivery around milking times, should be encouraged to reduce the risk of cows experiencing new eSCC. Copyright © 2013 Elsevier B.V. All rights reserved.

Disease dynamics in a stochastic network game: a little empathy goes a long way in averting outbreaks

PubMed Central

Eksin, Ceyhun; Shamma, Jeff S.; Weitz, Joshua S.

2017-01-01

Individuals change their behavior during an epidemic in response to whether they and/or those they interact with are healthy or sick. Healthy individuals may utilize protective measures to avoid contracting a disease. Sick individuals may utilize preemptive measures to avoid spreading a disease. Yet, in practice both protective and preemptive changes in behavior come with costs. This paper proposes a stochastic network disease game model that captures the self-interests of individuals during the spread of a susceptible-infected-susceptible disease. In this model, individuals strategically modify their behavior based on current disease conditions. These reactions influence disease spread. We show that there is a critical level of concern, i.e., empathy, by the sick individuals above which disease is eradicated rapidly. Furthermore, we find that risk averse behavior by the healthy individuals cannot eradicate the disease without the preemptive measures of the sick individuals. Empathy is more effective than risk-aversion because when infectious individuals change behavior, they reduce all of their potential infections, whereas when healthy individuals change behavior, they reduce only a small portion of potential infections. This imbalance in the role played by the response of the infected versus the susceptible individuals on disease eradication affords critical policy insights. PMID:28290504

Modeling structural, dyadic, and individual factors: the inclusion and exclusion model of HIV related behavior.

PubMed

Albarracin, Dolores; Tannenbaum, Melanie B; Glasman, Laura R; Rothman, Alexander J

2010-12-01

Changing HIV-related behaviors requires addressing the individual, dyadic, and structural influences that shape them. This supplement of AIDS & Behavior presents frameworks that integrate these three influences on behavior. Concepts from these frameworks were selected to model the processes by which structural factors affect individual HIV-related behavior. In the Inclusion/Exclusion Model, material and symbolic inclusions and exclusions (sharing versus denying resources) regulate individuals' ability and motivation to detect, prevent, and treat HIV. Structural interventions create inclusions that increase one's ability or motivation to perform these behaviors or exclusions that hinder one's ability or motivation to execute counterproductive behaviors. The need to expand research regarding multilevel influences on HIV-related behavior is also discussed, particularly concerning further understanding of sustained behavior change and effective dissemination of evidence-based intervention strategies.

A representative-sandwich model for simultaneously coupled mechanical-electrical-thermal simulation of a lithium-ion cell under quasi-static indentation tests

DOE PAGES

Zhang, Chao; Santhanagopalan, Shriram; Sprague, Michael A.; ...

2015-08-29

The safety behavior of lithium-ion batteries under external mechanical crush is a critical concern, especially during large scale deployment. We previously presented a sequentially coupled mechanical-electrical-thermal modeling approach for studying mechanical abuse induced short circuit. Here in this work, we study different mechanical test conditions and examine the interaction between mechanical failure and electrical-thermal responses, by developing a simultaneous coupled mechanical-electrical-thermal model. The present work utilizes a single representative-sandwich (RS) to model the full pouch cell with explicit representations for each individual component such as the active material, current collector, separator, etc. Anisotropic constitutive material models are presented to describemore » the mechanical properties of active materials and separator. The model predicts accurately the force-strain response and fracture of battery structure, simulates the local failure of separator layer, and captures the onset of short circuit for lithium-ion battery cell under sphere indentation tests with three different diameters. Electrical-thermal responses to the three different indentation tests are elaborated and discussed. Lastly, numerical studies are presented to show the potential impact of test conditions on the electrical-thermal behavior of the cell after the occurrence of short circuit.« less

A representative-sandwich model for simultaneously coupled mechanical-electrical-thermal simulation of a lithium-ion cell under quasi-static indentation tests

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

Zhang, Chao; Santhanagopalan, Shriram; Sprague, Michael A.

The safety behavior of lithium-ion batteries under external mechanical crush is a critical concern, especially during large scale deployment. We previously presented a sequentially coupled mechanical-electrical-thermal modeling approach for studying mechanical abuse induced short circuit. Here in this work, we study different mechanical test conditions and examine the interaction between mechanical failure and electrical-thermal responses, by developing a simultaneous coupled mechanical-electrical-thermal model. The present work utilizes a single representative-sandwich (RS) to model the full pouch cell with explicit representations for each individual component such as the active material, current collector, separator, etc. Anisotropic constitutive material models are presented to describemore » the mechanical properties of active materials and separator. The model predicts accurately the force-strain response and fracture of battery structure, simulates the local failure of separator layer, and captures the onset of short circuit for lithium-ion battery cell under sphere indentation tests with three different diameters. Electrical-thermal responses to the three different indentation tests are elaborated and discussed. Lastly, numerical studies are presented to show the potential impact of test conditions on the electrical-thermal behavior of the cell after the occurrence of short circuit.« less

Non-Equilibrium Thermodynamics of Transcriptional Bursts

NASA Astrophysics Data System (ADS)

Hernández-Lemus, Enrique

Gene transcription or Gene Expression (GE) is the process which transforms the information encoded in DNA into a functional RNA message. It is known that GE can occur in bursts or pulses. Transcription is irregular, with strong periods of activity, interspersed by long periods of inactivity. If we consider the average behavior over millions of cells, this process appears to be continuous. But at the individual cell level, there is considerable variability, and for most genes, very little activity at any one time. Some have claimed that GE bursting can account for the high variability in gene expression occurring between cells in isogenic populations. This variability has a big impact on cell behavior and thus on phenotypic conditions and disease. In view of these facts, the development of a thermodynamic framework to study gene expression and transcriptional regulation to integrate the vast amount of molecular biophysical GE data is appealing. Application of such thermodynamic formalism is useful to observe various dissipative phenomena in GE regulatory dynamics. In this chapter we will examine at some detail the complex phenomena of transcriptional bursts (specially of a certain class of anomalous bursts) in the context of a non-equilibrium thermodynamics formalism and will make some initial comments on the relevance of some irreversible processes that may be connected to anomalous transcriptional bursts.

Diverse activities of viral cis-acting RNA regulatory elements revealed using multicolor, long-term, single-cell imaging

PubMed Central

Pocock, Ginger M.; Zimdars, Laraine L.; Yuan, Ming; Eliceiri, Kevin W.; Ahlquist, Paul; Sherer, Nathan M.

2017-01-01

Cis-acting RNA structural elements govern crucial aspects of viral gene expression. How these structures and other posttranscriptional signals affect RNA trafficking and translation in the context of single cells is poorly understood. Herein we describe a multicolor, long-term (>24 h) imaging strategy for measuring integrated aspects of viral RNA regulatory control in individual cells. We apply this strategy to demonstrate differential mRNA trafficking behaviors governed by RNA elements derived from three retroviruses (HIV-1, murine leukemia virus, and Mason-Pfizer monkey virus), two hepadnaviruses (hepatitis B virus and woodchuck hepatitis virus), and an intron-retaining transcript encoded by the cellular NXF1 gene. Striking behaviors include “burst” RNA nuclear export dynamics regulated by HIV-1’s Rev response element and the viral Rev protein; transient aggregations of RNAs into discrete foci at or near the nuclear membrane triggered by multiple elements; and a novel, pulsiform RNA export activity regulated by the hepadnaviral posttranscriptional regulatory element. We incorporate single-cell tracking and a data-mining algorithm into our approach to obtain RNA element–specific, high-resolution gene expression signatures. Together these imaging assays constitute a tractable, systems-based platform for studying otherwise difficult to access spatiotemporal features of viral and cellular gene regulation. PMID:27903772

Agent-based modeling of autophagy reveals emergent regulatory behavior of spatio-temporal autophagy dynamics.

PubMed

Börlin, Christoph S; Lang, Verena; Hamacher-Brady, Anne; Brady, Nathan R

2014-09-10

Autophagy is a vesicle-mediated pathway for lysosomal degradation, essential under basal and stressed conditions. Various cellular components, including specific proteins, protein aggregates, organelles and intracellular pathogens, are targets for autophagic degradation. Thereby, autophagy controls numerous vital physiological and pathophysiological functions, including cell signaling, differentiation, turnover of cellular components and pathogen defense. Moreover, autophagy enables the cell to recycle cellular components to metabolic substrates, thereby permitting prolonged survival under low nutrient conditions. Due to the multi-faceted roles for autophagy in maintaining cellular and organismal homeostasis and responding to diverse stresses, malfunction of autophagy contributes to both chronic and acute pathologies. We applied a systems biology approach to improve the understanding of this complex cellular process of autophagy. All autophagy pathway vesicle activities, i.e. creation, movement, fusion and degradation, are highly dynamic, temporally and spatially, and under various forms of regulation. We therefore developed an agent-based model (ABM) to represent individual components of the autophagy pathway, subcellular vesicle dynamics and metabolic feedback with the cellular environment, thereby providing a framework to investigate spatio-temporal aspects of autophagy regulation and dynamic behavior. The rules defining our ABM were derived from literature and from high-resolution images of autophagy markers under basal and activated conditions. Key model parameters were fit with an iterative method using a genetic algorithm and a predefined fitness function. From this approach, we found that accurate prediction of spatio-temporal behavior required increasing model complexity by implementing functional integration of autophagy with the cellular nutrient state. The resulting model is able to reproduce short-term autophagic flux measurements (up to 3 hours) under basal and activated autophagy conditions, and to measure the degree of cell-to-cell variability. Moreover, we experimentally confirmed two model predictions, namely (i) peri-nuclear concentration of autophagosomes and (ii) inhibitory lysosomal feedback on mTOR signaling. Agent-based modeling represents a novel approach to investigate autophagy dynamics, function and dysfunction with high biological realism. Our model accurately recapitulates short-term behavior and cell-to-cell variability under basal and activated conditions of autophagy. Further, this approach also allows investigation of long-term behaviors emerging from biologically-relevant alterations to vesicle trafficking and metabolic state.

The Stability of Individual Differences in Infant-Mother Attachment.

ERIC Educational Resources Information Center

Waters, Everett

This study compared three ways of analyzing individual mother-infant attachment behaviors in order to test the hypothesis that success in the search for stable individual differences in attachment behavior is in part a function of the level at which behavior individuality is assessed. Fifty infants were videotaped in the Ainsworth and Wittig…

The Sustainable Personality: Values and Behaviors in Individual Sustainability

ERIC Educational Resources Information Center

Pappas, Jesse B.; Pappas, Eric C.

2015-01-01

Meaningful societal change begins with individual change. One cannot do for a community what one cannot do for one's self. The topic of Individual Sustainability is a controversial one, as students often appear to be unable to align their demonstrated behaviors with their admirable values related to sustainability. Individual behavior creates the…

Mechanical Model of Geometric Cell and Topological Algorithm for Cell Dynamics from Single-Cell to Formation of Monolayered Tissues with Pattern

PubMed Central

Kachalo, Sëma; Naveed, Hammad; Cao, Youfang; Zhao, Jieling; Liang, Jie

2015-01-01

Geometric and mechanical properties of individual cells and interactions among neighboring cells are the basis of formation of tissue patterns. Understanding the complex interplay of cells is essential for gaining insight into embryogenesis, tissue development, and other emerging behavior. Here we describe a cell model and an efficient geometric algorithm for studying the dynamic process of tissue formation in 2D (e.g. epithelial tissues). Our approach improves upon previous methods by incorporating properties of individual cells as well as detailed description of the dynamic growth process, with all topological changes accounted for. Cell size, shape, and division plane orientation are modeled realistically. In addition, cell birth, cell growth, cell shrinkage, cell death, cell division, cell collision, and cell rearrangements are now fully accounted for. Different models of cell-cell interactions, such as lateral inhibition during the process of growth, can be studied in detail. Cellular pattern formation for monolayered tissues from arbitrary initial conditions, including that of a single cell, can also be studied in detail. Computational efficiency is achieved through the employment of a special data structure that ensures access to neighboring cells in constant time, without additional space requirement. We have successfully generated tissues consisting of more than 20,000 cells starting from 2 cells within 1 hour. We show that our model can be used to study embryogenesis, tissue fusion, and cell apoptosis. We give detailed study of the classical developmental process of bristle formation on the epidermis of D. melanogaster and the fundamental problem of homeostatic size control in epithelial tissues. Simulation results reveal significant roles of solubility of secreted factors in both the bristle formation and the homeostatic control of tissue size. Our method can be used to study broad problems in monolayered tissue formation. Our software is publicly available. PMID:25974182

Single Quantum Dot Tracking Reveals that an Individual Multivalent HIV-1 Tat Protein Transduction Domain Can Activate Machinery for Lateral Transport and Endocytosis

PubMed Central

Roy, Chandra Nath; Promjunyakul, Warunya; Hatakeyama, Hiroyasu; Gonda, Kohsuke; Imamura, Junji; Vasudevanpillai, Biju; Ohuchi, Noriaki; Kanzaki, Makoto; Higuchi, Hideo; Kaku, Mitsuo

2013-01-01

The mechanisms underlying the cellular entry of the HIV-1 Tat protein transduction domain (TatP) and the molecular information necessary to improve the transduction efficiency of TatP remain unclear due to the technical limitations for direct visualization of TatP's behavior in cells. Using confocal microscopy, total internal reflection fluorescence microscopy, and four-dimensional microscopy, we developed a single-molecule tracking assay for TatP labeled with quantum dots (QDs) to examine the kinetics of TatP initially and immediately before, at the beginning of, and immediately after entry into living cells. We report that even when the number of multivalent TatP (mTatP)-QDs bound to a cell was low, each single mTatP-QD first locally induced the cell's lateral transport machinery to move the mTatP-QD toward the center of the cell body upon cross-linking of heparan sulfate proteoglycans. The centripetal and lateral movements were linked to the integrity and flow of actomyosin and microtubules. Individual mTatP underwent lipid raft-mediated temporal confinement, followed by complete immobilization, which ultimately led to endocytotic internalization. However, bivalent TatP did not sufficiently promote either cell surface movement or internalization. Together, these findings provide clues regarding the mechanisms of TatP cell entry and indicate that increasing the valence of TatP on nanoparticles allows them to behave as cargo delivery nanomachines. PMID:23732912

Reprogramming cells and tissue patterning via bioelectrical pathways: molecular mechanisms and biomedical opportunities.

PubMed

Levin, Michael

2013-01-01

Transformative impact in regenerative medicine requires more than the reprogramming of individual cells: advances in repair strategies for birth defects or injuries, tumor normalization, and the construction of bioengineered organs and tissues all require the ability to control large-scale anatomical shape. Much recent work has focused on the transcriptional and biochemical regulation of cell behavior and morphogenesis. However, exciting new data reveal that bioelectrical properties of cells and their microenvironment exert a profound influence on cell differentiation, proliferation, and migration. Ion channels and pumps expressed in all cells, not just excitable nerve and muscle, establish resting potentials that vary across tissues and change with significant developmental events. Most importantly, the spatiotemporal gradients of these endogenous transmembrane voltage potentials (Vmem ) serve as instructive patterning cues for large-scale anatomy, providing organ identity, positional information, and prepattern template cues for morphogenesis. New genetic and pharmacological techniques for molecular modulation of bioelectric gradients in vivo have revealed the ability to initiate complex organogenesis, change tissue identity, and trigger regeneration of whole vertebrate appendages. A large segment of the spatial information processing that orchestrates individual cells' programs toward the anatomical needs of the host organism is electrical; this blurs the line between memory and decision-making in neural networks and morphogenesis in nonneural tissues. Advances in cracking this bioelectric code will enable the rational reprogramming of shape in whole tissues and organs, revolutionizing regenerative medicine, developmental biology, and synthetic bioengineering. Copyright © 2013 Wiley Periodicals, Inc.

Response of single bacterial cells to stress gives rise to complex history dependence at the population level

PubMed Central

Mathis, Roland; Ackermann, Martin

2016-01-01

Most bacteria live in ever-changing environments where periods of stress are common. One fundamental question is whether individual bacterial cells have an increased tolerance to stress if they recently have been exposed to lower levels of the same stressor. To address this question, we worked with the bacterium Caulobacter crescentus and asked whether exposure to a moderate concentration of sodium chloride would affect survival during later exposure to a higher concentration. We found that the effects measured at the population level depended in a surprising and complex way on the time interval between the two exposure events: The effect of the first exposure on survival of the second exposure was positive for some time intervals but negative for others. We hypothesized that the complex pattern of history dependence at the population level was a consequence of the responses of individual cells to sodium chloride that we observed: (i) exposure to moderate concentrations of sodium chloride caused delays in cell division and led to cell-cycle synchronization, and (ii) whether a bacterium would survive subsequent exposure to higher concentrations was dependent on the cell-cycle state. Using computational modeling, we demonstrated that indeed the combination of these two effects could explain the complex patterns of history dependence observed at the population level. Our insight into how the behavior of single cells scales up to processes at the population level provides a perspective on how organisms operate in dynamic environments with fluctuating stress exposure. PMID:26960998

Silver-silver sulfate reference electrodes for use in lead-acid batteries

NASA Astrophysics Data System (ADS)

Ruetschi, Paul

Electrochemical properties of silver-silver sulfate reference electrodes for lead-acid batteries are described, and the following possible applications discussed: Determination of individual capacities of positive and negative plates. Monitoring individual electrode behavior during deep discharge and cell reversal. Optimization charge or discharge parameters, by controlling the current such that pre-determined limits of positive or negative half-cell potential are respected. Observation of acid concentration differences, for example due to acid stratification, by measuring diffusion potentials (concentration-cell voltages). Detection of defective cells, and defective plate sets, in a string of cells, at the end of their service life. Silver-silver sulfate reference electrodes, permanently installed in lead-acid cells, may be a means to improve battery management, and therewith to improve reliability and service life. In vented batteries, reference electrodes may be used to limit positive plate polarization during charge, or float-charge. Limiting the positive half-cell potential to an upper, pre-set value would permit to keep anodic corrosion as low as possible. During cycling, discharge could be terminated when the half-cell potential of the positive electrode has dropped to a pre-set limit. This would prevent excessive discharge of the positive electrodes, which could result in an improvement of cycle life. In valve-regulated batteries, reference electrodes may be used to adjust float-charge conditions such as to assure sufficient cathodic polarization of the negative electrodes, in order to avoid sulfation. The use of such reference electrodes could be beneficial particularly in multi-cell batteries, with overall voltages above 12 V, operated in a partial-state-of-charge.

Motor neuronal activity varies least among individuals when it matters most for behavior

PubMed Central

Cullins, Miranda J.; Shaw, Kendrick M.; Gill, Jeffrey P.

2014-01-01

How does motor neuronal variability affect behavior? To explore this question, we quantified activity of multiple individual identified motor neurons mediating biting and swallowing in intact, behaving Aplysia californica by recording from the protractor muscle and the three nerves containing the majority of motor neurons controlling the feeding musculature. We measured multiple motor components: duration of the activity of identified motor neurons as well as their relative timing. At the same time, we measured behavioral efficacy: amplitude of grasping movement during biting and amplitude of net inward food movement during swallowing. We observed that the total duration of the behaviors varied: Within animals, biting duration shortened from the first to the second and third bites; between animals, biting and swallowing durations varied. To study other sources of variation, motor components were divided by behavior duration (i.e., normalized). Even after normalization, distributions of motor component durations could distinguish animals as unique individuals. However, the degree to which a motor component varied among individuals depended on the role of that motor component in a behavior. Motor neuronal activity that was essential for the expression of biting or swallowing was similar among animals, whereas motor neuronal activity that was not essential for that behavior varied more from individual to individual. These results suggest that motor neuronal activity that matters most for the expression of a particular behavior may vary least from individual to individual. Shaping individual variability to ensure behavioral efficacy may be a general principle for the operation of motor systems. PMID:25411463

Novel silicon microchannels device for use in red blood cell deformability studies

NASA Astrophysics Data System (ADS)

Zheng, Xiao-Lin; Liao, Yan-Jian; Zhang, Wen-Xian

2001-10-01

Currently, a number of techniques are used to access cell deformability. We study a novel silicon microchannels device for use in red blood cell deformability. The channels are produced in silicon substrate using microengineering technology. The microgrooves formed in the surface of a single-crystal silicon substrate. They were converted to channels by tightly covering them with an optical flat glass plate. An array of flow channels (number 950 in parallel) have typical dimensions of 5 micrometers width X 5.5 Xm depth, and 30 micrometers length. There the RBC's are forced to pass through channels. Thus, the microchannels are used to simulate human blood capillaries. It provides a specific measurement of individual cell in terms of both flow velocity profile and an index of cell volume while the cell flow through the channels. It dominates the complex cellular flow behavior, such as, the viscosity of whole blood is a nonlinear function of shear rate, index of filtration, etc.

Multiscale Model of Swarming Bacteria

NASA Astrophysics Data System (ADS)

Alber, Mark

2011-03-01

Many bacteria can rapidly traverse surfaces from which they are extracting nutrient for growth. They generate flat, spreading colonies, called swarms because they resemble swarms of insects. In the beginning of the talk, swarms of the M. xanthus will be described in detail. Individual M. xanthus cells are elongated; they always move in the direction of their long axis; and they are in constant motion, repeatedly touching each other. As a cell glides, the slime capsule of a cell interacts with the bare agar surface, non-oriented slime which arises from the surface contact with the slime capsule, or oriented slime trails. Remarkably, cells regularly reverse their gliding directions. In this talk a detailed cell- and behavior-based computational model of M. xanthus swarming will be used to demonstrate that reversals of gliding direction and cell bending are essential for swarming and that specific reversal frequencies result in optimal swarming rate of the whole population. This suggests that the circuit regulating reversals evolved to its current sensitivity under selection for growth achieved by swarming.

Distinct mechanisms underlie oral vs aboral regeneration in the cnidarian Hydractinia echinata.

PubMed

Bradshaw, Brian; Thompson, Kerry; Frank, Uri

2015-04-17

Cnidarians possess remarkable powers of regeneration, but the cellular and molecular mechanisms underlying this capability are unclear. Studying the hydrozoan Hydractinia echinata we show that a burst of stem cell proliferation occurs following decapitation, forming a blastema at the oral pole within 24 hr. This process is necessary for head regeneration. Knocking down Piwi1, Vasa, Pl10 or Ncol1 expressed by blastema cells inhibited regeneration but not blastema formation. EdU pulse-chase experiments and in vivo tracking of individual transgenic Piwi1(+) stem cells showed that the cellular source for blastema formation is migration of stem cells from a remote area. Surprisingly, no blastema developed at the aboral pole after stolon removal. Instead, polyps transformed into stolons and then budded polyps. Hence, distinct mechanisms act to regenerate different body parts in Hydractinia. This model, where stem cell behavior can be monitored in vivo at single cell resolution, offers new insights for regenerative biology.

Measuring single-cell gene expression dynamics in bacteria using fluorescence time-lapse microscopy

PubMed Central

Young, Jonathan W; Locke, James C W; Altinok, Alphan; Rosenfeld, Nitzan; Bacarian, Tigran; Swain, Peter S; Mjolsness, Eric; Elowitz, Michael B

2014-01-01

Quantitative single-cell time-lapse microscopy is a powerful method for analyzing gene circuit dynamics and heterogeneous cell behavior. We describe the application of this method to imaging bacteria by using an automated microscopy system. This protocol has been used to analyze sporulation and competence differentiation in Bacillus subtilis, and to quantify gene regulation and its fluctuations in individual Escherichia coli cells. The protocol involves seeding and growing bacteria on small agarose pads and imaging the resulting microcolonies. Images are then reviewed and analyzed using our laboratory's custom MATLAB analysis code, which segments and tracks cells in a frame-to-frame method. This process yields quantitative expression data on cell lineages, which can illustrate dynamic expression profiles and facilitate mathematical models of gene circuits. With fast-growing bacteria, such as E. coli or B. subtilis, image acquisition can be completed in 1 d, with an additional 1–2 d for progressing through the analysis procedure. PMID:22179594

Adaptability of non-genetic diversity in bacterial chemotaxis

PubMed Central

Frankel, Nicholas W; Pontius, William; Dufour, Yann S; Long, Junjiajia; Hernandez-Nunez, Luis; Emonet, Thierry

2014-01-01

Bacterial chemotaxis systems are as diverse as the environments that bacteria inhabit, but how much environmental variation can cells tolerate with a single system? Diversification of a single chemotaxis system could serve as an alternative, or even evolutionary stepping-stone, to switching between multiple systems. We hypothesized that mutations in gene regulation could lead to heritable control of chemotactic diversity. By simulating foraging and colonization of E. coli using a single-cell chemotaxis model, we found that different environments selected for different behaviors. The resulting trade-offs show that populations facing diverse environments would ideally diversify behaviors when time for navigation is limited. We show that advantageous diversity can arise from changes in the distribution of protein levels among individuals, which could occur through mutations in gene regulation. We propose experiments to test our prediction that chemotactic diversity in a clonal population could be a selectable trait that enables adaptation to environmental variability. DOI: http://dx.doi.org/10.7554/eLife.03526.001 PMID:25279698

Inhibition-Based Biomarkers for Autism Spectrum Disorder.

PubMed

Levin, April R; Nelson, Charles A

2015-07-01

Autism spectrum disorder (ASD) is a behaviorally defined and heterogeneous disorder. Biomarkers for ASD offer the opportunity to improve prediction, diagnosis, stratification by severity and subtype, monitoring over time and in response to interventions, and overall understanding of the underlying biology of this disorder. A variety of potential biomarkers, from the level of genes and proteins to network-level interactions, is currently being examined. Many of these biomarkers relate to inhibition, which is of particular interest because in many cases ASD is thought to be a disorder of imbalance between excitation and inhibition. Abnormalities in inhibition at the cellular level lead to emergent properties in networks of neurons. These properties take into account a more complete genetic and cellular background than findings at the level of individual genes or cells, and are able to be measured in live humans, offering additional potential as diagnostic biomarkers and predictors of behaviors. In this review we provide examples of how altered inhibition may inform the search for ASD biomarkers at multiple levels, from genes to cells to networks.

Diabetic Erythrocytes Test by Correlation Coefficient

PubMed Central

Korol, A.M; Foresto, P; Darrigo, M; Rosso, O.A

2008-01-01

Even when a healthy individual is studied, his/her erythrocytes in capillaries continually change their shape in a synchronized erratic fashion. In this work, the problem of characterizing the cell behavior is studied from the perspective of bounded correlated random walk, based on the assumption that diffractometric data involves both deterministic and stochastic components. The photometric readings are obtained by ektacytometry over several millions of shear elongated cells, using a home-made device called Erythrodeformeter. We have only a scalar signal and no governing equations; therefore the complete behavior has to be reconstructed in an artificial phase space. To analyze dynamics we used the technique of time delay coordinates suggested by Takens, May algorithm, and Fourier transform. The results suggest that on random-walk approach the samples from healthy controls exhibit significant differences from those from diabetic patients and these could allow us to claim that we have linked mathematical nonlinear tools with clinical aspects of diabetic erythrocytes’ rheological properties. PMID:19415139

Optimizing neuronal differentiation from induced pluripotent stem cells to model ASD

PubMed Central

Kim, Dae-Sung; Ross, P. Joel; Zaslavsky, Kirill; Ellis, James

2014-01-01

Autism spectrum disorder (ASD) is an early-onset neurodevelopmental disorder characterized by deficits in social communication, and restricted and repetitive patterns of behavior. Despite its high prevalence, discovery of pathophysiological mechanisms underlying ASD has lagged due to a lack of appropriate model systems. Recent advances in induced pluripotent stem cell (iPSC) technology and neural differentiation techniques allow for detailed functional analyses of neurons generated from living individuals with ASD. Refinement of cortical neuron differentiation methods from iPSCs will enable mechanistic studies of specific neuronal subpopulations that may be preferentially impaired in ASD. In this review, we summarize recent accomplishments in differentiation of cortical neurons from human pluripotent stems cells and efforts to establish in vitro model systems to study ASD using personalized neurons. PMID:24782713

A structural model of health behavior: a pragmatic approach to explain and influence health behaviors at the population level.

PubMed

Cohen, D A; Scribner, R A; Farley, T A

2000-02-01

Behavior is influenced by individual-level attributes as well as by the conditions under which people live. Altering policies, practices, and the conditions of life can directly and indirectly influence individual behavior. This paper builds on existing ecological theories of health behavior by specifying structural mechanisms by which population-level factors effect change in individual health behaviors. This paper moves ecological theory from model building to a pragmatic characterization of structural interventions. We examined social and environmental factors beyond individual control and mechanisms as to how they influence behavior. Four categories of structural factors are identified: (1) availability of protective or harmful consumer products, (2) physical structures (or physical characteristics of products), (3) social structures and policies, and (4) media and cultural messages. The first three can directly influence individuals through facilitating or constraining behavior. The fourth, media, operates by changing individual-level attitudes, beliefs, and cognitions, as well as group norms. Interventions that target the four identified structural factors are a means to provide conditions that not only reduce high-risk behavior but also prevent the adoption of high-risk behaviors. Structural interventions are important and underutilized approaches for improving our nation's health. Copyright 2000 American Health Foundation and Academic Press.

Examining driver behavior at the onset of yellow in a traffic simulator environment: Comparisons between random parameters and latent class logit models.

PubMed

Savolainen, Peter T

2016-11-01

This study involves an examination of driver behavior at the onset of a yellow signal indication. Behavioral data were obtained from a driving simulator study that was conducted through the National Advanced Driving Simulator (NADS) laboratory at the University of Iowa. These data were drawn from a series of events during which study participants drove through a series of intersections where the traffic signals changed from the green to yellow phase. The resulting dataset provides potential insights into how driver behavior is affected by distracted driving through an experimental design that alternated handheld, headset, and hands-free cell phone use with "normal" baseline driving events. The results of the study show that male drivers ages 18-45 were more likely to stop. Participants were also more likely to stop as they became more familiar with the simulator environment. Cell phone use was found to some influence on driver behavior in this setting, though the effects varied significantly across individuals. The study also demonstrates two methodological approaches for dealing with unobserved heterogeneity across drivers. These include random parameters and latent class logit models, each of which analyze the data as a panel. The results show each method to provide significantly better fit than a pooled, fixed parameter model. Differences in terms of the context of these two approaches are discussed, providing important insights as to the differences between these modeling frameworks. Copyright © 2016 Elsevier Ltd. All rights reserved.

Cell motility regulation on a stepped micro pillar array device (SMPAD) with a discrete stiffness gradient.

PubMed

Lee, Sujin; Hong, Juhee; Lee, Junghoon

2016-02-28

Our tissues consist of individual cells that respond to the elasticity of their environment, which varies between and within tissues. To better understand mechanically driven cell migration, it is necessary to manipulate the stiffness gradient across a substrate. Here, we have demonstrated a new variant of the microfabricated polymeric pillar array platform that can decouple the stiffness gradient from the ECM protein area. This goal is achieved via a "stepped" micro pillar array device (SMPAD) in which the contact area with the cell was kept constant while the diameter of the pillar bodies was altered to attain the proper mechanical stiffness. Using double-step SU-8 mold fabrication, the diameter of the top of every pillar was kept uniform, whereas that of the bottom was changed, to achieve the desired substrate rigidity. Fibronectin was immobilized on the pillar tops, providing a focal adhesion site for cells. C2C12, HeLa and NIH3T3 cells were cultured on the SMPAD, and the motion of the cells was observed by time-lapse microscopy. Using this simple platform, which produces a purely physical stimulus, we observed that various types of cell behavior are affected by the mechanical stimulus of the environment. We also demonstrated directed cell migration guided by a discrete rigidity gradient by varying stiffness. Interestingly, cell velocity was highest at the highest stiffness. Our approach enables the regulation of the mechanical properties of the polymeric pillar array device and eliminates the effects of the size of the contact area. This technique is a unique tool for studying cellular motion and behavior relative to various stiffness gradients in the environment.

Relationship of Near-Crash/Crash Risk to Time Spent on a Cell Phone While Driving.

PubMed

Farmer, Charles M; Klauer, Sheila G; McClafferty, Julie A; Guo, Feng

2015-01-01

The objective of this study was to examine in a naturalistic driving setting the dose-response relationship between cell phone usage while driving and risk of a crash or near crash. How is the increasing use of cell phones by drivers associated with overall near-crash/crash risk (i.e., during driving times both on and off the phone)? Day-to-day driving behavior of 105 volunteer subjects was monitored over a period of 1 year. A random sample was selected comprised of 4 trips from each month that each driver was in the study, and in-vehicle video was used to classify driver behavior. The proportion of driving time spent using a cell phone was estimated for each 3-month period and correlated with overall crash and near-crash rates for each period. Thus, it was possible to test whether changes in an individual driver's cell phone use over time were associated with changes in overall near-crash/crash risk. Drivers in the study spent 11.7% of their driving time interacting with a cell phone, primarily talking on the phone (6.5%) or simply holding the phone in their hand or lap (3.7%). The risk of a near-crash/crash event was approximately 17% higher when the driver was interacting with a cell phone, due primarily to actions of reaching for/answering/dialing, which nearly triples risk (relative risk = 2.84). However, the amount of driving time spent interacting with a cell phone did not affect a driver's overall near-crash/crash risk. Vehicle speeds within 6 s of the beginning of each call on average were 5-6 mph lower than speeds at other times. Results of this naturalistic driving study are consistent with the observation that increasing cell phone use in the general driving population has not led to increased crash rates. Although cell phone use can be distracting and crashes have occurred during this distraction, overall crash rates appear unaffected by changes in the rate of cell phone use, even for individual drivers. Drivers compensate somewhat for the distraction by conducting some of the more demanding tasks, such as reaching for or dialing a cell phone, at lower speeds. It is also possible that cell phones and other electronic devices in cars are changing how drivers manage their attention to various tasks and/or changing the kinds of secondary tasks in which they engage.

Behavioral Humanism.

ERIC Educational Resources Information Center

Thoresen, Carl E.

Behavioral humanism is defined as the synthesis of behavioral techniques with humanistic goals. Contemporary humanism, especially humanistic psychology, offers directions for the kind of behavior that individuals should be able to engage in; contemporary behaviorism offers principles and procedures to help individuals increase their humanistic…

Determination of physical health status and healthy lifestyle behaviors of individuals with mental illness.

PubMed

Erginer, Derya Kayar; Günüşen, Neslihan Partlak

2018-02-23

The aim of this study is to determine the physical health status and healthy lifestyle behaviors of individuals with mental illness. A descriptive research design was used. The sample of the study consisted of 115 individuals with mental illness. The Health Lifestyle Behaviors Scale II was used to assess the healthy lifestyle behaviors of the participants. Of the individuals, 49.6% were found to have metabolic syndrome. Individuals with mental illness obtained the lowest score from the physical activity dimension of the scale. Individuals with mental illness need to receive education and support, especially in terms of nutrition and exercise. © 2018 Wiley Periodicals, Inc.

[Consequences of disturbed sex-hormone action in the central nervous system: behavioral, anatomical and functional changes].

PubMed

Kula, Krzysztof; Słowikowska-Hilczer, Jolanta

2003-01-01

Experimental studies revealed that transient action of sex steroids during perinatal period is crucial for the development of male sexual behavior and sexually dimorphic brain anatomy. Meanwhile, the lack of gonadal steroids in female foetus and estrogen effects at puberty determine female behavior together with female type of anatomical brain structures and of endocrine functions. In men psychic sex consists of gender identity (self-estimation), gender role (objective estimation of sex behavior). In addition, a sexual psycho-orientation (hetero-, bi- or homosexual) has been distinguished. Although it is believed that gender depends on the socio-environmental influences such as rearing, learning and individual choice, the biological factors are considered to be most important. This concept arises from recent study on patients with gender dysphoria syndrome (transsexualism). In intersexualism, in genetic men with disturbances of sexual differentiation of external genitalia because of the lack of testoterone production or action in peripheral tissues (male pseudohermaphroditism) or in genetic women with ambiguous genitalia because of the presence and action of androgens (female pseudohermaphroditism), a discordance between the formal sex (assigned after the birth) and the psychic gender may appear. In these individuals the legal sex established according to somatic and/or genetic sex at birth may be incompatible with their actual gender identity and role. The knowledge about gender identity is necessary at the decision of eventual (!) surgical correction of sex organs in patients with ambiguous genitalia. This decision should depend not on the expected, but on the actual gender identity of the individual patient. Meantime, early bilateral gonadectomy in patients with gonadal dysgenesis and male pseudohermaphroditism is an indication for life because of the highest risk of germ cell carcinoma.

Borderline Personality and Externalized Aggression

PubMed Central

Sansone, Lori A.

2012-01-01

Individuals with borderline personality disorder are diagnostically and clinically characterized by self-harm behavior, as indicated by the criterion in the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision, “recurrent suicidal behavior, gestures, or threats, or self-mutilating behavior.” However, individuals with borderline personality disorder can display externalized aggressive behavior, as well. In an area characterized by considerably less research, empirical evidence indicates that individuals with borderline personality disorder may exhibit physical violence toward partners, physical violence toward known but nonintimate individuals, criminal behaviors that embody externalized violence (e.g., property damage), and, on very rare occasion, murderous behavior (either of family members or anonymous others through serial killing). Given this under-researched area, there are probably other types of externalized aggressive behaviors that have not been empirically revealed. However, externalized aggressive behaviors in individuals with borderline personality disorder clearly exist and need to be assessed in both psychiatric and primary care settings in an effort to promote safety of medical personnel and effective patient management. PMID:22567607

Medicaid Expenditures for Fee-for-Service Enrollees with Behavioral Diagnoses: Findings from a 50 State Claims Analysis.

PubMed

Ward, Martha C; Lally, Cathy; Druss, Benjamin G

2017-01-01

Medicaid is an important funder of care for individuals with behavioral (psychiatric and/or substance use) diagnoses, and expenditures will likely increase with expansion of services under the Affordable Care Act. This study provides national estimates of Medicaid expenditures using a comprehensive sample of fee-for-service Medicaid enrollees with behavioral diagnoses. Data for analysis came from 2003 to 2004 Medicaid Analytic eXtract (MAX) files for 50 states and the District of Columbia. Individuals with behavioral diagnoses had high rates of chronic medical comorbidities, and expenditures for medical (non-behavioral) diagnoses accounted for 74 % of their health care expenditures. Total Medicaid expenditure was approximately 15 billion dollars (equivalent to 18.91 billion in 2016 dollars) for individuals with any behavioral diagnosis. Medicaid fee-for-service beneficiaries with behavioral diagnoses have a high treated prevalence of individual medical comorbid conditions, and the majority of health care expenditures in these individuals are for medical, rather than behavioral health, services.

Introduction to the Special Issue: Interventions to Reduce Challenging Behavior Among Individuals With Autism Spectrum Disorder.

PubMed

Davis, Tonya N; Rispoli, Mandy

2018-05-01

The prevalence of autism spectrum disorder (ASD) is on the rise. In addition to the social communication skill deficits and restrictive repetitive behaviors and interests, many individuals with ASD engage in challenging behavior. Challenging behavior is associated with a multitude of negative outcomes. Challenging behavior may cause harm to the individual with ASD as well as limit opportunities for educational, vocational, and social participation and development. In addition, caregivers experience high stress and low quality of mental health. As a result, challenging behavior warrants intervention that is specifically tailored to the unique characteristics of individuals with ASD. The purpose of this Special Issue is to showcase recent research in the treatment of challenging behavior for individuals with ASD. This two-part Special Issue contains 12 studies that range from systematic and quality reviews of the intervention literature, to innovative treatment approaches, to studies that develop and evaluate treatments for restrictive and repetitive behaviors and interests.

Modeling the behavior of Listeria monocytogenes during enrichment in half Fraser broth; impact of pooling and the duration of enrichment on the detection of L. monocytogenes in food.

PubMed

Augustin, Jean-Christophe; Kalmokoff, Martin; Ells, Timothy; Favret, Sandra; Desreumaux, Jennifer; Decourseulles Brasseur, Emilie; Gnanou Besse, Nathalie

2016-12-01

A stochastic model describing the growth of Listeria monocytogenes during enrichment in half Fraser was developed for the purpose of estimating the effects of modifications to the first enrichment step of the EN ISO 11290-1 detection method. Information pertaining to the variability of growth rates, physiological state of the cell, and the behavior of individual cells contaminating the food were obtained from previously published studies. We used this model to investigate the impact of pooling enrichment broths (wet pooling) on the performance of the standard method. For validation of the model, the numbers of L. monocytogenes occurring in 88 naturally contaminated foods following pre-enrichment were compared to model-simulated microbial counts. The model was then used to perform simulations representative of the natural contamination observed for smoked salmon in the European baseline survey of 2010-2011. The model-estimated L. monocytogenes levels following individual enrichment or following the pooling of five broths where only one would be contaminated were compared. The model indicated a 10% loss of method sensitivity resulting from wet pooling. The model also predicted a 5% decrease in the sensitivity of the method when the duration of the enrichment was reduced from 24 to 22 h. Copyright © 2016 Elsevier Ltd. All rights reserved.

Spatial cognition in a virtual reality home-cage extension for freely moving rodents

PubMed Central

Kaupert, Ursula; Frei, Katja; Bagorda, Francesco; Schatz, Alexej; Tocker, Gilad; Rapoport, Sophie; Derdikman, Dori

2017-01-01

Virtual reality (VR) environments are a powerful tool to investigate brain mechanisms involved in the behavior of animals. With this technique, animals are usually head fixed or secured in a harness, and training for cognitively more complex VR paradigms is time consuming. A VR apparatus allowing free animal movement and the constant operator-independent training of tasks would enable many new applications. Key prospective usages include brain imaging of animal behavior when carrying a miniaturized mobile device such as a fluorescence microscope or an optetrode. Here, we introduce the Servoball, a spherical VR treadmill based on the closed-loop tracking of a freely moving animal and feedback counterrotation of the ball. Furthermore, we present the complete integration of this experimental system with the animals’ group home cage, from which single individuals can voluntarily enter through a tunnel with radio-frequency identification (RFID)-automated access control and commence experiments. This automated animal sorter functions as a mechanical replacement of the experimenter. We automatically trained rats using visual or acoustic cues to solve spatial cognitive tasks and recorded spatially modulated entorhinal cells. When electrophysiological extracellular recordings from awake behaving rats were performed, head fixation can dramatically alter results, so that any complex behavior that requires head movement is impossible to achieve. We circumvented this problem with the use of the Servoball in open-field scenarios, as it allows the combination of open-field behavior with the recording of nerve cells, along with all the flexibility that a virtual environment brings. This integrated home cage with a VR arena experimental system permits highly efficient experimentation for complex cognitive experiments. NEW & NOTEWORTHY Virtual reality (VR) environments are a powerful tool for the investigation of brain mechanisms. We introduce the Servoball, a VR treadmill for freely moving rodents. The Servoball is integrated with the animals’ group home cage. Single individuals voluntarily enter using automated access control. Training is highly time-efficient, even for cognitively complex VR paradigms. PMID:28077665

Multi-agent Simulations of Population Behavior: A Promising Tool for Systems Biology.

PubMed

Colosimo, Alfredo

2018-01-01

This contribution reports on the simulation of some dynamical events observed in the collective behavior of different kinds of populations, ranging from shape-changing cells in a Petri dish to functionally correlated brain areas in vivo. The unifying methodological approach, based upon a Multi-Agent Simulation (MAS) paradigm as incorporated in the NetLogo™ interpreter, is a direct consequence of the cornerstone that simple, individual actions within a population of interacting agents often give rise to complex, collective behavior.The discussion will mainly focus on the emergence and spreading of synchronous activities within the population, as well as on the modulation of the collective behavior exerted by environmental force-fields. A relevant section of this contribution is dedicated to the extension of the MAS paradigm to Brain Network models. In such a general framework some recent applications taken from the direct experience of the author, and exploring the activation patterns characteristic of specific brain functional states, are described, and their impact on the Systems-Biology universe underlined.

Mefloquine in the nucleus accumbens promotes social avoidance and anxiety-like behavior in mice.

PubMed

Heshmati, Mitra; Golden, Sam A; Pfau, Madeline L; Christoffel, Daniel J; Seeley, Elena L; Cahill, Michael E; Khibnik, Lena A; Russo, Scott J

2016-02-01

Mefloquine continues to be a key drug used for malaria chemoprophylaxis and treatment, despite reports of adverse events like depression and anxiety. It is unknown how mefloquine acts within the central nervous system to cause depression and anxiety or why some individuals are more vulnerable. We show that intraperitoneal injection of mefloquine in mice, when coupled to subthreshold social defeat stress, is sufficient to produce depression-like social avoidance behavior. Direct infusion of mefloquine into the nucleus accumbens (NAc), a key brain reward region, increased stress-induced social avoidance and anxiety behavior. In contrast, infusion into the ventral hippocampus had no effect. Whole cell recordings from NAc medium spiny neurons indicated that mefloquine application increases the frequency of spontaneous excitatory postsynaptic currents, a synaptic adaptation that we have previously shown to be associated with increased susceptibility to social defeat stress. Together, these data demonstrate a role for the NAc in mefloquine-induced depression and anxiety-like behaviors. Copyright © 2015 Elsevier Ltd. All rights reserved.

One (rating) from many (observations): Factors affecting the individual assessment of voice behavior in groups.

PubMed

Podsakoff, Nathan P; Maynes, Timothy D; Whiting, Steven W; Podsakoff, Philip M

2015-07-01

This article reports an investigation into how individuals form perceptions of overall voice behavior in group contexts. More specifically, the authors examine the effect of the proportion of group members exhibiting voice behavior in the group, the frequency of voice events in the group, and the measurement item referent (group vs. individual) on an individual's ratings of group voice behavior. In addition, the authors examine the effect that measurement item referent has on the magnitude of the relationship observed between an individual's ratings of group voice behavior and perceptions of group performance. Consistent with hypotheses, the results from 1 field study (N = 220) and 1 laboratory experiment (N = 366) indicate that: (a) When group referents were used, raters relied on the frequency of voice events (and not the proportion of group members exhibiting voice) to inform their ratings of voice behavior, whereas the opposite was true when individual-referent items were used, and (b) the magnitude of the relationship between observers' ratings of group voice behavior and their perceptions of group performance was higher when raters used group-referent, as opposed to an individual-referent, items. The authors discuss the implications of their findings for scholars interested in studying behavioral phenomena occurring in teams, groups, and work units in organizational behavior research. (c) 2015 APA, all rights reserved).

The effects of femtosecond laser-textured Ti-6Al-4V on wettability and cell response.

PubMed

Raimbault, Ophélie; Benayoun, Stephane; Anselme, Karine; Mauclair, Cyril; Bourgade, Tatiana; Kietzig, Anne-Marie; Girard-Lauriault, Pierre-Luc; Valette, Stephane; Donnet, Christophe

2016-12-01

To study the biological activity effects of femtosecond laser-induced structures on cell behavior, TA6V samples were micro-textured with focused femtosecond laser pulses generating grooves of various dimensions on the micrometer scale (width: 25-75μm; depth: 1-10μm). LIPSS (Laser Induced Periodic Surface Structures) were also generated during the laser irradiation, providing a supplementary structure (sinusoidal form) of hundreds of nanometers at the bottom of the grooves oriented perpendicular (⊥ LIPPS) or parallel (// LIPPS) to the direction of these grooves. C3H10 T1/2 murine mesenchymal stem cells were cultivated on the textured biomaterials. To have a preliminary idea of the spreading of biological media on the substrate, prior to cell culture, contact angle measurement were performed. This showed that the post-irradiation hydrophilicity of the samples can decrease with time according to its storage environment. The multiscale structuration either induced a collaborative or a competitive influence of the LIPSS and grooves on the cells. It has been shown that cells individually and collectively were most sensitive to microscale grooves which were narrower than 25μm and deeper than 5μm with ⊥ LIPPS. In some cases, cells were individually sensitive to the LIPSS but the cell layer organization did not exhibit significant differences in comparison to a non-textured surface. These results showed that cells are more sensitive to the nanoscale structures (LIPSS), unless the microstructures's size is close to the cell size and deeper than 5μm. There, the cells are sensitive to the microscale structures and go on spreading following these structures. Copyright © 2016 Elsevier B.V. All rights reserved.

Affective experience and motivated behavior in schizophrenia spectrum disorders: Evidence from clinical and nonclinical samples.

PubMed

Lui, Simon S Y; Shi, Yan-Fang; Au, Angie C W; Li, Zhi; Tsui, Chi F; Chan, Constance K Y; Leung, Meranda M W; Wong, Peony T Y; Wang, Yi; Yan, Chao; Heerey, Erin A; Cheung, Eric F C; Chan, Raymond C K

2016-09-01

Individuals with schizophrenia have been found to exhibit emotion-behavior decoupling, particularly with respect to anticipated, rather than experienced events. However, previous research has focused on how emotion valence translates into motivated behavior, ignoring the fact that emotion arousal should also modulate emotion-behavior coupling. Few studies have examined emotion-behavior coupling in prepsychotic conditions. This investigation aimed to examine the nature and extent of emotion valence- and arousal-behavior coupling across the schizophrenia spectrum. We examine how emotional valence and arousal couple with behavior in 3 groups of individuals (25 individuals with chronic schizophrenia; 27 individuals early in the disease course, and 31 individuals reporting negative schizotypal symptoms). Participants completed a task using slides to elicit emotion and evoke motivated behavior. We compared participants with their respective matched control groups to determine differences in the correspondence between self-reported emotion valence/arousal and motivated behavior. Both groups with schizophrenia reported similar affective experiences as their controls, whereas individuals reporting negative schizotypal symptoms showed "in-the-moment" anhedonia but not emotion-behavior decoupling. In addition, the schizophrenia groups' affective experiences corresponded less well to their behavior relative to controls. Our findings suggest emotion-behavior decoupling along both valence and arousal dimensions in schizophrenia but not in participants with high levels of schizotypal symptoms. Findings appear to support the idea that emotion-behavior decoupling differs in nature and extent across the schizophrenia spectrum. Interventions to recouple emotion and behavior may be particularly helpful in allowing people with schizophrenia to gain functional independence. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Rapid race perception despite individuation and accuracy goals.

PubMed

Kubota, Jennifer T; Ito, Tiffany

2017-08-01

Perceivers rapidly process social category information and form stereotypic impressions of unfamiliar others. However, a goal to individuate a target or to accurately predict their behavior can result in individuated impressions. It is unknown how the combination of both accuracy and individuation goals affects perceptual category processing. To explore this, participants were given both the goal to individuate targets and accurately predict behavior. We then recorded event-related brain potentials while participants viewed photos of black and white males along with four pieces of individuating information in the form of descriptions of past behavior. Even with explicit individuation and accuracy task goals, participants rapidly differentiated targets by race within 200 ms. Importantly, this rapid categorical processing did not influence behavioral outcomes as participants made individuated predictions. These findings indicate that individuals engage in category processing even when provided with individuation and accuracy goals, but that this processing does not necessarily result in category-based judgments.

Noninvasive method for assessing the human circadian clock using hair follicle cells

PubMed Central

Akashi, Makoto; Soma, Haruhiko; Yamamoto, Takuro; Tsugitomi, Asuka; Yamashita, Shiko; Yamamoto, Takuya; Nishida, Eisuke; Yasuda, Akio; Liao, James K.; Node, Koichi

2010-01-01

A thorough understanding of the circadian clock requires qualitative evaluation of circadian clock gene expression. Thus far, no simple and effective method for detecting human clock gene expression has become available. This limitation has greatly hampered our understanding of human circadian rhythm. Here we report a convenient, reliable, and less invasive method for detecting human clock gene expression using biopsy samples of hair follicle cells from the head or chin. We show that the circadian phase of clock gene expression in hair follicle cells accurately reflects that of individual behavioral rhythms, demonstrating that this strategy is appropriate for evaluating the human peripheral circadian clock. Furthermore, using this method, we indicate that rotating shift workers suffer from a serious time lag between circadian gene expression rhythms and lifestyle. Qualitative evaluation of clock gene expression in hair follicle cells, therefore, may be an effective approach for studying the human circadian clock in the clinical setting. PMID:20798039

Noncontact Cohesive Swimming of Bacteria in Two-Dimensional Liquid Films.

PubMed

Li, Ye; Zhai, He; Sanchez, Sandra; Kearns, Daniel B; Wu, Yilin

2017-07-07

Bacterial swimming in confined two-dimensional environments is ubiquitous in nature and in clinical settings. Characterizing individual interactions between swimming bacteria in 2D confinement will help to understand diverse microbial processes, such as bacterial swarming and biofilm formation. Here we report a novel motion pattern displayed by flagellated bacteria in 2D confinement: When two nearby cells align their moving directions, they tend to engage in cohesive swimming without direct cell body contact, as a result of hydrodynamic interaction but not flagellar intertwining. We further found that cells in cohesive swimming move with higher directional persistence, which can increase the effective diffusivity of cells by ∼3 times as predicted by computational modeling. As a conserved behavior for peritrichously flagellated bacteria, cohesive swimming in 2D confinement may be key to collective motion and self-organization in bacterial swarms; it may also promote bacterial dispersal in unsaturated soils and in interstitial space during infections.

From retinal waves to activity-dependent retinogeniculate map development.

PubMed

Markowitz, Jeffrey; Cao, Yongqiang; Grossberg, Stephen

2012-01-01

A neural model is described of how spontaneous retinal waves are formed in infant mammals, and how these waves organize activity-dependent development of a topographic map in the lateral geniculate nucleus, with connections from each eye segregated into separate anatomical layers. The model simulates the spontaneous behavior of starburst amacrine cells and retinal ganglion cells during the production of retinal waves during the first few weeks of mammalian postnatal development. It proposes how excitatory and inhibitory mechanisms within individual cells, such as Ca(2+)-activated K(+) channels, and cAMP currents and signaling cascades, can modulate the spatiotemporal dynamics of waves, notably by controlling the after-hyperpolarization currents of starburst amacrine cells. Given the critical role of the geniculate map in the development of visual cortex, these results provide a foundation for analyzing the temporal dynamics whereby the visual cortex itself develops.

Distribution Patterns Predict Individual Specialization in the Diet of Dolphin Gulls

PubMed Central

Masello, Juan F.; Wikelski, Martin; Voigt, Christian C.; Quillfeldt, Petra

2013-01-01

Many animals show some degree of individual specialization in foraging strategies and diet. This has profound ecological and evolutionary implications. For example, populations containing diverse individual foraging strategies will respond in different ways to changes in the environment, thus affecting the capacity of the populations to adapt to environmental changes and to diversify. However, patterns of individual specialization have been examined in few species. Likewise it is usually unknown whether specialization is maintained over time, because examining the temporal scale at which specialization occurs can prove difficult in the field. In the present study, we analyzed individual specialization in foraging in Dolphin Gulls Leucophaeus scoresbii, a scavenger endemic to the southernmost coasts of South America. We used GPS position logging and stable isotope analyses (SIA) to investigate individual specialization in feeding strategies and their persistence over time. The analysis of GPS data indicated two major foraging strategies in Dolphin Gulls from New I. (Falkland Is./Islas Malvinas). Tagged individuals repeatedly attended either a site with mussel beds or seabird and seal colonies during 5 to 7 days of tracking. Females foraging at mussel beds were heavier than those foraging at seabird colonies. Nitrogen isotope ratios (δ15N) of Dolphin Gull blood cells clustered in two groups, showing that individuals were consistent in their preferred foraging strategies over a period of at least several weeks. The results of the SIA as well as the foraging patterns recorded revealed a high degree of specialization for particular feeding sites and diets by individual Dolphin Gulls. Individual differences in foraging behavior were not related to sex. Specialization in Dolphin Gulls may be favored by the advantages of learning and memorizing optimal feeding locations and behaviors. Specialized individuals may reduce search and handling time and thus, optimize their energy gain and/or minimize time spent foraging. PMID:23844073

Electrophysiological Recordings from Lobula Plate Tangential Cells in Drosophila.

PubMed

Mauss, Alex S; Borst, Alexander

2016-01-01

Drosophila has emerged as an important model organism for the study of the neural basis of behavior. Its main asset is the experimental accessibility of identified neurons by genetic manipulation and physiological recordings. Drosophila therefore offers the opportunity to reach an integrative understanding of the development and neural underpinnings of behavior at all processing stages, from sensing to motor control, in a single species. Here, we will provide an account of the procedures involved in recording the electrical potential of individual neurons in the visual system of adult Drosophila using the whole-cell patch-clamp method. To this end, animals are fixed to a holder and mounted below a recording chamber. The head capsule is cut open and the glial sheath covering the brain is ruptured by a combination of shearing and enzymatic digest. Neuronal somata are thus exposed and targeted by low-resistance patch electrodes. After formation of a high resistance seal, electrical access to the cell is gained by small current pulses and suction. Stable recordings of large neurons are feasible for >1 h and can be combined with controlled visual stimulation as well as genetic and pharmacological manipulation of upstream circuit elements to infer circuit function in great detail.

Bacterial navigation in chemical and nonchemical environments

NASA Astrophysics Data System (ADS)

Hu, Bo; Tu, Yuhai

2014-03-01

Navigation of cells to the optimal environmental niches is critical for their survival and growth. E. coli cells, for example, can detect various chemicals and move up or down those chemical gradients (i.e., chemotaxis). Using the same signaling machinery, they can also sense other external factors such as pH and temperature and navigate from both sides toward some intermediate levels of those stimuli. This mode of precision sensing is more sophisticated than the (unidirectional) chemotaxis strategy and requires distinctive molecular mechanisms. To understand different bacterial taxis behaviors, we develop a theoretical model which incorporates microscopic signaling events in individual cells into macroscopic population dynamics. We find that the equilibrium population distribution is governed by an effective potential, the landscape of which depends on the external environment (chemical stimuli, pH, and temperature). We uncover the key conditions for various taxis behaviors and directly connects the cellular taxis performances with the underlying molecular parameters. This approach is used to examine and predict how background attractants and downstream temperature effects influence the performance and stability of thermotaxis, which can be tested in future experiments. This work is supported by the National Institutes of Health Grant GM081747.

Metabolism-independent sugar sensing in central orexin neurons.

PubMed

González, J Antonio; Jensen, Lise T; Fugger, Lars; Burdakov, Denis

2008-10-01

Glucose sensing by specialized neurons of the hypothalamus is vital for normal energy balance. In many glucose-activated neurons, glucose metabolism is considered a critical step in glucose sensing, but whether glucose-inhibited neurons follow the same strategy is unclear. Orexin/hypocretin neurons of the lateral hypothalamus are widely projecting glucose-inhibited cells essential for normal cognitive arousal and feeding behavior. Here, we used different sugars, energy metabolites, and pharmacological tools to explore the glucose-sensing strategy of orexin cells. We carried out patch-clamp recordings of the electrical activity of individual orexin neurons unambiguously identified by transgenic expression of green fluorescent protein in mouse brain slices. RESULTS- We show that 1) 2-deoxyglucose, a nonmetabolizable glucose analog, mimics the effects of glucose; 2) increasing intracellular energy fuel production with lactate does not reproduce glucose responses; 3) orexin cell glucose sensing is unaffected by glucokinase inhibitors alloxan, d-glucosamine, and N-acetyl-d-glucosamine; and 4) orexin glucosensors detect mannose, d-glucose, and 2-deoxyglucose but not galactose, l-glucose, alpha-methyl-d-glucoside, or fructose. Our new data suggest that behaviorally critical neurocircuits of the lateral hypothalamus contain glucose detectors that exhibit novel sugar selectivity and can operate independently of glucose metabolism.

Investigating host-pathogen behavior and their interaction using genome-scale metabolic network models.

PubMed

Sadhukhan, Priyanka P; Raghunathan, Anu

2014-01-01

Genome Scale Metabolic Modeling methods represent one way to compute whole cell function starting from the genome sequence of an organism and contribute towards understanding and predicting the genotype-phenotype relationship. About 80 models spanning all the kingdoms of life from archaea to eukaryotes have been built till date and used to interrogate cell phenotype under varying conditions. These models have been used to not only understand the flux distribution in evolutionary conserved pathways like glycolysis and the Krebs cycle but also in applications ranging from value added product formation in Escherichia coli to predicting inborn errors of Homo sapiens metabolism. This chapter describes a protocol that delineates the process of genome scale metabolic modeling for analysing host-pathogen behavior and interaction using flux balance analysis (FBA). The steps discussed in the process include (1) reconstruction of a metabolic network from the genome sequence, (2) its representation in a precise mathematical framework, (3) its translation to a model, and (4) the analysis using linear algebra and optimization. The methods for biological interpretations of computed cell phenotypes in the context of individual host and pathogen models and their integration are also discussed.

Metabolism as an Integral Cog in the Mammalian Circadian Clockwork

PubMed Central

Gamble, Karen L.; Young, Martin E.

2013-01-01

Circadian rhythms are an integral part of life. These rhythms are apparent in virtually all biological processes studies to date, ranging from the individual cell (e.g., DNA synthesis) to the whole organism (e.g., behaviors such as physical activity). Oscillations in metabolism have been characterized extensively in various organisms, including mammals. These metabolic rhythms often parallel behaviors such as sleep/wake and fasting/feeding cycles that occur on a daily basis. What has become increasingly clear over the past several decades is that many metabolic oscillations are driven by cell autonomous circadian clocks, which orchestrate metabolic processes in a temporally appropriate manner. During the process of identifying the mechanisms by which clocks influence metabolism, molecular-based studies have revealed that metabolism should be considered an integral circadian clock component. The implications of such an interrelationship include the establishment of a vicious cycle during cardiometabolic disease states, wherein metabolism-induced perturbations in the circadian clock exacerbate metabolic dysfunction. The purpose of this review is therefore to highlight recent insights gained regarding links between cell autonomous circadian clocks and metabolism, and the implications of clock dysfunction in the pathogenesis of cardiometabolic diseases. PMID:23594144

Individual effects of seasonal changes, visitor density, and concurrent bear behavior on stereotypical behaviors in captive polar bears (Ursus maritimus).

PubMed

Kelly, Krista R; Harrison, Michelle L; Size, Daniele D; MacDonald, Suzanne E

2015-01-01

Stereotypical behaviors in captive polar bears (Ursus maritimus) can be detrimental to their welfare. These behaviors can be reduced through enrichment programs but are often not completely eliminated, so identifying potential triggers is important. The present study investigated the influences of seasonal changes, visitor density, and concurrent bear activity on stereotypical behaviors exhibited by 3 captive polar bears at the Toronto Zoo. All bears exhibited these behaviors; however, individual differences were found in duration and form. The male exhibited less stereotypical behavior during spring, and the females exhibited less stereotypical behavior during winter. An increase in visitor density was associated with more stereotypical behavior in 1 female but less stereotypical behavior in the other 2 bears. All bears engaged in more stereotypical behaviors when the other bears were inactive, and 1 female engaged in more stereotypical behaviors when the other bears were out of sight. Further, when conspecifics were active, all bears engaged in less stereotypical behaviors. Given the variability among individual bears, future enrichment programs must be tailored to the needs of individuals to maximize efficacy.

Collective Cell Behavior in Mechanosensing of Substrate Thickness.

PubMed

Tusan, Camelia G; Man, Yu-Hin; Zarkoob, Hoda; Johnston, David A; Andriotis, Orestis G; Thurner, Philipp J; Yang, Shoufeng; Sander, Edward A; Gentleman, Eileen; Sengers, Bram G; Evans, Nicholas D

2018-06-05

Extracellular matrix stiffness has a profound effect on the behavior of many cell types. Adherent cells apply contractile forces to the material on which they adhere and sense the resistance of the material to deformation-its stiffness. This is dependent on both the elastic modulus and the thickness of the material, with the corollary that single cells are able to sense underlying stiff materials through soft hydrogel materials at low (<10 μm) thicknesses. Here, we hypothesized that cohesive colonies of cells exert more force and create more hydrogel deformation than single cells, therefore enabling them to mechanosense more deeply into underlying materials than single cells. To test this, we modulated the thickness of soft (1 kPa) elastic extracellular-matrix-functionalized polyacrylamide hydrogels adhered to glass substrates and allowed colonies of MG63 cells to form on their surfaces. Cell morphology and deformations of fluorescent fiducial-marker-labeled hydrogels were quantified by time-lapse fluorescence microscopy imaging. Single-cell spreading increased with respect to decreasing hydrogel thickness, with data fitting to an exponential model with half-maximal response at a thickness of 3.2 μm. By quantifying cell area within colonies of defined area, we similarly found that colony-cell spreading increased with decreasing hydrogel thickness but with a greater half-maximal response at 54 μm. Depth-sensing was dependent on Rho-associated protein kinase-mediated cellular contractility. Surface hydrogel deformations were significantly greater on thick hydrogels compared to thin hydrogels. In addition, deformations extended greater distances from the periphery of colonies on thick hydrogels compared to thin hydrogels. Our data suggest that by acting collectively, cells mechanosense rigid materials beneath elastic hydrogels at greater depths than individual cells. This raises the possibility that the collective action of cells in colonies or sheets may allow cells to sense structures of differing material properties at comparatively large distances. Copyright © 2018 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Estimating peer effects in networks with peer encouragement designs.

PubMed

Eckles, Dean; Kizilcec, René F; Bakshy, Eytan

2016-07-05

Peer effects, in which the behavior of an individual is affected by the behavior of their peers, are central to social science. Because peer effects are often confounded with homophily and common external causes, recent work has used randomized experiments to estimate effects of specific peer behaviors. These experiments have often relied on the experimenter being able to randomly modulate mechanisms by which peer behavior is transmitted to a focal individual. We describe experimental designs that instead randomly assign individuals' peers to encouragements to behaviors that directly affect those individuals. We illustrate this method with a large peer encouragement design on Facebook for estimating the effects of receiving feedback from peers on posts shared by focal individuals. We find evidence for substantial effects of receiving marginal feedback on multiple behaviors, including giving feedback to others and continued posting. These findings provide experimental evidence for the role of behaviors directed at specific individuals in the adoption and continued use of communication technologies. In comparison, observational estimates differ substantially, both underestimating and overestimating effects, suggesting that researchers and policy makers should be cautious in relying on them.

The EMO-model: an agent-based model of primate social behavior regulated by two emotional dimensions, anxiety-FEAR and satisfaction-LIKE.

PubMed

Evers, Ellen; de Vries, Han; Spruijt, Berry M; Sterck, Elisabeth H M

2014-01-01

Agent-based models provide a promising tool to investigate the relationship between individuals' behavior and emerging group-level patterns. An individual's behavior may be regulated by its emotional state and its interaction history with specific individuals. Emotional bookkeeping is a candidate mechanism to keep track of received benefits from specific individuals without requiring high cognitive abilities. However, how this mechanism may work is difficult to study in real animals, due to the complexity of primate social life. To explore this theoretically, we introduce an agent-based model, dubbed EMO-model, in which we implemented emotional bookkeeping. In this model the social behaviors of primate-like individuals are regulated by emotional processes along two dimensions. An individual's emotional state is described by an aversive and a pleasant dimension (anxiety and satisfaction) and by its activating quality (arousal). Social behaviors affect the individuals' emotional state. To implement emotional bookkeeping, the receiver of grooming assigns an accumulated affiliative attitude (LIKE) to the groomer. Fixed partner-specific agonistic attitudes (FEAR) reflect the stable dominance relations between group members. While the emotional state affects an individual's general probability of executing certain behaviors, LIKE and FEAR affect the individual's partner-specific behavioral probabilities. In this way, emotional processes regulate both spontaneous behaviors and appropriate responses to received behaviors, while emotional bookkeeping via LIKE attitudes regulates the development and maintenance of affiliative relations. Using an array of empirical data, the model processes were substantiated and the emerging model patterns were partially validated. The EMO-model offers a framework to investigate the emotional bookkeeping hypothesis theoretically and pinpoints gaps that need to be investigated empirically.

The role of sexual behavior in head and neck cancer: implications for prevention and therapy

PubMed Central

Rettig, Eleni; Kiess, Ana Ponce; Fakhry, Carole

2015-01-01

HPV-positive oropharyngeal squamous cell carcinoma (HPV-OSCC) is associated with oral sexual behaviors. The sharp rise in incidence of HPV-OSCC in the USA has been attributed to changes in sexual norms over the past five decades, with lower age at sexual debut and higher numbers of sexual partners per individual. In addition, variations in HPV-OSCC prevalence by race, age cohort and gender may be attributable to differences in oral sexual behaviors among these groups. Oral HPV infection is the putative precursor to HPV-OSCC. Risk factors for oral HPV incidence, prevalence, clearance and persistence are crucial to understanding how, and in whom, oral HPV infection progresses to malignancy. Future investigation should focus on elucidating the natural history of oral HPV infection persistence and malignant transformation, developing effective screening tools and exploring opportunities for prevention such as vaccination and public health education. PMID:25193346

Phenotypic plasticity as an adaptation to a functional trade-off

PubMed Central

Yi, Xiao; Dean, Antony M

2016-01-01

We report the evolution of a phenotypically plastic behavior that circumvents the hardwired trade-off that exists when resources are partitioned between growth and motility in Escherichia coli. We propagated cultures in a cyclical environment, alternating between growth up to carrying capacity and selection for chemotaxis. Initial adaptations boosted overall swimming speed at the expense of growth. The effect of the trade-off was subsequently eased through a change in behavior; while individual cells reduced motility during exponential growth, the faction of the population that was motile increased as the carrying capacity was approached. This plastic behavior was produced by a single amino acid replacement in FliA, a regulatory protein central to the chemotaxis network. Our results illustrate how phenotypic plasticity potentiates evolvability by opening up new regions of the adaptive landscape. DOI: http://dx.doi.org/10.7554/eLife.19307.001 PMID:27692064

The role of sexual behavior in head and neck cancer: implications for prevention and therapy.

PubMed

Rettig, Eleni; Kiess, Ana Ponce; Fakhry, Carole

2015-01-01

HPV-positive oropharyngeal squamous cell carcinoma (HPV-OSCC) is associated with oral sexual behaviors. The sharp rise in incidence of HPV-OSCC in the USA has been attributed to changes in sexual norms over the past five decades, with lower age at sexual debut and higher numbers of sexual partners per individual. In addition, variations in HPV-OSCC prevalence by race, age cohort and gender may be attributable to differences in oral sexual behaviors among these groups. Oral HPV infection is the putative precursor to HPV-OSCC. Risk factors for oral HPV incidence, prevalence, clearance and persistence are crucial to understanding how, and in whom, oral HPV infection progresses to malignancy. Future investigation should focus on elucidating the natural history of oral HPV infection persistence and malignant transformation, developing effective screening tools and exploring opportunities for prevention such as vaccination and public health education.

Humans as Superorganisms: How Microbes, Viruses, Imprinted Genes, and Other Selfish Entities Shape Our Behavior.

PubMed

Kramer, Peter; Bressan, Paola

2015-07-01

Psychologists and psychiatrists tend to be little aware that (a) microbes in our brains and guts are capable of altering our behavior; (b) viral DNA that was incorporated into our DNA millions of years ago is implicated in mental disorders; (c) many of us carry the cells of another human in our brains; and (d) under the regulation of viruslike elements, the paternally inherited and maternally inherited copies of some genes compete for domination in the offspring, on whom they have opposite physical and behavioral effects. This article provides a broad overview, aimed at a wide readership, of the consequences of our coexistence with these selfish entities. The overarching message is that we are not unitary individuals but superorganisms, built out of both human and nonhuman elements; it is their interaction that determines who we are. © The Author(s) 2015.

Effect of individual behavior on epidemic spreading in activity-driven networks.

PubMed

Rizzo, Alessandro; Frasca, Mattia; Porfiri, Maurizio

2014-10-01

In this work we study the effect of behavioral changes of individuals on the propagation of epidemic diseases. Specifically, we consider a susceptible-infected-susceptible model over a network of contacts that evolves in a time scale that is comparable to the individual disease dynamics. The phenomenon is modeled in the context of activity-driven networks, in which contacts occur on the basis of activity potentials. To offer insight into behavioral strategies targeting both susceptible and infected individuals, we consider two separate behaviors that may emerge in respiratory syndromes and sexually transmitted infections. The first is related to a reduction in the activity of infected individuals due to quarantine or illness. The second is instead associated with a selfish self-protective behavior of susceptible individuals, who tend to reduce contact with the rest of the population on the basis of a risk perception. Numerical and theoretical results suggest that behavioral changes could have a beneficial effect on the disease spreading, by increasing the epidemic threshold and decreasing the steady-state fraction of infected individuals.

Effect of individual behavior on epidemic spreading in activity-driven networks

NASA Astrophysics Data System (ADS)

Rizzo, Alessandro; Frasca, Mattia; Porfiri, Maurizio

2014-10-01

In this work we study the effect of behavioral changes of individuals on the propagation of epidemic diseases. Specifically, we consider a susceptible-infected-susceptible model over a network of contacts that evolves in a time scale that is comparable to the individual disease dynamics. The phenomenon is modeled in the context of activity-driven networks, in which contacts occur on the basis of activity potentials. To offer insight into behavioral strategies targeting both susceptible and infected individuals, we consider two separate behaviors that may emerge in respiratory syndromes and sexually transmitted infections. The first is related to a reduction in the activity of infected individuals due to quarantine or illness. The second is instead associated with a selfish self-protective behavior of susceptible individuals, who tend to reduce contact with the rest of the population on the basis of a risk perception. Numerical and theoretical results suggest that behavioral changes could have a beneficial effect on the disease spreading, by increasing the epidemic threshold and decreasing the steady-state fraction of infected individuals.

RNA Imaging with Multiplexed Error Robust Fluorescence in situ Hybridization

PubMed Central

Moffitt, Jeffrey R.; Zhuang, Xiaowei

2016-01-01

Quantitative measurements of both the copy number and spatial distribution of large fractions of the transcriptome in single-cells could revolutionize our understanding of a variety of cellular and tissue behaviors in both healthy and diseased states. Single-molecule Fluorescence In Situ Hybridization (smFISH)—an approach where individual RNAs are labeled with fluorescent probes and imaged in their native cellular and tissue context—provides both the copy number and spatial context of RNAs but has been limited in the number of RNA species that can be measured simultaneously. Here we describe Multiplexed Error Robust Fluorescence In Situ Hybridization (MERFISH), a massively parallelized form of smFISH that can image and identify hundreds to thousands of different RNA species simultaneously with high accuracy in individual cells in their native spatial context. We provide detailed protocols on all aspects of MERFISH, including probe design, data collection, and data analysis to allow interested laboratories to perform MERFISH measurements themselves. PMID:27241748

Automatic trajectory measurement of large numbers of crowded objects

NASA Astrophysics Data System (ADS)

Li, Hui; Liu, Ye; Chen, Yan Qiu

2013-06-01

Complex motion patterns of natural systems, such as fish schools, bird flocks, and cell groups, have attracted great attention from scientists for years. Trajectory measurement of individuals is vital for quantitative and high-throughput study of their collective behaviors. However, such data are rare mainly due to the challenges of detection and tracking of large numbers of objects with similar visual features and frequent occlusions. We present an automatic and effective framework to measure trajectories of large numbers of crowded oval-shaped objects, such as fish and cells. We first use a novel dual ellipse locator to detect the coarse position of each individual and then propose a variance minimization active contour method to obtain the optimal segmentation results. For tracking, cost matrix of assignment between consecutive frames is trainable via a random forest classifier with many spatial, texture, and shape features. The optimal trajectories are found for the whole image sequence by solving two linear assignment problems. We evaluate the proposed method on many challenging data sets.

Two-Photon Holographic Stimulation of ReaChR

PubMed Central

Chaigneau, Emmanuelle; Ronzitti, Emiliano; Gajowa, Marta A.; Soler-Llavina, Gilberto J.; Tanese, Dimitrii; Brureau, Anthony Y. B.; Papagiakoumou, Eirini; Zeng, Hongkui; Emiliani, Valentina

2016-01-01

Optogenetics provides a unique approach to remotely manipulate brain activity with light. Reaching the degree of spatiotemporal control necessary to dissect the role of individual cells in neuronal networks, some of which reside deep in the brain, requires joint progress in opsin engineering and light sculpting methods. Here we investigate for the first time two-photon stimulation of the red-shifted opsin ReaChR. We use two-photon (2P) holographic illumination to control the activation of individually chosen neurons expressing ReaChR in acute brain slices. We demonstrated reliable action potential generation in ReaChR-expressing neurons and studied holographic 2P-evoked spiking performances depending on illumination power and pulse width using an amplified laser and a standard femtosecond Ti:Sapphire oscillator laser. These findings provide detailed knowledge of ReaChR's behavior under 2P illumination paving the way for achieving in depth remote control of multiple cells with high spatiotemporal resolution deep within scattering tissue. PMID:27803649

Individual, group, and environmental influences on helping behavior in a social carnivore

USGS Publications Warehouse

Ausband, David E.; Mitchell, Michael S.; Bassing, Sarah B.; Morehouse, Andrea T.; Smith, Douglas W.; Stahler, Daniel R.; Struthers, Jennifer

2016-01-01

Variation in group composition and environment can affect helping behavior in cooperative breeders. Understanding of how group size, traits of individuals within groups, food abundance, and predation risk simultaneously influence helping behavior is limited. We evaluated pup-guarding behavior in gray wolves (Canis lupus) to assess how differences in individuals, groups, and environment affect helping behavior. We used data from 92 GPS-collared wolves in North America (2001–2012) to estimate individual pup-guarding rates. Individuals in groups with low helper-to-pup ratios spent more time guarding young than those in groups with more helpers, an indication of load-lightening. Female helpers guarded more than male helpers, but this relationship weakened as pups grew. Subset analyses including data on helper age and wolf and prey density showed such factors did not significantly influence pup-guarding rates. We show that characteristics of individuals and groups have strong influences on pup-guarding behavior in gray wolves, but environmental factors such as food abundance and predation risk from conspecifics were not influential.

Emergent Behaviors from a Cellular Automaton Model for Invasive Tumor Growth in Heterogeneous Microenvironments

PubMed Central

Jiao, Yang; Torquato, Salvatore

2011-01-01

Understanding tumor invasion and metastasis is of crucial importance for both fundamental cancer research and clinical practice. In vitro experiments have established that the invasive growth of malignant tumors is characterized by the dendritic invasive branches composed of chains of tumor cells emanating from the primary tumor mass. The preponderance of previous tumor simulations focused on non-invasive (or proliferative) growth. The formation of the invasive cell chains and their interactions with the primary tumor mass and host microenvironment are not well understood. Here, we present a novel cellular automaton (CA) model that enables one to efficiently simulate invasive tumor growth in a heterogeneous host microenvironment. By taking into account a variety of microscopic-scale tumor-host interactions, including the short-range mechanical interactions between tumor cells and tumor stroma, degradation of the extracellular matrix by the invasive cells and oxygen/nutrient gradient driven cell motions, our CA model predicts a rich spectrum of growth dynamics and emergent behaviors of invasive tumors. Besides robustly reproducing the salient features of dendritic invasive growth, such as least-resistance paths of cells and intrabranch homotype attraction, we also predict nontrivial coupling between the growth dynamics of the primary tumor mass and the invasive cells. In addition, we show that the properties of the host microenvironment can significantly affect tumor morphology and growth dynamics, emphasizing the importance of understanding the tumor-host interaction. The capability of our CA model suggests that sophisticated in silico tools could eventually be utilized in clinical situations to predict neoplastic progression and propose individualized optimal treatment strategies. PMID:22215996

Impact of environmental conditions and chemicals on the neuronal epigenome.

PubMed

Del Blanco, Beatriz; Barco, Angel

2018-06-15

During development, chromatin changes contribute to establishing and maintaining the distinct gene-expression profiles of each individual cell type in a multicellular organism. This feat is especially remarkable in the human brain considering the sheer number of distinct cell types that make up this organ. This epigenetic programing is sensitive to environmental influences such as the presence of toxicants, diet, temperature, maternal behavior and many other external factors that can lead to sustained differences in neuronal gene expression. Here, we review a number of studies that demonstrate the existence of these environmental fingerprints in the neuronal epigenome and discuss the current challenges and prospects of environmental neuroepigenetics research. Copyright © 2018 Elsevier Ltd. All rights reserved.

Using Zipf-Mandelbrot law and graph theory to evaluate animal welfare

NASA Astrophysics Data System (ADS)

de Oliveira, Caprice G. L.; Miranda, José G. V.; Japyassú, Hilton F.; El-Hani, Charbel N.

2018-02-01

This work deals with the construction and testing of metrics of welfare based on behavioral complexity, using assumptions derived from Zipf-Mandelbrot law and graph theory. To test these metrics we compared yellow-breasted capuchins (Sapajus xanthosternos) (Wied-Neuwied, 1826) (PRIMATES CEBIDAE) found in two institutions, subjected to different captive conditions: a Zoobotanical Garden (hereafter, ZOO; n = 14), in good welfare condition, and a Wildlife Rescue Center (hereafter, WRC; n = 8), in poor welfare condition. In the Zipf-Mandelbrot-based analysis, the power law exponent was calculated using behavior frequency values versus behavior rank value. These values allow us to evaluate variations in individual behavioral complexity. For each individual we also constructed a graph using the sequence of behavioral units displayed in each recording (average recording time per individual: 4 h 26 min in the ZOO, 4 h 30 min in the WRC). Then, we calculated the values of the main graph attributes, which allowed us to analyze the complexity of the connectivity of the behaviors displayed in the individuals' behavioral sequences. We found significant differences between the two groups for the slope values in the Zipf-Mandelbrot analysis. The slope values for the ZOO individuals approached -1, with graphs representing a power law, while the values for the WRC individuals diverged from -1, differing from a power law pattern. Likewise, we found significant differences for the graph attributes average degree, weighted average degree, and clustering coefficient when comparing the ZOO and WRC individual graphs. However, no significant difference was found for the attributes modularity and average path length. Both analyses were effective in detecting differences between the patterns of behavioral complexity in the two groups. The slope values for the ZOO individuals indicated a higher behavioral complexity when compared to the WRC individuals. Similarly, graph construction and the calculation of its attributes values allowed us to show that the complexity of the connectivity among the behaviors was higher in the ZOO than in the WRC individual graphs. These results show that the two measuring approaches introduced and tested in this paper were capable of capturing the differences in welfare levels between the two conditions, as shown by differences in behavioral complexity.

Neurons as sensors: individual and cascaded chemical sensing.

PubMed

Prasad, Shalini; Zhang, Xuan; Yang, Mo; Ozkan, Cengiz S; Ozkan, Mihrimah

2004-07-15

A single neuron sensor has been developed based on the interaction of gradient electric fields and the cell membrane. Single neurons are rapidly positioned over individual microelectrodes using positive dielectrophoretic traps. This enables the continuous extracellular electrophysiological measurements from individual neurons. The sensor developed using this technique provides the first experimental method for determining single cell sensitivity; the speed of response and the associated physiological changes to a broad spectrum of chemical agents. Binding of specific chemical agents to a specific combination of receptors induces changes to the extracellular membrane potential of a single neuron, which can be translated into unique "signature patterns" (SP), which function as identification tags. Signature patterns are derived using Fast Fourier Transformation (FFT) analysis and Wavelet Transformation (WT) analysis of the modified extracellular action potential. The validity and the sensitivity of the system are demonstrated for a variety of chemical agents ranging from behavior altering chemicals (ethanol), environmentally hazardous agents (hydrogen peroxide, EDTA) to physiologically harmful agents (pyrethroids) at pico- and femto-molar concentrations. The ability of a single neuron to selectively identify specific chemical agents when injected in a serial manner is demonstrated in "cascaded sensing".

Stem Cell Monitoring with a Direct or Indirect Labeling Method.

PubMed

Kim, Min Hwan; Lee, Yong Jin; Kang, Joo Hyun

2016-12-01

The molecular imaging techniques allow monitoring of the transplanted cells in the same individuals over time, from early localization to the survival, migration, and differentiation. Generally, there are two methods of stem cell labeling: direct and indirect labeling methods. The direct labeling method introduces a labeling agent into the cell, which is stably incorporated or attached to the cells prior to transplantation. Direct labeling of cells with radionuclides is a simple method with relatively fewer adverse events related to genetic responses. However, it can only allow short-term distribution of transplanted cells because of the decreasing imaging signal with radiodecay, according to the physical half-lives, or the signal becomes more diffuse with cell division and dispersion. The indirect labeling method is based on the expression of a reporter gene transduced into the cell before transplantation, which is then visualized upon the injection of an appropriate probe or substrate. In this review, various imaging strategies to monitor the survival and behavior change of transplanted stem cells are covered. Taking these new approaches together, the direct and indirect labeling methods may provide new insights on the roles of in vivo stem cell monitoring, from bench to bedside.

Behavioral Phenotype of Fragile X Syndrome in Adolescence and Adulthood

PubMed Central

Smith, Leann E.; Barker, Erin T.; Seltzer, Marsha Mailick; Abbeduto, Leonard; Greenberg, Jan S.

2012-01-01

The present study explored the behavioral profile of individuals with fragile X syndrome during adolescence and adulthood. Individuals with both fragile X syndrome and autism (n = 30) were compared with (a) individuals diagnosed with fragile X syndrome (but not autism; n = 106) and (b) individuals diagnosed with autism (but not fragile X syndrome; n = 135) on measures of autism symptoms, adaptive functioning, behavior problems, and psychological symptoms. Results indicated that individuals dually diagnosed with fragile X syndrome and autism displayed greater communication and social reciprocity impairments than individuals with fragile X syndrome only. Individuals in the dually diagnosed group also exhibited higher levels of repetitive and challenging behaviors than either comparison group, suggesting a unique profile of vulnerability for those diagnosed with both fragile X syndrome and autism. PMID:22264109

Behavioral and Metabolic Phenotype Indicate Personality in Zebrafish (Danio rerio).

PubMed

Yuan, Mingzhe; Chen, Yan; Huang, Yingying; Lu, Weiqun

2018-01-01

Consistency of individual differences of animal behavior and personality in reactions to various environmental stresses among their life stages could reflect basic divergences in coping style which may affect survival, social rank, and reproductive success in the wild. However, the physiological mechanisms determining personality remain poorly understood. In order to study whether behavior, metabolism and physiological stress responses relate to the personality, we employed post-stress recovery assays to separate zebrafish into two behavioral types (proactive and reactive). The results demonstrated consistent difference among personality, behavior and metabolism in which proactive individuals were more aggressive, had higher standard metabolic rates and showed lower shuttled frequencies between dark and light compartments than the reactive ones. The behavioral variations were also linked to divergent acute salinity stress responses: proactive individuals adopted a swift locomotion behavior in response to acute salinity challenge while reactive individuals remain unchanged. Our results provide useful insight into how personality acts on correlated traits and the importance of a holistic approach to understanding the mechanisms driving persistent inter-individual differences.

Exploratory behavior is linked to stress physiology and social network centrality in free-living house finches (Haemorhous mexicanus).

PubMed

Moyers, Sahnzi C; Adelman, James S; Farine, Damien R; Moore, Ignacio T; Hawley, Dana M

2018-06-01

Animal personality has been linked to individual variation in both stress physiology and social behaviors, but few studies have simultaneously examined covariation between personality traits, stress hormone levels, and behaviors in free-living animals. We investigated relationships between exploratory behavior (one aspect of animal personality), stress physiology, and social and foraging behaviors in wild house finches (Haemorhous mexicanus). We conducted novel environment assays after collecting samples of baseline and stress-induced plasma corticosterone concentrations from a subset of house finches. We then fitted individuals with Passive Integrated Transponder tags and monitored feeder use and social interactions at radio-frequency identification equipped bird feeders. First, we found that individuals with higher baseline corticosterone concentrations exhibit more exploratory behaviors in a novel environment. Second, more exploratory individuals interacted with more unique conspecifics in the wild, though this result was stronger for female than for male house finches. Third, individuals that were quick to begin exploring interacted more frequently with conspecifics than slow-exploring individuals. Finally, exploratory behaviors were unrelated to foraging behaviors, including the amount of time spent on bird feeders, a behavior previously shown to be predictive of acquiring a bacterial disease that causes annual epidemics in house finches. Overall, our results indicate that individual differences in exploratory behavior are linked to variation in both stress physiology and social network traits in free-living house finches. Such covariation has important implications for house finch ecology, as both traits can contribute to fitness in the wild. Copyright © 2018 Elsevier Inc. All rights reserved.

Cadherin Composition and Multicellular Aggregate Invasion In Organotypic Models of Epithelial Ovarian Cancer Intraperitoneal Metastasis

PubMed Central

Klymenko, Yuliya; Kim, Oleg; Loughran, Elizabeth; Yang, Jing; Lombard, Rachel; Alber, Mark; Stack, M. Sharon

2017-01-01

During epithelial ovarian cancer (EOC) progression, intraperitoneally disseminating tumor cells and multi-cellular aggregates (MCAs) present in ascites fluid adhere to the peritoneum and induce retraction of the peritoneal mesothelial monolayer prior to invasion of the collagen-rich sub-mesothelial matrix and proliferation into macro-metastases. Clinical studies have shown heterogeneity among EOC metastatic units with respect to cadherin expression profiles and invasive behavior, however the impact of distinct cadherin profiles on peritoneal anchoring of metastatic lesions remains poorly understood. In the current study, we demonstrate that metastasis-associated behaviors of ovarian cancer cells and MCAs are influenced by cellular cadherin composition. Our results show that mesenchymal N-cadherin expressing (Ncad+) cells and MCAs invade much more efficiently than E-cadherin expressing (Ecad+) cells. Ncad+ MCAs exhibit rapid lateral dispersal prior to penetration of three-dimensional collagen matrices. When seeded as individual cells, lateral migration and cell-cell junction formation precede matrix invasion. Neutralizing the Ncad extracellular domain with the monoclonal antibody GC-4 suppresses lateral dispersal and cell penetration of collagen gels. In contrast, use of a broad spectrum matrix metalloproteinase (MMP) inhibitor (GM6001) to block endogenous membrane type 1 matrix metalloproteinase (MT1-MMP) activity does not fully inhibit cell invasion. Using intact tissue explants, Ncad+ MCAs were also shown to efficiently rupture peritoneal mesothelial cells, exposing the sub-mesothelial collagen matrix. Acquisition of Ncad by E-cadherin expressing cells (Ecad+) increased mesothelial clearance activity, but was not sufficient to induce matrix invasion. Furthermore, co-culture of Ncad+ with Ecad+ cells did not promote a “leader-follower” mode of collective cell invasion, demonstrating that matrix remodeling and creation of invasive micro-tracks are not sufficient for cell penetration of collagen matrices in the absence of Ncad. Collectively, our data emphasize the role of Ncad in intraperitoneal seeding of EOC and provide the rationale for future studies targeting Ncad+ in pre-clinical models of EOC metastasis. PMID:28628116

Cadherin composition and multicellular aggregate invasion in organotypic models of epithelial ovarian cancer intraperitoneal metastasis.

PubMed

Klymenko, Y; Kim, O; Loughran, E; Yang, J; Lombard, R; Alber, M; Stack, M S

2017-10-19

During epithelial ovarian cancer (EOC) progression, intraperitoneally disseminating tumor cells and multicellular aggregates (MCAs) present in ascites fluid adhere to the peritoneum and induce retraction of the peritoneal mesothelial monolayer prior to invasion of the collagen-rich submesothelial matrix and proliferation into macro-metastases. Clinical studies have shown heterogeneity among EOC metastatic units with respect to cadherin expression profiles and invasive behavior; however, the impact of distinct cadherin profiles on peritoneal anchoring of metastatic lesions remains poorly understood. In the current study, we demonstrate that metastasis-associated behaviors of ovarian cancer cells and MCAs are influenced by cellular cadherin composition. Our results show that mesenchymal N-cadherin-expressing (Ncad+) cells and MCAs invade much more efficiently than E-cadherin-expressing (Ecad+) cells. Ncad+ MCAs exhibit rapid lateral dispersal prior to penetration of three-dimensional collagen matrices. When seeded as individual cells, lateral migration and cell-cell junction formation precede matrix invasion. Neutralizing the Ncad extracellular domain with the monoclonal antibody GC-4 suppresses lateral dispersal and cell penetration of collagen gels. In contrast, use of a broad-spectrum matrix metalloproteinase (MMP) inhibitor (GM6001) to block endogenous membrane type 1 matrix metalloproteinase (MT1-MMP) activity does not fully inhibit cell invasion. Using intact tissue explants, Ncad+ MCAs were also shown to efficiently rupture peritoneal mesothelial cells, exposing the submesothelial collagen matrix. Acquisition of Ncad by Ecad+ cells increased mesothelial clearance activity but was not sufficient to induce matrix invasion. Furthermore, co-culture of Ncad+ with Ecad+ cells did not promote a 'leader-follower' mode of collective cell invasion, demonstrating that matrix remodeling and creation of invasive micro-tracks are not sufficient for cell penetration of collagen matrices in the absence of Ncad. Collectively, our data emphasize the role of Ncad in intraperitoneal seeding of EOC and provide the rationale for future studies targeting Ncad in preclinical models of EOC metastasis.

The Role of Mechanical Variance and Spatial Clustering on the Likelihood of Tumor Incidence and Growth

NASA Astrophysics Data System (ADS)

Mirzakhel, Zibah

When considering factors that contribute to cancer progression, modifications to both the biological and mechanical pathways play significant roles. However, less attention is placed on how the mechanical pathways can specifically contribute to cancerous behavior. Experimental studies have found that malignant cells are significantly softer than healthy, normal cells. In a tissue environment where healthy or malignant cells exist, a distribution of cell stiffness values is observed, with the mean values used to differentiate between these two populations. Rather than focus on the mean values, emphasis will be placed on the distribution, where instances of soft and stiff cells exist in the healthy tissue environment. Since cell deformability is a trait associated with cancer, the question arises as to whether the mechanical variation observed in healthy tissue cell stiffness distributions can influence any instances of tumor growth. To approach this, a 3D discrete model of cells is used, able to monitor and predict the behavior of individual cells while determining any instances of tumor growth in a healthy tissue. In addition to the mechanical variance, the spatial arrangement of cells will also be modeled, as cell interaction could further implicate any incidences of tumor-like malignant populations within the tissue. Results have shown that the likelihood of tumor incidence is driven by both by the increases in the mechanical variation in the distributions as well as larger clustering of cells that are mechanically similar, quantified primarily through higher proliferation rates of tumor-like soft cells. This can be observed though prominent negative shifts in the mean of the distribution, as it begins to transition and show instances of earlystage tumor growth. The model reveals the impact that both the mechanical variation and spatial arrangement of cells has on tumor progression, suggesting the use of these parameters as potential novel biomarkers. With a patient-specific approach in mind, the model may be applied for early-stage cancer detection, useful to establish a timeline on tumor progression.

Nonsuicidal Self-Injury and Suicidal Behavior: A Latent Class Analysis among Young Adults

PubMed Central

Hamza, Chloe A.; Willoughby, Teena

2013-01-01

Although there is a general consensus among researchers that engagement in nonsuicidal self-injury (NSSI) is associated with increased risk for suicidal behavior, little attention has been given to whether suicidal risk varies among individuals engaging in NSSI. To identify individuals with a history of NSSI who are most at risk for suicidal behavior, we examined individual variability in both NSSI and suicidal behavior among a sample of young adults with a history of NSSI (N = 439, Mage = 19.1). Participants completed self-report measures assessing NSSI, suicidal behavior, and psychosocial adjustment (e.g., depressive symptoms, daily hassles). We conducted a latent class analysis using several characteristics of NSSI and suicidal behaviors as class indicators. Three subgroups of individuals were identified: 1) an infrequent NSSI/not high risk for suicidal behavior group, 2) a frequent NSSI/not high risk for suicidal behavior group, and 3) a frequent NSSI/high risk for suicidal behavior group. Follow-up analyses indicated that individuals in the ‘frequent NSSI/high risk for suicidal behavior’ group met the clinical-cut off score for high suicidal risk and reported significantly greater levels of suicidal ideation, attempts, and risk for future suicidal behavior as compared to the other two classes. Thus, this study is the first to identity variability in suicidal risk among individuals engaging in frequent and multiple methods of NSSI. Class 3 was also differentiated by higher levels of psychosocial impairment relative to the other two classes, as well as a comparison group of non-injuring young adults. Results underscore the importance of assessing individual differences in NSSI characteristics, as well as psychosocial impairment, when assessing risk for suicidal behavior. PMID:23544113

Sexuality in autism: hypersexual and paraphilic behavior in women and men with high-functioning autism spectrum disorder

PubMed Central

Schöttle, Daniel; Briken, Peer; Tüscher, Oliver; Turner, Daniel

2017-01-01

Like nonaffected adults, individuals with autism spectrum disorders (ASDs) show the entire range of sexual behaviors. However, due to the core symptoms of the disorder spectrum, including deficits in social skills, sensory hypo- and hypersensitivities, and repetitive behaviors, some ASD individuals might develop quantitatively above-average or nonnormative sexual behaviors and interests. After reviewing the relevant literature on sexuality in high-functioning ASD individuals, we present novel findings on the frequency of normal sexual behaviors and those about the assessment of hypersexual and paraphilic fantasies and behaviors in ASD individuals from our own study. Individuals with ASD seem to have more hypersexual and paraphilic fantasies and behaviors than general-population studies suggest. However, this inconsistency is mainly driven by the observations for male participants with ASD. This could be due to the fact that women with ASD are usually more socially adapted and show less ASD symptomatology. The peculiarities in sexual behaviors in ASD patients should be considered both for sexual education and in therapeutic approaches. PMID:29398933

Power and affordances: when the situation has more power over powerful than powerless individuals.

PubMed

Guinote, Ana

2008-08-01

Six studies examined how power affects responses to situational affordances. Participants were assigned to a powerful or a powerless condition and were exposed to various situations that afford different classes of behavior. Study 1 examined behavior intentions for weekdays and weekends. Studies 2 and 3 focused on responses to imaginary social and work situations. Study 4 examined planned behavior for winter and summer days. Finally, Studies 5 and 6 examined behavior and attention in the presence of situation-relevant and irrelevant information. Consistently across these studies, powerful individuals acted more in situation-consistent ways, and less in situation-inconsistent ways, compared with powerless individuals. These findings are interpreted as a result of the greater tendency for powerful individuals to process information selectively in line with the primary factors that drive cognition, such as affordances. One consequence of these findings is that powerful individuals change behavior across situations more than powerless individuals.

Thermodynamics of protein destabilization in live cells

PubMed Central

Danielsson, Jens; Mu, Xin; Lang, Lisa; Wang, Huabing; Binolfi, Andres; Theillet, François-Xavier; Bekei, Beata; Logan, Derek T.; Selenko, Philipp; Wennerström, Håkan; Oliveberg, Mikael

2015-01-01

Although protein folding and stability have been well explored under simplified conditions in vitro, it is yet unclear how these basic self-organization events are modulated by the crowded interior of live cells. To find out, we use here in-cell NMR to follow at atomic resolution the thermal unfolding of a β-barrel protein inside mammalian and bacterial cells. Challenging the view from in vitro crowding effects, we find that the cells destabilize the protein at 37 °C but with a conspicuous twist: While the melting temperature goes down the cold unfolding moves into the physiological regime, coupled to an augmented heat-capacity change. The effect seems induced by transient, sequence-specific, interactions with the cellular components, acting preferentially on the unfolded ensemble. This points to a model where the in vivo influence on protein behavior is case specific, determined by the individual protein’s interplay with the functionally optimized “interaction landscape” of the cellular interior. PMID:26392565

Manipulating the Cellular Circadian Period of Arginine Vasopressin Neurons Alters the Behavioral Circadian Period.

PubMed

Mieda, Michihiro; Okamoto, Hitoshi; Sakurai, Takeshi

2016-09-26

As the central pacemaker in mammals, the circadian clock in the suprachiasmatic nucleus (SCN) of the hypothalamus is a heterogeneous structure consisting of multiple types of GABAergic neurons with distinct chemical identities [1, 2]. Although individual cells have a cellular clock driven by autoregulatory transcriptional/translational feedback loops of clock genes, interneuronal communication among SCN clock neurons is likely essential for the SCN to generate a highly robust, coherent circadian rhythm [1]. However, neuronal mechanisms that determine circadian period length remain unclear. The SCN is composed of two subdivisions: a ventral core region containing vasoactive intestinal peptide (VIP)-producing neurons and a dorsal shell region characterized by arginine vasopressin (AVP)-producing neurons. Here we examined whether AVP neurons act as pacemaker cells that regulate the circadian period of behavior rhythm in mice. The deletion of casein kinase 1 delta (CK1δ) specific to AVP neurons, which was expected to lengthen the period of cellular clocks [3-6], lengthened the free-running period of circadian behavior as well. Conversely, the overexpression of CK1δ specific to SCN AVP neurons shortened the free-running period. PER2::LUC imaging in slices confirmed that cellular circadian periods of the SCN shell were lengthened in mice without CK1δ in AVP neurons. Thus, AVP neurons may be an essential component of circadian pacemaker cells in the SCN. Remarkably, the alteration of the shell-core phase relationship in the SCN of these mice did not impair the generation per se of circadian behavior rhythm, thereby underscoring the robustness of the SCN network. Copyright © 2016 Elsevier Ltd. All rights reserved.

Space Processing Applications Rocket project, SPAR 2

NASA Technical Reports Server (NTRS)

1977-01-01

Experiment objectives, design/operational concepts, and final results are summarized for six materials science experiments conducted during the second space processing applications rocket mission flown by NASA. The individual experiments discussed are: (1) solidification of Pb-Sb eutectic; (2) feasibility of producing closed-cell metal foams; (3) direct observation of dendrite remelting and macrosegregation in castings; (4) agglomeration in immiscible liquids; (5) casting dispersion - strengthened composites at zero gravity; and (6) solidification behavior of Al-In alloys under zero gravity conditions.

Hematopoietic stem cell fate through metabolic control.

PubMed

Ito, Kyoko; Ito, Keisuke

2018-05-25

Hematopoietic stem cells (HSCs) maintain a quiescent state in the bone marrow to preserve their self-renewal capacity, but also undergo cell divisions as required. Organelles such as the mitochondria sustain cumulative damage during these cell divisions, and this damage may eventually compromise the cells' self-renewal capacity. HSC divisions result in either self-renewal or differentiation, with the balance between the two directly impacting hematopoietic homeostasis; but the heterogeneity of available HSC-enriched fractions, together with the technical challenges of observing HSC behavior, has long hindered the analysis of individual HSCs, and prevented the elucidation of this process. However, recent advances in genetic models, metabolomics analyses and single-cell approaches have revealed the contributions made to HSC self-renewal by metabolic cues, mitochondrial biogenesis, and autophagy/mitophagy, which have highlighted mitochondrial quality as a key control factor in the equilibrium of HSCs. A deeper understanding of precisely how specific modes of metabolism control HSC fate at the single cell level is therefore not only of great biological interest, but will have clear clinical implications for the development of therapies for hematological disease. Copyright © 2018. Published by Elsevier Inc.

Vertex Models of Epithelial Morphogenesis

PubMed Central

Fletcher, Alexander G.; Osterfield, Miriam; Baker, Ruth E.; Shvartsman, Stanislav Y.

2014-01-01

The dynamic behavior of epithelial cell sheets plays a central role during numerous developmental processes. Genetic and imaging studies of epithelial morphogenesis in a wide range of organisms have led to increasingly detailed mechanisms of cell sheet dynamics. Computational models offer a useful means by which to investigate and test these mechanisms, and have played a key role in the study of cell-cell interactions. A variety of modeling approaches can be used to simulate the balance of forces within an epithelial sheet. Vertex models are a class of such models that consider cells as individual objects, approximated by two-dimensional polygons representing cellular interfaces, in which each vertex moves in response to forces due to growth, interfacial tension, and pressure within each cell. Vertex models are used to study cellular processes within epithelia, including cell motility, adhesion, mitosis, and delamination. This review summarizes how vertex models have been used to provide insight into developmental processes and highlights current challenges in this area, including progressing these models from two to three dimensions and developing new tools for model validation. PMID:24896108

Variation is function: Are single cell differences functionally important?: Testing the hypothesis that single cell variation is required for aggregate function.

PubMed

Dueck, Hannah; Eberwine, James; Kim, Junhyong

2016-02-01

There is a growing appreciation of the extent of transcriptome variation across individual cells of the same cell type. While expression variation may be a byproduct of, for example, dynamic or homeostatic processes, here we consider whether single-cell molecular variation per se might be crucial for population-level function. Under this hypothesis, molecular variation indicates a diversity of hidden functional capacities within an ensemble of identical cells, and this functional diversity facilitates collective behavior that would be inaccessible to a homogenous population. In reviewing this topic, we explore possible functions that might be carried by a heterogeneous ensemble of cells; however, this question has proven difficult to test, both because methods to manipulate molecular variation are limited and because it is complicated to define, and measure, population-level function. We consider several possible methods to further pursue the hypothesis that variation is function through the use of comparative analysis and novel experimental techniques. © 2015 The Authors. BioEssays published by WILEY Periodicals, Inc.

Confocal observation of hydrophilic and lipophilic photosensitizers in endothelial cells, lumen of the vessels, interstitium, and tumor cells using the chicken chorioallantoic membrane

NASA Astrophysics Data System (ADS)

Rueck, Angelika C.; Akguen, Nermin; Heckelsmiller, K.; Beck, Gerd C.; Genze, Felicitas; Steiner, Rudolf W.

1998-05-01

The dynamic behavior of lipophilic and hydrophilic sensitizers in cell cultures and non animal in vivo systems with varying incubation but also during the photodynamic therapy will be summarized within the presentation. As an appropriate in vivo system we used the chorioallantoic membrane (CAM) of fertilized eggs, which served as a substrate for tumor cells. Because the CAM is a transparent membrane it is possible to view individual blood vessels and to examine tumor cells as well as structural changes of the supplying vasculature. To adapt this system to high magnification microscopy, we established a new technique for in vivo observation of the CAM tissue. This technique enables online investigations of alterations at cellular level induced by drugs with confocal laser scanning microscopy. The localization of the drugs with clinical importance was observed after different application times in the lumen of the vessels, the endothelial cells and the tumor cells. In addition light induced subcellular Ca2+-changes were observed and correlated with the photodynamic process.

38 CFR 3.815 - Monetary allowance under 38 U.S.C. chapter 18 for an individual with disability from covered...

Code of Federal Regulations, 2010 CFR

2010-07-01

... communication, behavior, social interaction, and intellectual functioning are appropriate for age; or (B) The... difficulty; (C) The individual's communication, behavior, social interaction, and intellectual functioning..., grooming, and carrying out personal hygiene; (B) The individual's communication, behavior, social...

Individual Differences in Consumer Buying Patterns: A Behavioral Economic Analysis

ERIC Educational Resources Information Center

Cavalcanti, Paulo R.; Oliveira-Castro, Jorge M.; Foxall, Gordon R.

2013-01-01

Although previous studies have identified several regularities in buying behavior, no integrated view of individual differences related to such patterns has been yet proposed. The present research examined individual differences in patterns of buying behavior of fast-moving consumer goods, using panel data with information concerning purchases of…

Deciphering the Combinatorial Roles of Geometric, Mechanical, and Adhesion Cues in Regulation of Cell Spreading

PubMed Central

Harris, Greg M.; Shazly, Tarek; Jabbarzadeh, Ehsan

2013-01-01

Significant effort has gone towards parsing out the effects of surrounding microenvironment on macroscopic behavior of stem cells. Many of the microenvironmental cues, however, are intertwined, and thus, further studies are warranted to identify the intricate interplay among the conflicting downstream signaling pathways that ultimately guide a cell response. In this contribution, by patterning adhesive PEG (polyethylene glycol) hydrogels using Dip Pen Nanolithography (DPN), we demonstrate that substrate elasticity, subcellular elasticity, ligand density, and topography ultimately define mesenchymal stem cells (MSCs) spreading and shape. Physical characteristics are parsed individually with 7 kilopascal (kPa) hydrogel islands leading to smaller, spindle shaped cells and 105 kPa hydrogel islands leading to larger, polygonal cell shapes. In a parallel effort, a finite element model was constructed to characterize and confirm experimental findings and aid as a predictive tool in modeling cell microenvironments. Signaling pathway inhibition studies suggested that RhoA is a key regulator of cell response to the cooperative effect of the tunable substrate variables. These results are significant for the engineering of cell-extra cellular matrix interfaces and ultimately decoupling matrix bound cues presented to cells in a tissue microenvironment for regenerative medicine. PMID:24282570

Single-cell measurement of red blood cell oxygen affinity.

PubMed

Di Caprio, Giuseppe; Stokes, Chris; Higgins, John M; Schonbrun, Ethan

2015-08-11

Oxygen is transported throughout the body by hemoglobin (Hb) in red blood cells (RBCs). Although the oxygen affinity of blood is well-understood and routinely assessed in patients by pulse oximetry, variability at the single-cell level has not been previously measured. In contrast, single-cell measurements of RBC volume and Hb concentration are taken millions of times per day by clinical hematology analyzers, and they are important factors in determining the health of the hematologic system. To better understand the variability and determinants of oxygen affinity on a cellular level, we have developed a system that quantifies the oxygen saturation, cell volume, and Hb concentration for individual RBCs in high throughput. We find that the variability in single-cell saturation peaks at an oxygen partial pressure of 2.9%, which corresponds to the maximum slope of the oxygen-Hb dissociation curve. In addition, single-cell oxygen affinity is positively correlated with Hb concentration but independent of osmolarity, which suggests variation in the Hb to 2,3-diphosphoglycerate (2-3 DPG) ratio on a cellular level. By quantifying the functional behavior of a cellular population, our system adds a dimension to blood cell analysis and other measurements of single-cell variability.

Single-cell measurement of red blood cell oxygen affinity

PubMed Central

Di Caprio, Giuseppe; Stokes, Chris; Higgins, John M.; Schonbrun, Ethan

2015-01-01

Oxygen is transported throughout the body by hemoglobin (Hb) in red blood cells (RBCs). Although the oxygen affinity of blood is well-understood and routinely assessed in patients by pulse oximetry, variability at the single-cell level has not been previously measured. In contrast, single-cell measurements of RBC volume and Hb concentration are taken millions of times per day by clinical hematology analyzers, and they are important factors in determining the health of the hematologic system. To better understand the variability and determinants of oxygen affinity on a cellular level, we have developed a system that quantifies the oxygen saturation, cell volume, and Hb concentration for individual RBCs in high throughput. We find that the variability in single-cell saturation peaks at an oxygen partial pressure of 2.9%, which corresponds to the maximum slope of the oxygen–Hb dissociation curve. In addition, single-cell oxygen affinity is positively correlated with Hb concentration but independent of osmolarity, which suggests variation in the Hb to 2,3-diphosphoglycerate (2–3 DPG) ratio on a cellular level. By quantifying the functional behavior of a cellular population, our system adds a dimension to blood cell analysis and other measurements of single-cell variability. PMID:26216973

Quantum dot multiplexing for the profiling of cellular receptors

NASA Astrophysics Data System (ADS)

Lee-Montiel, Felipe T.; Li, Peter; Imoukhuede, P. I.

2015-11-01

The profiling of cellular heterogeneity has wide-reaching importance for our understanding of how cells function and react to their environments in healthy and diseased states. Our ability to interpret and model cell behavior has been limited by the difficulties of measuring cell differences, for example, comparing tumor and non-tumor cells, particularly at the individual cell level. This demonstrates a clear need for a generalizable approach to profile fluorophore sites on cells or molecular assemblies on beads. Here, a multiplex immunoassay for simultaneous detection of five different angiogenic markers was developed. We targeted angiogenic receptors in the vascular endothelial growth factor family (VEGFR1, VEGFR2 and VEGFR3) and Neuropilin (NRP) family (NRP1 and NRP2), using multicolor quantum dots (Qdots). Copper-free click based chemistry was used to conjugate the monoclonal antibodies with 525, 565, 605, 655 and 705 nm CdSe/ZnS Qdots. We tested and performed colocalization analysis of our nanoprobes using the Pearson correlation coefficient statistical analysis. Human umbilical vein endothelial cells (HUVEC) were tested. The ability to easily monitor the molecular indicators of angiogenesis that are a precursor to cancer in a fast and cost effective system is an important step towards personalized nanomedicine.The profiling of cellular heterogeneity has wide-reaching importance for our understanding of how cells function and react to their environments in healthy and diseased states. Our ability to interpret and model cell behavior has been limited by the difficulties of measuring cell differences, for example, comparing tumor and non-tumor cells, particularly at the individual cell level. This demonstrates a clear need for a generalizable approach to profile fluorophore sites on cells or molecular assemblies on beads. Here, a multiplex immunoassay for simultaneous detection of five different angiogenic markers was developed. We targeted angiogenic receptors in the vascular endothelial growth factor family (VEGFR1, VEGFR2 and VEGFR3) and Neuropilin (NRP) family (NRP1 and NRP2), using multicolor quantum dots (Qdots). Copper-free click based chemistry was used to conjugate the monoclonal antibodies with 525, 565, 605, 655 and 705 nm CdSe/ZnS Qdots. We tested and performed colocalization analysis of our nanoprobes using the Pearson correlation coefficient statistical analysis. Human umbilical vein endothelial cells (HUVEC) were tested. The ability to easily monitor the molecular indicators of angiogenesis that are a precursor to cancer in a fast and cost effective system is an important step towards personalized nanomedicine. Electronic supplementary information (ESI) available: Additional information of Qdot size, spectra, images of HUVEC, HDFa cells, confocal microscopy setting and colocalization analysis results. See DOI: 10.1039/c5nr01455g

How does variation in the environment and individual cognition explain the existence of consistent behavioral differences?

PubMed Central

Niemelä, Petri T; Vainikka, Anssi; Forsman, Jukka T; Loukola, Olli J; Kortet, Raine

2013-01-01

According to recent studies on animal personalities, the level of behavioral plasticity, which can be viewed as the slope of the behavioral reaction norm, varies among individuals, populations, and species. Still, it is conceptually unclear how the interaction between environmental variation and variation in animal cognition affect the evolution of behavioral plasticity and expression of animal personalities. Here, we (1) use literature to review how environmental variation and individual variation in cognition explain population and individual level expression of behavioral plasticity and (2) draw together empirically yet nontested, conceptual framework to clarify how these factors affect the evolution and expression of individually consistent behavior in nature. The framework is based on simple principles: first, information acquisition requires cognition that is inherently costly to build and maintain. Second, individual differences in animal cognition affect the differences in behavioral flexibility, i.e. the variance around the mean of the behavioral reaction norm, which defines plasticity. Third, along the lines of the evolution of cognition, we predict that environments with moderate variation favor behavioral flexibility. This occurs since in those environments costs of cognition are covered by being able to recognize and use information effectively. Similarly, nonflexible, stereotypic behaviors may be favored in environments that are either invariable or highly variable, since in those environments cognition does not give any benefits to cover the costs or cognition is not able to keep up with environmental change, respectively. If behavioral plasticity develops in response to increasing environmental variability, plasticity should dominate in environments that are moderately variable, and expression of animal personalities and behavioral syndromes may differ between environments. We give suggestions how to test our hypothesis and propose improvements to current behavioral testing protocols in the field of animal personality. PMID:23467316

[The growth behavior of mouse fibroblasts on intraocular lens surface of various silicone and PMMA materials].

PubMed

Kammann, J; Kreiner, C F; Kaden, P

1994-08-01

Experience with intraocular lenses (IOL) made of PMMA dates back ca. 40 years, while silicone IOLs have been in use for only about 10 years. The biocompatibility of PMMA and silicone caoutchouc was tested in a comparative study investigating the growth of mouse fibroblasts on different IOL materials. Spectrophotometric determination of protein synthesis and liquid scintillation counting of DNA synthesis were carried out. The spreading of cells was planimetrically determined, and the DNA synthesis of individual cells in direct contact with the test sample was tested. The results showed that the biocompatibility of silicone lenses made of purified caoutchouc is comparable with that of PMMA lenses; there is no statistically significant difference. However, impurities arising during material synthesis result in a statistically significant inhibition of cell growth on the IOL surfaces.

Erythrocyte Membrane Failure by Electromechanical Stress.

PubMed

Du, E; Qiang, Yuhao; Liu, Jia

2018-01-01

We envision that electrodeformation of biological cells through dielectrophoresis as a new technique to elucidate the mechanistic details underlying membrane failure by electrical and mechanical stresses. Here we demonstrate the full control of cellular uniaxial deformation and tensile recovery in biological cells via amplitude-modified electric field at radio frequency by an interdigitated electrode array in microfluidics. Transient creep and cyclic experiments were performed on individually tracked human erythrocytes. Observations of the viscoelastic-to-viscoplastic deformation behavior and the localized plastic deformations in erythrocyte membranes suggest that electromechanical stress results in irreversible membrane failure. Examples of membrane failure can be separated into different groups according to the loading scenarios: mechanical stiffening, physical damage, morphological transformation from discocyte to echinocyte, and whole cell lysis. These results show that this technique can be potentially utilized to explore membrane failure in erythrocytes affected by other pathophysiological processes.

Modeling autism spectrum disorders with human neurons.

PubMed

Beltrão-Braga, Patricia C B; Muotri, Alysson R

2017-02-01

Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders characterized by impaired social communication and interactions and by restricted and repetitive behaviors. Although ASD is suspected to have a heritable or sporadic genetic basis, its underlying etiology and pathogenesis are not well understood. Therefore, viable human neurons and glial cells produced using induced pluripotent stem cells (iPSC) to reprogram cells from individuals affected with ASD provide an unprecedented opportunity to elucidate the pathophysiology of these disorders, providing novel insights regarding ASD and a potential platform to develop and test therapeutic compounds. Herein, we discuss the state of art with regards to ASD modeling, including limitations of this technology, as well as potential future directions. This article is part of a Special Issue entitled SI: Exploiting human neurons. Copyright © 2016 Elsevier B.V. All rights reserved.

The effect of metal loading on Cd adsorption onto Shewanella oneidensis bacterial cell envelopes: The role of sulfhydryl sites

NASA Astrophysics Data System (ADS)

Yu, Qiang; Fein, Jeremy B.

2015-10-01

The adsorption and desorption of Cd onto Shewanella oneidensis bacterial cells with and without blocking of sulfhydryl sites was measured in order to determine the effect of metal loading and to understand the role of sulfhydryl sites in the adsorption reactions. The observed adsorption/desorption behaviors display strong dependence on metal loading. Under a high loading of 40 μmol Cd/g bacterial cells, blocking the sulfhydryl sites within the cell envelope by exposure of the biomass to monobromo(trimethylammonio)bimane bromide (qBBr) does not significantly affect the extent of Cd adsorption, and we observed fully reversible adsorption under this condition. In contrast, under a low metal loading of 1.3 μmol Cd/g bacterial cells, the extent of Cd adsorption onto sulfhydryl-blocked S. oneidensis cells was significantly lower than that onto untreated cells, and only approximately 50-60% of the adsorbed Cd desorbed from the cells upon acidification. In conjunction with previous EXAFS results, our findings demonstrate that Cd adsorption onto S. oneidensis under low metal loading conditions is dominated by sulfhydryl binding, and thus is controlled by a distinct adsorption mechanism from the non-sulfhydryl site binding which controls Cd adsorption under high metal loading conditions. We use the data to develop a surface complexation model that constrains the values of the stability constants for individual Cd-sulfhydryl and Cd-non-sulfhydryl bacterial complexes, and we use this approach to account for the Cd adsorption behavior as a function of both pH and metal loading. This approach is crucial in order to predict metal adsorption onto bacteria under environmentally relevant metal loading conditions where sulfhydryl binding sites can dominate the adsorption reaction.

Biophysical Regulation of Cell Behavior—Cross Talk between Substrate Stiffness and Nanotopography

PubMed Central

Yang, Yong; Wang, Kai; Gu, Xiaosong; Leong, Kam W.

2017-01-01

The stiffness and nanotopographical characteristics of the extracellular matrix (ECM) influence numerous developmental, physiological, and pathological processes in vivo. These biophysical cues have therefore been applied to modulate almost all aspects of cell behavior, from cell adhesion and spreading to proliferation and differentiation. Delineation of the biophysical modulation of cell behavior is critical to the rational design of new biomaterials, implants, and medical devices. The effects of stiffness and topographical cues on cell behavior have previously been reviewed, respectively; however, the interwoven effects of stiffness and nanotopographical cues on cell behavior have not been well described, despite similarities in phenotypic manifestations. Herein, we first review the effects of substrate stiffness and nanotopography on cell behavior, and then focus on intracellular transmission of the biophysical signals from integrins to nucleus. Attempts are made to connect extracellular regulation of cell behavior with the biophysical cues. We then discuss the challenges in dissecting the biophysical regulation of cell behavior and in translating the mechanistic understanding of these cues to tissue engineering and regenerative medicine. PMID:29071164

Effects of pretransport handling stress on physiological and behavioral response of ostriches.

PubMed

Bejaei, M; Cheng, K M

2014-05-01

Ostrich (Struthio camelus) production is a relatively young industry and there has been little research on ostrich welfare during pretransport handling and the transportation process. A heavy body with a high center of gravity makes ostriches' handling and transportation problems different from other livestock. The main objective of this study was to investigate the effects of the pretransport holding time duration on ostrich behavior and physiological responses. A second objective was to identify and validate behavioral indicator(s) that could be used to identify stressed birds during pretransport handling. Prior to shipping, twenty-four 2.5-yr-old ostriches were moved into a holding pen. Birds were then individually restrained, hooded, and walked from the holding pen (approximately 12 min/bird) to a sampling pen (visually isolated from the holding pen) where they were weighed and a 10-mL blood sample obtained. A second blood sample was taken from each bird after a 1,100-km transportation. Blood samples were analyzed for concentrations of blood metabolites, enzymes, corticosterone, and white blood cell and differential counts. Behavioral responses and physical damages of ostriches were also recorded before and after transport. Results indicated that birds that spent longer time in the pretransport holding pen had higher pretransport plasma concentrations of aspartate aminotransferase, alanine aminotransferase, sodium, and packed cell volume. Immobile sitting behavior, observed in 5 out of the last 11 birds handled, was positively correlated with higher pretransport handling stress, higher posttransport aspartate aminotransferase, alanine aminotransferase, creatine phosphokinase, and glucose concentrations, and transport losses. Knowledge of pretransport handling impacts on ostrich stress and availability of behavioral indicators (e.g., immobile sitting response) could be used to improve handing processes, thereby decreasing potential weight loss, injury, and mortality.

Microfabrication and characterization of an array of dielectric elastomer actuators generating uniaxial strain to stretch individual cells

NASA Astrophysics Data System (ADS)

Akbari, S.; Shea, H. R.

2012-04-01

Cells regulate their behavior in response to mechanical strains. Cell cultures to study mechanotransuction are typically cm2 in area, far too large to monitor single cell response. We have developed an array of dielectric elastomer microactuators as a tool to study mechanotransduction of individual cells. The array consists of 72 100 µm × 200 µm electroactive polymer actuators which expand uniaxially when a voltage is applied. Single cells will be attached on each actuator to study their response to periodic mechanical strains. The device is fabricated by patterning compliant microelectrodes on both sides of a 30 µm thick polydimethylsiloxane membrane, which is bonded to a Pyrex chip with 200 µm wide trenches. Low-energy metal ion implantation is used to make stretchable electrodes and we demonstrate here the successful miniaturization of such ion-implanted electrodes. The top electrode covers the full membrane area, while the bottom electrodes are 100 µm wide parallel lines, perpendicular to the trenches. Applying a voltage between the top and bottom electrodes leads to uniaxial expansion of the membrane at the intersection of the bottom electrodes and the trenches. To characterize the in-plane strain, an array of 4 µm diameter aluminum dots is deposited on each actuator. The position of each dot is tracked, allowing displacement and strain profiles to be measured as a function of voltage. The uniaxial strain reaches 4.7% at 2.9 kV with a 0.2 s response time, sufficient to stimulate most cells with relevant biological strains and frequencies.

Predictive oncology: multidisciplinary, multi-scale in-silico modeling linking phenotype, morphology and growth

PubMed Central

Sanga, Sandeep; Frieboes, Hermann B.; Zheng, Xiaoming; Gatenby, Robert; Bearer, Elaine L.; Cristini, Vittorio

2007-01-01

Empirical evidence and theoretical studies suggest that the phenotype, i.e., cellular- and molecular-scale dynamics, including proliferation rate and adhesiveness due to microenvironmental factors and gene expression that govern tumor growth and invasiveness, also determine gross tumor-scale morphology. It has been difficult to quantify the relative effect of these links on disease progression and prognosis using conventional clinical and experimental methods and observables. As a result, successful individualized treatment of highly malignant and invasive cancers, such as glioblastoma, via surgical resection and chemotherapy cannot be offered and outcomes are generally poor. What is needed is a deterministic, quantifiable method to enable understanding of the connections between phenotype and tumor morphology. Here, we critically review advantages and disadvantages of recent computational modeling efforts (e.g., continuum, discrete, and cellular automata models) that have pursued this understanding. Based on this assessment, we propose and discuss a multi-scale, i.e., from the molecular to the gross tumor scale, mathematical and computational “first-principle” approach based on mass conservation and other physical laws, such as employed in reaction-diffusion systems. Model variables describe known characteristics of tumor behavior, and parameters and functional relationships across scales are informed from in vitro, in vivo and ex vivo biology. We demonstrate that this methodology, once coupled to tumor imaging and tumor biopsy or cell culture data, should enable prediction of tumor growth and therapy outcome through quantification of the relation between the underlying dynamics and morphological characteristics. In particular, morphologic stability analysis of this mathematical model reveals that tumor cell patterning at the tumor-host interface is regulated by cell proliferation, adhesion and other phenotypic characteristics: histopathology information of tumor boundary can be inputted to the mathematical model and used as phenotype-diagnostic tool and thus to predict collective and individual tumor cell invasion of surrounding host. This approach further provides a means to deterministically test effects of novel and hypothetical therapy strategies on tumor behavior. PMID:17629503

Behavioral flexibility in an invasive bird is independent of other behaviors

PubMed Central

2016-01-01

Behavioral flexibility is considered important for a species to adapt to environmental change. However, it is unclear how behavioral flexibility works: it relates to problem solving ability and speed in unpredictable ways, which leaves an open question of whether behavioral flexibility varies with differences in other behaviors. If present, such correlations would mask which behavior causes individuals to vary. I investigated whether behavioral flexibility (reversal learning) performances were linked with other behaviors in great-tailed grackles, an invasive bird. I found that behavioral flexibility did not significantly correlate with neophobia, exploration, risk aversion, persistence, or motor diversity. This suggests that great-tailed grackle performance in behavioral flexibility tasks reflects a distinct source of individual variation. Maintaining multiple distinct sources of individual variation, and particularly variation in behavioral flexibility, may be a mechanism for coping with the diversity of novel elements in their environments and facilitate this species’ invasion success. PMID:27478705

Emergence of Critical Behavior in β-Cell Network

NASA Astrophysics Data System (ADS)

Westacott, Matthew; Hraha, Thomas; McClatchey, Mason; Pozzoli, Marina; Benninger, Richard

2014-03-01

The β-cell is a cell type located in the Islet of Langerhans, a micro-organ of the pancreas which maintains glucose homeostasis through secretion of insulin. An electrophysiological process governing insulin release occurs through initial uptake of blood glucose and generation of ATP which inhibits the ATP sensitive potassium channel (K-ATP) causing membrane depolarization (activation). Neighboring β-cells are electrically coupled through gap junctions which allow passage of cationic molecules, creating a network of coupled electrical oscillators. Cells exhibiting hyperpolzarized (inactive) membrane potential affect behavior of neighboring cells by electrically suppressing their depolarization. Here we observe critical behavior between global active-inactive states by increasing the number of inactive elements with the K-ATP inhibitor Diazoxide and a tunable ATP insensitive transgenic mouse model. We show this behavior occurs due to from cell-cell coupling as mice lacking β-cell gap junctions show no critical behavior. Also, a computational β-cell model was expanded to construct a coupled β-cell network and we show this model replicates the critical behavior seen in-vitro.While electrical activity of single β-cells is well studied these data highlight a newly defined characteristic of their emergent multicellular behavior within the Islet of Langerhans and may elucidate pathophysiology of Diabetes due to mutations in the K-ATP channel.

Cells as strain-cued automata

NASA Astrophysics Data System (ADS)

Cox, Brian N.; Snead, Malcolm L.

2016-02-01

We argue in favor of representing living cells as automata and review demonstrations that autonomous cells can form patterns by responding to local variations in the strain fields that arise from their individual or collective motions. An autonomous cell's response to strain stimuli is assumed to be effected by internally-generated, internally-powered forces, which generally move the cell in directions other than those implied by external energy gradients. Evidence of cells acting as strain-cued automata have been inferred from patterns observed in nature and from experiments conducted in vitro. Simulations that mimic particular cases of pattern forming share the idealization that cells are assumed to pass information among themselves solely via mechanical boundary conditions, i.e., the tractions and displacements present at their membranes. This assumption opens three mechanisms for pattern formation in large cell populations: wavelike behavior, kinematic feedback in cell motility that can lead to sliding and rotational patterns, and directed migration during invasions. Wavelike behavior among ameloblast cells during amelogenesis (the formation of dental enamel) has been inferred from enamel microstructure, while strain waves in populations of epithelial cells have been observed in vitro. One hypothesized kinematic feedback mechanism, "enhanced shear motility", accounts successfully for the spontaneous formation of layered patterns during amelogenesis in the mouse incisor. Directed migration is exemplified by a theory of invader cells that sense and respond to the strains they themselves create in the host population as they invade it: analysis shows that the strain fields contain positional information that could aid the formation of cell network structures, stabilizing the slender geometry of branches and helping govern the frequency of branch bifurcation and branch coalescence (the formation of closed networks). In simulations of pattern formation in homogeneous populations and network formation by invaders, morphological outcomes are governed by the ratio of the rates of two competing time dependent processes, one a migration velocity and the other a relaxation velocity related to the propagation of strain information. Relaxation velocities are approximately constant for different species and organs, whereas cell migration rates vary by three orders of magnitude. We conjecture that developmental processes use rapid cell migration to achieve certain outcomes, and slow migration to achieve others. We infer from analysis of host relaxation during network formation that a transition exists in the mechanical response of a host cell from animate to inanimate behavior when its strain changes at a rate that exceeds 10-4-10-3 s-1. The transition has previously been observed in experiments conducted in vitro.

Active Brownian Particles. From Individual to Collective Stochastic Dynamics

NASA Astrophysics Data System (ADS)

Romanczuk, P.; Bär, M.; Ebeling, W.; Lindner, B.; Schimansky-Geier, L.

2012-03-01

We review theoretical models of individual motility as well as collective dynamics and pattern formation of active particles. We focus on simple models of active dynamics with a particular emphasis on nonlinear and stochastic dynamics of such self-propelled entities in the framework of statistical mechanics. Examples of such active units in complex physico-chemical and biological systems are chemically powered nano-rods, localized patterns in reaction-diffusion system, motile cells or macroscopic animals. Based on the description of individual motion of point-like active particles by stochastic differential equations, we discuss different velocity-dependent friction functions, the impact of various types of fluctuations and calculate characteristic observables such as stationary velocity distributions or diffusion coefficients. Finally, we consider not only the free and confined individual active dynamics but also different types of interaction between active particles. The resulting collective dynamical behavior of large assemblies and aggregates of active units is discussed and an overview over some recent results on spatiotemporal pattern formation in such systems is given.

Antiepileptic Drug Behavioral Side Effects in Individuals with Mental Retardation and the Use of Behavioral Measurement Techniques.

ERIC Educational Resources Information Center

Kalachnik, John E.; And Others

1995-01-01

Behavioral psychology measurement methods helped assess antiepileptic drug behavioral side effects in five individuals with mental retardation who could not verbally communicate presence of side effects. When the suspected antiepileptic drug was altered, an 81% reduction of maladaptive behaviors occurred. The measurement methods enabled systematic…

The Effects of Multi-Sensory Environments on the Stereotypic Behaviors of Children with Autism

ERIC Educational Resources Information Center

Brandenburg, Linda A.

2012-01-01

A significant problem for individuals with autism is the presence of stereotypic behaviors, that is, repetitive, invariant behavior patterns with no obvious goal or function. Stereotypic behaviors interfere with an individual's ability to participate in the daily activities of life, including learning. By reducing stereotypic behaviors in…

The Development of Individual Physically Aggressive Behaviors from Infancy to Toddlerhood

ERIC Educational Resources Information Center

Lorber, Michael F.; Del Vecchio, Tamara; Smith Slep, Amy M.

2018-01-01

In the present investigation, we studied the development of 6 physically aggressive behaviors in infancy and toddlerhood, posing 3 questions (a) How do the prevalences of individual physically aggressive behaviors change from 8, 15, and 24 months? (b) Are there groups of children who show distinctive patterns in the way individual physically…

Adverse Behavioral Effects in Individuals with Mental Retardation and Mood Disorders Treated with Carbamazepine.

ERIC Educational Resources Information Center

Friedman, Debra L.; And Others

1992-01-01

This study with 65 individuals with mental retardation and additional seizure and/or psychiatric or behavioral disorders found that 9.2 percent experienced medication (carbamazepine) side effects, ranging from irritability to mania. More side effects were experienced by individuals with behavioral or psychiatric disorders than by those with an…

Germline disruption of Pten localization causes enhanced sex-dependent social motivation and increased glial production.

PubMed

Tilot, Amanda K; Gaugler, Mary K; Yu, Qi; Romigh, Todd; Yu, Wanfeng; Miller, Robert H; Frazier, Thomas W; Eng, Charis

2014-06-15

PTEN Hamartoma Tumor Syndrome (PHTS) is an autosomal-dominant genetic condition underlying a subset of autism spectrum disorder (ASD) with macrocephaly. Caused by germline mutations in PTEN, PHTS also causes increased risks of multiple cancers via dysregulation of the PI3K and MAPK signaling pathways. Conditional knockout models have shown that neural Pten regulates social behavior, proliferation and cell size. Although much is known about how the intracellular localization of PTEN regulates signaling in cancer cell lines, we know little of how PTEN localization influences normal brain physiology and behavior. To address this, we generated a germline knock-in mouse model of cytoplasm-predominant Pten and characterized its behavioral and cellular phenotypes. The homozygous Pten(m3m4) mice have decreased total Pten levels including a specific drop in nuclear Pten and exhibit region-specific increases in brain weight. The Pten(m3m4) model displays sex-specific increases in social motivation, poor balance and normal recognition memory-a profile reminiscent of some individuals with high functioning ASD. The cytoplasm-predominant protein caused cellular hypertrophy limited to the soma and led to increased NG2 cell proliferation and accumulation of glia. The animals also exhibit significant astrogliosis and microglial activation, indicating a neuroinflammatory phenotype. At the signaling level, Pten(m3m4) mice show brain region-specific differences in Akt activation. These results demonstrate that differing alterations to the same autism-linked gene can cause distinct behavioral profiles. The Pten(m3m4) model is the first murine model of inappropriately elevated social motivation in the context of normal cognition and may expand the range of autism-related behaviors replicated in animal models. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Dynamic fluctuations in single-molecule biophysics experiments. Comment on "Extracting physics of life at the molecular level: A review of single-molecule data analyses" by W. Colomb and S.K. Sarkar

NASA Astrophysics Data System (ADS)

Krapf, Diego

2015-06-01

Single-molecule biophysics includes the study of isolated molecules and that of individual molecules within living cells. In both cases, dynamic fluctuations at the nanoscale play a critical role. Colomb and Sarkar emphasize how different noise sources affect the analysis of single molecule data [1]. Fluctuations in biomolecular systems arise from two very different mechanisms. On one hand thermal fluctuations are a predominant feature in the behavior of individual molecules. On the other hand, non-Gaussian fluctuations can arise from inter- and intramolecular interactions [2], spatial heterogeneities [3], non-Poisson external perturbations [4] and complex non-linear dynamics in general [5,6].

Self Organized Sorting in Swarms

NASA Astrophysics Data System (ADS)

Copenhagen, Katherine; Quint, David; Gopinathan, Ajay

2014-03-01

Swarming behavior extends across multiple length scales in biology ranging from bacteria to whales. Natural swarms are affected by erratic, or dissenting behavior by individuals within the swarm who may display different types of behaviors than the rest of the swarm. This research investigates the introduction of heterogenous behavior amongst individuals within a swarm and their impact on swarm formation and robustness. We model swarms with a finite number of agents utilizing a velocity alignment interaction and a Lennard-Jones potential, which provides both cohesive and repulsive interactions between neighboring agents. Depending on the parameters governing the swarming interactions and the level of heterogeneity in behavior introduced, we found a variety of collective behavior including sharp transitions from swarming to non-swarming regimes and self organized sorting of individuals based on their types of behavior. Our research sheds light on the varied responses of swarms to internal dissent and suggests optimal strategies to tolerate errant individuals.

Behavior of Caulobacter Crescentus Diagnosed Using a 3-Channel Microfluidic Device

NASA Astrophysics Data System (ADS)

Tang, Jay; Morse, Michael; Colin, Remy; Wilson, Laurence

2015-03-01

Many motile microorganisms are able to detect chemical gradients in their surroundings in order to bias their motion towards more favorable conditions. We study the biased motility of Caulobacter crescentus, a singly flagellated bacteria, which alternate between forward and backward swimming, driven by its flagella motor, which switches in rotation direction. We observe the swimming patterns of C. crescents in an oxygen gradient, which is established by flowing atmospheric air and pure nitrogen through a 3 parallel channel microfluidic device. In this setup, oxygen diffuses through the PDMS device and the bacterial medium, creating a linear gradient. Using low magnification, dark field microscopy, individual cells are tracked over a large field of view, with particular interest in the cells' motion relative to the oxygen gradient. Utilizing observable differences between backward and forward swimming motion, motor switching events can be identified. By analyzing these run time intervals between motor switches as a function of a cell's local oxygen level, we demonstrate that C. crescentus displays aerotacitc behavior by extending forward swimming run times while moving up an oxygen gradient, resulting in directed motility towards oxygen sources. Additionally, motor switching response is sensitive to both the steepness of the gradient experienced and background oxygen levels with cells exhibiting a logarithmic response to oxygen levels. Work funded by the United States National Science Foundation and by the Rowland Institute at Harvard University.

Assessing the Feasibility of Smartphone Apps for HIV-Care Research with MSM and Transgender Individuals in Mpumalanga, South Africa.

PubMed

Daniels, Joseph; Lane, Tim; Struthers, Helen; Maleke, Kabelo; Moges, Winta; McIntyre, James; Coates, Thomas

There is an urgent need to develop the HIV treatment cascade for men who have sex with men (MSM) and transgender individuals in rural Mpumalanga, South Africa. Mhealth tools such as smartphone applications have the potential to support HIV self-care behaviors. We conducted an exploratory study with HIV-positive community leaders to understand their current uses of cell phones and smartphones and to assess their interest in an HIV research study that utilized a smartphone application for HIV care support. A total of 18 community leaders were recruited to complete a questionnaire and focus group. We found that a large proportion of participants had smartphone access and were interested in a research study that utilized a smartphone application with secure access measures. We conclude that smartphone applications for HIV care research are feasible based on access and interest by MSM and transgender individuals in this rural setting.

Ex vivo study for the assessment of behavioral factor and gene polymorphisms in individual susceptibility to oxidative DNA damage metals-induced.

PubMed

Di Pietro, Angela; Baluce, Barbara; Visalli, Giuseppa; La Maestra, Sebastiano; Micale, Rosanna; Izzotti, Alberto

2011-06-01

Transition metals in fine particulate matter generated by combustion induce oxidative DNA damage and inflammation. However, there is remarkable inter-individual variability in susceptibility to these damages. To assess this variability, an ex vivo study was performed using lymphocytes of 47 Caucasian healthy subjects. Cell samples were exposed to a water solution of oil fly ash (OFA). This was formed by the distinctive transition metals vanadium, iron, and nickel. Oxidative DNA damage was evaluated by testing cell viability, intracellular ROS production and 8-oxo-dG. DNA fragmentation and DNA repair capacity were assessed by using the Alkaline-Halo assay. GSTM1, GSTT1, hOGG1, and C677T and A1298C MTHFR gene polymorphisms were tested. Demographic and behavioral factors, collected by questionnaire, were also considered. OFA induced damages showed: (a) a 20-fold variation in range among different subjects in ROS production, (b) a 7-fold variation in range of 8-oxo-dG, and (c) a 25-fold variation in range in DNA repair capacity. A significant increase in DNA damage was detected in GSTT1-deficent subjects compared with wild type genotype carriers. Increases in cytoplasmic ROS and decreases in DNA repair capacity (P<0.05) were observed in C677T and A1298C variants of MTHFR. A remarkable protective effect of high fruits and vegetable intake was observed for ROS production and DNA damage. Conversely, an adverse effect of meat intake was observed on ROS increase, DNA damage and repair capacity, probably due to the increased intake of bioavailable iron. Smoking decreased DNA repair capacity, while age increased OFA-induced DNA damage. The wide comparative analysis of the complex interactions network, between genetic and behavioral factors provides evidence of the remarkable role of several lifestyle factors. In comparison to genetic polymorphisms they seem to have a higher weight in determining individual susceptibility to the adverse effects of airborne pollutants as transition metals. Copyright © 2011 Elsevier GmbH. All rights reserved.

Hydrogel Droplet Microfluidics for High-Throughput Single Molecule/Cell Analysis.

PubMed

Zhu, Zhi; Yang, Chaoyong James

2017-01-17

Heterogeneity among individual molecules and cells has posed significant challenges to traditional bulk assays, due to the assumption of average behavior, which would lose important biological information in heterogeneity and result in a misleading interpretation. Single molecule/cell analysis has become an important and emerging field in biological and biomedical research for insights into heterogeneity between large populations at high resolution. Compared with the ensemble bulk method, single molecule/cell analysis explores the information on time trajectories, conformational states, and interactions of individual molecules/cells, all key factors in the study of chemical and biological reaction pathways. Various powerful techniques have been developed for single molecule/cell analysis, including flow cytometry, atomic force microscopy, optical and magnetic tweezers, single-molecule fluorescence spectroscopy, and so forth. However, some of them have the low-throughput issue that has to analyze single molecules/cells one by one. Flow cytometry is a widely used high-throughput technique for single cell analysis but lacks the ability for intercellular interaction study and local environment control. Droplet microfluidics becomes attractive for single molecule/cell manipulation because single molecules/cells can be individually encased in monodisperse microdroplets, allowing high-throughput analysis and manipulation with precise control of the local environment. Moreover, hydrogels, cross-linked polymer networks that swell in the presence of water, have been introduced into droplet microfluidic systems as hydrogel droplet microfluidics. By replacing an aqueous phase with a monomer or polymer solution, hydrogel droplets can be generated on microfluidic chips for encapsulation of single molecules/cells according to the Poisson distribution. The sol-gel transition property endows the hydrogel droplets with new functionalities and diversified applications in single molecule/cell analysis. The hydrogel can act as a 3D cell culture matrix to mimic the extracellular environment for long-term single cell culture, which allows further heterogeneity study in proliferation, drug screening, and metastasis at the single-cell level. The sol-gel transition allows reactions in solution to be performed rapidly and efficiently with product storage in the gel for flexible downstream manipulation and analysis. More importantly, controllable sol-gel regulation provides a new way to maintain phenotype-genotype linkages in the hydrogel matrix for high throughput molecular evolution. In this Account, we will review the hydrogel droplet generation on microfluidics, single molecule/cell encapsulation in hydrogel droplets, as well as the progress made by our group and others in the application of hydrogel droplet microfluidics for single molecule/cell analysis, including single cell culture, single molecule/cell detection, single cell sequencing, and molecular evolution.

Understanding environment-influenced swarm behavior from a social force perspective

NASA Astrophysics Data System (ADS)

Jiang, J.; Lu, D.; Jiang, Y.; Lee, Z.; Zhang, Y.; Yu, J.

2018-02-01

The relevant research on swarm behavior has focused on the facts that when individuals agree with other members in the system globally consistent behaviors are generated and that individual decisions are completely dominated by other members. In fact, when individuals generate their own behavior strategies, they tend to consider not only the influences of other members but also autonomically consider their current environment. For example, in the social foraging of flocks, the behavior strategy of each individual animal is influenced by the food distribution, and individual movement patterns are characterized by a highly efficient search strategy-Lévy walks. To investigate this, this paper proposes using an environment-driven social force perspective to explore the Lévy walks of individuals in a group in patchy food environments. This model adopts the concept of social force to quantify the social effects and the interactions between individuals and food. The coordination between forces is a key in the formation of individual behavior strategies. Our simulation results show a power-law frequency distribution for agent flight lengths that conforms to Lévy walks and verifies the hypothesis of a relationship between food density and the Lévy index. In our model, the flock still exhibits collective consistency and cohesion and yields a high value for the order parameter and population density when moving between food patches. In addition, our model explains the intraspecific cooperation and competition that occurs during foraging as proposed in related work. The simulation also validates the impact of two inducements for individual behaviors compared with several benchmark models.

Brief Report: Developmental Trajectories of Adaptive Behavior in Children and Adolescents with ASD.

PubMed

Meyer, Allison T; Powell, Patrick S; Butera, Nicole; Klinger, Mark R; Klinger, Laura G

2018-03-17

Research suggests that individuals with autism spectrum disorder (ASD) have significant difficulties with adaptive behavior skills including daily living and functional communication skills. Few studies have examined the developmental trajectory of adaptive behavior across childhood and adolescence. The present study examined longitudinal trajectories of adaptive behavior in a community-based clinic sample of 186 individuals with ASD. The overall pattern indicated an initial increase in adaptive behavior during early childhood followed by a plateau in skills during adolescence for individuals of all IQ groups. Given the importance of adaptive behavior for employment and quality of life, this study emphasizes the importance of targeting adaptive behavior during adolescence to insure continued gains.

Individual differences in the peripheral immune system promote resilience versus susceptibility to social stress.

PubMed

Hodes, Georgia E; Pfau, Madeline L; Leboeuf, Marylene; Golden, Sam A; Christoffel, Daniel J; Bregman, Dana; Rebusi, Nicole; Heshmati, Mitra; Aleyasin, Hossein; Warren, Brandon L; Lebonté, Benoit; Horn, Sarah; Lapidus, Kyle A; Stelzhammer, Viktoria; Wong, Erik H F; Bahn, Sabine; Krishnan, Vaishnav; Bolaños-Guzman, Carlos A; Murrough, James W; Merad, Miriam; Russo, Scott J

2014-11-11

Depression and anxiety disorders are associated with increased release of peripheral cytokines; however, their functional relevance remains unknown. Using a social stress model in mice, we find preexisting individual differences in the sensitivity of the peripheral immune system that predict and promote vulnerability to social stress. Cytokine profiles were obtained 20 min after the first social stress exposure. Of the cytokines regulated by stress, IL-6 was most highly up-regulated only in mice that ultimately developed a susceptible behavioral phenotype following a subsequent chronic stress, and levels remained elevated for at least 1 mo. We confirmed a similar elevation of serum IL-6 in two separate cohorts of patients with treatment-resistant major depressive disorder. Before any physical contact in mice, we observed individual differences in IL-6 levels from ex vivo stimulated leukocytes that predict susceptibility versus resilience to a subsequent stressor. To shift the sensitivity of the peripheral immune system to a pro- or antidepressant state, bone marrow (BM) chimeras were generated by transplanting hematopoietic progenitor cells from stress-susceptible mice releasing high IL-6 or from IL-6 knockout (IL-6(-/-)) mice. Stress-susceptible BM chimeras exhibited increased social avoidance behavior after exposure to either subthreshold repeated social defeat stress (RSDS) or a purely emotional stressor termed witness defeat. IL-6(-/-) BM chimeric and IL-6(-/-) mice, as well as those treated with a systemic IL-6 monoclonal antibody, were resilient to social stress. These data establish that preexisting differences in stress-responsive IL-6 release from BM-derived leukocytes functionally contribute to social stress-induced behavioral abnormalities.

A somatic marker perspective of immoral and corrupt behavior.

PubMed

Sobhani, Mona; Bechara, Antoine

2011-01-01

Individuals who engage in corrupt and immoral behavior are in some ways similar to individuals with psychopathy. Normal people refrain from engaging in such behaviors because they tie together the moral value of society and the risk of punishment when they violate social rules. What is it, then, that allows these immoral individuals to behave in this manner, and in some situations even to prosper? When there is a dysfunction of somatic markers, specific disadvantageous impairments in decision-making arise, as in moral judgment, but, paradoxically, under some circumstances, the damage can cause the patient to make optimal financial investment decisions. Interestingly, individuals with psychopathy, a personality disorder, share many of the same behavioral characteristics seen in VMPFC and amygdala lesion patients, suggesting that defective somatic markers may serve as a neural framework for explaining immoral and corrupt behaviors. While these sociopathic behaviors of sometimes famous and powerful individuals have long been discussed, primarily within the realm of social science and psychology, here we offer a neurocognitive perspective on the possible neural roots of immoral and corrupt behaviors.

Planning horizon affects prophylactic decision-making and epidemic dynamics

DOE PAGES

Nardin, Luis G.; Miller, Craig R.; Ridenhour, Benjamin J.; ...

2016-11-08

The spread of infectious diseases can be impacted by human behavior, and behavioral decisions often depend implicitly on a planning horizon?the time in the future over which options are weighed. We investigate the effects of planning horizons on epidemic dynamics. We developed an epidemiological agent-based model (along with an ODE analog) to explore the decision-making of self-interested individuals on adopting prophylactic behavior. The decision-making process incorporates prophylaxis efficacy and disease prevalence with the individuals? payoffs and planning horizon. Our results show that for short and long planning horizons individuals do not consider engaging in prophylactic behavior. In contrast, individuals adoptmore » prophylactic behavior when considering intermediate planning horizons. Such adoption, however, is not always monotonically associated with the prevalence of the disease, depending on the perceived protection efficacy and the disease parameters. Adoption of prophylactic behavior reduces the epidemic peak size while prolonging the epidemic and potentially generates secondary waves of infection. Lastly, these effects can be made stronger by increasing the behavioral decision frequency or distorting an individual's perceived risk of infection.« less

Behavioral and Metabolic Phenotype Indicate Personality in Zebrafish (Danio rerio)

PubMed Central

Yuan, Mingzhe; Chen, Yan; Huang, Yingying; Lu, Weiqun

2018-01-01

Consistency of individual differences of animal behavior and personality in reactions to various environmental stresses among their life stages could reflect basic divergences in coping style which may affect survival, social rank, and reproductive success in the wild. However, the physiological mechanisms determining personality remain poorly understood. In order to study whether behavior, metabolism and physiological stress responses relate to the personality, we employed post-stress recovery assays to separate zebrafish into two behavioral types (proactive and reactive). The results demonstrated consistent difference among personality, behavior and metabolism in which proactive individuals were more aggressive, had higher standard metabolic rates and showed lower shuttled frequencies between dark and light compartments than the reactive ones. The behavioral variations were also linked to divergent acute salinity stress responses: proactive individuals adopted a swift locomotion behavior in response to acute salinity challenge while reactive individuals remain unchanged. Our results provide useful insight into how personality acts on correlated traits and the importance of a holistic approach to understanding the mechanisms driving persistent inter-individual differences. PMID:29899710

Planning horizon affects prophylactic decision-making and epidemic dynamics

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

Nardin, Luis G.; Miller, Craig R.; Ridenhour, Benjamin J.

The spread of infectious diseases can be impacted by human behavior, and behavioral decisions often depend implicitly on a planning horizon?the time in the future over which options are weighed. We investigate the effects of planning horizons on epidemic dynamics. We developed an epidemiological agent-based model (along with an ODE analog) to explore the decision-making of self-interested individuals on adopting prophylactic behavior. The decision-making process incorporates prophylaxis efficacy and disease prevalence with the individuals? payoffs and planning horizon. Our results show that for short and long planning horizons individuals do not consider engaging in prophylactic behavior. In contrast, individuals adoptmore » prophylactic behavior when considering intermediate planning horizons. Such adoption, however, is not always monotonically associated with the prevalence of the disease, depending on the perceived protection efficacy and the disease parameters. Adoption of prophylactic behavior reduces the epidemic peak size while prolonging the epidemic and potentially generates secondary waves of infection. Lastly, these effects can be made stronger by increasing the behavioral decision frequency or distorting an individual's perceived risk of infection.« less

Planning horizon affects prophylactic decision-making and epidemic dynamics.

PubMed

Nardin, Luis G; Miller, Craig R; Ridenhour, Benjamin J; Krone, Stephen M; Joyce, Paul; Baumgaertner, Bert O

2016-01-01

The spread of infectious diseases can be impacted by human behavior, and behavioral decisions often depend implicitly on a planning horizon-the time in the future over which options are weighed. We investigate the effects of planning horizons on epidemic dynamics. We developed an epidemiological agent-based model (along with an ODE analog) to explore the decision-making of self-interested individuals on adopting prophylactic behavior. The decision-making process incorporates prophylaxis efficacy and disease prevalence with the individuals' payoffs and planning horizon. Our results show that for short and long planning horizons individuals do not consider engaging in prophylactic behavior. In contrast, individuals adopt prophylactic behavior when considering intermediate planning horizons. Such adoption, however, is not always monotonically associated with the prevalence of the disease, depending on the perceived protection efficacy and the disease parameters. Adoption of prophylactic behavior reduces the epidemic peak size while prolonging the epidemic and potentially generates secondary waves of infection. These effects can be made stronger by increasing the behavioral decision frequency or distorting an individual's perceived risk of infection.

Estimating peer effects in networks with peer encouragement designs

PubMed Central

Eckles, Dean; Kizilcec, René F.; Bakshy, Eytan

2016-01-01

Peer effects, in which the behavior of an individual is affected by the behavior of their peers, are central to social science. Because peer effects are often confounded with homophily and common external causes, recent work has used randomized experiments to estimate effects of specific peer behaviors. These experiments have often relied on the experimenter being able to randomly modulate mechanisms by which peer behavior is transmitted to a focal individual. We describe experimental designs that instead randomly assign individuals’ peers to encouragements to behaviors that directly affect those individuals. We illustrate this method with a large peer encouragement design on Facebook for estimating the effects of receiving feedback from peers on posts shared by focal individuals. We find evidence for substantial effects of receiving marginal feedback on multiple behaviors, including giving feedback to others and continued posting. These findings provide experimental evidence for the role of behaviors directed at specific individuals in the adoption and continued use of communication technologies. In comparison, observational estimates differ substantially, both underestimating and overestimating effects, suggesting that researchers and policy makers should be cautious in relying on them. PMID:27382145

Individual behavioral phenotypes: an integrative meta-theoretical framework. Why "behavioral syndromes" are not analogs of "personality".

PubMed

Uher, Jana

2011-09-01

Animal researchers are increasingly interested in individual differences in behavior. Their interpretation as meaningful differences in behavioral strategies stable over time and across contexts, adaptive, heritable, and acted upon by natural selection has triggered new theoretical developments. However, the analytical approaches used to explore behavioral data still address population-level phenomena, and statistical methods suitable to analyze individual behavior are rarely applied. I discuss fundamental investigative principles and analytical approaches to explore whether, in what ways, and under which conditions individual behavioral differences are actually meaningful. I elaborate the meta-theoretical ideas underlying common theoretical concepts and integrate them into an overarching meta-theoretical and methodological framework. This unravels commonalities and differences, and shows that assumptions of analogy to concepts of human personality are not always warranted and that some theoretical developments may be based on methodological artifacts. Yet, my results also highlight possible directions for new theoretical developments in animal behavior research. Copyright © 2011 Wiley Periodicals, Inc.

An opinion-driven behavioral dynamics model for addictive behaviors

NASA Astrophysics Data System (ADS)

Moore, Thomas W.; Finley, Patrick D.; Apelberg, Benjamin J.; Ambrose, Bridget K.; Brodsky, Nancy S.; Brown, Theresa J.; Husten, Corinne; Glass, Robert J.

2015-04-01

We present a model of behavioral dynamics that combines a social network-based opinion dynamics model with behavioral mapping. The behavioral component is discrete and history-dependent to represent situations in which an individual's behavior is initially driven by opinion and later constrained by physiological or psychological conditions that serve to maintain the behavior. Individuals are modeled as nodes in a social network connected by directed edges. Parameter sweeps illustrate model behavior and the effects of individual parameters and parameter interactions on model results. Mapping a continuous opinion variable into a discrete behavioral space induces clustering on directed networks. Clusters provide targets of opportunity for influencing the network state; however, the smaller the network the greater the stochasticity and potential variability in outcomes. This has implications both for behaviors that are influenced by close relationships verses those influenced by societal norms and for the effectiveness of strategies for influencing those behaviors.

Behavior and emotional disturbance in Prader-Willi syndrome.

PubMed

Einfeld, S L; Smith, A; Durvasula, S; Florio, T; Tonge, B J

1999-01-15

To determine if persons with the Prader-Willi syndrome (PWS) have increased psychopathology when compared with matched controls, and whether there is a specific behavior phenotype in PWS, the behavior of 46 persons with PWS was compared with that of control individuals derived from a community sample (N = 454) of persons with mental retardation (MR). Behaviors were studied using the Developmental Behaviour Checklist, an instrument of established validity in the evaluation of behavioral disturbance in individuals with MR. PWS subjects were found to be more behaviorally disturbed than controls overall, and especially in antisocial behavior. In addition, some individual behaviors were more common in PWS subjects than controls. When these behaviors are considered together with findings from other studies using acceptably rigorous methods, a consensus behavior phenotype for PWS can be formulated. This will provide a valid foundation for studies of the mechanism of genetic pathogenesis of behavior in PWS.

Abnormal melatonin synthesis in autism spectrum disorders.

PubMed

Melke, J; Goubran Botros, H; Chaste, P; Betancur, C; Nygren, G; Anckarsäter, H; Rastam, M; Ståhlberg, O; Gillberg, I C; Delorme, R; Chabane, N; Mouren-Simeoni, M-C; Fauchereau, F; Durand, C M; Chevalier, F; Drouot, X; Collet, C; Launay, J-M; Leboyer, M; Gillberg, C; Bourgeron, T

2008-01-01

Melatonin is produced in the dark by the pineal gland and is a key regulator of circadian and seasonal rhythms. A low melatonin level has been reported in individuals with autism spectrum disorders (ASD), but the underlying cause of this deficit was unknown. The ASMT gene, encoding the last enzyme of melatonin synthesis, is located on the pseudo-autosomal region 1 of the sex chromosomes, deleted in several individuals with ASD. In this study, we sequenced all ASMT exons and promoters in individuals with ASD (n=250) and compared the allelic frequencies with controls (n=255). Non-conservative variations of ASMT were identified, including a splicing mutation present in two families with ASD, but not in controls. Two polymorphisms located in the promoter (rs4446909 and rs5989681) were more frequent in ASD compared to controls (P=0.0006) and were associated with a dramatic decrease in ASMT transcripts in blood cell lines (P=2 x 10(-10)). Biochemical analyses performed on blood platelets and/or cultured cells revealed a highly significant decrease in ASMT activity (P=2 x 10(-12)) and melatonin level (P=3 x 10(-11)) in individuals with ASD. These results indicate that a low melatonin level, caused by a primary deficit in ASMT activity, is a risk factor for ASD. They also support ASMT as a susceptibility gene for ASD and highlight the crucial role of melatonin in human cognition and behavior.

Brain mast cells link the immune system to anxiety-like behavior

PubMed Central

Nautiyal, Katherine M.; Ribeiro, Ana C.; Pfaff, Donald W.; Silver, Rae

2008-01-01

Mast cells are resident in the brain and contain numerous mediators, including neurotransmitters, cytokines, and chemokines, that are released in response to a variety of natural and pharmacological triggers. The number of mast cells in the brain fluctuates with stress and various behavioral and endocrine states. These properties suggest that mast cells are poised to influence neural systems underlying behavior. Using genetic and pharmacological loss-of-function models we performed a behavioral screen for arousal responses including emotionality, locomotor, and sensory components. We found that mast cell deficient KitW−sh/W−sh (sash−/−) mice had a greater anxiety-like phenotype than WT and heterozygote littermate control animals in the open field arena and elevated plus maze. Second, we show that blockade of brain, but not peripheral, mast cell activation increased anxiety-like behavior. Taken together, the data implicate brain mast cells in the modulation of anxiety-like behavior and provide evidence for the behavioral importance of neuroimmune links. PMID:19004805

Brain mast cells link the immune system to anxiety-like behavior.

PubMed

Nautiyal, Katherine M; Ribeiro, Ana C; Pfaff, Donald W; Silver, Rae

2008-11-18

Mast cells are resident in the brain and contain numerous mediators, including neurotransmitters, cytokines, and chemokines, that are released in response to a variety of natural and pharmacological triggers. The number of mast cells in the brain fluctuates with stress and various behavioral and endocrine states. These properties suggest that mast cells are poised to influence neural systems underlying behavior. Using genetic and pharmacological loss-of-function models we performed a behavioral screen for arousal responses including emotionality, locomotor, and sensory components. We found that mast cell deficient Kit(W-sh/W-sh) (sash(-/-)) mice had a greater anxiety-like phenotype than WT and heterozygote littermate control animals in the open field arena and elevated plus maze. Second, we show that blockade of brain, but not peripheral, mast cell activation increased anxiety-like behavior. Taken together, the data implicate brain mast cells in the modulation of anxiety-like behavior and provide evidence for the behavioral importance of neuroimmune links.

Long-term in vivo single-cell tracking reveals the switch of migration patterns in adult-born juxtaglomerular cells of the mouse olfactory bulb

PubMed Central

Liang, Yajie; Li, Kaizhen; Riecken, Kristoffer; Maslyukov, Anatoliy; Gomez-Nicola, Diego; Kovalchuk, Yury; Fehse, Boris; Garaschuk, Olga

2016-01-01

The behavior of adult-born cells can be easily monitored in cell culture or in lower model organisms, but longitudinal observation of individual mammalian adult-born cells in their native microenvironment still proves to be a challenge. Here we have established an approach named optical cell positioning system for long-term in vivo single-cell tracking, which integrates red-green-blue cell labeling with repeated angiography. By combining this approach with in vivo two-photon imaging technique, we characterized the in vivo migration patterns of adult-born neurons in the olfactory bulb. In contrast to the traditional view of mere radial migration of adult-born cells within the bulb, we found that juxtaglomerular cells switch from radial migration to long distance lateral migration upon arrival in their destination layer. This unique long-distance lateral migration has characteristic temporal (stop-and-go) and spatial (migratory, unidirectional or multidirectional) patterns, with a clear cell age-dependent decrease in the migration speed. The active migration of adult-born cells coincides with the time period of initial fate determination and is likely to impact on the integration sites of adult-born cells, their odor responsiveness, as well as their survival rate. PMID:27174051

Traffic jam functions in a branched pathway from Notch activation to niche cell fate.

PubMed

Wingert, Lindsey; DiNardo, Stephen

2015-07-01

The niche directs key behaviors of its resident stem cells, and is thus crucial for tissue maintenance, repair and longevity. However, little is known about the genetic pathways that guide niche specification and development. The male germline stem cell niche in Drosophila houses two stem cell populations and is specified within the embryonic gonad, thus making it an excellent model for studying niche development. The hub cells that form the niche are specified early by Notch activation. Over the next few hours, these individual cells then cluster together and take up a defined position before expressing markers of hub cell differentiation. This timing suggests that there are other factors for niche development yet to be defined. Here, we have identified a role for the large Maf transcription factor Traffic jam (Tj) in hub cell specification downstream of Notch. Tj downregulation is the first detectable effect of Notch activation in hub cells. Furthermore, Tj depletion is sufficient to generate ectopic hub cells that can recruit stem cells. Surprisingly, ectopic niche cells in tj mutants remain dispersed in the absence of Notch activation. This led us to uncover a branched pathway downstream of Notch in which Bowl functions to direct hub cell assembly in parallel to Tj downregulation. © 2015. Published by The Company of Biologists Ltd.

Examining exercise dependence symptomatology from a self-determination perspective.

PubMed

Edmunds, Jemma; Ntoumanis, Nikos; Duda, Joan L

2006-11-01

Background Pulling from Self-Determination Theory (SDT; Deci & Ryan, 1985), this study examined whether individuals classified as 'nondependent-symptomatic' and 'nondependent-asymptomatic' for exercise dependence differed in terms of reported levels of exercise-related psychological need satisfaction, self-determined versus controlling motivation and exercise behavior. In addition, we examined the type of motivational regulations predicting exercise behavior among these different groups, and their role as mediators between psychological need satisfaction and behavioral outcomes. Methods Participants (N = 339) completed measures of exercise-specific psychological need satisfaction, motivational regulations, exercise behavior and exercise dependence. Results Nondependent-symptomatic individuals reported higher levels of competence need satisfaction and all forms of motivational regulation, compared to nondependent-asymptomatic individuals. Introjected regulation approached significance as a positive predictor of strenuous exercise behavior for symptomatic individuals. Identified regulation was a positive predictor of strenuous exercise, and completely mediated the relationship between competence need satisfaction and strenuous exercise behavior, for asymptomatic individuals. Conclusions The findings reinforce the applicability of SDT to understanding the quantity and quality of engagement in exercise.

Impacts of opinion leaders on social contagions

NASA Astrophysics Data System (ADS)

Liu, Quan-Hui; Lü, Feng-Mao; Zhang, Qian; Tang, Ming; Zhou, Tao

2018-05-01

Opinion leaders are ubiquitous in both online and offline social networks, but the impacts of opinion leaders on social behavior contagions are still not fully understood, especially by using a mathematical model. Here, we generalize the classical Watts threshold model and address the influences of the opinion leaders, where an individual adopts a new behavior if one of his/her opinion leaders adopts the behavior. First, we choose the opinion leaders randomly from all individuals in the network and find that the impacts of opinion leaders make other individuals adopt the behavior more easily. Specifically, the existence of opinion leaders reduces the lowest mean degree of the network required for the global behavior adoption and increases the highest mean degree of the network that the global behavior adoption can occur. Besides, the introduction of opinion leaders accelerates the behavior adoption but does not change the adoption order of individuals. The developed theoretical predictions agree with the simulation results. Second, we randomly choose the opinion leaders from the top h % of the highest degree individuals and find an optimal h % for the network with the lowest mean degree that the global behavior adoption can occur. Meanwhile, the influences of opinion leaders on accelerating the adoption of behaviors become less significant and can even be ignored when reducing the value of h % .

A cell culture technique for human epiretinal membranes to describe cell behavior and membrane contraction in vitro.

PubMed

Wertheimer, Christian; Eibl-Lindner, Kirsten H; Compera, Denise; Kueres, Alexander; Wolf, Armin; Docheva, Denitsa; Priglinger, Siegfried G; Priglinger, Claudia; Schumann, Ricarda G

2017-11-01

To introduce a human cell culture technique for investigating in-vitro behavior of primary epiretinal cells and membrane contraction of fibrocellular tissue surgically removed from eyes with idiopathic macular pucker. Human epiretinal membranes were harvested from ten eyes with idiopathic macular pucker during standard vitrectomy. Specimens were fixed on cell culture plastic using small entomological pins to apply horizontal stress to the tissue, and then transferred to standard cell culture conditions. Cell behavior of 400 epiretinal cells from 10 epiretinal membranes was observed in time-lapse microscopy and analyzed in terms of cell migration, cell velocity, and membrane contraction. Immunocytochemistry was performed for cell type-specific antigens. Cell specific differences in migration behavior were observed comprising two phenotypes: (PT1) epiretinal cells moving fast, less directly, with small round phenotype and (PT2) epiretinal cells moving slowly, directly, with elongated large phenotype. No mitosis, no outgrowth and no migration onto the plastic were seen. Horizontal contraction measurements showed variation between specimens. Masses of epiretinal cells with a myofibroblast-like phenotype expressed cytoplasmatic α-SMA stress fibers and correlated with cell behavior characteristics (PT2). Fast moving epiretinal cells (PT1) were identified as microglia by immunostaining. This in-vitro technique using traction application allows for culturing surgically removed epiretinal membranes from eyes with idiopathic macular pucker, demonstrating cell behavior and membrane contraction of primary human epiretinal cells. Our findings emphasize the abundance of myofibroblasts, the presence of microglia and specific differences of cell behavior in these membranes. This technique has the potential to improve the understanding of pathologies at the vitreomacular interface and might be helpful in establishing anti-fibrotic treatment strategies.

Usual Populations, Unusual Individuals: Insights into the Behavior and Management of Asian Elephants in Fragmented Landscapes

PubMed Central

Srinivasaiah, Nishant M.; Vaidyanathan, Srinivas; Sinha, Anindya

2012-01-01

Background A dearth in understanding the behavior of Asian elephants (Elephas maximus) at the scale of populations and individuals has left important management issues, particularly related to human-elephant conflict (HEC), unresolved. Evaluation of differences in behavior and decision-making among individual elephants across groups in response to changing local ecological settings is essential to fill this gap in knowledge and to improve our approaches towards the management and conservation of elephants. Methodology/Principal Findings We hypothesized certain behavioral decisions that would be made by Asian elephants as reflected in their residence time and movement rates, time-activity budgets, social interactions and group dynamics in response to resource availability and human disturbance in their habitat. This study is based on 200 h of behavioral observations on 60 individually identified elephants and a 184-km2 grid-based survey of their natural and anthropogenic habitats within and outside the Bannerghatta National Park, southern India during the dry season. At a general population level, the behavioral decisions appeared to be guided by the gender, age and group-type of the elephants. At the individual level, the observed variation could be explained only by the idiosyncratic behaviors of individuals and that of their associating conspecific individuals. Recursive partitioning classification trees for residence time of individual elephants indicated that the primary decisions were taken by individuals, independently of their above-mentioned biological and ecological attributes. Conclusions/Significance Decision-making by Asian elephants thus appears to be determined at two levels, that of the population and, more importantly, the individual. Models based on decision-making by individual elephants have the potential to predict conflict in fragmented landscapes that, in turn, could aid in mitigating HEC. Thus, we must target individuals, in addition to populations, in our efforts to manage and conserve this threatened species, particularly in human-dominated landscapes. PMID:22916135

Usual populations, unusual individuals: insights into the behavior and management of Asian elephants in fragmented landscapes.

PubMed

Srinivasaiah, Nishant M; Anand, Vijay D; Vaidyanathan, Srinivas; Sinha, Anindya

2012-01-01

A dearth in understanding the behavior of Asian elephants (Elephas maximus) at the scale of populations and individuals has left important management issues, particularly related to human-elephant conflict (HEC), unresolved. Evaluation of differences in behavior and decision-making among individual elephants across groups in response to changing local ecological settings is essential to fill this gap in knowledge and to improve our approaches towards the management and conservation of elephants. We hypothesized certain behavioral decisions that would be made by Asian elephants as reflected in their residence time and movement rates, time-activity budgets, social interactions and group dynamics in response to resource availability and human disturbance in their habitat. This study is based on 200 h of behavioral observations on 60 individually identified elephants and a 184-km(2) grid-based survey of their natural and anthropogenic habitats within and outside the Bannerghatta National Park, southern India during the dry season. At a general population level, the behavioral decisions appeared to be guided by the gender, age and group-type of the elephants. At the individual level, the observed variation could be explained only by the idiosyncratic behaviors of individuals and that of their associating conspecific individuals. Recursive partitioning classification trees for residence time of individual elephants indicated that the primary decisions were taken by individuals, independently of their above-mentioned biological and ecological attributes. Decision-making by Asian elephants thus appears to be determined at two levels, that of the population and, more importantly, the individual. Models based on decision-making by individual elephants have the potential to predict conflict in fragmented landscapes that, in turn, could aid in mitigating HEC. Thus, we must target individuals, in addition to populations, in our efforts to manage and conserve this threatened species, particularly in human-dominated landscapes.

Behavioral differences among subjects with Prader-Willi syndrome and type I or type II deletion and maternal disomy.

PubMed

Butler, Merlin G; Bittel, Douglas C; Kibiryeva, Nataliya; Talebizadeh, Zohreh; Thompson, Travis

2004-03-01

To determine whether phenotypic differences exist among individuals with Prader-Willi syndrome with either type I or type II deletions of chromosome 15 or maternal disomy 15 leading to a better understanding of cause and pathophysiology of this classical genetic syndrome. We analyzed clinical, anthropometric, and behavioral data in 12 individuals (5 men, 7 women; mean age: 25.9 +/- 8.8 years) with PWS and a type I (TI) deletion, 14 individuals (6 men, 8 women; mean age: 19.6 +/- 6.5 years) with PWS and a type II (TII) deletion, and 21 individuals (10 men, 11 women; mean age: 23.6 +/- 9.2 years) with PWS and maternal disomy 15 (UPD). The deletion type was determined by genotyping of DNA markers between proximal chromosome 15 breakpoints BP1 and BP2. TI deletions are approximately 500 kb larger than TII deletions. Several validated psychological and behavioral tests were used to assess phenotypic characteristics of individuals with PWS representing the 3 genetic subtypes. Significant differences were found between the 2 deletion groups and those with UPD in multiple psychological and behavioral tests, but no differences were observed in other clinical or anthropometric data studied. Adaptive behavior scores were generally worse in individuals with PWS and the TI deletion, and specific obsessive-compulsive behaviors were more evident in the TI individuals compared with those with UPD. Individuals with PWS with TI deletions also had poorer reading and math skills as well as visual-motor integration. Our study indicates that individuals with TI deletion generally have more behavioral and psychological problems than individuals with the TII deletion or UPD. Four recently identified genes have been identified in the chromosome region between BP1 and BP2 with 1 of the genes (NIPA-1) expressed in mouse brain tissue but not thought to be imprinted. It may be important for brain development or function. These genes are deleted in individuals with TI deletion and are implicated in compulsive behavior and lower intellectual ability in individuals with TI versus TII.

Cell Phone-Related Near Accidents Among Young Drivers: Associations With Mindfulness.

PubMed

Terry, Christopher P; Terry, Danielle L

2015-01-01

Cell phone use while driving (CPWD) has been shown to significantly reduce driver safety. This is a particular concern among young drivers who possess less driving experience and tend to engage in high rates of cell phone use. The present study identified psychological predictors of near accidents related to CPWD among a sample of 385 college student drivers. Participants answered a series of questions regarding their use of a cell phone while driving and completed measures of mindfulness, polychronicity, and intrusive thinking. Students who reported talking on their phone or texting more frequently while driving reported a higher incidence of near accidents related to each behavior. However, after controlling for CPWD, multiple regression analysis indicated that those who reported experiencing more cell phone-related intrusive thoughts also experienced more near accidents. Furthermore, two facets of mindfulness--acting with awareness and nonjudging of inner experience--were negatively associated with near accidents. These findings suggest that individuals who are more aware of the present moment and accepting of their affective responses may better regulate their attention while using a cell phone behind the wheel.

2D and 3D Stem Cell Models of Primate Cortical Development Identify Species-Specific Differences in Progenitor Behavior Contributing to Brain Size.

PubMed

Otani, Tomoki; Marchetto, Maria C; Gage, Fred H; Simons, Benjamin D; Livesey, Frederick J

2016-04-07

Variation in cerebral cortex size and complexity is thought to contribute to differences in cognitive ability between humans and other animals. Here we compare cortical progenitor cell output in humans and three nonhuman primates using directed differentiation of pluripotent stem cells (PSCs) in adherent two-dimensional (2D) and organoid three-dimensional (3D) culture systems. Clonal lineage analysis showed that primate cortical progenitors proliferate for a protracted period of time, during which they generate early-born neurons, in contrast to rodents, where this expansion phase largely ceases before neurogenesis begins. The extent of this additional cortical progenitor expansion differs among primates, leading to differences in the number of neurons generated by each progenitor cell. We found that this mechanism for controlling cortical size is regulated cell autonomously in culture, suggesting that primate cerebral cortex size is regulated at least in part at the level of individual cortical progenitor cell clonal output. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Adaptive Behavior Ratings Correlate with Symptomatology and IQ among Individuals with High-Functioning Autism Spectrum Disorders

ERIC Educational Resources Information Center

Kenworthy, Lauren; Case, Laura; Harms, Madeline B.; Martin, Alex; Wallace, Gregory L.

2010-01-01

Caregiver report on the Adaptive Behavior Assessment System-II (ABAS) for 40 high-functioning individuals with Autism Spectrum Disorders (ASD) and 30 typically developing (TD) individuals matched for age, IQ, and sex ratio revealed global adaptive behavior deficits in ASD, with social skills impairments particularly prominent. Within the ASD…

Phenotypic Heterogeneity in Attachment of Marine Bacteria toward Antifouling Copolymers Unraveled by AFM.

PubMed

El-Kirat-Chatel, Sofiane; Puymege, Aurore; Duong, The H; Van Overtvelt, Perrine; Bressy, Christine; Belec, Lénaïk; Dufrêne, Yves F; Molmeret, Maëlle

2017-01-01

Up to recent years, bacterial adhesion has mostly been evaluated at the population level. Single cell level has improved in the past few years allowing a better comprehension of the implication of individual behaviors as compared to the one of a whole community. A new approach using atomic force microscopy (AFM) to measure adhesion forces between a live bacterium attached via a silica microbead to the AFM tipless cantilever and the surface has been recently developed. The objectives of this study is to examine the bacterial adhesion to a surface dedicated to ship hulls at the population and the cellular level to understand to what extent these two levels could be correlated. Adhesion of marine bacteria on inert surfaces are poorly studied in particular when substrata are dedicated to ship hulls. Studying these interactions in this context are worthwhile as they may involve different adhesion behaviors, taking place in salty conditions, using different surfaces than the ones usually utilized in the literacy. FRC (fouling release coatings)-SPC (self-polishing coatings) hybrids antifouling coatings have been used as substrata and are of particular interest for designing environmentally friendly surfaces, combining progressive surface erosion and low adhesion properties. In this study, a hybrid coating has been synthetized and used to study the adhesion of three marine bacteria, displaying different surface characteristics, using microplate assays associated with confocal scanning laser microscopy (CSLM) and AFM. This study shows that the bacterial strain that appeared to have the weakest adhesion and biofilm formation abilities when evaluated at the population level using microplates assays and CSLM, displayed stronger adhesion forces on the same surfaces at the single cell level using AFM. In addition, one of the strains tested which presented a strong ability to adhere and to form biofilm at the population level, displayed a heterogeneous phenotypic behavior at the single cell level. Therefore, these results suggest that the evaluation of adhesion at the population level cannot always be correlated with adhesion forces measured individually by AFM and that some bacteria are prone to phenotypic heterogeneity among their population.

Monitoring the diffusion behavior of Na,K-ATPase by fluorescence correlation spectroscopy (FCS) upon fluorescence labelling with eGFP or Dreiklang

NASA Astrophysics Data System (ADS)

Junghans, Cornelia; Schmitt, Franz-Josef; Vukojević, Vladana; Friedrich, Thomas

2016-02-01

Measurement of lateral mobility of membraneembedded proteins in living cells with high spatial and temporal precision is a challenging task of optofluidics. Biological membranes are complex structures, whose physico-chemical properties depend on the local lipid composition, cholesterol content and the presence of integral or peripheral membrane proteins, which may be involved in supramolecular complexes or are linked to cellular matrix proteins or the cytoskeleton. The high proteinto- lipid ratios in biomembranes indicate that membrane proteins are particularly subject to molecular crowding, making it difficult to follow the track of individual molecules carrying a fluorescence label. Novel switchable fluorescence proteins such as Dreiklang [1], are, in principle, promising tools to study the diffusion behavior of individual molecules in situations of molecular crowding due to excellent spectral control of the ON- and OFF-switching process. In this work, we expressed an integral membrane transport protein, the Na,K-ATPase comprising the human α2-subunit carrying an N-terminal eGFP or Dreiklang tag and human β1-subunit, in HEK293T cells and measured autocorrelation curves by fluorescence correlation spectroscopy (FCS). Furthermore,we measured diffusion times and diffusion constants of eGFP and Dreiklang by FCS, first, in aqueous solution after purification of the proteins upon expression in E. coli, and, second, upon expression as soluble proteins in the cytoplasm of HEK293T cells. Our data show that the diffusion behavior of the purified eGFP and Dreiklang in solution as well as the properties of the proteins expressed in the cytoplasm are very similar. However, the autocorrelation curves of eGFP- and Dreiklanglabeled Na,K-ATPase measured in the plasma membrane exhibit marked differences, with the Dreiklang-labeled construct showing shorter diffusion times. This may be related to an additional, as yet unrecognized quenching process that occurs on the same time scale as the diffusion of the labeled complexes through the detection volume (1- 100 ms). Since the origin of this quenching process is currently unclear, care has to be taken when the Dreiklang label is intended to be used in FCS applications.

Monitoring the diffusion behavior of Na,K-ATPase by fluorescence correlation spectroscopy (FCS) upon fluorescence labelling with eGFP or Dreiklang

NASA Astrophysics Data System (ADS)

Junghans, Cornelia; Schmitt, Franz-Josef; Vukojević, Vladana; Friedrich, Thomas

2015-12-01

Measurement of lateral mobility of membraneembedded proteins in living cells with high spatial and temporal precision is a challenging task of optofluidics. Biological membranes are complex structures, whose physico-chemical properties depend on the local lipid composition, cholesterol content and the presence of integral or peripheral membrane proteins, which may be involved in supramolecular complexes or are linked to cellular matrix proteins or the cytoskeleton. The high proteinto- lipid ratios in biomembranes indicate that membrane proteins are particularly subject to molecular crowding, making it difficult to follow the track of individual molecules carrying a fluorescence label. Novel switchable fluorescence proteins such as Dreiklang [1], are, in principle, promising tools to study the diffusion behavior of individual molecules in situations of molecular crowding due to excellent spectral control of the ON- and OFF-switching process. In this work, we expressed an integral membrane transport protein, the Na,K-ATPase comprising the human α2-subunit carrying an N-terminal eGFP or Dreiklang tag and human β1-subunit, in HEK293T cells and measured autocorrelation curves by fluorescence correlation spectroscopy (FCS). Furthermore,we measured diffusion times and diffusion constants of eGFP and Dreiklang by FCS, first, in aqueous solution after purification of the proteins upon expression in E. coli, and, second, upon expression as soluble proteins in the cytoplasm of HEK293T cells. Our data show that the diffusion behavior of the purified eGFP and Dreiklang in solution as well as the properties of the proteins expressed in the cytoplasm are very similar. However, the autocorrelation curves of eGFP- and Dreiklanglabeled Na,K-ATPase measured in the plasma membrane exhibit marked differences, with the Dreiklang-labeled construct showing shorter diffusion times. This may be related to an additional, as yet unrecognized quenching process that occurs on the same time scale as the diffusion of the labeled complexes through the detection volume (1- 100 ms). Since the origin of this quenching process is currently unclear, care has to be taken when the Dreiklang label is intended to be used in FCS applications.

Mapping sleeping bees within their nest: spatial and temporal analysis of worker honey bee sleep.

PubMed

Klein, Barrett Anthony; Stiegler, Martin; Klein, Arno; Tautz, Jürgen

2014-01-01

Patterns of behavior within societies have long been visualized and interpreted using maps. Mapping the occurrence of sleep across individuals within a society could offer clues as to functional aspects of sleep. In spite of this, a detailed spatial analysis of sleep has never been conducted on an invertebrate society. We introduce the concept of mapping sleep across an insect society, and provide an empirical example, mapping sleep patterns within colonies of European honey bees (Apis mellifera L.). Honey bees face variables such as temperature and position of resources within their colony's nest that may impact their sleep. We mapped sleep behavior and temperature of worker bees and produced maps of their nest's comb contents as the colony grew and contents changed. By following marked bees, we discovered that individuals slept in many locations, but bees of different worker castes slept in different areas of the nest relative to position of the brood and surrounding temperature. Older worker bees generally slept outside cells, closer to the perimeter of the nest, in colder regions, and away from uncapped brood. Younger worker bees generally slept inside cells and closer to the center of the nest, and spent more time asleep than awake when surrounded by uncapped brood. The average surface temperature of sleeping foragers was lower than the surface temperature of their surroundings, offering a possible indicator of sleep for this caste. We propose mechanisms that could generate caste-dependent sleep patterns and discuss functional significance of these patterns.

Morphology and dynamics of tumor cell colonies propagating in epidermal growth factor supplemented media

NASA Astrophysics Data System (ADS)

Muzzio, N. E.; Carballido, M.; Pasquale, M. A.; González, P. H.; Azzaroni, O.; Arvia, A. J.

2018-07-01

The epidermal growth factor (EGF) plays a key role in physiological and pathological processes. This work reports on the influence of EGF concentration (c EGF) on the modulation of individual cell phenotype and cell colony kinetics with the aim of perturbing the colony front roughness fluctuations. For this purpose, HeLa cell colonies that remain confluent along the whole expansion process with initial quasi-radial geometry and different initial cell populations, as well as colonies with initial quasi-linear geometry and large cell population, are employed. Cell size and morphology as well as its adhesive characteristics depend on c EGF. Quasi-radial colonies (QRC) expansion kinetics in EGF-containing medium exhibits a complex behavior. Namely, at the first stages of growth, the average QRC radius evolution can be described by a t 1/2 diffusion term coupled with exponential growth kinetics up to a critical time, and afterwards a growth regime approaching constant velocity. The extension of each regime depends on c EGF and colony history. In the presence of EGF, the initial expansion of quasi-linear colonies (QLCs) also exhibits morphological changes at both the cell and the colony levels. In these cases, the cell density at the colony border region becomes smaller than in the absence of EGF and consequently, the extension of the effective rim where cell duplication and motility contribute to the colony expansion increases. QLC front displacement velocity increases with c EGF up to a maximum value in the 2–10 ng ml‑1 range. Individual cell velocity is increased by EGF, and an enhancement in both the persistence and the ballistic characteristics of cell trajectories can be distinguished. For an intermediate c EGF, collective cell displacements contribute to the roughening of the colony contours. This global dynamics becomes compatible with the standard Kardar–Parisi–Zhang growth model, although a faster colony roughness saturation in EGF-containing medium than in the control medium is observed.

Diffusion of Responsibility and Extreme Behavior.

ERIC Educational Resources Information Center

Mathes, Eugene W.; Kahn, Arnold

The results of this investigation support, in part, the diffusion of responsibility hypothesis which states that antisocial behavior will occur whenever individuals are motivated to engage in socially-unacceptable behavior, and find themselves in a group of similarly motivated individuals. The mechanism by which this antisocial behavior is…

Revealing the hidden networks of interaction in mobile animal groups allows prediction of complex behavioral contagion.

PubMed

Rosenthal, Sara Brin; Twomey, Colin R; Hartnett, Andrew T; Wu, Hai Shan; Couzin, Iain D

2015-04-14

Coordination among social animals requires rapid and efficient transfer of information among individuals, which may depend crucially on the underlying structure of the communication network. Establishing the decision-making circuits and networks that give rise to individual behavior has been a central goal of neuroscience. However, the analogous problem of determining the structure of the communication network among organisms that gives rise to coordinated collective behavior, such as is exhibited by schooling fish and flocking birds, has remained almost entirely neglected. Here, we study collective evasion maneuvers, manifested through rapid waves, or cascades, of behavioral change (a ubiquitous behavior among taxa) in schooling fish (Notemigonus crysoleucas). We automatically track the positions and body postures, calculate visual fields of all individuals in schools of ∼150 fish, and determine the functional mapping between socially generated sensory input and motor response during collective evasion. We find that individuals use simple, robust measures to assess behavioral changes in neighbors, and that the resulting networks by which behavior propagates throughout groups are complex, being weighted, directed, and heterogeneous. By studying these interaction networks, we reveal the (complex, fractional) nature of social contagion and establish that individuals with relatively few, but strongly connected, neighbors are both most socially influential and most susceptible to social influence. Furthermore, we demonstrate that we can predict complex cascades of behavioral change at their moment of initiation, before they actually occur. Consequently, despite the intrinsic stochasticity of individual behavior, establishing the hidden communication networks in large self-organized groups facilitates a quantitative understanding of behavioral contagion.

Revealing the hidden networks of interaction in mobile animal groups allows prediction of complex behavioral contagion

PubMed Central

Rosenthal, Sara Brin; Twomey, Colin R.; Hartnett, Andrew T.; Wu, Hai Shan; Couzin, Iain D.

2015-01-01

Coordination among social animals requires rapid and efficient transfer of information among individuals, which may depend crucially on the underlying structure of the communication network. Establishing the decision-making circuits and networks that give rise to individual behavior has been a central goal of neuroscience. However, the analogous problem of determining the structure of the communication network among organisms that gives rise to coordinated collective behavior, such as is exhibited by schooling fish and flocking birds, has remained almost entirely neglected. Here, we study collective evasion maneuvers, manifested through rapid waves, or cascades, of behavioral change (a ubiquitous behavior among taxa) in schooling fish (Notemigonus crysoleucas). We automatically track the positions and body postures, calculate visual fields of all individuals in schools of ∼150 fish, and determine the functional mapping between socially generated sensory input and motor response during collective evasion. We find that individuals use simple, robust measures to assess behavioral changes in neighbors, and that the resulting networks by which behavior propagates throughout groups are complex, being weighted, directed, and heterogeneous. By studying these interaction networks, we reveal the (complex, fractional) nature of social contagion and establish that individuals with relatively few, but strongly connected, neighbors are both most socially influential and most susceptible to social influence. Furthermore, we demonstrate that we can predict complex cascades of behavioral change at their moment of initiation, before they actually occur. Consequently, despite the intrinsic stochasticity of individual behavior, establishing the hidden communication networks in large self-organized groups facilitates a quantitative understanding of behavioral contagion. PMID:25825752

Consistent Individual Differences Drive Collective Behavior and Group Functioning of Schooling Fish.

PubMed

Jolles, Jolle W; Boogert, Neeltje J; Sridhar, Vivek H; Couzin, Iain D; Manica, Andrea

2017-09-25

The ubiquity of consistent inter-individual differences in behavior ("animal personalities") [1, 2] suggests that they might play a fundamental role in driving the movements and functioning of animal groups [3, 4], including their collective decision-making, foraging performance, and predator avoidance. Despite increasing evidence that highlights their importance [5-16], we still lack a unified mechanistic framework to explain and to predict how consistent inter-individual differences may drive collective behavior. Here we investigate how the structure, leadership, movement dynamics, and foraging performance of groups can emerge from inter-individual differences by high-resolution tracking of known behavioral types in free-swimming stickleback (Gasterosteus aculeatus) shoals. We show that individual's propensity to stay near others, measured by a classic "sociability" assay, was negatively linked to swim speed across a range of contexts, and predicted spatial positioning and leadership within groups as well as differences in structure and movement dynamics between groups. In turn, this trait, together with individual's exploratory tendency, measured by a classic "boldness" assay, explained individual and group foraging performance. These effects of consistent individual differences on group-level states emerged naturally from a generic model of self-organizing groups composed of individuals differing in speed and goal-orientedness. Our study provides experimental and theoretical evidence for a simple mechanism to explain the emergence of collective behavior from consistent individual differences, including variation in the structure, leadership, movement dynamics, and functional capabilities of groups, across social and ecological scales. In addition, we demonstrate individual performance is conditional on group composition, indicating how social selection may drive behavioral differentiation between individuals. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Leader identity as an antecedent of the frequency and consistency of transformational, consideration, and abusive leadership behaviors.

PubMed

Johnson, Russell E; Venus, Merlijn; Lanaj, Klodiana; Mao, Changguo; Chang, Chu-Hsiang

2012-11-01

Drawing from identity-based theories of leadership, we examined relations of leader identity with leader behavior and perceived effectiveness. To do so, we employed multiwave methodology to examine the differential impact of leaders' chronic collective, relational, and individual identities on the frequency and consistency of their subsequent transformational, consideration, and abusive behaviors over a 3-week period. We also examined the relative importance of these leadership behaviors for predicting perceived leader effectiveness as rated by subordinates and peers. Results indicated that leaders' collective and individual identities were uniquely related to transformational and abusive behaviors, respectively. We also observed a significant collective by individual identity interaction, such that abusive behaviors were most frequent when a strong individual identity was paired with a weak collective identity. Frequency of transformational behaviors accounted for the largest proportion of variance in perceived leader effectiveness, followed by frequency of abusive behaviors and consistency of transformational behaviors. We discuss the implications of these findings for leadership theory and development. (c) 2012 APA, all rights reserved.

Handed behavior in hagfish--an ancient vertebrate lineage--and a survey of lateralized behaviors in other invertebrate chordates and elongate vertebrates.

PubMed

Miyashita, Tetsuto; Palmer, A Richard

2014-04-01

Hagfish represent an ancient lineage of boneless and jawless vertebrates. Among several curious behaviors they exhibit, solitary individuals in one dominant genus of hagfish (Eptatretus spp.) regularly rest in a tightly coiled posture. We present the first systematic treatment of this distinctive behavior. Individual northeastern Pacific hagfish (E. stoutii) exhibited significant handedness (preferred orientation of coiling). However, right-coiling and left-coiling individuals were equally common in the population. Individual hagfish likely develop a preference for one direction by repeating the preceding coiling direction. We also revisit classical accounts of chordate natural history and compare the coiling behavior of Eptatretus with other handed or lateralized behaviors in non-vertebrate chordates, lampreys, and derived vertebrates with elongate bodies. Handed behaviors occur in many of these groups, but they likely evolved independently. In contrast to vertebrates, morphological asymmetries may bias lateralized larval behaviors toward one side in cephalochordates and tunicates. As a consequence, no known handed behavior can be inferred to have existed in the common ancestor of vertebrates.

Habit, custom, and power: a multi-level theory of population health.

PubMed

Zimmerman, Frederick J

2013-03-01

In multi-level theory, individual behavior flows from cognitive habits, either directly through social referencing, rules of thumb, or automatic behaviors; or indirectly through the shaping of rationality itself by framing or heuristics. Although behavior does not arise from individually rational optimization, it generally appears to be rational, because the cognitive habits that guide behavior evolve toward optimality. However, power imbalances shaped by particular social, political, and economic structures can distort this evolution, leading to individual behavior that fails to maximize individual or social well-being. Replacing the dominant rational-choice paradigm with a multi-level theoretical paradigm involving habit, custom, and power will enable public health to engage in rigorous new areas of research. Copyright © 2013 Elsevier Ltd. All rights reserved.

Peer group socialization of homophobic attitudes and behavior during adolescence.

PubMed

Poteat, V Paul

2007-01-01

A social developmental framework was applied to test for the socialization of homophobic attitudes and behavior within adolescent peer groups (Grades 7-11; aged 12-17 years). Substantial similarity within and differences across groups were documented. Multilevel models identified a group socializing contextual effect, predicting homophobic attitudes and behavior of individuals within the group 8 months later, even after controlling for the predictive effect of individuals' own previously reported attitudes and behavior. Several group characteristics moderated the extent to which individuals' previously reported attitudes predicted later attitudes. Findings indicate the need to integrate the concurrent assessment of individual and social factors to inform the construction of more comprehensive models of how prejudiced attitudes and behaviors develop and are perpetuated.

Friend influence on prosocial behavior: The role of motivational factors and friendship characteristics.

PubMed

Barry, Carolyn McNamara; Wentzel, Kathryn R

2006-01-01

This study examined motivation (prosocial goals), individual characteristics (sex, ethnicity, and grade), and friendship characteristics (affective quality, interaction frequency, and friendship stability) in relation to middle adolescents' prosocial behavior over time. Ninth- and 10th-grade students (N = 208) attending a suburban, mid-Atlantic public high school and having at least 1 reciprocated friendship were followed for 1 year. Hierarchical regression analyses revealed that a friend's behavior is related to an individual's prosocial goal pursuit, which in turn, is related to an individual's prosocial behavior. Further, the affective quality of a friendship and the frequency with which friends interact moderate relations of a friend's prosocial behavior to an individual's prosocial goal pursuit. Copyright 2006 APA, all rights reserved.

Friendship networks and physical activity and sedentary behavior among youth: a systematized review.

PubMed

Sawka, Keri Jo; McCormack, Gavin R; Nettel-Aguirre, Alberto; Hawe, Penelope; Doyle-Baker, Patricia K

2013-12-01

Low levels of physical activity and increased participation in sedentary leisure-time activities are two important obesity-risk behaviors that impact the health of today's youth. Friend's health behaviors have been shown to influence individual health behaviors; however, current evidence on the specific role of friendship networks in relation to levels of physical activity and sedentary behavior is limited. The purpose of this review was to summarize evidence on friendship networks and both physical activity and sedentary behavior among children and adolescents. After a search of seven scientific databases and reference scans, a total of thirteen articles were eligible for inclusion. All assessed the association between friendship networks and physical activity, while three also assessed sedentary behavior. Overall, higher levels of physical activity among friends are associated with higher levels of physical activity of the individual. Longitudinal studies reveal that an individual's level of physical activity changes to reflect his/her friends' higher level of physical activity. Boys tend to be influenced by their friendship network to a greater extent than girls. There is mixed evidence surrounding a friend's sedentary behavior and individual sedentary behavior. Friends' physical activity level appears to have a significant influence on individual's physical activity level. Evidence surrounding sedentary behavior is limited and mixed. Results from this review could inform effective public health interventions that harness the influence of friends to increase physical activity levels among children and adolescents.

Planarians as a Model to Assess In Vivo the Role of Matrix Metalloproteinase Genes during Homeostasis and Regeneration

PubMed Central

Isolani, Maria Emilia; Abril, Josep F.; Saló, Emili; Deri, Paolo; Bianucci, Anna Maria; Batistoni, Renata

2013-01-01

Matrix metalloproteinases (MMPs) are major executors of extracellular matrix remodeling and, consequently, play key roles in the response of cells to their microenvironment. The experimentally accessible stem cell population and the robust regenerative capabilities of planarians offer an ideal model to study how modulation of the proteolytic system in the extracellular environment affects cell behavior in vivo. Genome-wide identification of Schmidtea mediterranea MMPs reveals that planarians possess four mmp-like genes. Two of them (mmp1 and mmp2) are strongly expressed in a subset of secretory cells and encode putative matrilysins. The other genes (mt-mmpA and mt-mmpB) are widely expressed in postmitotic cells and appear structurally related to membrane-type MMPs. These genes are conserved in the planarian Dugesia japonica. Here we explore the role of the planarian mmp genes by RNA interference (RNAi) during tissue homeostasis and regeneration. Our analyses identify essential functions for two of them. Following inhibition of mmp1 planarians display dramatic disruption of tissues architecture and significant decrease in cell death. These results suggest that mmp1 controls tissue turnover, modulating survival of postmitotic cells. Unexpectedly, the ability to regenerate is unaffected by mmp1(RNAi). Silencing of mt-mmpA alters tissue integrity and delays blastema growth, without affecting proliferation of stem cells. Our data support the possibility that the activity of this protease modulates cell migration and regulates anoikis, with a consequent pivotal role in tissue homeostasis and regeneration. Our data provide evidence of the involvement of specific MMPs in tissue homeostasis and regeneration and demonstrate that the behavior of planarian stem cells is critically dependent on the microenvironment surrounding these cells. Studying MMPs function in the planarian model provides evidence on how individual proteases work in vivo in adult tissues. These results have high potential to generate significant information for development of regenerative and anti cancer therapies. PMID:23405188

Planarians as a model to assess in vivo the role of matrix metalloproteinase genes during homeostasis and regeneration.

PubMed

Isolani, Maria Emilia; Abril, Josep F; Saló, Emili; Deri, Paolo; Bianucci, Anna Maria; Batistoni, Renata

2013-01-01

Matrix metalloproteinases (MMPs) are major executors of extracellular matrix remodeling and, consequently, play key roles in the response of cells to their microenvironment. The experimentally accessible stem cell population and the robust regenerative capabilities of planarians offer an ideal model to study how modulation of the proteolytic system in the extracellular environment affects cell behavior in vivo. Genome-wide identification of Schmidtea mediterranea MMPs reveals that planarians possess four mmp-like genes. Two of them (mmp1 and mmp2) are strongly expressed in a subset of secretory cells and encode putative matrilysins. The other genes (mt-mmpA and mt-mmpB) are widely expressed in postmitotic cells and appear structurally related to membrane-type MMPs. These genes are conserved in the planarian Dugesia japonica. Here we explore the role of the planarian mmp genes by RNA interference (RNAi) during tissue homeostasis and regeneration. Our analyses identify essential functions for two of them. Following inhibition of mmp1 planarians display dramatic disruption of tissues architecture and significant decrease in cell death. These results suggest that mmp1 controls tissue turnover, modulating survival of postmitotic cells. Unexpectedly, the ability to regenerate is unaffected by mmp1(RNAi). Silencing of mt-mmpA alters tissue integrity and delays blastema growth, without affecting proliferation of stem cells. Our data support the possibility that the activity of this protease modulates cell migration and regulates anoikis, with a consequent pivotal role in tissue homeostasis and regeneration. Our data provide evidence of the involvement of specific MMPs in tissue homeostasis and regeneration and demonstrate that the behavior of planarian stem cells is critically dependent on the microenvironment surrounding these cells. Studying MMPs function in the planarian model provides evidence on how individual proteases work in vivo in adult tissues. These results have high potential to generate significant information for development of regenerative and anti cancer therapies.

Growth and instability of a phospholipid vesicle in a bath of fatty acids

NASA Astrophysics Data System (ADS)

Dervaux, J.; Noireaux, V.; Libchaber, A. J.

2017-06-01

Using a microfluidic trap, we study the behavior of individual phospholipid vesicles in contact with fatty acids. We show that spontaneous fatty acids insertion inside the bilayer is controlled by the vesicle size, osmotic pressure difference across the membrane and fatty acids concentration in the external bath. Depending on these parameters, vesicles can grow spherically or become unstable and fragment into several daughter vesicles. We establish the phase diagram for vesicle growth and we derive a simple thermodynamic model that reproduces the time evolution of the vesicle volume. Finally, we show that stable growth can be achieved on an artificial cell expressing a simple set of bacterial cytoskeletal proteins, paving the way toward artificial cell reproduction.

The group migration of Dictyostelium cells is regulated by extracellular chemoattractant degradation.

PubMed

Garcia, Gene L; Rericha, Erin C; Heger, Christopher D; Goldsmith, Paul K; Parent, Carole A

2009-07-01

Starvation of Dictyostelium induces a developmental program in which cells form an aggregate that eventually differentiates into a multicellular structure. The aggregate formation is mediated by directional migration of individual cells that quickly transition to group migration in which cells align in a head-to-tail manner to form streams. Cyclic AMP acts as a chemoattractant and its production, secretion, and degradation are highly regulated. A key protein is the extracellular phosphodiesterase PdsA. In this study we examine the role and localization of PdsA during chemotaxis and streaming. We find that pdsA(-) cells respond chemotactically to a narrower range of chemoattractant concentrations compared with wild-type (WT) cells. Moreover, unlike WT cells, pdsA(-) cells do not form streams at low cell densities and form unusual thick and transient streams at high cell densities. We find that the intracellular pool of PdsA is localized to the endoplasmic reticulum, which may provide a compartment for storage and secretion of PdsA. Because we find that cAMP synthesis is normal in cells lacking PdsA, we conclude that signal degradation regulates the external cAMP gradient field generation and that the group migration behavior of these cells is compromised even though their signaling machinery is intact.

The Group Migration of Dictyostelium Cells Is Regulated by Extracellular Chemoattractant Degradation

PubMed Central

Garcia, Gene L.; Rericha, Erin C.; Heger, Christopher D.; Goldsmith, Paul K.

2009-01-01

Starvation of Dictyostelium induces a developmental program in which cells form an aggregate that eventually differentiates into a multicellular structure. The aggregate formation is mediated by directional migration of individual cells that quickly transition to group migration in which cells align in a head-to-tail manner to form streams. Cyclic AMP acts as a chemoattractant and its production, secretion, and degradation are highly regulated. A key protein is the extracellular phosphodiesterase PdsA. In this study we examine the role and localization of PdsA during chemotaxis and streaming. We find that pdsA− cells respond chemotactically to a narrower range of chemoattractant concentrations compared with wild-type (WT) cells. Moreover, unlike WT cells, pdsA− cells do not form streams at low cell densities and form unusual thick and transient streams at high cell densities. We find that the intracellular pool of PdsA is localized to the endoplasmic reticulum, which may provide a compartment for storage and secretion of PdsA. Because we find that cAMP synthesis is normal in cells lacking PdsA, we conclude that signal degradation regulates the external cAMP gradient field generation and that the group migration behavior of these cells is compromised even though their signaling machinery is intact. PMID:19477920

Laser bioprinting of human induced pluripotent stem cells-the effect of printing and biomaterials on cell survival, pluripotency, and differentiation.

PubMed

Koch, Lothar; Deiwick, Andrea; Franke, Annika; Schwanke, Kristin; Haverich, Axel; Zweigerdt, Robert; Chichkov, Boris

2018-04-25

Research on human induced pluripotent stem cells (hiPSCs) is one of the fastest growing fields in biomedicine. Generated from patient's own somatic cells, hiPSCs can be differentiated towards all functional cell types and returned to the patient without immunological concerns. 3D printing of hiPSCs could enable the generation of functional organs for replacement therapies or realization of organ-on-chip systems for individualized medicine. Printing of living cells was demonstrated with immortalized cell lines, primary cells, and adult stem cells with different printing technologies and biomaterials. However, hiPSCs are more sensitive to handling procedures, in particular, when dissociated into single cells. Both pluripotency and directed differentiation are influenced by numerous environmental factors including culture media, biomaterials, and cell density. Notably, existing literature on the effect of applied biomaterials on pluripotency is rather ambiguous. In this study, laser bioprinting of undifferentiated hiPSCs in combination with different biomaterials was performed and the impact on cells' behavior, pluripotency, and differentiation was investigated. Our findings suggest that hiPSCs are indeed more sensitive to the applied biomaterials, but not to laser printing itself. With appropriate biomaterials, such as the hyaluronic acid based solutions applied in this study, hiPSCs can be successfully laser printed without losing their pluripotency.

Dancing Styles of Collective Cell Migration: Image-Based Computational Analysis of JRAB/MICAL-L2.

PubMed

Sakane, Ayuko; Yoshizawa, Shin; Yokota, Hideo; Sasaki, Takuya

2018-01-01

Collective cell migration is observed during morphogenesis, angiogenesis, and wound healing, and this type of cell migration also contributes to efficient metastasis in some kinds of cancers. Because collectively migrating cells are much better organized than a random assemblage of individual cells, there seems to be a kind of order in migrating clusters. Extensive research has identified a large number of molecules involved in collective cell migration, and these factors have been analyzed using dramatic advances in imaging technology. To date, however, it remains unclear how myriad cells are integrated as a single unit. Recently, we observed unbalanced collective cell migrations that can be likened to either precision dancing or awa-odori , Japanese traditional dancing similar to the style at Rio Carnival, caused by the impairment of the conformational change of JRAB/MICAL-L2. This review begins with a brief history of image-based computational analyses on cell migration, explains why quantitative analysis of the stylization of collective cell behavior is difficult, and finally introduces our recent work on JRAB/MICAL-L2 as a successful example of the multidisciplinary approach combining cell biology, live imaging, and computational biology. In combination, these methods have enabled quantitative evaluations of the "dancing style" of collective cell migration.

Histone H4 acetylation regulates behavioral inter-individual variability in zebrafish.

PubMed

Román, Angel-Carlos; Vicente-Page, Julián; Pérez-Escudero, Alfonso; Carvajal-González, Jose M; Fernández-Salguero, Pedro M; de Polavieja, Gonzalo G

2018-04-25

Animals can show very different behaviors even in isogenic populations, but the underlying mechanisms to generate this variability remain elusive. We use the zebrafish (Danio rerio) as a model to test the influence of histone modifications on behavior. We find that laboratory and isogenic zebrafish larvae show consistent individual behaviors when swimming freely in identical wells or in reaction to stimuli. This behavioral inter-individual variability is reduced when we impair the histone deacetylation pathway. Individuals with high levels of histone H4 acetylation, and specifically H4K12, behave similarly to the average of the population, but those with low levels deviate from it. More precisely, we find a set of genomic regions whose histone H4 acetylation is reduced with the distance between the individual and the average population behavior. We find evidence that this modulation depends on a complex of Yin-yang 1 (YY1) and histone deacetylase 1 (HDAC1) that binds to and deacetylates these regions. These changes are not only maintained at the transcriptional level but also amplified, as most target regions are located near genes encoding transcription factors. We suggest that stochasticity in the histone deacetylation pathway participates in the generation of genetic-independent behavioral inter-individual variability.

Alcohol, aging, and innate immunity.

PubMed

Boule, Lisbeth A; Kovacs, Elizabeth J

2017-07-01

The global population is aging: in 2010, 8% of the population was older than 65 y, and that is expected to double to 16% by 2050. With advanced age comes a heightened prevalence of chronic diseases. Moreover, elderly humans fair worse after acute diseases, namely infection, leading to higher rates of infection-mediated mortality. Advanced age alters many aspects of both the innate and adaptive immune systems, leading to impaired responses to primary infection and poor development of immunologic memory. An often overlooked, yet increasingly common, behavior in older individuals is alcohol consumption. In fact, it has been estimated that >40% of older adults consume alcohol, and evidence reveals that >10% of this group is drinking more than the recommended limit by the National Institute on Alcohol Abuse and Alcoholism. Alcohol consumption, at any level, alters host immune responses, including changes in the number, phenotype, and function of innate and adaptive immune cells. Thus, understanding the effect of alcohol ingestion on the immune system of older individuals, who are already less capable of combating infection, merits further study. However, there is currently almost nothing known about how drinking alters innate immunity in older subjects, despite innate immune cells being critical for host defense, resolution of inflammation, and maintenance of immune homeostasis. Here, we review the effects of aging and alcohol consumption on innate immune cells independently and highlight the few studies that have examined the effects of alcohol ingestion in aged individuals. © Society for Leukocyte Biology.

Fitness landscape transformation through a single amino acid change in the rho terminator.

PubMed

Freddolino, Peter L; Goodarzi, Hani; Tavazoie, Saeed

2012-05-01

Regulatory networks allow organisms to match adaptive behavior to the complex and dynamic contingencies of their native habitats. Upon a sudden transition to a novel environment, the mismatch between the native behavior and the new niche provides selective pressure for adaptive evolution through mutations in elements that control gene expression. In the case of core components of cellular regulation and metabolism, with broad control over diverse biological processes, such mutations may have substantial pleiotropic consequences. Through extensive phenotypic analyses, we have characterized the systems-level consequences of one such mutation (rho*) in the global transcriptional terminator Rho of Escherichia coli. We find that a single amino acid change in Rho results in a massive change in the fitness landscape of the cell, with widely discrepant fitness consequences of identical single locus perturbations in rho* versus rho(WT) backgrounds. Our observations reveal the extent to which a single regulatory mutation can transform the entire fitness landscape of the cell, causing a massive change in the interpretation of individual mutations and altering the evolutionary trajectories which may be accessible to a bacterial population.

Competing dynamic phases of active polymer networks

NASA Astrophysics Data System (ADS)

Freedman, Simon; Banerjee, Shiladitya; Dinner, Aaron R.

Recent experiments on in-vitro reconstituted assemblies of F-actin, myosin-II motors, and cross-linking proteins show that tuning local network properties can changes the fundamental biomechanical behavior of the system. For example, by varying cross-linker density and actin bundle rigidity, one can switch between contractile networks useful for reshaping cells, polarity sorted networks ideal for directed molecular transport, and frustrated networks with robust structural properties. To efficiently investigate the dynamic phases of actomyosin networks, we developed a coarse grained non-equilibrium molecular dynamics simulation of model semiflexible filaments, molecular motors, and cross-linkers with phenomenologically defined interactions. The simulation's accuracy was verified by benchmarking the mechanical properties of its individual components and collective behavior against experimental results at the molecular and network scales. By adjusting the model's parameters, we can reproduce the qualitative phases observed in experiment and predict the protein characteristics where phase crossovers could occur in collective network dynamics. Our model provides a framework for understanding cells' multiple uses of actomyosin networks and their applicability in materials research. Supported by the Department of Defense (DoD) through the National Defense Science & Engineering Graduate Fellowship (NDSEG) Program.

Individual and Network Interventions With Injection Drug Users in 5 Ukraine Cities

PubMed Central

Lehman, Wayne E. K.; Latkin, Carl A.; Dvoryak, Sergey; Brewster, John T.; Royer, Mark S.; Sinitsyna, Larisa

2011-01-01

Objectives. We evaluated the effects of an individual intervention versus a network intervention on HIV-related injection and sexual risk behaviors among street-recruited opiate injection drug users in 5 Ukraine cities. Methods. Between 2004 and 2006, 722 opiate injection drug users were recruited to participate in interventions that were either individually based or based on a social network model in which peer educators intervened with their network members. Audio computer-assisted self-interview techniques were used to interview participants at baseline and follow-up. Results. Multiple logistic analyses controlling for baseline injection and sexual risks revealed that both peer educators and network members in the network intervention reduced injection-related risk behaviors significantly more than did those in the individually based intervention and that peer educators increased condom use significantly more than did those in the individual intervention. Individual intervention participants, however, showed significantly greater improvements than did network members with respect to reductions in sexual risk behaviors. Conclusions. Social network interventions may be more effective than individually based interventions in changing injection risk behaviors among both peer educators and network members. The effectiveness of network interventions in changing sexual risk behaviors is less clear, probably owing to network composition and inhibitions regarding discussing sexual risk behaviors. PMID:20395584

The Attitude-Behavior Linkage in Behavioral Cascades

ERIC Educational Resources Information Center

Friedkin, Noah E.

2010-01-01

The assumption that individual behavior has an antecedent evaluative foundation is an important component of theories in sociology, psychology, political science, and economics. In its simplest form, the antecedent evaluation is a positive or negative attitude toward an object that may affect an individual's object-related behavior. This attitude…

Stigmatizing Images in Obesity Health Campaign Messages and Healthy Behavioral Intentions

ERIC Educational Resources Information Center

Young, Rachel; Subramanian, Roma; Hinnant, Amanda

2016-01-01

Background: Antiobesity campaigns blaming individual behaviors for obesity have sparked concern that an emphasis on individual behavior may lead to stigmatization of overweight or obese people. Past studies have shown that perpetuating stigma is not effective for influencing behavior. Purpose: This study examined whether stigmatizing or…

Pubertal Timing as a Potential Mediator of Adoption Effects on Problem Behaviors

ERIC Educational Resources Information Center

Brooker, Rebecca J.; Berenbaum, Sheri A.; Bricker, Josh; Corley, Robin P.; Wadsworth, Sally A.

2012-01-01

Adopted children show more problem behaviors than nonadopted children. Given that internationally adopted individuals show earlier puberty than nonadopted individuals, and early puberty is associated with problem behaviors in nonadopted youth, we analyzed data from adopted domestic adoptees to determine whether problem behaviors could be explained…

Understanding Light Harvesting in Radial Junction Amorphous Silicon Thin Film Solar Cells

PubMed Central

Yu, Linwei; Misra, Soumyadeep; Wang, Junzhuan; Qian, Shengyi; Foldyna, Martin; Xu, Jun; Shi, Yi; Johnson, Erik; Cabarrocas, Pere Roca i

2014-01-01

The radial junction (RJ) architecture has proven beneficial for the design of a new generation of high performance thin film photovoltaics. We herein carry out a comprehensive modeling of the light in-coupling, propagation and absorption profile within RJ thin film cells based on an accurate set of material properties extracted from spectroscopic ellipsometry measurements. This has enabled us to understand and evaluate the impact of varying several key parameters on the light harvesting in radially formed thin film solar cells. We found that the resonance mode absorption and antenna-like light in-coupling behavior in the RJ cell cavity can lead to a unique absorption distribution in the absorber that is very different from the situation expected in a planar thin film cell, and that has to be taken into account in the design of high performance RJ thin film solar cells. When compared to the experimental EQE response of real RJ solar cells, this modeling also provides an insightful and powerful tool to resolve the wavelength-dependent contributions arising from individual RJ units and/or from strong light trapping due to the presence of the RJ cell array. PMID:24619197

Nanog Fluctuations in Embryonic Stem Cells Highlight the Problem of Measurement in Cell Biology.

PubMed

Smith, Rosanna C G; Stumpf, Patrick S; Ridden, Sonya J; Sim, Aaron; Filippi, Sarah; Harrington, Heather A; MacArthur, Ben D

2017-06-20

A number of important pluripotency regulators, including the transcription factor Nanog, are observed to fluctuate stochastically in individual embryonic stem cells. By transiently priming cells for commitment to different lineages, these fluctuations are thought to be important to the maintenance of, and exit from, pluripotency. However, because temporal changes in intracellular protein abundances cannot be measured directly in live cells, fluctuations are typically assessed using genetically engineered reporter cell lines that produce a fluorescent signal as a proxy for protein expression. Here, using a combination of mathematical modeling and experiment, we show that there are unforeseen ways in which widely used reporter strategies can systematically disturb the dynamics they are intended to monitor, sometimes giving profoundly misleading results. In the case of Nanog, we show how genetic reporters can compromise the behavior of important pluripotency-sustaining positive feedback loops, and induce a bifurcation in the underlying dynamics that gives rise to heterogeneous Nanog expression patterns in reporter cell lines that are not representative of the wild-type. These findings help explain the range of published observations of Nanog variability and highlight the problem of measurement in live cells. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Method to study cell migration under uniaxial compression

PubMed Central

Srivastava, Nishit; Kay, Robert R.; Kabla, Alexandre J.

2017-01-01

The chemical, physical, and mechanical properties of the extracellular environment have a strong effect on cell migration. Aspects such as pore size or stiffness of the matrix influence the selection of the mechanism used by cells to propel themselves, including by pseudopods or blebbing. How a cell perceives its environment and how such a cue triggers a change in behavior are largely unknown, but mechanics is likely to be involved. Because mechanical conditions are often controlled by modifying the composition of the environment, separating chemical and physical contributions is difficult and requires multiple controls. Here we propose a simple method to impose a mechanical compression on individual cells without altering the composition of the matrix. Live imaging during compression provides accurate information about the cell's morphology and migratory phenotype. Using Dictyostelium as a model, we observe that a compression of the order of 500 Pa flattens the cells under gel by up to 50%. This uniaxial compression directly triggers a transition in the mode of migration from primarily pseudopodial to bleb driven in <30 s. This novel device is therefore capable of influencing cell migration in real time and offers a convenient approach with which to systematically study mechanotransduction in confined environments. PMID:28122819

X-linked Inhibitor of Apoptosis Protein (XIAP) Mediates Cancer Cell Motility via Rho GDP Dissociation Inhibitor (RhoGDI)-dependent Regulation of the Cytoskeleton*

PubMed Central

Liu, Jinyi; Zhang, Dongyun; Luo, Wenjing; Yu, Yonghui; Yu, Jianxiu; Li, Jingxia; Zhang, Xinhai; Zhang, Baolin; Chen, Jingyuan; Wu, Xue-Ru; Rosas-Acosta, Germán; Huang, Chuanshu

2011-01-01

X-linked inhibitor of apoptosis protein (XIAP) overexpression has been found to be associated with malignant cancer progression and aggression in individuals with many types of cancers. However, the molecular basis of XIAP in the regulation of cancer cell biological behavior remains largely unknown. In this study, we found that a deficiency of XIAP expression in human cancer cells by either knock-out or knockdown leads to a marked reduction in β-actin polymerization and cytoskeleton formation. Consistently, cell migration and invasion were also decreased in XIAP-deficient cells compared with parental wild-type cells. Subsequent studies demonstrated that the regulation of cell motility by XIAP depends on its interaction with the Rho GDP dissociation inhibitor (RhoGDI) via the XIAP RING domain. Furthermore, XIAP was found to negatively regulate RhoGDI SUMOylation, which might affect its activity in controlling cell motility. Collectively, our studies provide novel insights into the molecular mechanisms by which XIAP regulates cancer invasion and offer a further theoretical basis for setting XIAP as a potential prognostic marker and specific target for treatment of cancers with metastatic properties. PMID:21402697

Specific role of VTA dopamine neuronal firing rates and morphology in the reversal of anxiety-related, but not depression-related behavior in the ClockΔ19 mouse model of mania.

PubMed

Coque, Laurent; Mukherjee, Shibani; Cao, Jun-Li; Spencer, Sade; Marvin, Marian; Falcon, Edgardo; Sidor, Michelle M; Birnbaum, Shari G; Graham, Ami; Neve, Rachael L; Gordon, Elizabeth; Ozburn, Angela R; Goldberg, Matthew S; Han, Ming-Hu; Cooper, Donald C; McClung, Colleen A

2011-06-01

Lithium has been used extensively for mood stabilization, and it is particularly efficacious in the treatment of bipolar mania. Like other drugs used in the treatment of psychiatric diseases, it has little effect on the mood of healthy individuals. Our previous studies found that mice with a mutation in the Clock gene (ClockΔ19) have a complete behavioral profile that is very similar to human mania, which can be reversed with chronic lithium treatment. However, the cellular and physiological effects that underlie its targeted therapeutic efficacy remain unknown. Here we find that ClockΔ19 mice have an increase in dopaminergic activity in the ventral tegmental area (VTA), and that lithium treatment selectively reduces the firing rate in the mutant mice with no effect on activity in wild-type mice. Furthermore, lithium treatment reduces nucleus accumbens (NAc) dopamine levels selectively in the mutant mice. The increased dopaminergic activity in the Clock mutants is associated with cell volume changes in dopamine neurons, which are also rescued by lithium treatment. To determine the role of dopaminergic activity and morphological changes in dopamine neurons in manic-like behavior, we manipulated the excitability of these neurons by overexpressing an inwardly rectifying potassium channel subunit (Kir2.1) selectively in the VTA of ClockΔ19 mice and wild-type mice using viral-mediated gene transfer. Introduction of this channel mimics the effects of lithium treatment on the firing rate of dopamine neurons in ClockΔ19 mice and leads to a similar change in dopamine cell volume. Furthermore, reduction of dopaminergic firing rates in ClockΔ19 animals results in a normalization of locomotor- and anxiety-related behavior that is very similar to lithium treatment; however, it is not sufficient to reverse depression-related behavior. These results suggest that abnormalities in dopamine cell firing and associated morphology underlie alterations in anxiety-related behavior in bipolar mania, and that the therapeutic effects of lithium come from a reversal of these abnormal phenotypes.

Incoordination among Subcellular Compartments Is Associated with Depression-Like Behavior Induced by Chronic Mild Stress

PubMed Central

Xu, Aiping; Cui, Shan

2016-01-01

Background: Major depressive disorder is characterized as persistent low mood. A chronically stressful life in genetically susceptible individuals is presumably the major etiology that leads to dysfunctions of monoamine and hypothalamus-pituitary-adrenal axis. These pathogenic factors cause neuron atrophy in the limbic system for major depressive disorder. Cell-specific pathophysiology is unclear, so we investigated prelimbic cortical GABAergic neurons and their interaction with glutamatergic neurons in depression-like mice. Methods: Mice were treated with chronic unpredictable mild stress for 3 weeks until they expressed depression-like behaviors confirmed by sucrose preference, Y-maze, and forced swimming tests. The structures and functions of GABAergic and glutamatergic units in prelimbic cortices were studied by cell imaging and electrophysiology in chronic unpredictable mild stress-induced depression mice vs controls. Results: In depression-like mice, prelimbic cortical GABAergic neurons show incoordination among the subcellular compartments, such as decreased excitability and synaptic outputs as well as increased reception from excitatory inputs. GABAergic synapses on glutamatergic cells demonstrate decreased presynaptic innervation and increased postsynaptic responsiveness. Conclusions: Chronic unpredictable mild stress-induced incoordination in prelimbic cortical GABAergic and glutamatergic neurons dysregulates their target neurons, which may be the pathological basis for depressive mood. The rebalance of compatibility among subcellular compartments would be an ideal strategy to treat neural disorders. PMID:26506857

Functional characterization of individual human hematopoietic stem cells cultured at limiting dilution on supportive marrow stromal layers.

PubMed Central

Sutherland, H J; Lansdorp, P M; Henkelman, D H; Eaves, A C; Eaves, C J

1990-01-01

A major goal of current hematopoiesis research is to develop in vitro methods suitable for the measurement and characterization of stem cells with long-term in vivo repopulating potential. Previous studies from several centers have suggested the presence in normal human or murine marrow of a population of very primitive cells that are biologically, physically, and pharmacologically different from cells detectable by short-term colony assays and that can give rise to the latter in long-term cultures (LTCs) containing a competent stromal cell layer. In this report, we show that such cultures can be used to provide a quantitative assay for human "LTC-initiating cells" based on an assessment of the number of clonogenic cells present after 5-8 weeks. Production of derivative clonogenic cells is shown to be absolutely dependent on the presence of a stromal cell feeder. When this requirement is met, the clonogenic cell output (determined by assessment of 5-week-old cultures) is linearly related to the input cell number over a wide range of cell concentrations. Using limiting dilution analysis techniques, we have established the frequency of LTC-initiating cells in normal human marrow to be approximately 1 per 2 X 10(4) cells and in a highly purified CD34-positive subpopulation to be approximately 1 per 50-100 cells. The proliferative capacity exhibited by individual LTC-initiating cells cultured under apparently identical culture conditions was found to be highly variable. Values for the number of clonogenic cells per LTC-initiating cell in 5-week-old cultures ranged from 1 to 30 (the average being 4) with similar levels being detected in positive 8-week-old cultures. Some LTC-initiating cells are multipotent as evidenced by their generation of erythroid as well as granulopoietic progeny. The availability of a system for quantitative analysis of the proliferative and differentiative behavior of this newly defined compartment of primitive human hematopoietic cells should facilitate future studies of specific genetic or microenvironmental parameters involved in the regulation of these cells. Images PMID:2333304

Thin Layer Sensory Cues Affect Antarctic Krill Swimming Kinematics

NASA Astrophysics Data System (ADS)

True, A. C.; Webster, D. R.; Weissburg, M. J.; Yen, J.

2013-11-01

A Bickley jet (laminar, planar free jet) is employed in a recirculating flume system to replicate thin shear and phytoplankton layers for krill behavioral assays. Planar laser-induced fluorescence (LIF) and particle image velocimetry (PIV) measurements quantify the spatiotemporal structure of the chemical and free shear layers, respectively, ensuring a close match to in situ hydrodynamic and biochemical conditions. Path kinematics from digitized trajectories of free-swimming Euphausia superba examine the effects of hydrodynamic sensory cues (deformation rate) and bloom level phytoplankton patches (~1000 cells/mL, Tetraselamis spp.) on krill behavior (body orientation, swimming modes and kinematics, path fracticality). Krill morphology is finely tuned for receiving and deciphering both hydrodynamic and chemical information that is vital for basic life processes such as schooling behaviors, predator/prey, and mate interactions. Changes in individual krill behavior in response to ecologically-relevant sensory cues have the potential to produce population-scale phenomena with significant ecological implications. Krill are a vital trophic link between primary producers (phytoplankton) and larger animals (seabirds, whales, fish, penguins, seals) as well as the subjects of a valuable commercial fishery in the Southern Ocean; thus quantifying krill behavioral responses to relevant sensory cues is an important step towards accurately modeling Antarctic ecosystems.

Neural and behavioral correlates of food allergy.

PubMed

Costa-Pinto, Frederico Azevedo; Basso, Alexandre Salgado

2012-01-01

Food allergy accounts for a great number of reactions leading to diminished quality of life in western countries. There has been an abundance of reports of behavioral changes, as well as psychiatric conditions associated with food allergy over the past decades. Most of this field inspired little medical attention for its lack of a solid scientific ground. We review the literature on the association of food allergy and brain activity, leading to changes in emotion and behavior. Moreover, we describe an experimental paradigm employed to dissect the biological relevance of this association. Mice allergic to ovalbumin avoid a palatable sweet solution in order to escape contact with antigen. This choice is associated with increased levels of anxiety, compatible with a conflicting situation. These responses are associated with increased activity in brain areas associated with emotional and affective behavior, which are also important for anxiety and stress responses. Higher levels of corticosterone accompany these changes in behavior. These responses are mediated by specific antibodies and prevented by depletion or immunological tolerance. They are also partially mediated by C-sensitive afferents and mast cells. Far from anecdote, neural repercussions of food allergy should be considered when planning a therapeutic strategy in affected individuals. Copyright © 2012 S. Karger AG, Basel.

The Built Environment and Health: Introducing Individual Space-Time Behavior

PubMed Central

Saarloos, Dick; Kim, Jae-Eun; Timmermans, Harry

2009-01-01

Many studies have examined the relationship between the built environment and health. Yet, the question of how and why the environment influences health behavior remains largely unexplored. As health promotion interventions work through the individuals in a targeted population, an explicit understanding of individual behavior is required to formulate and evaluate intervention strategies. Bringing in concepts from various fields, this paper proposes the use of an activity-based modeling approach for understanding and predicting, from the bottom up, how individuals interact with their environment and each other in space and time, and how their behaviors aggregate to population-level health outcomes. PMID:19578457

Conformity does not perpetuate suboptimal traditions in a wild population of songbirds

PubMed Central

Aplin, Lucy M.; Sheldon, Ben C.; McElreath, Richard

2017-01-01

Social learning is important to the life history of many animals, helping individuals to acquire new adaptive behavior. However despite long-running debate, it remains an open question whether a reliance on social learning can also lead to mismatched or maladaptive behavior. In a previous study, we experimentally induced traditions for opening a bidirectional door puzzle box in replicate subpopulations of the great tit Parus major. Individuals were conformist social learners, resulting in stable cultural behaviors. Here, we vary the rewards gained by these techniques to ask to what extent established behaviors are flexible to changing conditions. When subpopulations with established foraging traditions for one technique were subjected to a reduced foraging payoff, 49% of birds switched their behavior to a higher-payoff foraging technique after only 14 days, with younger individuals showing a faster rate of change. We elucidated the decision-making process for each individual, using a mechanistic learning model to demonstrate that, perhaps surprisingly, this population-level change was achieved without significant asocial exploration and without any evidence for payoff-biased copying. Rather, by combining conformist social learning with payoff-sensitive individual reinforcement (updating of experience), individuals and populations could both acquire adaptive behavior and track environmental change. PMID:28739943

Neural Substrates of Sexual Desire in Individuals with Problematic Hypersexual Behavior

PubMed Central

Seok, Ji-Woo; Sohn, Jin-Hun

2015-01-01

Studies on the characteristics of individuals with hypersexual disorder have been accumulating due to increasing concerns about problematic hypersexual behavior (PHB). Currently, relatively little is known about the underlying behavioral and neural mechanisms of sexual desire. Our study aimed to investigate the neural correlates of sexual desire with event-related functional magnetic resonance imaging (fMRI). Twenty-three individuals with PHB and 22 age-matched healthy controls were scanned while they passively viewed sexual and nonsexual stimuli. The subjects' levels of sexual desire were assessed in response to each sexual stimulus. Relative to controls, individuals with PHB experienced more frequent and enhanced sexual desire during exposure to sexual stimuli. Greater activation was observed in the caudate nucleus, inferior parietal lobe, dorsal anterior cingulate gyrus, thalamus, and dorsolateral prefrontal cortex in the PHB group than in the control group. In addition, the hemodynamic patterns in the activated areas differed between the groups. Consistent with the findings of brain imaging studies of substance and behavior addiction, individuals with the behavioral characteristics of PHB and enhanced desire exhibited altered activation in the prefrontal cortex and subcortical regions. In conclusion, our results will help to characterize the behaviors and associated neural mechanisms of individuals with PHB. PMID:26648855

Motivational Antecedents of Individual Innovation

NASA Astrophysics Data System (ADS)

Picci, Patrizia; Battistelli, Adalgisa

The current work seeks to focus on the innovative work behavior and, in particular, on the stage of idea generation. An important factor that stimulates the individual to carry out the various emergent processes of change and innovation within the organization is known as intrinsic motivation, but under certain conditions, the presence of different forms of extrinsic motivation, as external regulation, introjection, identification and integration, positively influences innovative behavior at work, specifically the creative stage of the process. Starting from this evidence, the organizational environment could be capable of stimulating or indeed inhibiting potential creativity and innovation of individuals. About 100 individuals employees of a local government health department in Central Italy were given an explicit questionnaire. The results show that among external factors that effect the individual such as control, rewards and recognition for work well done, controlled motivation influences overall innovative behavior whereas autonomous motivation plays a significant role in the specific behavior of idea generation. At the same time, it must also be acknowledged that a clearly articulated task which allows an individual to identify with said task, seems to favor overall innovative behavior, whilst a task which allows a fair degree of autonomy influences the behavior of generating ideas.

Phototactic personality in fruit flies and its suppression by serotonin and white.

PubMed

Kain, Jamey S; Stokes, Chris; de Bivort, Benjamin L

2012-11-27

Drosophila typically move toward light (phototax positively) when startled. The various species of Drosophila exhibit some variation in their respective mean phototactic behaviors; however, it is not clear to what extent genetically identical individuals within each species behave idiosyncratically. Such behavioral individuality has indeed been observed in laboratory arthropods; however, the neurobiological factors underlying individual-to-individual behavioral differences are unknown. We developed "FlyVac," a high-throughput device for automatically assessing phototaxis in single animals in parallel. We observed surprising variability within every species and strain tested, including identically reared, isogenic strains. In an extreme example, a domesticated strain of Drosophila simulans harbored both strongly photopositive and strongly photonegative individuals. The particular behavior of an individual fly is not heritable and, because it persists for its lifetime, constitutes a model system for elucidating the molecular mechanisms of personality. Although all strains assayed had greater than expected variation (assuming binomial sampling), some had more than others, implying a genetic basis. Using genetics and pharmacology, we identified the metabolite transporter White and white-dependent serotonin as suppressors of phototactic personality. Because we observed behavioral idiosyncrasy in all experimental groups, we suspect it is present in most behaviors of most animals.

Consumer Brand Choice: Individual and Group Analyses of Demand Elasticity

ERIC Educational Resources Information Center

Oliveira-Castro, Jorge M.; Foxall, Gordon R.; Schrezenmaier, Teresa C.

2006-01-01

Following the behavior-analytic tradition of analyzing individual behavior, the present research investigated demand elasticity of individual consumers purchasing supermarket products, and compared individual and group analyses of elasticity. Panel data from 80 UK consumers purchasing 9 product categories (i.e., baked beans, biscuits, breakfast…

Increased Survival Among HIV-Infected PWID Receiving a Multi-Level HIV Risk and Stigma Reduction Intervention: Results From a Randomized Controlled Trial.

PubMed

Go, Vivian F; Frangakis, Constantine; Le Minh, Nguyen; Ha, Tran Viet; Latkin, Carl A; Sripaipan, Teerada; Zelaya, Carla E; Davis, Wendy W; Celentano, David D; Quan, Vu Minh

2017-02-01

In Vietnam, where 58% of prevalent HIV cases are attributed to people who inject drugs, we evaluated whether a multi-level intervention could improve care outcomes and increase survival. We enrolled 455 HIV-infected males who inject drugs from 32 communes in Thai Nguyen Province. Communes were randomized to a community stigma reduction intervention or standard of care and then within each commune, to an individual enhanced counseling intervention or standard of care, resulting into 4 arms: Arm 1 (standard of care); Arm 2 (community intervention alone); Arm 3 (individual intervention alone); and Arm 4 (community + individual interventions). Follow-up was conducted at 6, 12, 18, and 24 months to assess survival. Overall mortality was 23% (n = 103/455) more than 2 years. There were no losses to follow-up for the mortality endpoint. Survival at 24 months was different across arms: Arm 4 (87%) vs Arm 1 (82%) vs Arm 2 (68%) vs Arm 3 (73%); log-rank test for comparison among arms: P = 0.001. Among those with CD4 cell count <200 cells/mm and not on antiretroviral therapy at baseline (n = 162), survival at 24 months was higher in Arm 4 (84%) compared with other arms (Arm 1: 61%; Arm 2: 50%; Arm 3: 53%; P-value = 0.002). Overall, Arm 4 (community + individual interventions) had increased uptake of antiretroviral therapy compared with Arms 1, 2, and 3. This multi-level behavioral intervention seemed to increase survival of HIV-infected participants more than a 2-year period. Relative to the standard of care, the greatest intervention effect was among those with lower CD4 cell counts.

Changes in Purkinje cell simple spike encoding of reach kinematics during adaption to a mechanical perturbation.

PubMed

Hewitt, Angela L; Popa, Laurentiu S; Ebner, Timothy J

2015-01-21

The cerebellum is essential in motor learning. At the cellular level, changes occur in both the simple spike and complex spike firing of Purkinje cells. Because simple spike discharge reflects the main output of the cerebellar cortex, changes in simple spike firing likely reflect the contribution of the cerebellum to the adapted behavior. Therefore, we investigated in Rhesus monkeys how the representation of arm kinematics in Purkinje cell simple spike discharge changed during adaptation to mechanical perturbations of reach movements. Monkeys rapidly adapted to a novel assistive or resistive perturbation along the direction of the reach. Adaptation consisted of matching the amplitude and timing of the perturbation to minimize its effect on the reach. In a majority of Purkinje cells, simple spike firing recorded before and during adaptation demonstrated significant changes in position, velocity, and acceleration sensitivity. The timing of the simple spike representations change within individual cells, including shifts in predictive versus feedback signals. At the population level, feedback-based encoding of position increases early in learning and velocity decreases. Both timing changes reverse later in learning. The complex spike discharge was only weakly modulated by the perturbations, demonstrating that the changes in simple spike firing can be independent of climbing fiber input. In summary, we observed extensive alterations in individual Purkinje cell encoding of reach kinematics, although the movements were nearly identical in the baseline and adapted states. Therefore, adaption to mechanical perturbation of a reaching movement is accompanied by widespread modifications in the simple spike encoding. Copyright © 2015 the authors 0270-6474/15/351106-19$15.00/0.

Changes in Purkinje Cell Simple Spike Encoding of Reach Kinematics during Adaption to a Mechanical Perturbation

PubMed Central

Hewitt, Angela L.; Popa, Laurentiu S.

2015-01-01

The cerebellum is essential in motor learning. At the cellular level, changes occur in both the simple spike and complex spike firing of Purkinje cells. Because simple spike discharge reflects the main output of the cerebellar cortex, changes in simple spike firing likely reflect the contribution of the cerebellum to the adapted behavior. Therefore, we investigated in Rhesus monkeys how the representation of arm kinematics in Purkinje cell simple spike discharge changed during adaptation to mechanical perturbations of reach movements. Monkeys rapidly adapted to a novel assistive or resistive perturbation along the direction of the reach. Adaptation consisted of matching the amplitude and timing of the perturbation to minimize its effect on the reach. In a majority of Purkinje cells, simple spike firing recorded before and during adaptation demonstrated significant changes in position, velocity, and acceleration sensitivity. The timing of the simple spike representations change within individual cells, including shifts in predictive versus feedback signals. At the population level, feedback-based encoding of position increases early in learning and velocity decreases. Both timing changes reverse later in learning. The complex spike discharge was only weakly modulated by the perturbations, demonstrating that the changes in simple spike firing can be independent of climbing fiber input. In summary, we observed extensive alterations in individual Purkinje cell encoding of reach kinematics, although the movements were nearly identical in the baseline and adapted states. Therefore, adaption to mechanical perturbation of a reaching movement is accompanied by widespread modifications in the simple spike encoding. PMID:25609626